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

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

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 preferredmore » 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.« less

Engineering Archeal Surrogate Systems for the Development of Protein-Protein Interaction Inhibitors against Human RAD51.

PubMed

Moschetti, Tommaso; Sharpe, Timothy; Fischer, Gerhard; Marsh, May E; Ng, Hong Kin; Morgan, Matthew; Scott, Duncan E; Blundell, Tom L; R Venkitaraman, Ashok; Skidmore, John; Abell, Chris; Hyvönen, Marko

2016-11-20

Protein-protein interactions (PPIs) are increasingly important targets for drug discovery. Efficient fragment-based drug discovery approaches to tackle PPIs are often stymied by difficulties in the production of stable, unliganded target proteins. Here, we report an approach that exploits protein engineering to "humanise" thermophilic archeal surrogate proteins as targets for small-molecule inhibitor discovery and to exemplify this approach in the development of inhibitors against the PPI between the recombinase RAD51 and tumour suppressor BRCA2. As human RAD51 has proved impossible to produce in a form that is compatible with the requirements of fragment-based drug discovery, we have developed a surrogate protein system using RadA from Pyrococcus furiosus. Using a monomerised RadA as our starting point, we have adopted two parallel and mutually instructive approaches to mimic the human enzyme: firstly by mutating RadA to increase sequence identity with RAD51 in the BRC repeat binding sites, and secondly by generating a chimeric archaeal human protein. Both approaches generate proteins that interact with a fourth BRC repeat with affinity and stoichiometry comparable to human RAD51. Stepwise humanisation has also allowed us to elucidate the determinants of RAD51 binding to BRC repeats and the contributions of key interacting residues to this interaction. These surrogate proteins have enabled the development of biochemical and biophysical assays in our ongoing fragment-based small-molecule inhibitor programme and they have allowed us to determine hundreds of liganded structures in support of our structure-guided design process, demonstrating the feasibility and advantages of using archeal surrogates to overcome difficulties in handling human proteins. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

PERSISTENCE OF A SURROGATE FOR A GENETICALLY ENGINEERED CELLULOLYTIC MICROORGANISM AND EFFECTS ON AQUATIC COMMUNITY AND ECOSYSTEM PROPERTIES: MICROCOSM AND STREAM COMPARISONS

EPA Science Inventory

Our research objectives were to: (1) determine the persistence of an introduced surrogate (Cellulomonas sp NRC 2406) for a genetically engineered microorganism (GEM) in three streamlined habitats; sediments, growths of Cladophora (Chlorophyta), and leaf packs, (2) test ommunity a...

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.

A reduced mechanism for biodiesel surrogates with low temperature chemistry for compression ignition engine applications

NASA Astrophysics Data System (ADS)

Luo, Zhaoyu; Plomer, Max; Lu, Tianfeng; Som, Sibendu; Longman, Douglas E.

2012-04-01

Biodiesel is a promising alternative fuel for compression ignition (CI) engines. It is a renewable energy source that can be used in these engines without significant alteration in design. The detailed chemical kinetics of biodiesel is however highly complex. In the present study, a skeletal mechanism with 123 species and 394 reactions for a tri-component biodiesel surrogate, which consists of methyl decanoate, methyl 9-decanoate and n-heptane was developed for simulations of 3-D turbulent spray combustion under engine-like conditions. The reduction was based on an improved directed relation graph (DRG) method that is particularly suitable for mechanisms with many isomers, followed by isomer lumping and DRG-aided sensitivity analysis (DRGASA). The reduction was performed for pressures from 1 to 100 atm and equivalence ratios from 0.5 to 2 for both extinction and ignition applications. The initial temperatures for ignition were from 700 to 1800 K. The wide parameter range ensures the applicability of the skeletal mechanism under engine-like conditions. As such the skeletal mechanism is applicable for ignition at both low and high temperatures. Compared with the detailed mechanism that consists of 3299 species and 10806 reactions, the skeletal mechanism features a significant reduction in size while still retaining good accuracy and comprehensiveness. The validations of ignition delay time, flame lift-off length and important species profiles were also performed in 3-D engine simulations and compared with the experimental data from Sandia National Laboratories under CI engine conditions.

Computer-Simulation Surrogates for Optimization: Application to Trapezoidal Ducts and Axisymmetric Bodies

NASA Technical Reports Server (NTRS)

Otto, John C.; Paraschivoiu, Marius; Yesilyurt, Serhat; Patera, Anthony T.

1995-01-01

Engineering design and optimization efforts using computational systems rapidly become resource intensive. The goal of the surrogate-based approach is to perform a complete optimization with limited resources. In this paper we present a Bayesian-validated approach that informs the designer as to how well the surrogate performs; in particular, our surrogate framework provides precise (albeit probabilistic) bounds on the errors incurred in the surrogate-for-simulation substitution. The theory and algorithms of our computer{simulation surrogate framework are first described. The utility of the framework is then demonstrated through two illustrative examples: maximization of the flowrate of fully developed ow in trapezoidal ducts; and design of an axisymmetric body that achieves a target Stokes drag.

Role of Volatility in the Development of JP-8 Surrogates for Diesel Engine Application

DTIC Science & Technology

2014-01-01

distillation curves of the surrogate fuels were calculated using the Aspen HYSYS [41] software package, and the Peng- Robinson model was chosen to...distillation curves for the surrogate fuels developed in this investigation, the accuracy of Aspen HYSYS software predictions were compared with...and SF3. The distillation curves calculated using Aspen HYSYS software for the five surrogate fuels of Table 1 are shown in Figure 7, along with the

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

DOE PAGES

Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.; ...

2012-05-22

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 revolutionizemore » 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

Choice of Tuning Parameters on 3D IC Engine Simulations Using G-Equation

DOE PAGES

Liu, Jinlong; Szybist, James; Dumitrescu, Cosmin

2018-04-03

3D CFD spark-ignition IC engine simulations are extremely complex for the regular user. Truly-predictive CFD simulations for the turbulent flame combustion that solve fully coupled transport/chemistry equations may require large computational capabilities unavailable to regular CFD users. A solution is to use a simpler phenomenological model such as the G-equation that decouples transport/chemistry result. Such simulation can still provide acceptable and faster results at the expense of predictive capabilities. While the G-equation is well understood within the experienced modeling community, the goal of this paper is to document some of them for a novice or less experienced CFD user whomore » may not be aware that phenomenological models of turbulent flame combustion usually require heavy tuning and calibration from the user to mimic experimental observations. This study used ANSYS® Forte, Version 17.2, and the built-in G-equation model, to investigate two tuning constants that influence flame propagation in 3D CFD SI engine simulations: the stretch factor coefficient, Cms and the flame development coefficient, Cm2. After identifying several Cm2-Cms pairs that matched experimental data at one operating conditions, simulation results showed that engine models that used different Cm2-Cms sets predicted similar combustion performance, when the spark timing, engine load, and engine speed were changed from the operating condition used to validate the CFD simulation. A dramatic shift was observed when engine speed was doubled, which suggested that the flame stretch coefficient, Cms, had a much larger influence at higher engine speeds compared to the flame development coefficient, Cm2. Therefore, the Cm2-Cms sets that predicted a higher turbulent flame under higher in-cylinder pressure and temperature increased the peak pressure and efficiency. This suggest that the choice of the Cm2-Cms will affect the G-equation-based simulation accuracy when engine speed increases

Choice of Tuning Parameters on 3D IC Engine Simulations Using G-Equation

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

Liu, Jinlong; Szybist, James; Dumitrescu, Cosmin

3D CFD spark-ignition IC engine simulations are extremely complex for the regular user. Truly-predictive CFD simulations for the turbulent flame combustion that solve fully coupled transport/chemistry equations may require large computational capabilities unavailable to regular CFD users. A solution is to use a simpler phenomenological model such as the G-equation that decouples transport/chemistry result. Such simulation can still provide acceptable and faster results at the expense of predictive capabilities. While the G-equation is well understood within the experienced modeling community, the goal of this paper is to document some of them for a novice or less experienced CFD user whomore » may not be aware that phenomenological models of turbulent flame combustion usually require heavy tuning and calibration from the user to mimic experimental observations. This study used ANSYS® Forte, Version 17.2, and the built-in G-equation model, to investigate two tuning constants that influence flame propagation in 3D CFD SI engine simulations: the stretch factor coefficient, Cms and the flame development coefficient, Cm2. After identifying several Cm2-Cms pairs that matched experimental data at one operating conditions, simulation results showed that engine models that used different Cm2-Cms sets predicted similar combustion performance, when the spark timing, engine load, and engine speed were changed from the operating condition used to validate the CFD simulation. A dramatic shift was observed when engine speed was doubled, which suggested that the flame stretch coefficient, Cms, had a much larger influence at higher engine speeds compared to the flame development coefficient, Cm2. Therefore, the Cm2-Cms sets that predicted a higher turbulent flame under higher in-cylinder pressure and temperature increased the peak pressure and efficiency. This suggest that the choice of the Cm2-Cms will affect the G-equation-based simulation accuracy when engine speed increases

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

PubMed

Chen, En-Qiang; Feng, Shu; Wang, Meng-Lan; Liang, Ling-Bo; Zhou, Ling-Yun; Du, Ling-Yao; Yan, Li-Bo; Tao, Chuan-Min; Tang, Hong

2017-03-14

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

A Multicomponent Blend as a Diesel Fuel Surrogate for Compression Ignition Engine Applications

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

Pei, Yuanjiang; Mehl, Marco; Liu, Wei

A mixture of n-dodecane and m-xylene is investigated as a diesel fuel surrogate for compression ignition engine applications. Compared to neat n-dodecane, this binary mixture is more representative of diesel fuel because it contains an alkyl-benzene which represents an important chemical class present in diesel fuels. A detailed multi-component mechanism for n-dodecane and m-xylene was developed by combining a previously developed n-dodecane mechanism with a recently developed mechanism for xylenes. The xylene mechanism is shown to reproduce experimental ignition data from a rapid compression machine and shock tube, speciation data from the jet stirred reactor and flame speed data. Thismore » combined mechanism was validated by comparing predictions from the model with experimental data for ignition in shock tubes and for reactivity in a flow reactor. The combined mechanism, consisting of 2885 species and 11754 reactions, was reduced to a skeletal mechanism consisting 163 species and 887 reactions for 3D diesel engine simulations. The mechanism reduction was performed using directed relation graph (DRG) with expert knowledge (DRG-X) and DRG-aided sensitivity analysis (DRGASA) at a fixed fuel composition of 77% of n-dodecane and 23% m-xylene by volume. The sample space for the reduction covered pressure of 1 – 80 bar, equivalence ratio of 0.5 – 2.0, and initial temperature of 700 – 1600 K for ignition. The skeletal mechanism was compared with the detailed mechanism for ignition and flow reactor predictions. Finally, the skeletal mechanism was validated against a spray flame dataset under diesel engine conditions documented on the Engine Combustion Network (ECN) website. These multi-dimensional simulations were performed using a Representative Interactive Flame (RIF) turbulent combustion model. Encouraging results were obtained compared to the experiments with regards to the predictions of ignition delay and lift-off length at different ambient temperatures.« less

Solving the 56Ni Puzzle of Magnetar-powered Broad-lined Type IC Supernovae

NASA Astrophysics Data System (ADS)

Wang, Ling-Jun; Han, Yan-Hui; Xu, Dong; Wang, Shan-Qin; Dai, Zi-Gao; Wu, Xue-Feng; Wei, Jian-Yan

2016-11-01

Broad-lined Type Ic supernovae (SNe Ic-BL) are of great importance because their association with long-duration gamma-ray bursts (LGRBs) holds the key to deciphering the central engine of LGRBs, which refrains from being unveiled despite decades of investigation. Among the two popularly hypothesized types of central engine, I.e., black holes and strongly magnetized neutron stars (magnetars), there is mounting evidence that the central engine of GRB-associated SNe (GRB-SNe) is rapidly rotating magnetars. Theoretical analysis also suggests that magnetars could be the central engine of SNe Ic-BL. What puzzled the researchers is the fact that light-curve modeling indicates that as much as 0.2{--}0.5 {M}⊙ of 56Ni was synthesized during the explosion of the SNe Ic-BL, which is unfortunately in direct conflict with current state-of-the-art understanding of magnetar-powered 56Ni synthesis. Here we propose a dynamic model of magnetar-powered SNe to take into account the acceleration of the ejecta by the magnetar, as well as the thermalization of the injected energy. Assuming that the SN kinetic energy comes exclusively from the magnetar acceleration, we find that although a major fraction of the rotational energy of the magnetar is to accelerate the SN ejecta, a tiny fraction of this energy deposited as thermal energy of the ejecta is enough to reduce the needed 56Ni to 0.06 M ⊙ for both SN 1997ef and SN 2007ru. We therefore suggest that magnetars could power SNe Ic-BL in aspects both of energetics and of 56Ni synthesis.

Construction Progress of the S-IC Test Stand Complex Bunker House

NASA Technical Reports Server (NTRS)

1963-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC stand, additional related facilities were built during this time frame. Built to the east of the S-IC stand, the block house served as the control room. To the south of the blockhouse was a newly constructed pump house used for delivering water to the S-IC stand during testing. North of the massive test stand, the F-1 Engine test stand was built for testing a single F-1 engine. Just southeast of the S-IC stand a concrete bunker house was constructed. The bunker housed

The Nutating Engine-Prototype Engine Progress Report and Test Results

NASA Technical Reports Server (NTRS)

Meitner, Peter L.; Boruta, Mike

2006-01-01

A prototype of a new, internal combustion (IC) engine concept has been completed. The Nutating Engine features an internal disk nutating (wobbling) on a Z-shaped power shaft. The engine is exceedingly compact, and several times more power dense than any conventional (reciprocating or rotary) IC engine. This paper discusses lessons learned during the prototype engine's development and provides details of its construction. In addition, results of the initial performance tests of the various components, as well as the complete engine, are summarized.

Simultaneous Study of Intake and In-Cylinder IC Engine Flow Fields to Provide an Insight into Intake Induced Cyclic Variations

NASA Astrophysics Data System (ADS)

Justham, T.; Jarvis, S.; Clarke, A.; Garner, C. P.; Hargrave, G. K.; Halliwell, N. A.

2006-07-01

Simultaneous intake and in-cylinder digital particle image velocimetry (DPIV) experimental data is presented for a motored spark ignition (SI) optical internal combustion (IC) engine. Two individual DPIV systems were employed to study the inter-relationship between the intake and in-cylinder flow fields at an engine speed of 1500 rpm. Results for the intake runner velocity field at the time of maximum intake valve lift are compared to incylinder velocity fields later in the same engine cycle. Relationships between flow structures within the runner and cylinder were seen to be strong during the intake stroke but less significant during compression. Cyclic variations within the intake runner were seen to affect the large scale bulk flow motion. The subsequent decay of the large scale motions into smaller scale turbulent structures during the compression stroke appear to reduce the relationship with the intake flow variations.

Surrogate matrix and surrogate analyte approaches for definitive quantitation of endogenous biomolecules.

PubMed

Jones, Barry R; Schultz, Gary A; Eckstein, James A; Ackermann, Bradley L

2012-10-01

Quantitation of biomarkers by LC-MS/MS is complicated by the presence of endogenous analytes. This challenge is most commonly overcome by calibration using an authentic standard spiked into a surrogate matrix devoid of the target analyte. A second approach involves use of a stable-isotope-labeled standard as a surrogate analyte to allow calibration in the actual biological matrix. For both methods, parallelism between calibration standards and the target analyte in biological matrix must be demonstrated in order to ensure accurate quantitation. In this communication, the surrogate matrix and surrogate analyte approaches are compared for the analysis of five amino acids in human plasma: alanine, valine, methionine, leucine and isoleucine. In addition, methodology based on standard addition is introduced, which enables a robust examination of parallelism in both surrogate analyte and surrogate matrix methods prior to formal validation. Results from additional assays are presented to introduce the standard-addition methodology and to highlight the strengths and weaknesses of each approach. For the analysis of amino acids in human plasma, comparable precision and accuracy were obtained by the surrogate matrix and surrogate analyte methods. Both assays were well within tolerances prescribed by regulatory guidance for validation of xenobiotic assays. When stable-isotope-labeled standards are readily available, the surrogate analyte approach allows for facile method development. By comparison, the surrogate matrix method requires greater up-front method development; however, this deficit is offset by the long-term advantage of simplified sample analysis.

Surrogate data--a secure way to share corporate data.

PubMed

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

2005-01-01

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.

Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

PubMed

Rasnake, Crystal M; Trumbo, Paula R; Heinonen, Therese M

2008-02-01

This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim.

Men Working on Mock-Up of S-IC Thrust Structure

NASA Technical Reports Server (NTRS)

1963-01-01

This photograph depicts Marshall Space Flight Center employees, James Reagin, machinist (top); Floyd McGinnis, machinist; and Ernest Davis, experimental test mechanic (foreground), working on a mock up of the S-IC thrust structure. The S-IC stage is the first stage, or booster, of the 364-foot long Saturn V rocket that ultimately took astronauts to the Moon. The S-IC stage, burned over 15 tons of propellant per second during its 2.5 minutes of operation to take the vehicle to a height of about 36 miles and to a speed of about 6,000 miles per hour. The stage was 138 feet long and 33 feet in diameter. Operating at maximum power, all five of the engines produced 7,500,000 pounds of thrust.

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.

Mod 1 ICS TI Report: ICS Conversion of a 140% HPGe Detector

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

Bounds, John Alan

This report evaluates the Mod 1 ICS, an electrically cooled 140% HPGe detector. It is a custom version of the ORTEC Integrated Cooling System (ICS) modified to make it more practical for us to use in the field. Performance and operating characteristics of the Mod 1 ICS are documented, noting both pros and cons. The Mod 1 ICS is deemed a success. Recommendations for a Mod 2 ICS, a true field prototype, are provided.

Institutional computing (IC) information session

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

Koch, Kenneth R; Lally, Bryan R

2011-01-19

The LANL Institutional Computing Program (IC) will host an information session about the current state of unclassified Institutional Computing at Los Alamos, exciting plans for the future, and the current call for proposals for science and engineering projects requiring computing. Program representatives will give short presentations and field questions about the call for proposals and future planned machines, and discuss technical support available to existing and future projects. Los Alamos has started making a serious institutional investment in open computing available to our science projects, and that investment is expected to increase even more.

Chemistry and the Internal Combustion Engine II: Pollution Problems.

ERIC Educational Resources Information Center

Hunt, C. B.

1979-01-01

Discusses pollution problems which arise from the use of internal combustion (IC) engines in the United Kingdom (UK). The IC engine exhaust emissions, controlling IC engine pollution in the UK, and some future developments are also included. (HM)

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

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

Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.

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 revolutionizemore » 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

Airfoil Shape Optimization based on Surrogate Model

NASA Astrophysics Data System (ADS)

Mukesh, R.; Lingadurai, K.; Selvakumar, U.

2018-02-01

Engineering design problems always require enormous amount of real-time experiments and computational simulations in order to assess and ensure the design objectives of the problems subject to various constraints. In most of the cases, the computational resources and time required per simulation are large. In certain cases like sensitivity analysis, design optimisation etc where thousands and millions of simulations have to be carried out, it leads to have a life time of difficulty for designers. Nowadays approximation models, otherwise called as surrogate models (SM), are more widely employed in order to reduce the requirement of computational resources and time in analysing various engineering systems. Various approaches such as Kriging, neural networks, polynomials, Gaussian processes etc are used to construct the approximation models. The primary intention of this work is to employ the k-fold cross validation approach to study and evaluate the influence of various theoretical variogram models on the accuracy of the surrogate model construction. Ordinary Kriging and design of experiments (DOE) approaches are used to construct the SMs by approximating panel and viscous solution algorithms which are primarily used to solve the flow around airfoils and aircraft wings. The method of coupling the SMs with a suitable optimisation scheme to carryout an aerodynamic design optimisation process for airfoil shapes is also discussed.

Challenge of surrogate endpoints.

PubMed

Furgerson, James L; Hannah, William N; Thompson, Jennifer C

2012-03-01

Surrogate endpoints are biomarkers that are intended to substitute for clinical endpoints. They have been used to find novel therapeutic targets, improve the statistical power and shorten the duration of clinical trials, and control the cost of conducting research studies. The more generalized use of surrogate endpoints in clinical decision making can be hazardous and should be undertaken with great caution. This article reviews prior work with surrogate endpoints and highlights caveats and lessons learned from studies using surrogate endpoints.

Surrogate Agreement in Tzotzil.

ERIC Educational Resources Information Center

Aissen, Judith L.

This study investigates whether other relationships in sentence structure besides the "brother-in-law" relation sanction surrogate agreement in Zinacanteco Tzotzil (Mayan). Surrogate agreement refers to cases in which an element that lies outside the class of regular agreement controllers in a language (the surrogate) controls…

ICS logging solution for network-based attacks using Gumistix technology

NASA Astrophysics Data System (ADS)

Otis, Jeremy R.; Berman, Dustin; Butts, Jonathan; Lopez, Juan

2013-05-01

Industrial Control Systems (ICS) monitor and control operations associated with the national critical infrastructure (e.g., electric power grid, oil and gas pipelines and water treatment facilities). These systems rely on technologies and architectures that were designed for system reliability and availability. Security associated with ICS was never an inherent concern, primarily due to the protections afforded by network isolation. However, a trend in ICS operations is to migrate to commercial networks via TCP/IP in order to leverage commodity benefits and cost savings. As a result, system vulnerabilities are now exposed to the online community. Indeed, recent research has demonstrated that many exposed ICS devices are being discovered using readily available applications (e.g., ShodanHQ search engine and Google-esque queries). Due to the lack of security and logging capabilities for ICS, most knowledge about attacks are derived from real world incidents after an attack has already been carried out and the damage has been done. This research provides a method for introducing sensors into the ICS environment that collect information about network-based attacks. The sensors are developed using an inexpensive Gumstix platform that can be deployed and incorporated with production systems. Data obtained from the sensors provide insight into attack tactics (e.g., port scans, Nessus scans, Metasploit modules, and zero-day exploits) and characteristics (e.g., attack origin, frequency, and level of persistence). Findings enable security professionals to draw an accurate, real-time awareness of the threats against ICS devices and help shift the security posture from reactionary to preventative.

Development of a surrogate biomodel for the investigation of clubfoot bracing.

PubMed

Dimeo, Andrew J; Lalush, David S; Grant, Edward; Morcuende, Jose A

2012-01-01

Congenital talipes equinovarus (clubfoot) is a complex deformity of the lower extremity and foot occurring in 1/1000 live births. Regardless of treatment, whether conservative or surgical, clubfoot has a stubborn tendency to relapse, thus requiring postcorrection bracing. However, to date, there are no investigations specifically focused on clubfoot bracing from a bioengineering perspective. This study applied engineering principles to clubfoot bracing through construction of a surrogate biomodel. The surrogate was developed to represent an average 5-year-old human subject capable of biomechanical characteristics including joint articulation and kinematics. The components include skeleton, articulating joints, muscle-tendon systems, and ligaments. A protocol was developed to measure muscle-tendon tension in resting and braced positions of the surrogate. Measurement error ranged from 1% to 6% and was considered variance due to brace and investigator. In conclusion, this study shows that surrogate biomodeling is an accurate and repeatable method to investigate clubfoot bracing. The methodology is an effective means to evaluate wide ranging brace options and can be used to assist in future brace development and the tuning of brace parameters. Such patient-specific brace tuning may also lead to advanced braces that increase compliance.

Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

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

Wayne, David Matthew

The actinide engineering and science group (MET-1) have completed simultaneous thermal analysis and offgas analysis by mass spectrometry (STA-MS) of remediated nitrate salt (RNS) surrogates formulated by the high explosives science and technology group (M-7). The 1.0 to 1.5g surrogate samples were first analyzed as received, then a new set was analyzed with 100-200mL 10M HNO 3 +0.3 MHF added, and a third set was analyzed after 200 mL of a concentrated Pu-AM spike (in 10M HNO 3 +0.3 MHF) was added. The acid and spike solutions were formulated by the actinide analytical chemistry group (C-AAC) using reagent-grade HNO 3more » and HF, which was also used to dissolve a small quantity of mixed, high-fired PuO 2/ AmO 2 oxide.« less

Surrogate waveform models

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Surrogate Poster Artist Concept

NASA Image and Video Library

2015-03-11

This artist's concept shows Surrogate, a robot that could one day assist in disasters or hazardous situations such as a dangerous chemical laboratory. Surrogate was designed and built at the Jet Propulsion Laboratory in Pasadena, California. Its components came from RoboSimian, another JPL-built robot designed for disaster relief and mitigation (see PIA19313). Surrogate rolls on a track rather than moving on its limbs. http://photojournal.jpl.nasa.gov/catalog/PIA19314

Licensing Surrogate Decision-Makers.

PubMed

Rosoff, Philip M

2017-06-01

As medical technology continues to improve, more people will live longer lives with multiple chronic illnesses with increasing cumulative debilitation, including cognitive dysfunction. Combined with the aging of society in most developed countries, an ever-growing number of patients will require surrogate decision-makers. While advance care planning by patients still capable of expressing their preferences about medical interventions and end-of-life care can improve the quality and accuracy of surrogate decisions, this is often not the case, not infrequently leading to demands for ineffective, inappropriate and prolonged interventions. In 1980 LaFollette called for the licensing of prospective parents, basing his argument on the harm they can do to vulnerable people (children). In this paper, I apply his arguments to surrogate decision-makers for cognitively incapacitated patients, rhetorically suggesting that we require potential surrogates to qualify for this position by demonstrating their ability to make reasonable and rational decisions for others. I employ this theoretical approach to argue that the loose criteria by which we authorize surrogates' generally unchallenged power should be reconsidered.

R&D100: IC ID

ScienceCinema

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

2018-06-25

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Surrogate losses: Understandings of pregnancy loss and assisted reproduction among surrogate mothers.

PubMed

Berend, Zsuzsa

2010-06-01

I explore surrogate mothers' narrative construction of pregnancy loss on surrogacy support websites. Communicating via the Internet, women construct the public online world of surrogacy. Drawing on anthropological and sociological literature I investigate the connections between conceptualizations of loss and understandings of technological practices and the consequences of these understandings for assisted reproduction. Surrogate mothers define loss broadly, ranging from failure to conceive to miscarriage and stillbirth; loss means the failure to give a baby to the intended parents. Assisted reproductive technologies contribute to loss by raising expectations of success, by attempting to maximize results through the transfer of multiple fertilized ova, and by early monitoring and testing. However, surrogates collectively understand technology as a positive force and advocate for reproductive technology. Surrogates' resolve to "give the gift of life" makes them vulnerable to failure and loss, yet also informs repeated efforts to bear children for others with technological assistance.

Evaluating Candidate Principal Surrogate Endpoints

PubMed Central

Gilbert, Peter B.; Hudgens, Michael G.

2009-01-01

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection. PMID:18363776

Surrogacy: the experiences of surrogate mothers.

PubMed

Jadva, Vasanti; Murray, Clare; Lycett, Emma; MacCallum, Fiona; Golombok, Susan

2003-10-01

This study examined the motivations, experiences and psychological consequences of surrogacy for surrogate mothers. Thirty-four women who had given birth to a surrogate child approximately 1 year previously were interviewed by trained researchers, and the data rated using standardized coding criteria. Information was obtained on: (i) reasons for the woman's decision to become a surrogate mother; (ii) her retrospective view of the relationship with the commissioning couple before the pregnancy, during the pregnancy, and after the birth; (iii) her experiences during and after relinquishing the child; and (iv) how others reacted to her decision to become a surrogate mother. It was found that surrogate mothers do not generally experience major problems in their relationship with the commissioning couple, in handing over the baby, or from the reactions of those around them. The emotional problems experienced by some surrogate mothers in the weeks following the birth appeared to lessen over time. Surrogate mothers do not appear to experience psychological problems as a result of the surrogacy arrangement.

Surrogate outcomes: experiences at the Common Drug Review

PubMed Central

2013-01-01

Background Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. Methods Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability. Results Of 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance. Conclusions The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Automotive Stirling engine development program

NASA Technical Reports Server (NTRS)

Ernst, W.; Richey, A.; Farrell, R.; Riecke, G.; Smith, G.; Howarth, R.; Cronin, M.; Simetkosky, M.; Meacher, J.

1986-01-01

The major accomplishments were the completion of the Basic Stirling Engine (BSE) and the Stirling Engine System (SES) designs on schedule, the approval and acceptance of those designs by NASA, and the initiation of manufacture of BSE components. The performance predictions indicate the Mod II engine design will meet or exceed the original program goals of 30% improvement in fuel economy over a conventional Internal Combustion (IC) powered vehicle, while providing acceptable emissions. This was accomplished while simultaneously reducing Mod II engine weight to a level comparable with IC engine power density, and packaging the Mod II in a 1985 Celebrity with no external sheet metal changes. The projected mileage of the Mod II Celebrity for the combined urban and highway CVS cycle is 40.9 mpg which is a 32% improvement over the IC Celebrity. If additional potential improvements are verified and incorporated in the Mod II, the mileage could increase to 42.7 mpg.

Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors.

PubMed

Wu, Yun; Xu, Kun; Ren, Chonghua; Li, Xinyi; Lv, Huijiao; Han, Furong; Wei, Zehui; Wang, Xin; Zhang, Zhiying

2017-03-01

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has recently emerged as a simple, yet powerful genome engineering tool, which has been widely used for genome modification in various organisms and cell types. However, screening biallelic genome-modified cells is often time-consuming and technically challenging. In this study, we incorporated two different surrogate reporter cassettes into paired donor plasmids, which were used as both the surrogate reporters and the knock-in donors. By applying our dual surrogate reporter-integrated donor system, we demonstrate high frequency of CRISPR/Cas9-mediated biallelic genome integration in both human HEK293T and porcine PK15 cells (34.09% and 18.18%, respectively). Our work provides a powerful genetic tool for assisting the selection and enrichment of cells with targeted biallelic genome modification. © 2017 Federation of European Biochemical Societies.

Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody.

PubMed

Leung, Shui-On; Gao, Kai; Wang, Guang Yu; Cheung, Benny Ka-Wa; Lee, Kwan-Yeung; Zhao, Qi; Cheung, Wing-Tai; Wang, Jun Zhi

2015-01-01

SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel "surrogate target cells" for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these "surrogate target cells" proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.

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. © The Author(s) 2015.

Plutonium radiation surrogate

DOEpatents

Frank, Michael I [Dublin, CA

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.

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

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.

Methanol decomposition bottoming cycle for IC engines

NASA Technical Reports Server (NTRS)

Purohit, G.; Houseman, J.

1979-01-01

This paper presents the concept of methanol decomposition using engine exhaust heat, and examines its potential for use in the operation of passenger cars, diesel trucks, and diesel-electric locomotives. Energy economy improvements of 10-20% are calculated over the representative driving cycles without a net loss in power. Some reductions in exhaust emissions are also projected.

Surrogate endpoints in randomized cardiovascular clinical trials.

PubMed

Domanski, Michael; Pocock, Stuart; Bernaud, Corine; Borer, Jeffrey; Geller, Nancy; Revkin, James; Zannad, Faiez

2011-08-01

Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

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.

CFD and Thermo Mechanical Analysis on Effect of Curved vs Step Surface in IC Engine Cylinder Head

NASA Astrophysics Data System (ADS)

Balaji, S.; Ganesh, N.; Kumarasamy, A.

2017-05-01

Current research in IC engines mainly focus on various methods to achieve higher efficiency and high specific power. As a single design parameter, combustion chamber peak spring pressure has increased more than before. Apart from the structural aspects of withstanding these loads, designer faces challenges of resolving thermal aspects of cylinder head. Methods to enhance the heat transfer without compromising load withstanding capability are being constantly explored. Conventional cylinder heads have got sat inner surface. In this paper we have suggested a modification in inner surface to enhance the heat transfer capability. To increase the heat transfer rate, inner same deck surface is configured as a curved and stepped surface instead of sat. We have reported the effectiveness of extend of curvature in the inner same deck surface in a different technical paper. Here, we are making a direct comparison between stepped and curved surface only. From this analysis it has been observed that curved surface reduces the ame deck temperature considerably without compromising the structural strength factors compared to step and sat surface.

Surrogate versus couple therapy in vaginismus.

PubMed

Ben-Zion, Itzhak; Rothschild, Shelly; Chudakov, Bella; Aloni, Ronit

2007-05-01

Women who do not have a cooperative partner cannot complete the usual therapeutic process in the treatment of vaginismus, because they cannot progress to the stage of practicing the insertion of the man partner's fingers and the insertion of a penis. To compare traditional couple therapy with therapy utilizing a surrogate partner. The study was controlled and retrospective. Data were obtained from the treatment charts of patients who had come to the clinic for treatment of vaginismus. Sixteen vaginismus patients who were treated with a man surrogate partner were compared with 16 vaginismus patients who were treated with their own partners. Successful pain-free intercourse upon completion of therapy. One hundred percent of the surrogate patients succeeded in penile-vaginal intercourse compared with 75% in the couples group (P = 0.1). All surrogate patients ended the therapy because it was fully successful, compared with 69% in the couples group. Twelve percent of the couples group ended the therapy because it failed, and 19% because the couples decided to separate. Treating vaginismus with a man surrogate partner was at least as effective as couple therapy. Surrogate therapy may be considered for vaginismus patients who have no cooperative partner.

Nonspinning numerical relativity waveform surrogates: assessing the model

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Construction Progress of the S-IC Test Stand-Pumps

NASA Technical Reports Server (NTRS)

1962-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken April 4, 1961, shows the S-IC test stand dry once again when workers resumed construction after a 6 month delay due to booster size reconfiguration back in September of 1961. The disturbance of a natural spring during the excavation of the site required water to be pumped from the site continuously. The site was completely flooded after the pumps were shut down during the construction delay.

Interpretations, perspectives and intentions in surrogate motherhood

PubMed Central

van Zyl, L.; van Niekerk, A.

2000-01-01

In this paper we examine the questions "What does it mean to be a surrogate mother?" and "What would be an appropriate perspective for a surrogate mother to have on her pregnancy?" In response to the objection that such contracts are alienating or dehumanising since they require women to suppress their evolving perspective on their pregnancies, liberal supporters of surrogate motherhood argue that the freedom to contract includes the freedom to enter a contract to bear a child for an infertile couple. After entering the contract the surrogate may not be free to interpret her pregnancy as that of a non-surrogate mother, but there is more than one appropriate way of interpreting one's pregnancy. To restrict or ban surrogacy contracts would be to prohibit women from making other particular interpretations of their pregnancies they may wish to make, requiring them to live up to a culturally constituted image of ideal motherhood. We examine three interpretations of a "surrogate pregnancy" that are implicit in the views and arguments put forward by ethicists, surrogacy agencies, and surrogate mothers themselves. We hope to show that our concern in this regard goes beyond the view that surrogacy contracts deny or suppress the natural, instinctive or conventional interpretation of pregnancy. Key Words: Surrogate motherhood • parental rights and responsibilities PMID:11055048

On Using Surrogates with Genetic Programming.

PubMed

Hildebrandt, Torsten; Branke, Jürgen

2015-01-01

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

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…

Psychosocial aspects of surrogate motherhood.

PubMed

van den Akker, Olga B A

2007-01-01

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

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.

Comparing biomarkers as principal surrogate endpoints.

PubMed

Huang, Ying; Gilbert, Peter B

2011-12-01

Recently a new definition of surrogate endpoint, the "principal surrogate," was proposed based on causal associations between treatment effects on the biomarker and on the clinical endpoint. Despite its appealing interpretation, limited research has been conducted to evaluate principal surrogates, and existing methods focus on risk models that consider a single biomarker. How to compare principal surrogate value of biomarkers or general risk models that consider multiple biomarkers remains an open research question. We propose to characterize a marker or risk model's principal surrogate value based on the distribution of risk difference between interventions. In addition, we propose a novel summary measure (the standardized total gain) that can be used to compare markers and to assess the incremental value of a new marker. We develop a semiparametric estimated-likelihood method to estimate the joint surrogate value of multiple biomarkers. This method accommodates two-phase sampling of biomarkers and is more widely applicable than existing nonparametric methods by incorporating continuous baseline covariates to predict the biomarker(s), and is more robust than existing parametric methods by leaving the error distribution of markers unspecified. The methodology is illustrated using a simulated example set and a real data set in the context of HIV vaccine trials. © 2011, The International Biometric Society.

A perfect correlate does not a surrogate make

PubMed Central

Baker, Stuart G; Kramer, Barnett S

2003-01-01

Background There is common belief among some medical researchers that if a potential surrogate endpoint is highly correlated with a true endpoint, then a positive (or negative) difference in potential surrogate endpoints between randomization groups would imply a positive (or negative) difference in unobserved true endpoints between randomization groups. We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each randomization group. Methods We use a graphical approach. The vertical axis is the unobserved true endpoint and the horizontal axis is the potential surrogate endpoint. Perfect correlation within each randomization group implies that, for each randomization group, potential surrogate and true endpoints are related by a straight line. In this scenario the investigator does not know the slopes or intercepts. We consider a plausible example where the slope of the line is higher for the experimental group than for the control group. Results In our example with unknown lines, a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups. Thus the potential surrogate endpoints give the wrong inference. Similar results hold for binary potential surrogate and true outcomes (although the notion of correlation does not apply). The potential surrogate endpointwould give the correct inference if either (i) the unknown lines for the two group coincided, which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group, which is called the Prentice Criterion or (ii) if one could accurately predict the lines based on data from prior studies. Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within randomized groups does not guarantee correct inference based on a potential surrogate endpoint. Even in

Surrogate Robot

NASA Image and Video Library

2014-08-21

The Surrogate robot Surge, built at NASA Jet Propulsion Laboratory in Pasadena, CA., is being developed in order to extend humanity reach into hazardous environments to perform tasks such as using environmental test equipment.

Putting engineering back into protein engineering: bioinformatic approaches to catalyst design.

PubMed

Gustafsson, Claes; Govindarajan, Sridhar; Minshull, Jeremy

2003-08-01

Complex multivariate engineering problems are commonplace and not unique to protein engineering. Mathematical and data-mining tools developed in other fields of engineering have now been applied to analyze sequence-activity relationships of peptides and proteins and to assist in the design of proteins and peptides with specified properties. Decreasing costs of DNA sequencing in conjunction with methods to quickly synthesize statistically representative sets of proteins allow modern heuristic statistics to be applied to protein engineering. This provides an alternative approach to expensive assays or unreliable high-throughput surrogate screens.

Overcoming Present-Day Powerplant Limitations Via Unconventional Engine Configurations

NASA Technical Reports Server (NTRS)

Meitner, Peter L.

2006-01-01

The Army Research Laboratory s Vehicle Technology Directorate is sponsoring the prototype development of three unconventional engine concepts - two intermittent combustion (IC) engines and one turbine engine (via SBIR (Small Business Innovative Research) contracts). The IC concepts are the Nutating Engine and the Bonner Engine, and the turbine concept is the POWER Engine. Each of the three engines offers unique and greatly improved capabilities (which cannot be achieved by present-day powerplants), while offering significant reductions in size and weight. This paper presents brief descriptions of the physical characteristics of the three engines, and discusses their performance potentials, as well as their development status.

Surrogate outcomes in health technology assessment: an international comparison.

PubMed

Velasco Garrido, Marcial; Mangiapane, Sandra

2009-07-01

Our aim was to review the recommendations given by health technology assessment (HTA) institutions in their methodological guidelines concerning the use of surrogate outcomes in their assessments. In a second step, we aimed at quantifying the role surrogate parameters take in assessment reports. We analyzed methodological papers and guidelines from HTA agencies with International Network of Agencies for Health Technology Assessment membership as well as from institutions related to pharmaceutical regulation (i.e., reimbursement, pricing). We analyzed the use of surrogate outcomes in a sample of HTA reports randomly drawn from the HTA database. We checked methods, results (including evidence tables), and conclusions sections and extracted the outcomes reported. We report descriptive statistics on the presence of surrogate outcomes in the reports. We identified thirty-four methodological guidelines, twenty of them addressing the issue of outcome parameter choice and the problematic of surrogate outcomes. Overall HTA agencies call on caution regarding the reliance on surrogate outcomes. None of the agencies has provided a list or catalog of acceptable and validated surrogate outcomes. We extracted the outcome parameter of 140 HTA reports. Only around half of the reports determined the outcomes for the assessment prospectively. Surrogate outcomes had been used in 62 percent of the reports. However, only 3.6 percent were based upon surrogate outcomes exclusively. All of them assessed diagnostic or screening technologies and the surrogate outcomes were predominantly test characteristics. HTA institutions seem to agree on a cautious approach to the use of surrogate outcomes in technology assessment. Thorough assessment of health technologies should not rely exclusively on surrogate outcomes.

On the thermodynamics of waste heat recovery from internal combustion engine exhaust gas

NASA Astrophysics Data System (ADS)

Meisner, G. P.

2013-03-01

The ideal internal combustion (IC) engine (Otto Cycle) efficiency ηIC = 1-(1/r)(γ - 1) is only a function of engine compression ratio r =Vmax/Vmin and exhaust gas specific heat ratio γ = cP/cV. Typically r = 8, γ = 1.4, and ηIC = 56%. Unlike the Carnot Cycle where ηCarnot = 1-(TC/TH) for a heat engine operating between hot and cold heat reservoirs at TH and TC, respectively, ηIC is not a function of the exhaust gas temperature. Instead, the exhaust gas temperature depends only on the intake gas temperature (ambient), r, γ, cV, and the combustion energy. The ejected exhaust gas heat is thermally decoupled from the IC engine and conveyed via the exhaust system (manifold, pipe, muffler, etc.) to ambient, and the exhaust system is simply a heat engine that does no useful work. The maximum fraction of fuel energy that can be extracted from the exhaust gas stream as useful work is (1-ηIC) × ηCarnot = 32% for TH = 850 K (exhaust) and TC = 370 K (coolant). This waste heat can be recovered using a heat engine such as a thermoelectric generator (TEG) with ηTEG> 0 in the exhaust system. A combined IC engine and TEG system can generate net useful work from the exhaust gas waste heat with efficiency ηWH = (1-ηIC) × ηCarnot ×ηTEG , and this will increase the overall fuel efficiency of the total system. Recent improvements in TEGs yield ηTEG values approaching 15% giving a potential total waste heat conversion efficiency of ηWH = 4.6%, which translates into a fuel economy improvement approaching 5%. This work is supported by the US DOE under DE-EE0005432.

Surrogate markers for time-varying treatments and outcomes

PubMed Central

Hsu, Jesse Y; Kennedy, Edward H; Roy, Jason A; Stephens-Shields, Alisa J; Small, Dylan S; Joffe, Marshall M

2015-01-01

Background A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point and one ultimate outcome of interest, and discuss new issues arising when variables are time-varying. Methods Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this paper, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. Conclusions In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this paper has provided some motivation for future work on estimation and inference in such settings. PMID:25948621

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.

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

PubMed

Price, David B; Colice, Gene; Israel, Elliot; Roche, Nicolas; Postma, Dirkje S; Guilbert, Theresa W; van Aalderen, Willem M C; Grigg, Jonathan; Hillyer, Elizabeth V; Thomas, Victoria; Martin, Richard J

2016-04-01

Asthma management guidelines recommend adding a long-acting β 2 -agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.

I.C. Engine emission reduction by copper oxide catalytic converter

NASA Astrophysics Data System (ADS)

Venkatesan, S. P.; Shubham Uday, Desai; Karan Hemant, Borana; Rajarshi Kushwanth Goud, Kagita; Lakshmana Kumar, G.; Pavan Kumar, K.

2017-05-01

The toxic gases emitted from diesel engines are more than petrol engines. Predicting the use of diesel engines, even more in future, this system is developed and can be used to minimize the harmful gases. Toxic gases include NOX, CO, HC and Smoke which are harmful to the atmosphere as well as to the human beings. The main aim of this work is to fabricate system, where the level of intensity of toxic gases is controlled through chemical reaction to more agreeable level. This system acts itself as an exhaust system; hence there is no needs to fit separate the silencer. The whole assembly is fitted in the exhaust pipe from engine. In this work, catalytic converter with copper oxide as a catalyst, by replacing noble catalysts such as platinum, palladium and rhodium is fabricated and fitted in the engine exhaust. With and without catalytic converter, the experimentations are carried out at different loads such as 0%, 25%, 50%, 75%, and 100% of maximum rated load. From the experimental results it is found that the maximum reduction is 32%, 61% and 21% for HC, NOx and CO respectively at 100% of maximum rated load when compared to that of without catalytic converter. This catalytic converter system is cash effective and more economical than the existing catalytic converter.

Biomarkers and Surrogate Markers: An FDA Perspective

PubMed Central

Katz, Russell

2004-01-01

Summary: Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. Many such surrogate markers have been proposed as potential candidates for use in definitive effectiveness trials of agents to treat neurologic or psychiatric disease, but as of this date, there are no such markers that have been adequately “validated,” that is, shown to predict the effect of the treatment on the clinical outcome of interest. While the current law and regulations permit the United States Food and Drug Administration to base the approval of a drug product on a determination the effect of the drug on an unvalidated surrogate marker (that is, one for which it is not known that an effect on the surrogate actually predicts the desired clinical benefit), there are a number of difficulties in interpreting trials that use surrogate markers as primary measures of drug effect. In this article, the relevant regulatory context will be discussed, as well as the epistemological problems related to the interpretation of clinical trials in which unvalidated surrogate markers are used as primary outcomes. PMID:15717019

An Efficient Variable Screening Method for Effective Surrogate Models for Reliability-Based Design Optimization

DTIC Science & Technology

2014-04-01

surrogate model generation is difficult for high -dimensional problems, due to the curse of dimensionality. Variable screening methods have been...a variable screening model was developed for the quasi-molecular treatment of ion-atom collision [16]. In engineering, a confidence interval of...for high -level radioactive waste [18]. Moreover, the design sensitivity method can be extended to the variable screening method because vital

So not mothers: responsibility for surrogate orphans.

PubMed

Parks, Jennifer A; Murphy, Timothy F

2018-04-12

The law ordinarily recognises the woman who gives birth as the mother of a child, but in certain jurisdictions, it will recognise the commissioning couple as the legal parents of a child born to a commercial surrogate. Some commissioning parents have, however, effectively abandoned the children they commission, and in such cases, commercial surrogates may find themselves facing unexpected maternal responsibility for children they had fully intended to give up. Any assumption that commercial surrogates ought to assume maternal responsibility for abandoned children runs contrary to the moral suppositions that typically govern contract surrogacy, in particular, assumptions that gestational carriers are not 'mothers' in any morally significant sense. In general, commercial gestational surrogates are almost entirely conceptualised as 'vessels'. In a moral sense, it is deeply inconsistent to expect commercial surrogates to assume maternal responsibility simply because commissioning parents abandon children for one reason or another. We identify several instances of child abandonment and discuss their implications with regard to the moral conceptualisation of commercial gestational surrogates. We conclude that if gestational surrogates are to remain conceptualised as mere vessels, they should not be expected to assume responsibility for children abandoned by commissioning parents, not even the limited responsibility of giving them up for adoption or surrendering them to the state. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hypothesis test for synchronization: twin surrogates revisited.

PubMed

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.

Holographic aids for internal combustion engine flow studies

NASA Technical Reports Server (NTRS)

Regan, C.

1984-01-01

Worldwide interest in improving the fuel efficiency of internal combustion (I.C.) engines has sparked research efforts designed to learn more about the flow processes of these engines. The flow fields must be understood prior to fuel injection in order to design efficient valves, piston geometries, and fuel injectors. Knowledge of the flow field is also necessary to determine the heat transfer to combustion chamber surfaces. Computational codes can predict velocity and turbulence patterns, but experimental verification is mandatory to justify their basic assumptions. Due to their nonintrusive nature, optical methods are ideally suited to provide the necessary velocity verification data. Optical sytems such as Schlieren photography, laser velocimetry, and illuminated particle visualization are used in I.C. engines, and now their versatility is improved by employing holography. These holographically enhanced optical techniques are described with emphasis on their applications in I.C. engines.

Advanced topics in evidence-based urologic oncology: surrogate endpoints.

PubMed

Lavallée, Luke T; Montori, Victor M; Canfield, Stephen E; Breau, Rodney H

2011-01-01

Clinical trials often report surrogate endpoint data. A surrogate endpoint is a biological marker or clinical sign that can be substituted for a patient-important outcome. Using surrogate endpoints correctly may facilitate and expedite clinical trials and may improve medical decisions. However, rigorous criteria must be met for an endpoint to be considered a valid surrogate. The purpose of this article is to review the topic of surrogate endpoints in the context of a urologic encounter. Copyright © 2011 Elsevier Inc. All rights reserved.

Self-Patterning of Silica/Epoxy Nanocomposite Underfill by Tailored Hydrophilic-Superhydrophobic Surfaces for 3D Integrated Circuit (IC) Stacking.

PubMed

Tuan, Chia-Chi; James, Nathan Pataki; Lin, Ziyin; Chen, Yun; Liu, Yan; Moon, Kyoung-Sik; Li, Zhuo; Wong, C P

2017-03-15

As microelectronics are trending toward smaller packages and integrated circuit (IC) stacks nowadays, underfill, the polymer composite filled in between the IC chip and the substrate, becomes increasingly important for interconnection reliability. However, traditional underfills cannot meet the requirements for low-profile and fine pitch in high density IC stacking packages. Post-applied underfills have difficulties in flowing into the small gaps between the chip and the substrate, while pre-applied underfills face filler entrapment at bond pads. In this report, we present a self-patterning underfilling technology that uses selective wetting of underfill on Cu bond pads and Si 3 N 4 passivation via surface energy engineering. This novel process, fully compatible with the conventional underfilling process, eliminates the issue of filler entrapment in typical pre-applied underfilling process, enabling high density and fine pitch IC die bonding.

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

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

Construction Progress of the S-IC Test Stand-Steel Reinforcements

NASA Technical Reports Server (NTRS)

1961-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 15, 1961, shows the installation of the reinforcing steel prior to the pouring of the concrete foundation walls.

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…

The psychological well-being and prenatal bonding of gestational surrogates.

PubMed

Lamba, N; Jadva, V; Kadam, K; Golombok, S

2018-02-23

How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4-9 months of pregnancy and 4-6 months after the birth. Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. As this is the first study of the psychological well-being of surrogates in low-income countries, the

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.

SPROC: A multiple-processor DSP IC

NASA Technical Reports Server (NTRS)

Davis, R.

1991-01-01

A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

SEM probe of IC radiation sensitivity

NASA Technical Reports Server (NTRS)

Gauthier, M. K.; Stanley, A. G.

1979-01-01

Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

Emotional experiences in surrogate mothers: A qualitative study.

PubMed

Ahmari Tehran, Hoda; Tashi, Shohreh; Mehran, Nahid; Eskandari, Narges; Dadkhah Tehrani, Tahmineh

2014-07-01

Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. The purpose of this study was to assess the emotional experiences of surrogate mothers. This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in-depth interview to collect the information. The data analysis was fulfilled via Colaizzi's seven-stage method. Reliability and validity study of the roots in the four-axis was done. The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy.

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990-2011.

PubMed

Bikdeli, Behnood; Punnanithinont, Natdanai; Akram, Yasir; Lee, Ike; Desai, Nihar R; Ross, Joseph S; Krumholz, Harlan M

2017-03-21

Surrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. We identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine , Lancet , and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high-impact journals. Although cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high-profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Error modeling for surrogates of dynamical systems using machine learning: Machine-learning-based error model for surrogates of dynamical systems

DOE PAGES

Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

2017-07-14

A machine learning–based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (eg, random forests, and LASSO) to map a large set of inexpensively computed “error indicators” (ie, features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed bymore » simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering) and subsequently constructs a “local” regression model to predict the time-instantaneous error within each identified region of feature space. We consider 2 uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (eg, time-integrated errors). We then apply the proposed framework to model errors in reduced-order models of nonlinear oil-water subsurface flow simulations, with time-varying well-control (bottom-hole pressure) parameters. The reduced-order models used in this work entail application of trajectory piecewise linearization in conjunction with proper orthogonal decomposition. Moreover, when the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and

Error modeling for surrogates of dynamical systems using machine learning: Machine-learning-based error model for surrogates of dynamical systems

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

Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

A machine learning–based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (eg, random forests, and LASSO) to map a large set of inexpensively computed “error indicators” (ie, features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed bymore » simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering) and subsequently constructs a “local” regression model to predict the time-instantaneous error within each identified region of feature space. We consider 2 uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (eg, time-integrated errors). We then apply the proposed framework to model errors in reduced-order models of nonlinear oil-water subsurface flow simulations, with time-varying well-control (bottom-hole pressure) parameters. The reduced-order models used in this work entail application of trajectory piecewise linearization in conjunction with proper orthogonal decomposition. Moreover, when the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and

The psychological well-being and prenatal bonding of gestational surrogates

PubMed Central

Lamba, N; Jadva, V; Kadam, K; Golombok, S

2018-01-01

Abstract STUDY QUESTION How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? SUMMARY ANSWER Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. WHAT IS ALREADY KNOWN Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. STUDY, DESIGN, SIZE, DURATION This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4–9 months of pregnancy and 4–6 months after the birth. PARTICIPANTS/MATERIALS, SETTING, METHODS Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. MAIN RESULTS AND THE ROLE OF CHANCE Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. LIMITATIONS, REASONS FOR CAUTION All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not

Autoignition Chemistry of Surrogate Fuel Components in an Engine Environment

DTIC Science & Technology

2015-08-21

compression ratio (CR) on the auto - ignition of decane. Crank angle resolved cylinder pressure data was acquired and analyzed using an engine heat...schematic shown in Fig. 1, consists of a modified CFR (Cooperative Fuel Research) engine coupled to a dynamometer. In practical compression 2 ignition ...engines, auto - ignition occurs in the premixed spray envelope that forms during the fuel injection process. To focus on this regime without the

Present, future of automotive hybrid IC applications discussed

NASA Astrophysics Data System (ADS)

Matsuda, Nobuyoshi; Fukuoka, Atuhisa

1987-09-01

Hybrid ICs are presently utilized in various fields such as commercial televisions, VTRs, and audio devices, industrial usage of communication equipment, computers, terminals, and automobiles. Its applications and environments are various and diverse. The functions required for hybrid ICs vary from simple high density mounting for a system to the realization of high mechanisms with the application of function timing. The functions are properly used depending upon the system with its hybrid ICs and its circuit composition. Considering structure and reliability requirements for automotive hybrid ICs, an application example for hybrid ICs which use the package (COMPACT), will be discussed.

The Magnetics Information Consortium (MagIC)

NASA Astrophysics Data System (ADS)

Johnson, C.; Constable, C.; Tauxe, L.; Koppers, A.; Banerjee, S.; Jackson, M.; Solheid, P.

2003-12-01

The Magnetics Information Consortium (MagIC) is a multi-user facility to establish and maintain a state-of-the-art relational database and digital archive for rock and paleomagnetic data. The goal of MagIC is to make such data generally available and to provide an information technology infrastructure for these and other research-oriented databases run by the international community. As its name implies, MagIC will not be restricted to paleomagnetic or rock magnetic data only, although MagIC will focus on these kinds of information during its setup phase. MagIC will be hosted under EarthRef.org at http://earthref.org/MAGIC/ where two "integrated" web portals will be developed, one for paleomagnetism (currently functional as a prototype that can be explored via the http://earthref.org/databases/PMAG/ link) and one for rock magnetism. The MagIC database will store all measurements and their derived properties for studies of paleomagnetic directions (inclination, declination) and their intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Ultimately, this database will allow researchers to study "on the internet" and to download important data sets that display paleo-secular variations in the intensity of the Earth's magnetic field over geological time, or that display magnetic data in typical Zijderveld, hysteresis/FORC and various magnetization/remanence diagrams. The MagIC database is completely integrated in the EarthRef.org relational database structure and thus benefits significantly from already-existing common database components, such as the EarthRef Reference Database (ERR) and Address Book (ERAB). The ERR allows researchers to find complete sets of literature resources as used in GERM (Geochemical Earth Reference Model), REM (Reference Earth Model) and MagIC. The ERAB contains addresses for all contributors to the EarthRef.org databases, and also for those who participated in data collection, archiving and

A surrogate model for thermal characteristics of stratospheric airship

NASA Astrophysics Data System (ADS)

Zhao, Da; Liu, Dongxu; Zhu, Ming

2018-06-01

A simple and accurate surrogate model is extremely needed to reduce the analysis complexity of thermal characteristics for a stratospheric airship. In this paper, a surrogate model based on the Least Squares Support Vector Regression (LSSVR) is proposed. The Gravitational Search Algorithm (GSA) is used to optimize hyper parameters. A novel framework consisting of a preprocessing classifier and two regression models is designed to train the surrogate model. Various temperature datasets of the airship envelope and the internal gas are obtained by a three-dimensional transient model for thermal characteristics. Using these thermal datasets, two-factor and multi-factor surrogate models are trained and several comparison simulations are conducted. Results illustrate that the surrogate models based on LSSVR-GSA have good fitting and generalization abilities. The pre-treated classification strategy proposed in this paper plays a significant role in improving the accuracy of the surrogate model.

Surrogate end points in clinical research: hazardous to your health.

PubMed

Grimes, David A; Schulz, Kenneth F

2005-05-01

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.

[Ethical issues concerning surrogate assisted sex therapy].

PubMed

Aloni, Ronit; Heruti, Rafi J

2009-09-01

Sex therapy, by definition, is a couple therapy as well as behavioral therapy by origin. As such, practicing a series of exercises is an essential part of the therapy. Masters and Johnson, in their book "Human Sexual Inadequacy", wrote that "one cannot learn about sexuality in any practical way without actually experiencing intimate behavior with a partner". This ethical approach directed them to develop the therapeutic method of working with surrogate partners, as they thought all people are entitled to receive therapy, if they so wish, including people without partners. Surrogate is a form of mentoring; this is a one-on-one relationship that allows practicing classic behavioral methods such as gradual progress, breaking the task into small goals, onsite feedback, rehearsals, role-play, modifying the environment, etc. The content and the skills that are practiced are related to sexual dysfunction as well as social, couple and intimate skills. The lack of those critical skills prevents the clients from fulfilling their wish to develop social or intimate relationships in which they will be able to accomplish their sexuality. Ethical procedures should be strictly kept in order to protect the clients and the surrogates, in a three-way therapeutic team, working together to reach the goals of the therapy. During the therapy process a weekly meeting is held between the therapist and the client, between the therapist and the surrogate and, only then, between the surrogate and the client. At the end of the therapy process the relationship between the client and the surrogate is terminated, completely. In this article, the authors illuminate the complexity of this therapy process, as well as dealing with some of the ethical issues that are raised. The article also identifies types of patients who can benefit from surrogate therapy.

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.

New generation QuIC assays for prion seeding activity.

PubMed

Orrù, Christina D; Wilham, Jason M; Vascellari, Sarah; Hughson, Andrew G; Caughey, Byron

2012-01-01

The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrP(Sen) has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma.

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

Dynamical Competition of IC-Industry Clustering from Taiwan to China

NASA Astrophysics Data System (ADS)

Tsai, Bi-Huei; Tsai, Kuo-Hui

2009-08-01

Most studies employ qualitative approach to explore the industrial clusters; however, few research has objectively quantified the evolutions of industry clustering. The purpose of this paper is to quantitatively analyze clustering among IC design, IC manufacturing as well as IC packaging and testing industries by using the foreign direct investment (FDI) data. The Lotka-Volterra system equations are first adopted here to capture the competition or cooperation among such three industries, thus explaining their clustering inclinations. The results indicate that the evolution of FDI into China for IC design industry significantly inspire the subsequent FDI of IC manufacturing as well as IC packaging and testing industries. Since IC design industry lie in the upstream stage of IC production, the middle-stream IC manufacturing and downstream IC packing and testing enterprises tend to cluster together with IC design firms, in order to sustain a steady business. Finally, Taiwan IC industry's FDI amount into China is predicted to cumulatively increase, which supports the industrial clustering tendency for Taiwan IC industry. Particularly, the FDI prediction of Lotka-Volterra model performs superior to that of the conventional Bass model after the forecast accuracy of these two models are compared. The prediction ability is dramatically improved as the industrial mutualism among each IC production stage is taken into account.

Emotional experiences in surrogate mothers: A qualitative study

PubMed Central

Ahmari Tehran, Hoda; Tashi, Shohreh; Mehran, Nahid; Eskandari, Narges; Dadkhah Tehrani, Tahmineh

2014-01-01

Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. Objective: The purpose of this study was to assess the emotional experiences of surrogate mothers. Materials and Methods: This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in-depth interview to collect the information. The data analysis was fulfilled via Colaizzi’s seven-stage method. Reliability and validity study of the roots in the four-axis was done. Results: The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). Conclusion: Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy. PMID:25114669

Biomarkers and surrogate endpoints in glaucoma clinical trials

PubMed Central

Medeiros, Felipe A

2015-01-01

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. PMID:25034049

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

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

Altruistic surrogacy: the necessary objectification of surrogate mothers.

PubMed

Tieu, M M

2009-03-01

One of the major concerns about surrogacy is the potential harm that may be inflicted upon the surrogate mother and the child after relinquishment. Even if one were to take the liberal view that surrogacy should be presumptively allowed on the basis of autonomy and/or compassion, evidence of harm must be taken seriously. In this paper I review the evidence from psychological studies on the effect that relinquishing a child has on the surrogate mother and while it appears that many surrogates are able to cope with relinquishment, I argue that there are good reasons, grounded in empirical evidence, to support the view that the subsequent management of the relinquishment necessarily objectifies the surrogate mother.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identifying taxonomic and functional surrogates for spring biodiversity conservation.

PubMed

Jyväsjärvi, Jussi; Virtanen, Risto; Ilmonen, Jari; Paasivirta, Lauri; Muotka, Timo

2018-02-27

Surrogate approaches are widely used to estimate overall taxonomic diversity for conservation planning. Surrogate taxa are frequently selected based on rarity or charisma, whereas selection through statistical modeling has been applied rarely. We used boosted-regression-tree models (BRT) fitted to biological data from 165 springs to identify bryophyte and invertebrate surrogates for taxonomic and functional diversity of boreal springs. We focused on these 2 groups because they are well known and abundant in most boreal springs. The best indicators of taxonomic versus functional diversity differed. The bryophyte Bryum weigelii and the chironomid larva Paratrichocladius skirwithensis best indicated taxonomic diversity, whereas the isopod Asellus aquaticus and the chironomid Macropelopia spp. were the best surrogates of functional diversity. In a scoring algorithm for priority-site selection, taxonomic surrogates performed only slightly better than random selection for all spring-dwelling taxa, but they were very effective in representing spring specialists, providing a distinct improvement over random solutions. However, the surrogates for taxonomic diversity represented functional diversity poorly and vice versa. When combined with cross-taxon complementarity analyses, surrogate selection based on statistical modeling provides a promising approach for identifying groundwater-dependent ecosystems of special conservation value, a key requirement of the EU Water Framework Directive. © 2018 Society for Conservation Biology.

Surrogate measures: A proposed alternative in human factors assessment of operational measures of performance

NASA Technical Reports Server (NTRS)

Kennedy, Robert S.; Lane, Norman E.; Kuntz, Lois A.

1987-01-01

Surrogate measures are proposed as an alternative to direct assessment of operational performance for purposes of screening agents who may have to work under unusual stresses or in exotic environments. Such measures are particularly proposed when the surrogate can be empirically validated against the operational criterion. The focus is on cognitive (or throughput) performances in humans as opposed to sensory (input) or motor (output) measures, but the methods should be applicable for development of batteries which will tap input/output functions. A menu of performance tasks is under development for implementation on a battery-operated portable microcomputer, with 21 tests currently available. The tasks are reliable and become stable in minimum amounts of time; appear sensitive to some agents; comprise constructs related to actual job tasks; and are easily administered in most environments. Implications for human factors engineering studies in environmental stress are discussed.

High performance MPEG-audio decoder IC

NASA Technical Reports Server (NTRS)

Thorn, M.; Benbassat, G.; Cyr, K.; Li, S.; Gill, M.; Kam, D.; Walker, K.; Look, P.; Eldridge, C.; Ng, P.

1993-01-01

The emerging digital audio and video compression technology brings both an opportunity and a new challenge to IC design. The pervasive application of compression technology to consumer electronics will require high volume, low cost IC's and fast time to market of the prototypes and production units. At the same time, the algorithms used in the compression technology result in complex VLSI IC's. The conflicting challenges of algorithm complexity, low cost, and fast time to market have an impact on device architecture and design methodology. The work presented in this paper is about the design of a dedicated, high precision, Motion Picture Expert Group (MPEG) audio decoder.

Attitudes toward surrogate motherhood in Canada.

PubMed

Krishnan, V

1994-01-01

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

Bayesian Adaptive Trial Design for a Newly Validated Surrogate Endpoint

PubMed Central

Renfro, Lindsay A.; Carlin, Bradley P.; Sargent, Daniel J.

2011-01-01

Summary The evaluation of surrogate endpoints for primary use in future clinical trials is an increasingly important research area, due to demands for more efficient trials coupled with recent regulatory acceptance of some surrogates as ‘valid.’ However, little consideration has been given to how a trial which utilizes a newly-validated surrogate endpoint as its primary endpoint might be appropriately designed. We propose a novel Bayesian adaptive trial design that allows the new surrogate endpoint to play a dominant role in assessing the effect of an intervention, while remaining realistically cautious about its use. By incorporating multi-trial historical information on the validated relationship between the surrogate and clinical endpoints, then subsequently evaluating accumulating data against this relationship as the new trial progresses, we adaptively guard against an erroneous assessment of treatment based upon a truly invalid surrogate. When the joint outcomes in the new trial seem plausible given similar historical trials, we proceed with the surrogate endpoint as the primary endpoint, and do so adaptively–perhaps stopping the trial for early success or inferiority of the experimental treatment, or for futility. Otherwise, we discard the surrogate and switch adaptive determinations to the original primary endpoint. We use simulation to test the operating characteristics of this new design compared to a standard O’Brien-Fleming approach, as well as the ability of our design to discriminate trustworthy from untrustworthy surrogates in hypothetical future trials. Furthermore, we investigate possible benefits using patient-level data from 18 adjuvant therapy trials in colon cancer, where disease-free survival is considered a newly-validated surrogate endpoint for overall survival. PMID:21838811

Use of surrogate technologies to estimate suspended sediment in the Clearwater River, Idaho, and Snake River, Washington, 2008-10

USGS Publications Warehouse

Wood, Molly S.; Teasdale, Gregg N.

2013-01-01

Elevated levels of fluvial sediment can reduce the biological productivity of aquatic systems, impair freshwater quality, decrease reservoir storage capacity, and decrease the capacity of hydraulic structures. The need to measure fluvial sediment has led to the development of sediment surrogate technologies, particularly in locations where streamflow alone is not a good estimator of sediment load because of regulated flow, load hysteresis, episodic sediment sources, and non-equilibrium sediment transport. An effective surrogate technology is low maintenance and sturdy over a range of hydrologic conditions, and measured variables can be modeled to estimate suspended-sediment concentration (SSC), load, and duration of elevated levels on a real-time basis. Among the most promising techniques is the measurement of acoustic backscatter strength using acoustic Doppler velocity meters (ADVMs) deployed in rivers. The U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, Walla Walla District, evaluated the use of acoustic backscatter, turbidity, laser diffraction, and streamflow as surrogates for estimating real-time SSC and loads in the Clearwater and Snake Rivers, which adjoin in Lewiston, Idaho, and flow into Lower Granite Reservoir. The study was conducted from May 2008 to September 2010 and is part of the U.S. Army Corps of Engineers Lower Snake River Programmatic Sediment Management Plan to identify and manage sediment sources in basins draining into lower Snake River reservoirs. Commercially available acoustic instruments have shown great promise in sediment surrogate studies because they require little maintenance and measure profiles of the surrogate parameter across a sampling volume rather than at a single point. The strength of acoustic backscatter theoretically increases as more particles are suspended in the water to reflect the acoustic pulse emitted by the ADVM. ADVMs of different frequencies (0.5, 1.5, and 3 Megahertz) were tested to

Information Commons for Rice (IC4R)

PubMed Central

2016-01-01

Rice is the most important staple food for a large part of the world's human population and also a key model organism for plant research. Here, we present Information Commons for Rice (IC4R; http://ic4r.org), a rice knowledgebase featuring adoption of an extensible and sustainable architecture that integrates multiple omics data through community-contributed modules. Each module is developed and maintained by different committed groups, deals with data collection, processing and visualization, and delivers data on-demand via web services. In the current version, IC4R incorporates a variety of rice data through multiple committed modules, including genome-wide expression profiles derived entirely from RNA-Seq data, resequencing-based genomic variations obtained from re-sequencing data of thousands of rice varieties, plant homologous genes covering multiple diverse plant species, post-translational modifications, rice-related literatures and gene annotations contributed by the rice research community. Unlike extant related databases, IC4R is designed for scalability and sustainability and thus also features collaborative integration of rice data and low costs for database update and maintenance. Future directions of IC4R include incorporation of other omics data and association of multiple omics data with agronomically important traits, dedicating to build IC4R into a valuable knowledgebase for both basic and translational researches in rice. PMID:26519466

On Patarin's Attack against the lIC Scheme

NASA Astrophysics Data System (ADS)

Ogura, Naoki; Uchiyama, Shigenori

In 2007, Ding et al. proposed an attractive scheme, which is called the l-Invertible Cycles (lIC) scheme. lIC is one of the most efficient multivariate public-key cryptosystems (MPKC); these schemes would be suitable for using under limited computational resources. In 2008, an efficient attack against lIC using Gröbner basis algorithms was proposed by Fouque et al. However, they only estimated the complexity of their attack based on their experimental results. On the other hand, Patarin had proposed an efficient attack against some multivariate public-key cryptosystems. We call this attack Patarin's attack. The complexity of Patarin's attack can be estimated by finding relations corresponding to each scheme. In this paper, we propose an another practical attack against the lIC encryption/signature scheme. We estimate the complexity of our attack (not experimentally) by adapting Patarin's attack. The attack can be also applied to the lIC- scheme. Moreover, we show some experimental results of a practical attack against the lIC/lIC- schemes. This is the first implementation of both our proposed attack and an attack based on Gröbner basis algorithm for the even case, that is, a parameter l is even.

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

Development potential of Intermittent Combustion (I.C.) aircraft engines for commuter transport applications

NASA Technical Reports Server (NTRS)

Willis, E. A.

1982-01-01

An update on general aviation (g/a) and commuter aircraft propulsion research effort is reviewed. The following topics are discussed: on several advanced intermittent combustion engines emphasizing lightweight diesels and rotary stratified charge engines. The current state-of-the-art is evaluated for lightweight, aircraft suitable versions of each engine. This information is used to project the engine characteristics that can be expected on near-term and long-term time horizons. The key enabling technology requirements are identified for each engine on the long-term time horizon.

The Different Moral Bases of Patient and Surrogate Decision-Making.

PubMed

Brudney, Daniel

2018-01-01

My topic is a problem with our practice of surrogate decision-making in health care, namely, the problem of the surrogate who is not doing her job-the surrogate who cannot be reached or the surrogate who seems to refuse to understand or to be unable to understand the clinical situation. The analysis raises a question about the surrogate who simply disagrees with the medical team. One might think that such a surrogate is doing her job-the team just doesn't like how she is doing it. My analysis raises the question of whether (or perhaps when) she should be overridden. In approaching this problem, I focus not on the range of difficulties in practice but on the underlying moral conceptual issue. My concern will be to show that the moral values that underpin patient decision-making are fundamentally different from those that underpin surrogate decision-making. Identifying the distinctions will set parameters for any successful solution to the "Who should decide?" A patient has a specific kind of moral right to make her own medical decisions. A surrogate has no analogous moral right to decide for someone else. We want the surrogate to make the decision because we believe that she has a relevant epistemological advantage over anyone else on the scene. If and when she has no such advantage or if she refuses or is unable to use it, then there might not be sufficient reason to let her be the decision-maker. © 2018 The Hastings Center.

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.

Statistical characteristics of surrogate data based on geophysical measurements

NASA Astrophysics Data System (ADS)

Venema, V.; Bachner, S.; Rust, H. W.; Simmer, C.

2006-09-01

In this study, the statistical properties of a range of measurements are compared with those of their surrogate time series. Seven different records are studied, amongst others, historical time series of mean daily temperature, daily rain sums and runoff from two rivers, and cloud measurements. Seven different algorithms are used to generate the surrogate time series. The best-known method is the iterative amplitude adjusted Fourier transform (IAAFT) algorithm, which is able to reproduce the measured distribution as well as the power spectrum. Using this setup, the measurements and their surrogates are compared with respect to their power spectrum, increment distribution, structure functions, annual percentiles and return values. It is found that the surrogates that reproduce the power spectrum and the distribution of the measurements are able to closely match the increment distributions and the structure functions of the measurements, but this often does not hold for surrogates that only mimic the power spectrum of the measurement. However, even the best performing surrogates do not have asymmetric increment distributions, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found deviations of the structure functions on small scales.

Evaluation and comparison of predictive individual-level general surrogates.

PubMed

Gabriel, Erin E; Sachs, Michael C; Halloran, M Elizabeth

2018-07-01

An intermediate response measure that accurately predicts efficacy in a new setting at the individual level could be used both for prediction and personalized medical decisions. In this article, we define a predictive individual-level general surrogate (PIGS), which is an individual-level intermediate response that can be used to accurately predict individual efficacy in a new setting. While methods for evaluating trial-level general surrogates, which are predictors of trial-level efficacy, have been developed previously, few, if any, methods have been developed to evaluate individual-level general surrogates, and no methods have formalized the use of cross-validation to quantify the expected prediction error. Our proposed method uses existing methods of individual-level surrogate evaluation within a given clinical trial setting in combination with cross-validation over a set of clinical trials to evaluate surrogate quality and to estimate the absolute prediction error that is expected in a new trial setting when using a PIGS. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate individual-level general surrogates over a set of multi-national trials of a pentavalent rotavirus vaccine.

The Surrogate Self

ERIC Educational Resources Information Center

Gunnison, Hugh

1976-01-01

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

Reduced cost mission design using surrogate models

NASA Astrophysics Data System (ADS)

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

2016-01-01

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

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 7874(a)(2)(B...

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 7874(a)(2)(B...

Active Subspaces for Wind Plant Surrogate Modeling

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

King, Ryan N; Quick, Julian; Dykes, Katherine L

Understanding the uncertainty in wind plant performance is crucial to their cost-effective design and operation. However, conventional approaches to uncertainty quantification (UQ), such as Monte Carlo techniques or surrogate modeling, are often computationally intractable for utility-scale wind plants because of poor congergence rates or the curse of dimensionality. In this paper we demonstrate that wind plant power uncertainty can be well represented with a low-dimensional active subspace, thereby achieving a significant reduction in the dimension of the surrogate modeling problem. We apply the active sub-spaces technique to UQ of plant power output with respect to uncertainty in turbine axial inductionmore » factors, and find a single active subspace direction dominates the sensitivity in power output. When this single active subspace direction is used to construct a quadratic surrogate model, the number of model unknowns can be reduced by up to 3 orders of magnitude without compromising performance on unseen test data. We conclude that the dimension reduction achieved with active subspaces makes surrogate-based UQ approaches tractable for utility-scale wind plants.« less

Stable Electrical Operation of 6H-SiC JFETs and ICs for Thousands of Hours at 500 C

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Spry, David J.; Chen, Liang-Yu; Beheim, Glenn M.; Okojie, Robert S.; Chang, Carl W.; Meredith, Roger D.; Ferrier, Terry L.; Evans, Laura J.; Krasowski, Michael J.;

[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.

Parents and children: "surrogate" paradigm of modernity.

PubMed

Adam, Archimandrite; Akhaladze, Vakhtang

2011-06-01

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

Surrogate decision making: do we have to trade off accuracy and procedural satisfaction?

PubMed

Frey, Renato; Hertwig, Ralph; Herzog, Stefan M

2014-02-01

Making surrogate decisions on behalf of incapacitated patients can raise difficult questions for relatives, physicians, and society. Previous research has focused on the accuracy of surrogate decisions (i.e., the proportion of correctly inferred preferences). Less attention has been paid to the procedural satisfaction that patients' surrogates and patients attribute to specific approaches to making surrogate decisions. The objective was to investigate hypothetical patients' and surrogates' procedural satisfaction with specific approaches to making surrogate decisions and whether implementing these preferences would lead to tradeoffs between procedural satisfaction and accuracy. Study 1 investigated procedural satisfaction by assigning participants (618 in a mixed-age but relatively young online sample and 50 in an older offline sample) to the roles of hypothetical surrogates or patients. Study 2 (involving 64 real multigenerational families with a total of 253 participants) investigated accuracy using 24 medical scenarios. Hypothetical patients and surrogates had closely aligned preferences: Procedural satisfaction was highest with a patient-designated surrogate, followed by shared surrogate decision-making approaches and legally assigned surrogates. These approaches did not differ substantially in accuracy. Limitations are that participants' preferences regarding existing and novel approaches to making surrogate decisions can only be elicited under hypothetical conditions. Next to decision making by patient-designated surrogates, shared surrogate decision making is the preferred approach among patients and surrogates alike. This approach appears to impose no tradeoff between procedural satisfaction and accuracy. Therefore, shared decision making should be further studied in representative samples of the general population, and if people's preferences prove to be robust, they deserve to be weighted more strongly in legal frameworks in addition to patient

Adaptive surrogate model based multiobjective optimization for coastal aquifer management

NASA Astrophysics Data System (ADS)

Song, Jian; Yang, Yun; Wu, Jianfeng; Wu, Jichun; Sun, Xiaomin; Lin, Jin

2018-06-01

In this study, a novel surrogate model assisted multiobjective memetic algorithm (SMOMA) is developed for optimal pumping strategies of large-scale coastal groundwater problems. The proposed SMOMA integrates an efficient data-driven surrogate model with an improved non-dominated sorted genetic algorithm-II (NSGAII) that employs a local search operator to accelerate its convergence in optimization. The surrogate model based on Kernel Extreme Learning Machine (KELM) is developed and evaluated as an approximate simulator to generate the patterns of regional groundwater flow and salinity levels in coastal aquifers for reducing huge computational burden. The KELM model is adaptively trained during evolutionary search to satisfy desired fidelity level of surrogate so that it inhibits error accumulation of forecasting and results in correctly converging to true Pareto-optimal front. The proposed methodology is then applied to a large-scale coastal aquifer management in Baldwin County, Alabama. Objectives of minimizing the saltwater mass increase and maximizing the total pumping rate in the coastal aquifers are considered. The optimal solutions achieved by the proposed adaptive surrogate model are compared against those solutions obtained from one-shot surrogate model and original simulation model. The adaptive surrogate model does not only improve the prediction accuracy of Pareto-optimal solutions compared with those by the one-shot surrogate model, but also maintains the equivalent quality of Pareto-optimal solutions compared with those by NSGAII coupled with original simulation model, while retaining the advantage of surrogate models in reducing computational burden up to 94% of time-saving. This study shows that the proposed methodology is a computationally efficient and promising tool for multiobjective optimizations of coastal aquifer managements.

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.

When life imitates art: surrogate decision making at the end of life.

PubMed

Shapiro, Susan P

2007-01-01

The privileging of the substituted judgment standard as the gold standard for surrogate decision making in law and bioethics has constrained the research agenda in end-of-life decision making. The empirical literature is inundated with a plethora of "Newlywed Game" designs, in which potential patients and potential surrogates respond to hypothetical scenarios to see how often they "get it right." The preoccupation with determining the capacity of surrogates to accurately reproduce the judgments of another makes a number of assumptions that blind scholars to the variables central to understanding how surrogates actually make medical decisions on behalf of another. These assumptions include that patient preferences are knowable, surrogates have adequate and accurate information, time stands still, patients get the surrogates they want, patients want and surrogates utilize substituted judgment criteria, and surrogates are disinterested. This article examines these assumptions and considers the challenges of designing research that makes them problematic.

TDR method for determine IC's parameters

NASA Astrophysics Data System (ADS)

Timoshenkov, V.; Rodionov, D.; Khlybov, A.

2016-12-01

Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

Magnetar-powered Supernovae in Two Dimensions. II. Broad-line Supernovae Ic

NASA Astrophysics Data System (ADS)

Chen, Ke-Jung; Moriya, Takashi J.; Woosley, Stan; Sukhbold, Tuguldur; Whalen, Daniel J.; Suwa, Yudai; Bromm, Volker

2017-04-01

Nascent neutron stars (NSs) with millisecond periods and magnetic fields in excess of 1016 Gauss can drive highly energetic and asymmetric explosions known as magnetar-powered supernovae. These exotic explosions are one theoretical interpretation for supernovae Ic-BL, which are sometimes associated with long gamma-ray bursts. Twisted magnetic field lines extract the rotational energy of the NS and release it as a disk wind or a jet with energies greater than 1052 erg over ˜20 s. What fraction of the energy of the central engine go into the wind and the jet remain unclear. We have performed two-dimensional hydrodynamical simulations of magnetar-powered supernovae (SNe) driven by disk winds and jets with the CASTRO code to investigate the effect of the central engine on nucleosynthetic yields, mixing, and light curves. We find that these explosions synthesize less than 0.05 {M}⊙ of {}56{Ni} and that this mass is not very sensitive to central engine type. The morphology of the explosion can provide a powerful diagnostic of the properties of the central engine. In the absence of a circumstellar medium, these events are not very luminous, with peak bolometric magnitudes of {M}b˜ -16.5 due to low {}56{Ni} production.

Surrogate Plant Data Base : Volume 1. Introduction, Appendix A : The Development of Surrogate Plant Data ; Appendix B : Application of the Surrogate .

DOT National Transportation Integrated Search

1983-03-01

This four volume report consists of a data base describing "surrogate" automobile and truck manufacturing plants developed as part of a methodology for evaluating capital investment requirements in new manufacturing facilities to build new fleets of ...

Improving Communication With Surrogate Decision-Makers: A Pilot Initiative.

PubMed

Meltzer, Ellen C; Shi, Zhenzhen; Suppes, Alexandra; Hersh, Jennifer E; Orlander, Jay D; Calhoun, Aaron W; Tung, Judy; Logio, Lia; Manna, Ruth; Bialer, Philip A; Acres, Cathleen A; Fins, Joseph J

2017-08-01

Difficult conversations in medical care often occur between physicians and patients' surrogates, individuals entrusted with medical decisions for patients who lack the capacity to make them. Poor communication between patients' surrogates and physicians may exacerbate anxiety and guilt for surrogates, and may contribute to physician stress and burnout. This pilot study assesses the effectiveness of an experiential learning workshop that was conducted in a clinical setting, and aimed at improving resident physician communication skills with a focus on surrogate decision-making. From April through June 2016, we assessed internal medicine residents' baseline communication skills through an objective structured clinical examination (OSCE) with actors representing standardized surrogates. After an intensive, 6-hour communication skills workshop, residents were reassessed via an OSCE on the same day. A faculty facilitator and the surrogate evaluated participants' communication skills via the expanded Gap Kalamazoo Consensus Statement Assessment Form. Wilcoxon signed rank tests (α of .05) compared mean pre- and postworkshop scores. Of 44 residents, 33 (75%) participated. Participants' average preworkshop OSCE scores ( M  = 3.3, SD = 0.9) were significantly lower than postworkshop scores ( M  = 4.3; SD = 0.8; Z  = 4.193; P  < .001; effect size r  = 0.52). After the workshop, the majority of participants self-reported feeling "more confident." Residents' communication skills specific to surrogate decision-making benefit from focused interventions. Our pilot assessment of a workshop showed promise, and additionally demonstrated the feasibility of bringing OSCEs and simulated encounters into a busy clinical practice.

A Rigorous Framework for Optimization of Expensive Functions by Surrogates

NASA Technical Reports Server (NTRS)

Booker, Andrew J.; Dennis, J. E., Jr.; Frank, Paul D.; Serafini, David B.; Torczon, Virginia; Trosset, Michael W.

1998-01-01

The goal of the research reported here is to develop rigorous optimization algorithms to apply to some engineering design problems for which design application of traditional optimization approaches is not practical. This paper presents and analyzes a framework for generating a sequence of approximations to the objective function and managing the use of these approximations as surrogates for optimization. The result is to obtain convergence to a minimizer of an expensive objective function subject to simple constraints. The approach is widely applicable because it does not require, or even explicitly approximate, derivatives of the objective. Numerical results are presented for a 31-variable helicopter rotor blade design example and for a standard optimization test example.

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.

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surrogates and extra-familial interests.

PubMed

Baergen, Ralph; Woodhouse, William

2013-01-01

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

Outcomes for Gestational Carriers Versus Traditional Surrogates in the United States.

PubMed

Fuchs, Erika L; Berenson, Abbey B

2018-05-01

Little is known about the obstetric and procedural outcomes of traditional surrogates and gestational carriers. Participants included 222 women living in the United States who completed a brief online survey between November 2015 and February 2016. Differences between gestational carriers (n = 204) and traditional surrogates (n = 18) in demographic characteristics, pregnancy outcomes, and procedural outcomes were examined using chi-squared tests, Fisher's exact tests, and t-tests. Out of 248 eligible respondents, 222 surveys were complete, for a response rate of 89.5%. Overall, obstetric outcomes were similar among gestational carriers and traditional surrogates. Traditional surrogates were more likely than gestational carriers to have a Center for Epidemiologic Studies Depression Scale Revised score of 16 or higher (37.5% vs. 4.0%). Gestational carriers reported higher mean compensation ($27,162.80 vs. $17,070.07) and were more likely to travel over 400 miles (46.0% vs. 0.0%) than traditional surrogates. Procedural differences, but not differences in obstetric outcomes, emerged between gestational carriers and traditional surrogates. To ensure that both traditional surrogates and gestational carriers receive optimal medical care, it may be necessary to extend practice guidelines to ensure that traditional surrogates are offered the same level of care offered to gestational carriers.

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.

The open cluster IC 4665

NASA Technical Reports Server (NTRS)

Prosser, Charles F.

1993-01-01

The results of a combined astrometric, photometric, and spectroscopic program to identify members of the open cluster IC 4665 are presented. Numerous new proper motion/photometric candidate members and at least 23 M dwarfs with H-alpha emission have been identified. A reanalysis of IC 4665 age using different methods yields conflicting results ranging from about 3 X 10 exp 7 yr to the age of the Pleiades. This study provides a list of candidate cluster members in the intermediate and low-mass regime of this cluster. Future spectroscopic observations of these candidates should eventually identify true cluster members.

2nd International Conference on Rheology and Modeling of Materials (IC-RMM2)

NASA Astrophysics Data System (ADS)

2017-01-01

Understanding the rheological properties of materials and their rheological behaviors during their manufacturing processes and in their applications in many cases can help to increase the efficiency and competitiveness not only of the finished goods and products but the organizations and societies also. The more scientific supported and prepared organizations develop more competitive products with better thermal, mechanical, physical, chemical and biological properties and the leading companies apply more competitive equipment and technology processes. The aims of the 2nd International Conference on Rheology and Modeling of Materials (ic-rmm2) and the parallel organized symposiums of the 1st International Symposium on Powder Injection Molding (is-pim1) and the 1st International Symposium on Rheology and Fracture of Solids (is-rfs1) are the followings: Promote new methods and results of scientific research in the fields of modeling and measurements of rheological properties and behavior of materials under processing and applications; Change information between the theoretical and applied sciences as well as technical and technological implantations. Promote the communication and collaboration between the scientists, researchers and engineers of different disciplines, different nations, countries and continents. The international conference ic-rmm2 and symposiums of is-pim1 and is-rfs1 provide a platform among the leading international scientists, researchers, PhD students and engineers for discussing recent achievements in measurement, modeling and application of rheology in materials technology and materials science of liquids, melts, solids, crystals and amorphous structures. Among thr major fields of interest are the influence of materials structures, mechanical stresses, temperatures, deformation speeds and shear rates on rheological and physical properties, phase transformation of foams, foods, polymers, plastics and other competitive materials like ceramics

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... corporation. (a) Scope. This section provides rules for determining whether a foreign corporation is treated as a surrogate foreign corporation under section 7874(a)(2)(B). Paragraph (b) of this section...

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... corporation. (a) Scope. This section provides rules for determining whether a foreign corporation is treated as a surrogate foreign corporation under section 7874(a)(2)(B). Paragraph (b) of this section...

Engineering study of the rotary-vee engine concept

NASA Technical Reports Server (NTRS)

Willis, Edward A.; Bartrand, Timothy A.; Beard, John E.

1989-01-01

The applicable thermodynamic cycle and performance considerations when the rotary-vee mechanism is used as an internal combustion (I.C.) heat engine are reviewed. Included is a simplified kinematic analysis and studies of the effects of design parameters on the critical pressures, torques and parasitic losses. A discussion of the principal findings is presented.

Semiconductor/High-Tc-Superconductor Hybrid ICs

NASA Technical Reports Server (NTRS)

Burns, Michael J.

1995-01-01

Hybrid integrated circuits (ICs) containing both Si-based semiconducting and YBa(2)Cu(3)O(7-x) superconducting circuit elements on sapphire substrates developed. Help to prevent diffusion of Cu from superconductors into semiconductors. These hybrid ICs combine superconducting and semiconducting features unavailable in superconducting or semiconducting circuitry alone. For example, complementary metal oxide/semiconductor (CMOS) readout and memory devices integrated with fast-switching Josephson-junction super-conducting logic devices and zero-resistance interconnections.

An Open-Source Toolbox for Surrogate Modeling of Joint Contact Mechanics

PubMed Central

Eskinazi, Ilan

2016-01-01

Goal Incorporation of elastic joint contact models into simulations of human movement could facilitate studying the interactions between muscles, ligaments, and bones. Unfortunately, elastic joint contact models are often too expensive computationally to be used within iterative simulation frameworks. This limitation can be overcome by using fast and accurate surrogate contact models that fit or interpolate input-output data sampled from existing elastic contact models. However, construction of surrogate contact models remains an arduous task. The aim of this paper is to introduce an open-source program called Surrogate Contact Modeling Toolbox (SCMT) that facilitates surrogate contact model creation, evaluation, and use. Methods SCMT interacts with the third party software FEBio to perform elastic contact analyses of finite element models and uses Matlab to train neural networks that fit the input-output contact data. SCMT features sample point generation for multiple domains, automated sampling, sample point filtering, and surrogate model training and testing. Results An overview of the software is presented along with two example applications. The first example demonstrates creation of surrogate contact models of artificial tibiofemoral and patellofemoral joints and evaluates their computational speed and accuracy, while the second demonstrates the use of surrogate contact models in a forward dynamic simulation of an open-chain leg extension-flexion motion. Conclusion SCMT facilitates the creation of computationally fast and accurate surrogate contact models. Additionally, it serves as a bridge between FEBio and OpenSim musculoskeletal modeling software. Significance Researchers may now create and deploy surrogate models of elastic joint contact with minimal effort. PMID:26186761

Critical care physicians' approaches to negotiating with surrogate decision makers: a qualitative study.

PubMed

Brush, David R; Brown, Crystal E; Alexander, G Caleb

2012-04-01

To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients' life support. Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Three academic medical centers, one academic-affiliated medical center, and four private practice groups or private hospitals in a large Midwestern city Fourteen critical care physicians. None. Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: 1) building trust; 2) educating and informing; 3) providing surrogates more time; 4) adjusting surrogate and physician roles; and 5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before readdressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decisionmaking roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to "come to terms" with the patent's illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable such as providing misleading information, injecting their own values into the negotiation or behaving unprofessionally toward surrogates. Although some physicians viewed their efforts to encourage surrogates' agreement as persuasive, others strongly denied persuading surrogates and described their actions as "guiding" or "negotiating." Physicians reported using a tailored approach to resolve decisional conflicts about life

A review of selection-based tests of abiotic surrogates for species representation.

PubMed

Beier, Paul; Sutcliffe, Patricia; Hjort, Jan; Faith, Daniel P; Pressey, Robert L; Albuquerque, Fabio

2015-06-01

Because conservation planners typically lack data on where species occur, environmental surrogates--including geophysical settings and climate types--have been used to prioritize sites within a planning area. We reviewed 622 evaluations of the effectiveness of abiotic surrogates in representing species in 19 study areas. Sites selected using abiotic surrogates represented more species than an equal number of randomly selected sites in 43% of tests (55% for plants) and on average improved on random selection of sites by about 8% (21% for plants). Environmental diversity (ED) (42% median improvement on random selection) and biotically informed clusters showed promising results and merit additional testing. We suggest 4 ways to improve performance of abiotic surrogates. First, analysts should consider a broad spectrum of candidate variables to define surrogates, including rarely used variables related to geographic separation, distance from coast, hydrology, and within-site abiotic diversity. Second, abiotic surrogates should be defined at fine thematic resolution. Third, sites (the landscape units prioritized within a planning area) should be small enough to ensure that surrogates reflect species' environments and to produce prioritizations that match the spatial resolution of conservation decisions. Fourth, if species inventories are available for some planning units, planners should define surrogates based on the abiotic variables that most influence species turnover in the planning area. Although species inventories increase the cost of using abiotic surrogates, a modest number of inventories could provide the data needed to select variables and evaluate surrogates. Additional tests of nonclimate abiotic surrogates are needed to evaluate the utility of conserving nature's stage as a strategy for conservation planning in the face of climate change. © 2015 Society for Conservation Biology.

A cross-cultural study on surrogate mother's empathy and maternal-foetal attachment.

PubMed

Lorenceau, Ellen Schenkel; Mazzucca, Luis; Tisseron, Serge; Pizitz, Todd D

2015-06-01

Traditional and gestational surrogate mothers assist infertile couples by carrying their children. In 2005, a meta-analysis on surrogacy was conducted but no study had examined empathy and maternal-foetal attachment of surrogate mothers. Assessments of surrogate mothers show no sign of psychopathology, but one study showed differences on several MMPI-2 scales compared to a normative sample: surrogate mothers identified with stereotypically masculine traits such as assertiveness and competition. They had a higher self-esteem and lower levels of anxiety and depression. To determine if there is a difference in empathy and maternal-foetal attachment of surrogate mothers compared to a comparison group of mothers. Three groups of European traditional and gestational surrogate mothers (n=10), Anglo-Saxon traditional and gestational surrogate mothers (n=34) and a European normative sample of mothers (n=32) completed four published psychometric instruments: the Interpersonal Reactivity Index (empathy index), the Hospital Anxiety and Depressions Scale and the MC20, a social desirability scale. Pregnant surrogate mothers filled the Maternal Antenatal Attachment Scale (n=11). Statistical non-parametric analyses of variance were conducted. Depending on cultural background, surrogate mothers present differences in terms of empathy, anxiety and depression, social desirability and quality of attachment to the foetus compared to a normative sample. Environment plays a role for traditional and gestational surrogacy. Surrogate mothers of both groups are less anxious and depressed than normative samples. Maternal-foetal attachment is strong with a slightly lower quality of attachment. Surrogate mother's empathy indexes are similar to normative samples, sometimes higher. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Statistical Surrogate Models for Estimating Probability of High-Consequence Climate Change

NASA Astrophysics Data System (ADS)

Field, R.; Constantine, P.; Boslough, M.

2011-12-01

We have posed the climate change problem in a framework similar to that used in safety engineering, by acknowledging that probabilistic risk assessments focused on low-probability, high-consequence climate events are perhaps more appropriate than studies focused simply on best estimates. To properly explore the tails of the distribution requires extensive sampling, which is not possible with existing coupled atmospheric models due to the high computational cost of each simulation. We have developed specialized statistical surrogate models (SSMs) that can be used to make predictions about the tails of the associated probability distributions. A SSM is different than a deterministic surrogate model in that it represents each climate variable of interest as a space/time random field, that is, a random variable for every fixed location in the atmosphere at all times. The SSM can be calibrated to available spatial and temporal data from existing climate databases, or to a collection of outputs from general circulation models. Because of its reduced size and complexity, the realization of a large number of independent model outputs from a SSM becomes computationally straightforward, so that quantifying the risk associated with low-probability, high-consequence climate events becomes feasible. A Bayesian framework was also developed to provide quantitative measures of confidence, via Bayesian credible intervals, to assess these risks. To illustrate the use of the SSM, we considered two collections of NCAR CCSM 3.0 output data. The first collection corresponds to average December surface temperature for years 1990-1999 based on a collection of 8 different model runs obtained from the Program for Climate Model Diagnosis and Intercomparison (PCMDI). We calibrated the surrogate model to the available model data and make various point predictions. We also analyzed average precipitation rate in June, July, and August over a 54-year period assuming a cyclic Y2K ocean model. We

Using Approximations to Accelerate Engineering Design Optimization

NASA Technical Reports Server (NTRS)

Torczon, Virginia; Trosset, Michael W.

1998-01-01

Optimization problems that arise in engineering design are often characterized by several features that hinder the use of standard nonlinear optimization techniques. Foremost among these features is that the functions used to define the engineering optimization problem often are computationally intensive. Within a standard nonlinear optimization algorithm, the computational expense of evaluating the functions that define the problem would necessarily be incurred for each iteration of the optimization algorithm. Faced with such prohibitive computational costs, an attractive alternative is to make use of surrogates within an optimization context since surrogates can be chosen or constructed so that they are typically much less expensive to compute. For the purposes of this paper, we will focus on the use of algebraic approximations as surrogates for the objective. In this paper we introduce the use of so-called merit functions that explicitly recognize the desirability of improving the current approximation to the objective during the course of the optimization. We define and experiment with the use of merit functions chosen to simultaneously improve both the solution to the optimization problem (the objective) and the quality of the approximation. Our goal is to further improve the effectiveness of our general approach without sacrificing any of its rigor.

Engineering study on the rotary-vee engine concept

NASA Technical Reports Server (NTRS)

Willis, Edward A.; Bartland, Timothy A.; Beard, John E.

1989-01-01

This paper provides a review of the applicable thermodynamic cycle and performance considerations when the rotary-vee mechanism is used as an internal combustion (IC) heat engine. Included is a simplified kinematic analysis and studies of the effects of design parameters on the critical pressures, torques and parasitic losses. A discussion of the principal findings is presented.

Experiments on Induction Times of Diesel-Fuels and its Surrogates

NASA Astrophysics Data System (ADS)

Eigenbrod, Christian; Reimert, Manfredo; Marks, Guenther; Rickmers, Peter; Klinkov, Konstantin; Moriue, Osamu

Aiming for as low polluting combustion control as possible in Diesel-engines or gas-turbines, pre-vaporized and pre-mixed combustion at low mean temperature levels marks the goal. Low-est emissions of nitric-oxides are achievable at combustion temperatures associated to mixture ratios close to the lean flammability limit. In order to prevent local mixture ratios to be below the flammability limit (resulting in flame extinction or generation of unburned hydrocarbons and carbon-monoxide) or to be richer than required (resulting in more nitric-oxide than possi-ble), well-stirred conditioning is required. The time needed for spray generation, vaporization and turbulent mixing is limited through the induction time to self-ignition in a hot high-pressure ambiance. Therefore, detailed knowledge about the autoignition of fuels is a pre-requisit. Experiments were performed at the Bremen drop tower to investigate the self-ignition behavior of single droplets of fossil-Diesel oil, rapeseed-oil, Gas-to-Liquid (GTL) synthetic Diesel-oil and the fossil Diesel surrogates n-heptane, n-tetradecane, 50 n-tetradecane/ 50 1-methylnaphthalene as well as on the GTL-surrogates n-tetradecane / bicyclohexyl and n-tetradecane / 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). The rules for selection of the above fuels and the experimental results are presented and dis-cussed.

Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production.

PubMed

Zhang, Xiaojie; Lu, Chenyang; Bai, Linquan

2017-09-01

An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization, fast growth, abundant precursors and energy supply, and a pronounced gene expression. Streptomyces albus BK3-25 is a high-yield industrial strain producing type-I polyketide salinomycin, with a unique ability of bean oil utilization. Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein. Firstly, introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and salinomycin, and subsequent deletion of the salinomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors, including malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA. Secondly, the energy and reducing force were measured, and the improved accumulation of ATP and NADPH was observed in the mutant. Furthermore, the strength of a series of selected endogenous promoters based on microarray data was assessed at different growth phases, and a strong constitutive promoter was identified, providing a useful tool for further engineered gene expression. Finally, the potential of the BK3-25 derived host ZXJ-6 was evaluated with the introduction of the actinorhodin biosynthetic gene cluster from Streptomyces coelicolor, and the heterologous production of actinorhodin was obtained. This work clearly indicated the potential of the high-yield salinomycin producer as a surrogate host for heterologous production of polyketides, although more genetic manipulation should be conducted to streamline its performance.

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.

Conservative strategy-based ensemble surrogate model for optimal groundwater remediation design at DNAPLs-contaminated sites

NASA Astrophysics Data System (ADS)

Ouyang, Qi; Lu, Wenxi; Lin, Jin; Deng, Wenbing; Cheng, Weiguo

2017-08-01

The surrogate-based simulation-optimization techniques are frequently used for optimal groundwater remediation design. When this technique is used, surrogate errors caused by surrogate-modeling uncertainty may lead to generation of infeasible designs. In this paper, a conservative strategy that pushes the optimal design into the feasible region was used to address surrogate-modeling uncertainty. In addition, chance-constrained programming (CCP) was adopted to compare with the conservative strategy in addressing this uncertainty. Three methods, multi-gene genetic programming (MGGP), Kriging (KRG) and support vector regression (SVR), were used to construct surrogate models for a time-consuming multi-phase flow model. To improve the performance of the surrogate model, ensemble surrogates were constructed based on combinations of different stand-alone surrogate models. The results show that: (1) the surrogate-modeling uncertainty was successfully addressed by the conservative strategy, which means that this method is promising for addressing surrogate-modeling uncertainty. (2) The ensemble surrogate model that combines MGGP with KRG showed the most favorable performance, which indicates that this ensemble surrogate can utilize both stand-alone surrogate models to improve the performance of the surrogate model.

Rotary vane type IC engine with built-in scavenging air blower

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

Chang, V.

This patent describes a rotary internal combustion engine. This engine consists of: a housing assembly including three sections and having a single common power shaft, the three sections being integrally connected together and operatively connected together into a unitary self-contained engine, air and fuel mixture intake conduit means communicatively connected to a first of the three sections, means in the first section to perform admission and compression of the air and fuel mixture admitted from the conduit means, means to convey the compressed air and fuel mixture to a second of the three sections. A single internal partition wall meansmore » between the first and second sections, and the air and fuel mixture conveys means consisting of a port formed in the partition wall means. In the second section the compressed air is ignited with a fuel mixture and to permit expansion of the ignited air and fuel mixture to thereby furnish power strokes to the power shaft. In the second section for exhausting the gaseous products of combustion, air blower in the third of the three sections driven by the power shaft.« less

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

PubMed Central

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

2014-01-01

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

Deliberative assessment of surrogate consent in dementia research.

PubMed

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

2010-07-01

Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on 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. One hundred and seventy-eight 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") 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 1 month after DD date, for four research scenarios of varying risk-benefit profiles. At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 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. Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients. Copyright 2010 The Alzheimer

Choice of surrogate tissue influences neonatal EWAS findings.

PubMed

Lin, Xinyi; Teh, Ai Ling; Chen, Li; Lim, Ives Yubin; Tan, Pei Fang; MacIsaac, Julia L; Morin, Alexander M; Yap, Fabian; Tan, Kok Hian; Saw, Seang Mei; Lee, Yung Seng; Holbrook, Joanna D; Godfrey, Keith M; Meaney, Michael J; Kobor, Michael S; Chong, Yap Seng; Gluckman, Peter D; Karnani, Neerja

2017-12-05

Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

Study of Periodical Flow Heat Transfer in an Internal Combustion Engine

NASA Astrophysics Data System (ADS)

Luo, Xi

In-cylinder heat transfer is one of the most critical physical behaviors which has a direct influence on engine out emission and thermal efficiency for IC engine. In-cylinder wall temperature has to be precisely controlled to achieve high efficiency and low emission. However, this cannot be done without knowing gas-to-wall heat flux. This study reports on the development of a technique suitable for engine in-cylinder surface temperature measurement, as the traditional method is "hard to reach." A laser induced phosphorescence technique was used to study in-cylinder wall temperature effects on engine out unburned hydrocarbons during the engine transitional period (warm up). A linear correlation was found between the cylinder wall surface temperature and the unburned hydrocarbons at mediate and high charge densities. At low charge density, no clear correlation was observed because of miss-fire events. A new auto background correction infrared (IR) diagnostic was developed to measure the instantaneous in-cylinder surface temperature at 0.1 CAD resolution. A numerical mechanism was designed to suppress relatively low-frequency background noise and provide an accurate in-cylinder surface temperature measurements with an error of less than 1.4% inside the IC engine. In addition, a proposed optical coating reduced time delay errors by 50% compared to more conventional thermocouple techniques. A new cycle-averaged Res number was developed for an IC engine to capture the characteristics of engine flow. Comparison and scaling between different engine flow parameters are available by matching the averaged Res number. From experimental results, the engine flow motion was classified as intermittently turbulent, and it is different from the original fully developed turbulent assumption, which has previously been used in almost all engine simulations. The intermittent turbulence could have a great impact on engine heat transfer because of the transitional turbulence effect

Systematic review: the effect on surrogates of making treatment decisions for others.

PubMed

Wendler, David; Rid, Annette

2011-03-01

Clinical practice relies on surrogates to make or help to make treatment decisions for incapacitated adults; however, the effect of this practice on surrogates has not been evaluated. To assess the effect on surrogates of making treatment decisions for adults who cannot make their own decisions. Empirical studies published in English and listed in MEDLINE, EMBASE, CINAHL, BIOETHICSLINE, PsycINFO, or Scopus before 1 July 2010. Eligible studies provided quantitative or qualitative empirical data, by evaluating surrogates, regarding the effect on surrogates of making treatment decisions for an incapacitated adult. Information on study location, number and type of surrogates, timing of data collection, type of decisions, patient setting, methods, main findings, and limitations. 40 studies, 29 using qualitative and 11 using quantitative methods, provided data on 2854 surrogates, more than one half of whom were family members of the patient. Most surrogates were surveyed several months to years after making treatment decisions, the majority of which were end-of-life decisions. The quantitative studies found that at least one third of surrogates experienced a negative emotional burden as the result of making treatment decisions. The qualitative studies reported that many or most surrogates experienced negative emotional burden. The negative effects on surrogates were often substantial and typically lasted months or, in some cases, years. The most common negative effects cited by surrogates were stress, guilt over the decisions they made, and doubt regarding whether they had made the right decisions. Nine of the 40 studies also reported beneficial effects on a few surrogates, the most common of which were supporting the patient and feeling a sense of satisfaction. Knowing which treatment is consistent with the patient's preferences was frequently cited as reducing the negative effect on surrogates. Thirty-two of the 40 articles reported data collected in the United States

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.

An Integrated Optimization Design Method Based on Surrogate Modeling Applied to Diverging Duct Design

NASA Astrophysics Data System (ADS)

Hanan, Lu; Qiushi, Li; Shaobin, Li

2016-12-01

This paper presents an integrated optimization design method in which uniform design, response surface methodology and genetic algorithm are used in combination. In detail, uniform design is used to select the experimental sampling points in the experimental domain and the system performance is evaluated by means of computational fluid dynamics to construct a database. After that, response surface methodology is employed to generate a surrogate mathematical model relating the optimization objective and the design variables. Subsequently, genetic algorithm is adopted and applied to the surrogate model to acquire the optimal solution in the case of satisfying some constraints. The method has been applied to the optimization design of an axisymmetric diverging duct, dealing with three design variables including one qualitative variable and two quantitative variables. The method of modeling and optimization design performs well in improving the duct aerodynamic performance and can be also applied to wider fields of mechanical design and seen as a useful tool for engineering designers, by reducing the design time and computation consumption.

Embedded I&C for Extreme Environments

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

Kisner, Roger A.

2016-04-01

This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pumpmore » combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.« less

Molecular Hydrogen Fluorescence in IC 63

NASA Technical Reports Server (NTRS)

Andersson, B-G

2005-01-01

This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

An overview of NASA intermittent combustion engine research

NASA Technical Reports Server (NTRS)

Willis, E. A.; Wintucky, W. T.

1984-01-01

This paper overviews the current program, whose objective is to establish the generic technology base for advanced aircraft I.C. engines of the early 1990's and beyond. The major emphasis of this paper is on development of the past two years. Past studies and ongoing confirmatory experimental efforts are reviewed, which show unexpectly high potential when modern aerospace technologies are applied to inherently compact and balanced I.C. engine configurations. Currently, the program is focussed on two engine concepts the stratified-charge, multi-fuel rotary, and the lightweight two-stroke diesel. A review is given of contracted and planned high performance one-rotor and one-cylinder test engine work addressing several levels of technology. Also reviewed are basic supporting efforts, e.g., the development and experimental validation of computerized airflow and combustion process models, being performed in-house at Lewis Research Center and by university grants.

Host-pathogen-interaction reconstituted in 3-dimensional cocultures of mucosa and <i>C. albicans.

PubMed

Buchs, Romina; Lehner, Bruno; Meuwly, Phillippe; Schnyder, Bruno

2018-06-14

<i>C. albicans frequently causes recurrent intimal infectious disease (ID). This demands the treatment of multiple phases of the infection. The objective of this study was to uncover the host-pathogen-interaction using 2D epithelium cell-barrier and 3D subepithelium tissue cells of human mucosa. The 2D cell cultures assessed <i>C. albicans adhesion. Addition of the anti-fungal drug Fluconazol did not inhibit the adhesion, despite its pathogen growth inhibition (MIC value 0.08μg/mL). A 3D tissue was engineered in multi-transwells by placing human fibroblast cultures on a thick porous scaffold. This contained the yeast placed in the top compartment and prevented passive penetration. After 28h the pathogen transmigrated the barrier and was collected in the bottom compartment. A change in pathogen morphology was observed where hypha formed and grew to be 231μm long after 28h. The hypha was thus long enough to cross the 200μm thick 3D tissue. The 3D infection was inhibited by addition of Fluconazol (0.08μg/mL), confirming that penetration is dependent on pathogen growth. In conclusion, ID was reconstituted step-by-step on 2D epithelium surface and in 3D connective tissue of human mucosa. Fluconazol growth-inhibition of the pathogen <i>C. albicans was confirmed in the 3D tissue. We thus propose that this ID in vitro test is suitable for the identification and characterization of new treatments against <i>C. albicans..

Uncertainty quantification for accident management using ACE surrogates

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

Varuttamaseni, A.; Lee, J. C.; Youngblood, R. W.

The alternating conditional expectation (ACE) regression method is used to generate RELAP5 surrogates which are then used to determine the distribution of the peak clad temperature (PCT) during the loss of feedwater accident coupled with a subsequent initiation of the feed and bleed (F and B) operation in the Zion-1 nuclear power plant. The construction of the surrogates assumes conditional independence relations among key reactor parameters. The choice of parameters to model is based on the macroscopic balance statements governing the behavior of the reactor. The peak clad temperature is calculated based on the independent variables that are known tomore » be important in determining the success of the F and B operation. The relationship between these independent variables and the plant parameters such as coolant pressure and temperature is represented by surrogates that are constructed based on 45 RELAP5 cases. The time-dependent PCT for different values of F and B parameters is calculated by sampling the independent variables from their probability distributions and propagating the information through two layers of surrogates. The results of our analysis show that the ACE surrogates are able to satisfactorily reproduce the behavior of the plant parameters even though a quasi-static assumption is primarily used in their construction. The PCT is found to be lower in cases where the F and B operation is initiated, compared to the case without F and B, regardless of the F and B parameters used. (authors)« less

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) ...

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

PubMed Central

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

2014-01-01

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

One mum too few: maternal status in host surrogate motherhood arrangements.

PubMed

Oultram, Stuart

2015-06-01

In a host surrogate motherhood arrangement, the surrogate agrees to be implanted with, and carry to term, an embryo created from the commissioning couple's gametes. When the surrogate child is born, it is the surrogate mother who, according to UK law, holds the legal status of mother. By contrast, the commissioning mother possesses no maternal status and she can only attain it once the surrogate agrees to the completion of the arrangement. One consequence of this is that, in the event that a host arrangement fails, the commissioning mother is left without maternal status. In this paper, I argue that this denial of maternal status misrepresents the commissioning mother's role in the host arrangement and her relationship with the surrogate child. Consequently, I suggest that commissioning mothers participating in host surrogacy arrangements ought to be granted the status of mother in the event that the arrangement fails. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Legal regulation of surrogate motherhood in Israel.

PubMed

Frenkel, D A

2001-01-01

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

H I debris in the IC 1459 galaxy group

NASA Astrophysics Data System (ADS)

Saponara, Juliana; Koribalski, Bärbel S.; Benaglia, Paula; Fernández López, Manuel

2018-01-01

We present H I synthesis imaging of the giant elliptical galaxy IC 1459 and its surroundings with the Australia Telescope Compact Array. Our search for extended H I emission revealed a large complex of H I clouds near IC 1459, likely to be the debris from tidal interactions with neighbouring galaxies. The total H I mass (∼109 M⊙) in the detected clouds spans 250 kpc from the north-east of the gas-rich spiral NGC 7418A to the south-east of IC 1459. The extent and mass of the H I debris, which shows rather irregular morphology and kinematics, are similar to those in other nearby groups. Together with H I clouds recently detected near two other IC 1459 group members, namely IC 5270 and NGC 7418, using phased-array feeds on the Australian Square Kilometre Array Pathfinder, the detected debris make up a significant fraction of the group's intergalactic medium.

Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

PubMed

Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

2015-02-10

Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

Floor Plans Engine Removal Platform, Hold Down Arm Platform, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Engine Removal Platform, Hold Down Arm Platform, Hydraulic Equipment Platforms, Isometric Cutaway of Engine Removal Platform, Isometric Cutaway of Hold Down Arm Platform, Isometric Cutaway of Hydraulic Platforms and Engine Support System Access - Marshall Space Flight Center, Saturn V S-IC Static Test Facility, West Test Area, Huntsville, Madison County, AL

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.

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

PubMed

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

2016-12-01

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. Prospective qualitative study. Medical ICU of a major urban university hospital. Surrogate decision makers of intubated, mechanically ventilated patients in the medical ICU. 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. 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.

Endpoints and surrogate endpoints in colorectal cancer: a review of recent developments.

PubMed

Piedbois, Pascal; Buyse, Marc

2008-07-01

The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints. Most attempts to validate surrogate endpoints have estimated the correlation between the surrogate and the true endpoint, and between the treatment effects on these endpoints. The correlation approach has made it possible to validate disease-free survival and progression-free survival as acceptable surrogates for overall survival in early and advanced disease, respectively. The search for surrogate endpoints will intensify over the coming years. In parallel, efforts to either standardize or extend the endpoints or both will improve the reliability and relevance of clinical trial results.

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. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

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

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

DOE PAGES

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco; ...

2016-05-08

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

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

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying

An overview of NASA intermittent combustion engine research

NASA Technical Reports Server (NTRS)

Willis, E. A.; Wintucky, W. T.

1984-01-01

This paper overviews the current program, whose objective is to establish the generic technology base for advanced aircraft I.C. engines of the early 1990's and beyond. The major emphasis of this paper is on development of the past two years. Past studies and ongoing confirmatory experimental efforts are reviewed, which show unexpectedly high potential when modern aerospace technologies are applied to inherently compact and balanced I.C. engine configurations. Currently, the program is focussed on two engine concepts, the stratified-charge, multi-fuel rotary and the lightweight two-stroke diesel. A review is given of contracted and planned high performance one-rotor and one-cylinder test engine work addressing several levels of technology. Also reviewed are basic supporting efforts, e.g., the development and experimental validation of computerized airflow and combustion process models, being performed in-house at Lewis Research Center and by university grants. Previously announced in STAR as N84-24583

A Surrogate Technique for Investigating Deterministic Dynamics in Discrete Human Movement.

PubMed

Taylor, Paul G; Small, Michael; Lee, Kwee-Yum; Landeo, Raul; O'Meara, Damien M; Millett, Emma L

2016-10-01

Entropy is an effective tool for investigation of human movement variability. However, before applying entropy, it can be beneficial to employ analyses to confirm that observed data are not solely the result of stochastic processes. This can be achieved by contrasting observed data with that produced using surrogate methods. Unlike continuous movement, no appropriate method has been applied to discrete human movement. This article proposes a novel surrogate method for discrete movement data, outlining the processes for determining its critical values. The proposed technique reliably generated surrogates for discrete joint angle time series, destroying fine-scale dynamics of the observed signal, while maintaining macro structural characteristics. Comparison of entropy estimates indicated observed signals had greater regularity than surrogates and were not only the result of stochastic but also deterministic processes. The proposed surrogate method is both a valid and reliable technique to investigate determinism in other discrete human movement time series.

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.

The role of imperfect surrogate endpoint information in drug approval and reimbursement decisions.

PubMed

Bognar, Katalin; Romley, John A; Bae, Jay P; Murray, James; Chou, Jacquelyn W; Lakdawalla, Darius N

2017-01-01

Approval of new drugs is increasingly reliant on "surrogate endpoints," which correlate with but imperfectly predict clinical benefits. Proponents argue surrogate endpoints allow for faster approval, but critics charge they provide inadequate evidence. We develop an economic framework that addresses the value of improvement in the predictive power, or "quality," of surrogate endpoints, and clarifies how quality can influence decisions by regulators, payers, and manufacturers. For example, the framework shows how lower-quality surrogates lead to greater misalignment of incentives between payers and regulators, resulting in more drugs that are approved for use but not covered by payers. Efficient price-negotiation in the marketplace can help align payer incentives for granting access based on surrogates. Higher-quality surrogates increase manufacturer profits and social surplus from early access to new drugs. Since the return on better quality is shared between manufacturers and payers, private incentives to invest in higher-quality surrogates are inefficiently low. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

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

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

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.more » 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.« less

Assessing the potential of surrogate EPS to mimic natural biofilm mechanical properties

NASA Astrophysics Data System (ADS)

Thom, Moritz; Schimmels, Stefan

2017-04-01

Biofilms growing on benthic sediments may increase the resistance towards erosion considerably by the sticky nature of extracellular polymeric substances (EPS). The EPS is a biopolymer which is secreted by the microorganisms inhabiting the biofilm matrix and may be regarded as natural glue. However, laboratory studies on the biostabilization effect mediated by biofilms are often hampered by the unavailability of "environmental" flumes in which light intensities, water temperature and nutrient content can be controlled. To allow investigations on biostabilization in "traditional" flume settings the use of surrogate materials is studied. Another advantage of using appropriate surrogates is the potential to reduce the experimental time, as compared to cultivating natural biofilms, the surrogates can readily be designed to mimic biofilms at different growth stages. Furthermore, the use of surrogates which are expected to have more homogeneous mechanical properties could facilitate fundamental studies to improve our knowledge on biostabilization. Even though a number of studies have already utilized EPS surrogates it is not clear how to mix them to correctly mimic natural EPS mechanical properties. In this study the adhesiveness (a measure of stickiness) on the surface of several EPS surrogates (e.g. Xanthan Gum, sodium alginate) is measured. These surrogates which are originally used in the food industry as rheology modifiers are mixed by adding water to a powder at a desired concentration (C). The measured surface adhesion of different surrogates at different concentrations ranged from 0.5 to 6.7 N/m2, which is well in line with values found for laboratory cultured biofilms. We found that the surrogate characteristics differed largely especially in regard to a) the response of the adhesiveness to increased concentrations (powder to water) and b) in their rheological characteristics. A seemingly promising surrogate for the use in biostabilization studies is Xanthan Gum

Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective.

PubMed

Piedbois, Pascal; Miller Croswell, Jennifer

2008-10-01

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the

Trends in Utilization of Surrogate Endpoints in Contemporary Cardiovascular Clinical Trials.

PubMed

Patel, Ravi B; Vaduganathan, Muthiah; Samman-Tahhan, Ayman; Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Fonarow, Gregg C; Gheorghiade, Mihai; Butler, Javed

2016-06-01

Surrogate endpoints facilitate trial efficiency but are variably linked to clinical outcomes, and limited data are available exploring their utilization in cardiovascular clinical trials over time. We abstracted data regarding primary clinical, intermediate, and surrogate endpoints from all phase II to IV cardiovascular clinical trials from 2001 to 2012 published in the 8 highest Web of Science impact factor journals. Two investigators independently classified the type of primary endpoint. Of the 1,224 trials evaluated, 677 (55.3%) primary endpoints were clinical, 165 (13.5%) intermediate, and 382 (31.2%) surrogate. The relative proportions of these endpoints remained constant over time (p = 0.98). Trials using surrogate endpoints were smaller (187 vs 1,028 patients) and enrolled patients more expeditiously (1.4 vs 0.9 patients per site per month) compared with trials using clinical endpoints (p <0.001 for both comparisons). Surrogate endpoint trials were independently more likely to meet their primary endpoint compared to trials with clinical endpoints (adjusted odds ratio 1.56, 95% CI 1.05 to 2.34; p = 0.03). Rates of positive results in clinical endpoint trials have decreased over time from 66.1% in 2001 to 2003 to 47.2% in 2010 to 2012 (p = 0.001), whereas these rates have remained stable over the same period for surrogate (72.0% to 69.3%, p = 0.27) and intermediate endpoints (74.4% to 71.4%, p = 0.98). In conclusion, approximately a third of contemporary cardiovascular trials use surrogate endpoints. These trials are completed more expeditiously and are more likely to meet their primary outcomes. The overall scientific contribution of these surrogate endpoint trials requires further attention given their variable association with definitive outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Dr. von Braun Standing by Five F-1 Engines

NASA Technical Reports Server (NTRS)

2004-01-01

A pioneer of America's space program, Dr. von Braun stands by the five F-1 engines of the Saturn V launch vehicle. This Saturn V vehicle is an actual test vehicle which has been displayed at the U.S. Space Rocket Center in Huntsville, Alabama. Designed and developed by Rocketdyne under the direction of the Marshall Space Flight Center, a cluster of five F-1 engines was mounted on the Saturn V S-IC (first) stage. The engines measured 19-feet tall by 12.5-feet at the nozzle exit and burned 15 tons of liquid oxygen and kerosene each second to produce 7,500,000 pounds of thrust. The S-IC stage is the first stage, or booster, of a 364-foot long rocket that ultimately took astronauts to the Moon.

Interband cascade (IC) photovoltaic (PV) architecture for PV devices

DOEpatents

Yang, Rui Q.; Tian, Zhaobing; Mishima, Tetsuya D.; Santos, Michael B.; Johnson, Matthew B.; Klem, John F.

2015-10-20

A photovoltaic (PV) device, comprising a PV interband cascade (IC) stage, wherein the IC PV stage comprises an absorption region with a band gap, the absorption region configured to absorb photons, an intraband transport region configured to act as a hole barrier, and an interband tunneling region configured to act as an electron barrier. An IC PV architecture for a photovoltaic device, the IC PV architecture comprising an absorption region, an intraband transport region coupled to the absorption region, and an interband tunneling region coupled to the intraband transport region and to the adjacent absorption region, wherein the absorption region, the intraband transport region, and the interband tunneling region are positioned such that electrons will flow from the absorption region to the intraband transport region to the interband tunneling region.

EXTRACTION AND DETECTION OF A NEW ARSINE SULFIDE CONTAINING ARSENOSUGAR IN MOLLUSCS BY IC-ICP-MS AND IC-ESI-MS/MS

EPA Science Inventory

Using IC-ICP-MS and IC-ESI-MS/MS, an unknown arsenical compound in mollusks has been identified as a new arsine sulfide containing analog of a known arsenosugar and is referred to as As(498). This species has been observed in four separate shellfish species following a mild metha...

Communicating with Clinicians: The Experiences of Surrogate Decision Makers for Hospitalized Older Adults

PubMed Central

Torke, Alexia M.; Petronio, Sandra; Purnell, Christianna E.; Sachs, Greg A.; Helft, Paul R.; Callahan, Christopher M.

2012-01-01

Background/Objectives When hospitalized older adults have impaired cognition, family members or other surrogates must communicate with clinicians to provide information and make medical decisions for the patient. The present study describes communication experiences of surrogates who recently made a major medical decision for a hospitalized older adult. Design Semi-structured interviews about a recent hospitalization. Setting Two hospitals both affiliated with 1 large medical school: an urban, public hospital; and a university-affiliated tertiary referral hospital. Participants Surrogates were eligible if they had recently made a major medical decision for a hospitalized patient aged 65 or older and were available for an interview within 1 month (2-5 months if the patient died). Measurements Interviews were audio-recorded, transcribed, and analyzed using methods of grounded theory. Results We interviewed 35 surrogates. They were 80% female, 44% white and 56% African American. Three primary themes emerged. We found the Nature of Surrogate/Clinician Relationships was best characterized as a relationship with a “team” of clinicians rather than individual clinicians due to frequent staff changes and multiple clinicians. Surrogates reported their Communication Needs, including frequent communication, information, and emotional support. Surrogates valued communication from any member of the clinical team, including nurses, social workers, and physicians. Third, surrogates described Trust and Mistrust, which were formed largely through surrogates’ communication experiences. Conclusion In the hospital, surrogates form relationships with a “team” of clinicians rather than with individuals. Yet effective communication and expressions of emotional support frequently occur and are highly valued by surrogates. Future interventions should focus on meeting surrogates’ needs for frequent communication, high levels of information and emotional support. PMID:22881864

Surrogate mothering: exploitation or empowerment?

PubMed

Purdy, Laura M

1989-01-01

The morality of surrogate mothering is analyzed from a "consequentialist" framework which attempts to separate those consequences that invariably accompany a given act from those that accompany it only in particular circumstances. Critics of surrogacy argue that it transfers the burden and risk of pregnancy onto another woman, separates sex and reproduction, and separates reproduction and childrearing; none of these acts is necessarily wrong, either morally or for women's or society's basic interests. While surrogate mothering can be rendered immoral if women are coerced into the practice or become victims of subordinating or penalizing contracts, it has the potential to empower women and increase their status in society by providing a job that is less risky and more enjoyable than other jobs women are forced to take and by achieving greater social recognition for reproductive labor.

Selection of Surrogate Bacteria for Use in Food Safety Challenge Studies: A Review.

PubMed

Hu, Mengyi; Gurtler, Joshua B

2017-09-01

Nonpathogenic surrogate bacteria are prevalently used in a variety of food challenge studies in place of foodborne pathogens such as Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Clostridium botulinum because of safety and sanitary concerns. Surrogate bacteria should have growth characteristics and/or inactivation kinetics similar to those of target pathogens under given conditions in challenge studies. It is of great importance to carefully select and validate potential surrogate bacteria when verifying microbial inactivation processes. A validated surrogate responds similar to the targeted pathogen when tested for inactivation kinetics, growth parameters, or survivability under given conditions in agreement with appropriate statistical analyses. However, a considerable number of food studies involving putative surrogate bacteria lack convincing validation sources or adequate validation processes. Most of the validation information for surrogates in these studies is anecdotal and has been collected from previous publications but may not be sufficient for given conditions in the study at hand. This review is limited to an overview of select studies and discussion of the general criteria and approaches for selecting potential surrogate bacteria under given conditions. The review also includes a list of documented bacterial pathogen surrogates and their corresponding food products and treatments to provide guidance for future studies.

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

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.

Production of the forskolin precursor 11β-hydroxy-manoyl oxide in yeast using surrogate enzymatic activities.

PubMed

Ignea, Codruta; Ioannou, Efstathia; Georgantea, Panagiota; Trikka, Fotini A; Athanasakoglou, Anastasia; Loupassaki, Sofia; Roussis, Vassilios; Makris, Antonios M; Kampranis, Sotirios C

2016-02-26

Several plant diterpenes have important biological properties. Among them, forskolin is a complex labdane-type diterpene whose biological activity stems from its ability to activate adenylyl cyclase and to elevate intracellular cAMP levels. As such, it is used in the control of blood pressure, in the protection from congestive heart failure, and in weight-loss supplements. Chemical synthesis of forskolin is challenging, and production of forskolin in engineered microbes could provide a sustainable source. To this end, we set out to establish a platform for the production of forskolin and related epoxy-labdanes in yeast. Since the forskolin biosynthetic pathway has only been partially elucidated, and enzymes involved in terpene biosynthesis frequently exhibit relaxed substrate specificity, we explored the possibility of reconstructing missing steps of this pathway employing surrogate enzymes. Using CYP76AH24, a Salvia pomifera cytochrome P450 responsible for the oxidation of C-12 and C-11 of the abietane skeleton en route to carnosic acid, we were able to produce the forskolin precursor 11β-hydroxy-manoyl oxide in yeast. To improve 11β-hydroxy-manoyl oxide production, we undertook a chassis engineering effort involving the combination of three heterozygous yeast gene deletions (mct1/MCT1, whi2/WHI2, gdh1/GDH1) and obtained a 9.5-fold increase in 11β-hydroxy-manoyl oxide titers, reaching 21.2 mg L(-1). In this study, we identify a surrogate enzyme for the specific and efficient hydroxylation of manoyl oxide at position C-11β and establish a platform that will facilitate the synthesis of a broad range of tricyclic (8,13)-epoxy-labdanes in yeast. This platform forms a basis for the heterologous production of forskolin and will facilitate the elucidation of subsequent steps of forskolin biosynthesis. In addition, this study highlights the usefulness of using surrogate enzymes for the production of intermediates of complex biosynthetic pathways. The combination of

Surrogate decision making and intellectual virtue.

PubMed

Bock, Gregory L

2014-01-01

Patients can be harmed by a religiously motivated surrogate decision maker whose decisions are contrary to the standard of care; therefore, surrogate decision making should be held to a high standard. Stewart Eskew and Christopher Meyers proposed a two-part rule for deciding which religiously based decisions to honor: (1) a secular reason condition and (2) a rationality condition. The second condition is based on a coherence theory of rationality, which they claim is accessible, generous, and culturally sensitive. In this article, I will propose strengthening the rationality condition by grounding it in a theory of intellectual virtue, which is both rigorous and culturally sensitive. Copyright 2014 The Journal of Clinical Ethics. All rights reserved.

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

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

PubMed Central

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

2015-01-01

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

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

A radial velocity survey of the open cluster IC 4665

NASA Technical Reports Server (NTRS)

Prosser, Charles F.; Giampapa, Mark S.

1994-01-01

A radial velocity survey of the open cluster IC 4665 is reported for a group of candidate members previously identified on the basis of proper motion and photometry. Of those candidates observed, 20 out of 42 have radial velocities consistent with membership; these cluster members populate the F5-K0 dwarf region and represent the first relatively conclusive membership determinations for such solar-type stars in IC 4665. Three new spectroscopic binary members of the cluster have been identified. Rotational velocities have also been derived; the v sin i distribution among IC 4665 members reveals that most apparent G dwarf members of IC 4665 are seen to exhibit substantial rotation (v sin i greater than 10 km/s). When compared to evolutionary isochrones, the current list of intermediate-mass members appears to support earlier suggestions that IC 4665 has an age comparable to the Pleiades.

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

Biomarkers and surrogate endpoints in kidney disease.

PubMed

Hartung, Erum A

2016-03-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease.

Biomarkers and surrogate endpoints in kidney disease

PubMed Central

2015-01-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. “Hard” endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease. PMID:25980469

Critical care physicians’ approaches to negotiating with surrogate decision makers: a qualitative study

PubMed Central

Brush, David R.; Brown, Crystal E.; Alexander, G. Caleb

2013-01-01

Objective To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients’ life support. Design Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Setting 3 academic medical centers, 1 academic-affiliated medical center and 4 private practice groups or private hospitals in a large Midwestern city Subjects 14 critical care physicians Measurements and main results Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: (1) building trust, (2) educating and informing, (3) providing surrogates more time, (4) adjusting surrogate and physician roles, and (5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before re-addressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decision making roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to “come to terms” with the patent’s illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable, such as providing misleading information, injecting their own values into the negotiation, or behaving unprofessionally towards surrogates. While some physicians viewed their efforts to encourage surrogates’ agreement as persuasive, others strongly denied persuading surrogates and described their actions as “guiding” or “negotiating.” Conclusions Physicians

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

PubMed

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

2015-11-27

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. 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. 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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

DTIC Science & Technology

2013-03-01

as a criterion for “good” surrogate, why can’t we create a new, formal definition of “ surrogacy ” that (1) will automatically avoid the paradox and (2...requirement of avoiding the paradox could not, in itself, constitute a satisfactory definition of surrogacy . As with other paradoxes of causal...situation in practice. A treatment that has such a negative direct effect on outcome would rarely be a candidate for surrogacy analysis. In practice

Responding to surrogate requests that seem inconsistent with a patient's living will.

PubMed

Vig, Elizabeth K; Sudore, Rebecca L; Berg, Karina M; Fromme, Erik K; Arnold, Robert M

2011-11-01

Clinicians may feel conflicted when a patient's legal decision maker is making decisions that seem inconsistent with a patient's living will. We provide evidence-based information to help clinicians consider whether a surrogate's inconsistent decisions are ethically appropriate. Surrogates are not flawless translators of their loved one's preferences; they are influenced by their own hopes and the current clinical context. Patients may be aware of this, are often concerned about burdening their loved ones, and often grant their surrogates leeway in interpreting their wishes. When appropriate, clinicians should respect surrogates' interpretations of patient values and take steps to decrease surrogate stress during the decision-making process. Finally, if clinicians are cognizant of their own values and preferences, they may recognize how these may affect their responses to certain clinical cases. Copyright © 2011 U.S. Cancer Pain Relief Committee. All rights reserved.

Investigation of spray characteristics from a low-pressure common rail injector for use in a homogeneous charge compression ignition engine

NASA Astrophysics Data System (ADS)

Lee, Kihyung; Reitz, Rolf D.

2004-03-01

Homogeneous charge compression ignition (HCCI) combustion provides extremely low levels of pollutant emissions, and thus is an attractive alternative for future IC engines. In order to achieve a uniform mixture distribution within the engine cylinder, the characteristics of the fuel spray play an important role in the HCCI engine concept. It is well known that high-pressure common rail injection systems, mainly used in diesel engines, achieve poor mixture formation because of the possibility of direct fuel impingement on the combustion chamber surfaces. This paper describes spray characteristics of a low-pressure common rail injector which is intended for use in an HCCI engine. Optical diagnostics including laser diffraction and phase Doppler methods, and high-speed camera photography, were applied to measure the spray drop diameter and to investigate the spray development process. The drop sizing results of the laser diffraction method were compared with those of a phase Doppler particle analyser (PDPA) to validate the accuracy of the experiments. In addition, the effect of fuel properties on the spray characteristics was investigated using n-heptane, Stoddard solvent (gasoline surrogate) and diesel fuel because HCCI combustion is sensitive to the fuel composition. The results show that the injector forms a hollow-cone sheet spray rather than a liquid jet, and the atomization efficiency is high (small droplets are produced). The droplet SMD ranged from 15 to 30 µm. The spray break-up characteristics were found to depend on the fuel properties. The break-up time for n-heptane is shorter and the drop SMD is smaller than that of Stoddard solvent and diesel fuel.

A rank test for bivariate time-to-event outcomes when one event is a surrogate

PubMed Central

Shaw, Pamela A.; Fay, Michael P.

2016-01-01

In many clinical settings, improving patient survival is of interest but a practical surrogate, such as time to disease progression, is instead used as a clinical trial’s primary endpoint. A time-to-first endpoint (e.g. death or disease progression) is commonly analyzed but may not be adequate to summarize patient outcomes if a subsequent event contains important additional information. We consider a surrogate outcome very generally, as one correlated with the true endpoint of interest. Settings of interest include those where the surrogate indicates a beneficial outcome so that the usual time-to-first endpoint of death or surrogate event is nonsensical. We present a new two-sample test for bivariate, interval-censored time-to-event data, where one endpoint is a surrogate for the second, less frequently observed endpoint of true interest. This test examines whether patient groups have equal clinical severity. If the true endpoint rarely occurs, the proposed test acts like a weighted logrank test on the surrogate; if it occurs for most individuals, then our test acts like a weighted logrank test on the true endpoint. If the surrogate is a useful statistical surrogate, our test can have better power than tests based on the surrogate that naively handle the true endpoint. In settings where the surrogate is not valid (treatment affects the surrogate but not the true endpoint), our test incorporates the information regarding the lack of treatment effect from the observed true endpoints and hence is expected to have a dampened treatment effect compared to tests based on the surrogate alone. PMID:27059817

Surrogate marker evaluation from an information theory perspective.

PubMed

Alonso, Ariel; Molenberghs, Geert

2007-03-01

The last 20 years have seen lots of work in the area of surrogate marker validation, partly devoted to frame the evaluation in a multitrial framework, leading to definitions in terms of the quality of trial- and individual-level association between a potential surrogate and a true endpoint (Buyse et al., 2000, Biostatistics 1, 49-67). A drawback is that different settings have led to different measures at the individual level. Here, we use information theory to create a unified framework, leading to a definition of surrogacy with an intuitive interpretation, offering interpretational advantages, and applicable in a wide range of situations. Our method provides a better insight into the chances of finding a good surrogate endpoint in a given situation. We further show that some of the previous proposals follow as special cases of our method. We illustrate our methodology using data from a clinical study in psychiatry.

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

A review of surrogate models and their application to groundwater modeling

NASA Astrophysics Data System (ADS)

Asher, M. J.; Croke, B. F. W.; Jakeman, A. J.; Peeters, L. J. M.

2015-08-01

The spatially and temporally variable parameters and inputs to complex groundwater models typically result in long runtimes which hinder comprehensive calibration, sensitivity, and uncertainty analysis. Surrogate modeling aims to provide a simpler, and hence faster, model which emulates the specified output of a more complex model in function of its inputs and parameters. In this review paper, we summarize surrogate modeling techniques in three categories: data-driven, projection, and hierarchical-based approaches. Data-driven surrogates approximate a groundwater model through an empirical model that captures the input-output mapping of the original model. Projection-based models reduce the dimensionality of the parameter space by projecting the governing equations onto a basis of orthonormal vectors. In hierarchical or multifidelity methods the surrogate is created by simplifying the representation of the physical system, such as by ignoring certain processes, or reducing the numerical resolution. In discussing the application to groundwater modeling of these methods, we note several imbalances in the existing literature: a large body of work on data-driven approaches seemingly ignores major drawbacks to the methods; only a fraction of the literature focuses on creating surrogates to reproduce outputs of fully distributed groundwater models, despite these being ubiquitous in practice; and a number of the more advanced surrogate modeling methods are yet to be fully applied in a groundwater modeling context.

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 corporation (temporary). (a) Scope. This section provides rules for determining whether a foreign corporation...

Real-time characterization of partially observed epidemics using surrogate models.

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

Safta, Cosmin; Ray, Jaideep; Lefantzi, Sophia

We present a statistical method, predicated on the use of surrogate models, for the 'real-time' characterization of partially observed epidemics. Observations consist of counts of symptomatic patients, diagnosed with the disease, that may be available in the early epoch of an ongoing outbreak. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information on the dynamics of the etiologic agent in the affected population e.g., the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and epidemiologicalmore » parameters are estimated as distributions using a Markov chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. In some cases, the inverse problem can be computationally expensive, primarily due to the epidemic simulator used inside the inversion algorithm. We present a method, based on replacing the epidemiological model with computationally inexpensive surrogates, that can reduce the computational time to minutes, without a significant loss of accuracy. The surrogates are created by projecting the output of an epidemiological model on a set of polynomial chaos bases; thereafter, computations involving the surrogate model reduce to evaluations of a polynomial. We find that the epidemic characterizations obtained with the surrogate models is very close to that obtained with the original model. We also find that the number of projections required to construct a surrogate model is O(10)-O(10{sup 2}) less than the number of samples required by the MCMC to construct a stationary posterior distribution; thus, depending upon the epidemiological models in question, it may be possible to omit the offline creation and caching of surrogate models, prior to their use in an inverse problem. The technique is demonstrated on synthetic data as well as

Evaluation of Acanthamoeba Myosin-IC as a Potential Therapeutic Target

PubMed Central

Lorenzo-Morales, Jacob; López-Arencibia, Atteneri; Reyes-Batlle, María; Piñero, José E.; Valladares, Basilio; Maciver, Sutherland K.

2014-01-01

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by using small interfering RNA (siRNA) silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs against the Acanthamoeba myosin-IC gene were developed. Treated and control amoebae were cultured in growth and encystment media to evaluate the induced effects after myosin-IC gene knockdown, as we have anticipated that cyst formation may be impaired. The effects of myosin-IC gene silencing were inhibition of cyst formation, inhibition of completion of cytokinesis, inhibition of osmoregulation under osmotic stress conditions, and death of the amoebae. The finding that myosin-IC silencing caused incompletion of cytokinesis is in agreement with earlier suggestions that the protein plays a role in cell locomotion, which is necessary to pull daughter cells apart after mitosis in a process known as “traction-mediated cytokinesis”. We conclude that myosin-IC is a very promising potential drug target for the development of much-needed antiamoebal drugs and that it should be further exploited for Acanthamoeba therapy. PMID:24468784

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

PubMed Central

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

2007-01-01

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

Design and development of a probe-based multiplexed multi-species absorption spectroscopy sensor for characterizing transient gas-parameter distributions in the intake systems of I.C. engines

DOE PAGES

Jatana, Gurneesh; Geckler, Sam; Koeberlein, David; ...

2016-09-01

We designed and developed a 4-probe multiplexed multi-species absorption spectroscopy sensor system for gas property measurements on the intake side of commercial multi-cylinder internal-combustion (I.C.) engines; the resulting cycle- and cylinder-resolved concentration, temperature and pressure measurements are applicable for assessing spatial and temporal variations in the recirculated exhaust gas (EGR) distribution at various locations along the intake gas path, which in turn is relevant to assessing cylinder charge uniformity, control strategies, and CFD models. Furthermore, the diagnostic is based on absorption spectroscopy and includes an H 2O absorption system (utilizing a 1.39 m distributed feedback (DFB) diode laser) for measuringmore » gas temperature, pressure, and H 2O concentration, and a CO 2 absorption system (utilizing a 2.7 m DFB laser) for measuring CO 2 concentration. The various lasers, optical components and detectors were housed in an instrument box, and the 1.39- m and 2.7- m lasers were guided to and from the engine-mounted probes via optical fibers and hollow waveguides, respectively. The 5kHz measurement bandwidth allows for near-crank angle resolved measurements, with a resolution of 1.2 crank angle degrees at 1000 RPM. Our use of compact stainless steel measurement probes enables simultaneous multi-point measurements at various locations on the engine with minimal changes to the base engine hardware; in addition to resolving large-scale spatial variations via simultaneous multi-probe measurements, local spatial gradients can be resolved by translating individual probes. Along with details of various sensor design features and performance, we also demonstrate validation of the spectral parameters of the associated CO 2 absorption transitions using both a multi-pass heated cell and the sensor probes.« less

Children of surrogate mothers: psychological well-being, family relationships and experiences of surrogacy.

PubMed

Jadva, V; Imrie, S

2014-01-01

What impact does surrogacy have on the surrogates' own children? The children of surrogate mothers do not experience any negative consequences as a result of their mother's decision to be a surrogate, irrespective of whether or not the surrogate uses her own egg. Participants were recruited as part of a study of the long-term effects of surrogacy for surrogates and their family members. Data were collected from 36 children of surrogates at a single time point. Participants whose mother had been a surrogate 5-15 years prior to interview and who were aged over 12 years were eligible to take part. Thirty-six participants (14 male and 22 female) aged 12-25 years were interviewed (response rate = 52%). Questionnaires assessing psychological health and family functioning were administered. Forty-four per cent (15) of participants' mothers had undergone gestational surrogacy, 39% (14) had used their own egg (genetic surrogacy) and 19% (7) had completed both types of surrogacy. Most surrogates' children (86%, 31) had a positive view of their mother's surrogacy. Forty-seven per cent (17) of children were in contact with the surrogacy child and all reported good relationships with him/her. Forty per cent (14) of children referred to the child as a sibling or half-sibling and this did not differ between genetic and gestational surrogacy. Most children (89%, 32), reported a positive view of family life, with all enjoying spending time with their mother. Mean scores on the questionnaire assessments of psychological health and self-esteem were within the normal range and did not differ by surrogacy type. The sample size for this study was relatively small and not all children chose to take part, therefore their views cannot be known. Nevertheless, this is the first study to assess the experiences of surrogacy from the perspective of the surrogates' own children. There may be some bias from the inclusion of siblings from the same family. Findings of this study show that family

Identifying family members who may struggle in the role of surrogate decision maker.

PubMed

Majesko, Alyssa; Hong, Seo Yeon; Weissfeld, Lisa; White, Douglas B

2012-08-01

Although acting as a surrogate decision maker can be highly distressing for some family members of intensive care unit patients, little is known about whether there are modifiable risk factors for the occurrence of such difficulties. To identify: 1) factors associated with lower levels of confidence among family members to function as surrogates and 2) whether the quality of clinician-family communication is associated with the timing of decisions to forego life support. We conducted a prospective study of 230 surrogate decision makers for incapacitated, mechanically ventilated patients at high risk of death in four intensive care units at University of California San Francisco Medical Center from 2006 to 2007. Surrogates completed a questionnaire addressing their perceived ability to act as a surrogate and the quality of their communication with physicians. We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability to act as a surrogate and a Cox proportional hazard model to determine whether quality of communication was associated with the timing of decisions to withdraw life support. There was substantial variability in family members' confidence to act as surrogate decision makers, with 27% rating their perceived ability as 7 or lower on a 10-point scale. Independent predictors of lower role confidence were the lack of prior experience as a surrogate (odds ratio 2.2, 95% confidence interval [1.04-4.46], p=.04), no prior discussions with the patient about treatment preferences (odds ratio 3.7, 95% confidence interval [1.79-7.76], p<.001), and poor quality of communication with the ICU physician (odds ratio 1.2, 95% confidence interval [1.09-1.35] p<.001). Higher quality physician-family communication was associated with a significantly shorter duration of life-sustaining treatment among patients who died (β=0.11, p=.001). Family members without prior experience as a surrogate and those who had not engaged in

[Biomedical Perspective of the Surrogate Motherhood].

PubMed

Jouve de la Barreda, Nicolás

2017-01-01

The subrogated motherhood takes place when an embryo created by in vitro fertilization (IVF) technology is implanted in a surrogate, sometimes called a gestational mother, by means a contract with her. It can imply to natural families (woman and man) with or without infertility problems, or to monoparental or biparental families of the same sex. Concerning the origin of the gametes used in the IVF emerges different implications on the genetic relationship of the resulting child with the surrogate and the future parents. The subrogated motherhood was initially considered an option to solve infertility problems. Nevertheless this practice has become a possible and attractive option as a source of economic resources for poor women. The cases of benefit of a pregnancy without mediating a contract are exceptional and they are not properly cases of ″subrogated maternity″ but of ″altruistic maternity″ and must be considered as heterologous in vitro fertilization. In this article are analyzed the medical, genetic and bioethics aspects of this new derivation of the fertilization in vitro. As points of special attention are considered the following questions: Is it the surrogate motherhood used preferably to solve infertility problems? Is not this actually a new form of exploitation of the woman? Does not suppose an attack to the natural family? Does not suppose in addition an attack to the dignity of the human being?

Weighted Iterative Bayesian Compressive Sensing (WIBCS) for High Dimensional Polynomial Surrogate Construction

NASA Astrophysics Data System (ADS)

Sargsyan, K.; Ricciuto, D. M.; Safta, C.; Debusschere, B.; Najm, H. N.; Thornton, P. E.

2016-12-01

Surrogate construction has become a routine procedure when facing computationally intensive studies requiring multiple evaluations of complex models. In particular, surrogate models, otherwise called emulators or response surfaces, replace complex models in uncertainty quantification (UQ) studies, including uncertainty propagation (forward UQ) and parameter estimation (inverse UQ). Further, surrogates based on Polynomial Chaos (PC) expansions are especially convenient for forward UQ and global sensitivity analysis, also known as variance-based decomposition. However, the PC surrogate construction strongly suffers from the curse of dimensionality. With a large number of input parameters, the number of model simulations required for accurate surrogate construction is prohibitively large. Relatedly, non-adaptive PC expansions typically include infeasibly large number of basis terms far exceeding the number of available model evaluations. We develop Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth and PC surrogate construction leading to a sparse, high-dimensional PC surrogate with a very few model evaluations. The surrogate is then readily employed for global sensitivity analysis leading to further dimensionality reduction. Besides numerical tests, we demonstrate the construction on the example of Accelerated Climate Model for Energy (ACME) Land Model for several output QoIs at nearly 100 FLUXNET sites covering multiple plant functional types and climates, varying 65 input parameters over broad ranges of possible values. This work is supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research, Accelerated Climate Modeling for Energy (ACME) project. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration

Engagement in Advance Care Planning and Surrogates' Knowledge of Patients' Treatment Goals.

PubMed

Fried, Terri R; Zenoni, Maria; Iannone, Lynne; O'Leary, John; Fenton, Brenda T

2017-08-01

A key objective of advance care planning (ACP) is improving surrogates' knowledge of patients' treatment goals. Little is known about whether ACP outside of a trial accomplishes this. The objective was to examine patient and surrogate reports of ACP engagement and associations with surrogate knowledge of goals. Cohort study SETTING: Primary care in a Veterans Affairs Medical Center. 350 community-dwelling veterans age ≥55 years and the individual they would choose to make medical decisions on their behalf, interviewed separately. Treatment goals were assessed by veterans' ratings of 3 health states: severe physical disability, cognitive disability, and pain, as an acceptable or unacceptable result of treatment for severe illness. Surrogates had knowledge if they correctly predicted all 3 responses. Veterans and surrogates were asked about living will and health care proxy completion and communication about life-sustaining treatment and quality versus quantity of life (QOL). Over 40% of dyads agreed that the veteran had not completed a living will or health care proxy and that there was no QOL communication. For each activity, sizeable proportions (18-34%) disagreed about participation. In dyads who agreed QOL communication had occurred, 30% of surrogates had knowledge, compared to 21% in dyads who agreed communication had not occurred and 15% in dyads who disagreed (P = .01). This relationship persisted in multivariable analysis. Agreement about other ACP activities was not associated with knowledge. Disagreement about ACP participation was common. Agreement about communication regarding QOL was modestly associated with surrogate knowledge of treatment goals. Eliciting surrogates' perspectives is critical to ACP. Even dyads who agree about participation may need additional support for successful engagement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Validated surrogate endpoints needed for peri-implantitis.

PubMed

Lee, Dong Won

2011-01-01

Pubmed, Cochrane and Lilac databases, Google, Google Scholar, hand searching of websites of major dental journals. The reference list of five recently published systematic reviews on peri-implantitis treatment were also screened for potential studies. Randomised controlled trials and non-randomised studies in English, German, French, Spanish and Italian on peri-implantitis treatment in humans were included. Case series, case reports and cross sectional or non-therapy studies were excluded from the assessment of endpoints. No minimum follow up time was set for studies that were included. Data were extracted in duplicate by two reviewers and disagreements were resolved by consensus. True endpoints for peri-implantitis treatment were considered only if they provided evidence of tangible benefit to the patient. The outcome variables regarded as true endpoints were implant failure, aesthetic assessment and variables related to quality of life, but these were only considered if they were clearly identified as an objective of the research, not as an outcome of treatment. Surrogate endpoints were considered as those measurements of clinical outcomes such as probing pocket depth and clinical attachment level. Fourteen studies were included in this review with data on implant failure presented solely as consequence of peri-implantitis therapy. No true endpoint was described for any study on peri-implantitis. Mean pocket probing depth, clinical attachment level and bleeding on probing were the three surrogate endpoints cited most often in the literature. All endpoints used in the trials reviewed are surrogates of clinical events, such as implant failure. Clinical surrogate endpoints should be validated to assess the real effect of these measures on true endpoints.

Dynamic response due to behind helmet blunt trauma measured with a human head surrogate.

PubMed

Freitas, Christopher J; Mathis, James T; Scott, Nikki; Bigger, Rory P; Mackiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies.

Dynamic Response Due to Behind Helmet Blunt Trauma Measured with a Human Head Surrogate

PubMed Central

Freitas, Christopher J.; Mathis, James T.; Scott, Nikki; Bigger, Rory P.; MacKiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies. PMID:24688303

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

Patient Preferences and Surrogate Decision Making in Neuroscience Intensive Care Units

PubMed Central

Cai, Xuemei; Robinson, Jennifer; Muehlschlegel, Susanne; White, Douglas B.; Holloway, Robert G.; Sheth, Kevin N.; Fraenkel, Liana; Hwang, David Y.

2016-01-01

In the neuroscience intensive care unit (NICU), most patients lack the capacity to make their own preferences known. This fact leads to situations where surrogate decision makers must fill the role of the patient in terms of making preference-based treatment decisions, oftentimes in challenging situations where prognosis is uncertain. The neurointensivist has a large responsibility and role to play in this shared decision making process. This review covers how NICU patient preferences are determined through existing advance care documentation or surrogate decision makers and how the optimum roles of the physician and surrogate decision maker are addressed. We outline the process of reaching a shared decision between family and care team and describe a practice for conducting optimum family meetings based on studies of ICU families in crisis. We review challenges in the decision making process between surrogate decision makers and medical teams in neurocritical care settings, as well as methods to ameliorate conflicts. Ultimately, the goal of shared decision making is to increase knowledge amongst surrogates and care providers, decrease decisional conflict, promote realistic expectations and preference-centered treatment strategies, and lift the emotional burden on families of neurocritical care patients. PMID:25990137

The representation of healthcare end users' perspectives by surrogates in healthcare decisions: a literature review.

PubMed

Shah, Syed Ghulam Sarwar; Farrow, Alexandra; Robinson, Ian

2009-12-01

The representation of end users' perspectives in healthcare decisions requires involvement of their surrogates when the end users, i.e. certain patients, elderly people, children and people with disabilities, are unable to present their views. To review critical issues, and the advantages and disadvantages of involving surrogates in representing end users' perspectives in healthcare decisions. A systematic review of literature published in peer-reviewed journals from 1990 to 2005. Findings show that surrogates are used widely in health care and that they are necessary to represent end users' perspectives in healthcare decisions when the latter are unable to do so themselves. Critical issues in using surrogates include key ethical, social, cultural, legal and medico-technological factors; ascertaining the best interest of end users; potential conflict of interest; possible biased decisions and the burden on surrogates. The key advantage of surrogate involvement in healthcare decisions is their ability to represent end users' needs, values and wishes. The main disadvantages include potential discrepancies between the decisions and conclusions of surrogates and end users; the failure of surrogates to predict end users' preferences accurately and the lack of certainty that useful information will be obtained through the surrogacy process. This systematic review has revealed that the involvement of surrogates is an additional vital way to represent end users' perspectives in healthcare decisions where for a range of reasons their opinions are unable to be effectively ascertained. However, because of the heterogeneity of surrogates and end users, the selection of appropriate surrogates and deploying surrogate decisions require particularly careful consideration of their value in individual cases; thus, subsequent decision-making must be reviewed on a case-to-case basis to seek to ensure that the best interests, needs and wishes of the end user are fully and accurately

Development of brain injury criteria (BrIC).

PubMed

Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

2013-11-01

Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship

Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

PubMed Central

2012-01-01

Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure

Inactivation of Tulane virus, a novel surrogate for human norovirus

USDA-ARS?s Scientific Manuscript database

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...

IC-Finder: inferring robustly the hierarchical organization of chromatin folding

PubMed Central

Haddad, Noelle

2017-01-01

Abstract The spatial organization of the genome plays a crucial role in the regulation of gene expression. Recent experimental techniques like Hi-C have emphasized the segmentation of genomes into interaction compartments that constitute conserved functional domains participating in the maintenance of a proper cell identity. Here, we propose a novel method, IC-Finder, to identify interaction compartments (IC) from experimental Hi-C maps. IC-Finder is based on a hierarchical clustering approach that we adapted to account for the polymeric nature of chromatin. Based on a benchmark of realistic in silico Hi-C maps, we show that IC-Finder is one of the best methods in terms of reliability and is the most efficient numerically. IC-Finder proposes two original options: a probabilistic description of the inferred compartments and the possibility to explore the various hierarchies of chromatin organization. Applying the method to experimental data in fly and human, we show how the predicted segmentation may depend on the normalization scheme and how 3D compartmentalization is tightly associated with epigenomic information. IC-Finder provides a robust and generic ‘all-in-one’ tool to uncover the general principles of 3D chromatin folding and their influence on gene regulation. The software is available at http://membres-timc.imag.fr/Daniel.Jost/DJ-TIMC/Software.html. PMID:28130423

Hubble Space Telescope Image: Planetary Nebula IC 4406

NASA Technical Reports Server (NTRS)

2001-01-01

This Hubble Space Telescope image reveals a rainbow of colors in this dying star, called IC 446. Like many other so-called planetary nebulae, IC 4406 exhibits a high degree of symmetry. The nebula's left and right halves are nearly mirror images of the other. If we could fly around IC 446 in a spaceship, we would see that the gas and dust form a vast donut of material streaming outward from the dying star. We do not see the donut shape in this photograph because we are viewing IC 4406 from the Earth-orbiting HST. From this vantage point, we are seeing the side of the donut. This side view allows us to see the intricate tendrils of material that have been compared to the eye's retina. In fact, IC 4406 is dubbed the 'Retina Nebula.' The donut of material confines the intense radiation coming from the remnant of the dying star. Gas on the inside of the donut is ionized by light from the central star and glows. Light from oxygen atoms is rendered blue in this image; hydrogen is shown as green, and nitrogen as red. The range of color in the final image shows the differences in concentration of these three gases in the nebula. This image is a composite of data taken by HST's Wide Field Planetary Camera 2 in June 2001 and in January 2002 by Bob O'Dell (Vanderbilt University) and collaborators, and in January by the Hubble Heritage Team (STScI). Filters used to create this color image show oxygen, hydrogen, and nitrogen gas glowing in this object.

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

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria.

PubMed

Jeeyapant, Atthanee; Kingston, Hugh W; 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

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. 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. 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. 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 surrogate endpoints for mortality.

Pull out strength calculator for pedicle screws using a surrogate ensemble approach.

PubMed

Varghese, Vicky; Ramu, Palaniappan; Krishnan, Venkatesh; Saravana Kumar, Gurunathan

2016-12-01

Pedicle screw instrumentation is widely used in the treatment of spinal disorders and deformities. Currently, the surgeon decides the holding power of instrumentation based on the perioperative feeling which is subjective in nature. The objective of the paper is to develop a surrogate model which will predict the pullout strength of pedicle screw based on density, insertion angle, insertion depth and reinsertion. A Taguchi's orthogonal array was used to design an experiment to find the factors effecting pullout strength of pedicle screw. The pullout studies were carried using polyaxial pedicle screw on rigid polyurethane foam block according to American society for testing of materials (ASTM F543). Analysis of variance (ANOVA) and Tukey's honestly significant difference multiple comparison tests were done to find factor effect. Based on the experimental results, surrogate models based on Krigging, polynomial response surface and radial basis function were developed for predicting the pullout strength for different combination of factors. An ensemble of these surrogates based on weighted average surrogate model was also evaluated for prediction. Density, insertion depth, insertion angle and reinsertion have a significant effect (p <0.05) on pullout strength of pedicle screw. Weighted average surrogate performed the best in predicting the pull out strength amongst the surrogate models considered in this study and acted as insurance against bad prediction. A predictive model for pullout strength of pedicle screw was developed using experimental values and surrogate models. This can be used in pre-surgical planning and decision support system for spine surgeon. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Numerical simulation of the flow field and fuel sprays in an IC engine

NASA Technical Reports Server (NTRS)

Nguyen, H. L.; Schock, H. J.; Ramos, J. I.; Carpenter, M. H.; Stegeman, J. D.

1987-01-01

A two-dimensional model for axisymmetric piston-cylinder configurations is developed to study the flow field in two-stroke direct-injection Diesel engines under motored conditions. The model accounts for turbulence by a two-equation model for the turbulence kinetic energy and its rate of dissipation. A discrete droplet model is used to simulate the fuel spray, and the effects of the gas phase turbulence on the droplets is considered. It is shown that a fluctuating velocity can be added to the mean droplet velocity every time step if the step is small enough. Good agreement with experimental data is found for a range of ambient pressures in Diesel engine-type microenvironments. The effects of the intake swirl angle in the spray penetration, vaporization, and mixing in a uniflow-scavenged two-stroke Diesel engine are analyzed. It is found that the swirl increases the gas phase turbulence levels and the rates of vaporization.

Creating a FIESTA (Framework for Integrated Earth Science and Technology Applications) with MagIC

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.

2017-12-01

The Magnetics Information Consortium (https://earthref.org/MagIC) has recently developed a containerized web application to considerably reduce the friction in contributing, exploring and combining valuable and complex datasets for the paleo-, geo- and rock magnetic scientific community. The data produced in this scientific domain are inherently hierarchical and the communities evolving approaches to this scientific workflow, from sampling to taking measurements to multiple levels of interpretations, require a large and flexible data model to adequately annotate the results and ensure reproducibility. Historically, contributing such detail in a consistent format has been prohibitively time consuming and often resulted in only publishing the highly derived interpretations. The new open-source (https://github.com/earthref/MagIC) application provides a flexible upload tool integrated with the data model to easily create a validated contribution and a powerful search interface for discovering datasets and combining them to enable transformative science. MagIC is hosted at EarthRef.org along with several interdisciplinary geoscience databases. A FIESTA (Framework for Integrated Earth Science and Technology Applications) is being created by generalizing MagIC's web application for reuse in other domains. The application relies on a single configuration document that describes the routing, data model, component settings and external services integrations. The container hosts an isomorphic Meteor JavaScript application, MongoDB database and ElasticSearch search engine. Multiple containers can be configured as microservices to serve portions of the application or rely on externally hosted MongoDB, ElasticSearch, or third-party services to efficiently scale computational demands. FIESTA is particularly well suited for many Earth Science disciplines with its flexible data model, mapping, account management, upload tool to private workspaces, reference metadata, image

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.

Quantum Tunneling Affects Engine Performance.

PubMed

Som, Sibendu; Liu, Wei; Zhou, Dingyu D Y; Magnotti, Gina M; Sivaramakrishnan, Raghu; Longman, Douglas E; Skodje, Rex T; Davis, Michael J

2013-06-20

We study the role of individual reaction rates on engine performance, with an emphasis on the contribution of quantum tunneling. It is demonstrated that the effect of quantum tunneling corrections for the reaction HO2 + HO2 = H2O2 + O2 can have a noticeable impact on the performance of a high-fidelity model of a compression-ignition (e.g., diesel) engine, and that an accurate prediction of ignition delay time for the engine model requires an accurate estimation of the tunneling correction for this reaction. The three-dimensional model includes detailed descriptions of the chemistry of a surrogate for a biodiesel fuel, as well as all the features of the engine, such as the liquid fuel spray and turbulence. This study is part of a larger investigation of how the features of the dynamics and potential energy surfaces of key reactions, as well as their reaction rate uncertainties, affect engine performance, and results in these directions are also presented here.

Does the decision in a validation process of a surrogate endpoint change with level of significance of treatment effect? A proposal on validation of surrogate endpoints.

PubMed

Sertdemir, Y; Burgut, R

2009-01-01

In recent years the use of surrogate end points (S) has become an interesting issue. In clinical trials, it is important to get treatment outcomes as early as possible. For this reason there is a need for surrogate endpoints (S) which are measured earlier than the true endpoint (T). However, before a surrogate endpoint can be used it must be validated. For a candidate surrogate endpoint, for example time to recurrence, the validation result may change dramatically between clinical trials. The aim of this study is to show how the validation criterion (R(2)(trial)) proposed by Buyse et al. are influenced by the magnitude of treatment effect with an application using real data. The criterion R(2)(trial) proposed by Buyse et al. (2000) is applied to the four data sets from colon cancer clinical trials (C-01, C-02, C-03 and C-04). Each clinical trial is analyzed separately for treatment effect on survival (true endpoint) and recurrence free survival (surrogate endpoint) and this analysis is done also for each center in each trial. Results are used for standard validation analysis. The centers were grouped by the Wald statistic in 3 equal groups. Validation criteria R(2)(trial) were 0.641 95% CI (0.432-0.782), 0.223 95% CI (0.008-0.503), 0.761 95% CI (0.550-0.872) and 0.560 95% CI (0.404-0.687) for C-01, C-02, C-03 and C-04 respectively. The R(2)(trial) criteria changed by the Wald statistics observed for the centers used in the validation process. Higher the Wald statistic groups are higher the R(2)(trial) values observed. The recurrence free survival is not a good surrogate for overall survival in clinical trials with non significant treatment effects and moderate for significant treatment effects. This shows that the level of significance of treatment effect should be taken into account in validation process of surrogate endpoints.

Selecting surrogate endpoints for estimating pesticide effects on avian reproductive success.

PubMed

Bennett, Richard S; Etterson, Matthew A

2013-10-01

A Markov chain nest productivity model (MCnest) has been developed for projecting the effects of a specific pesticide-use scenario on the annual reproductive success of avian species of concern. A critical element in MCnest is the use of surrogate endpoints, defined as measured endpoints from avian toxicity tests that represent specific types of effects possible in field populations at specific phases of a nesting attempt. In this article, we discuss the attributes of surrogate endpoints and provide guidance for selecting surrogates from existing avian laboratory tests as well as other possible sources. We also discuss some of the assumptions and uncertainties related to using surrogate endpoints to represent field effects. The process of explicitly considering how toxicity test results can be used to assess effects in the field helps identify uncertainties and data gaps that could be targeted in higher-tier risk assessments. © 2013 SETAC.

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

Act relating to surrogate parenthood contracts, 10 February 1988.

PubMed

1988-01-01

This Nebraska Act provides that surrogate parenthood contracts are void and unenforceable and that the "biological father of a child born pursuant to such a contract shall have all the rights and obligations imposed by law with respect to the child." A surrogate parenthood contract is defined as "a contract by which a woman is to be compensated for bearing a child of a man who is not her husband." full text

Lithium Abundances in the Young Open Cluster IC 2602

NASA Technical Reports Server (NTRS)

Randich, S.; Aharpour, N.; Pallavicini, R.; Prosser, C. F.; Stauffer, J. R.

1997-01-01

We have obtained high-resolution spectra for 28 candidate late-type stars in the 30 Myr old cluster IC 2602. NLTE Li abundances have been derived from measured equivalent widths. The log n(Li) - T(sub eff) and log n(Li) - mass distributions for our sample stars have been compared with those of the Pleiades and alpha Persei. Our data show that F stars in the three clusters have the same lithium content, which corresponds to the initial content for Pop. I stars. G and early-K IC 2602 stars are, on average, somewhat more Li-rich than their counterparts in the two slightly older clusters. Finally, the latest-type IC 2602 stars are heavily Li depleted, with their Li content being as low as the lowest measured among the Pleiades. As in the Pleiades and alpha Per, a star-to-star scatter in lithium is observed among 30 Myr old late-K/early-K dwarfs in IC 2602, indicating that this spread develops in the pre-main sequence phases.

ASASSN-16fp (SN 2016coi): a transitional supernova between Type Ic and broad-lined Ic

NASA Astrophysics Data System (ADS)

Kumar, Brajesh; Singh, A.; Srivastav, S.; Sahu, D. K.; Anupama, G. C.

2018-01-01

We present results based on a well-sampled optical (UBVRI) and ultraviolet (Swift/UVOT) imaging, and low-resolution optical spectroscopic follow-up observations of the nearby Type Ic supernova (SN) ASASSN-16fp (SN 2016coi). The SN was monitored during the photospheric phase (-10 to +33 d with respect to the B-band maximum light). The rise to maximum light and early post-maximum decline of the light curves are slow. The peak absolute magnitude (MV = -17.7 ± 0.2 mag) of ASASSN-16fp is comparable with broad-lined Ic SN 2002ap, SN 2012ap and transitional Ic SN 2004aw but considerably fainter than the gamma-ray burst/X-ray flash associated SNe (e.g. SN 1998bw, 2006aj). Similar to the light curve, the spectral evolution is also slow. ASASSN-16fp shows distinct photospheric phase spectral lines along with the C II features. The expansion velocity of the ejecta near maximum light reached ∼16 000 km s-1 and settled to ∼8000 km s-1, ∼1 month post-maximum. Analytical modelling of the quasi-bolometric light curve of ASASSN-16fp suggests that ∼0.1 M⊙ 56Ni mass was synthesized in the explosion, with a kinetic energy of 6.9^{+1.5}_{-1.3} × 1051 erg and total ejected mass of ∼4.5 ± 0.3 M⊙.

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

PubMed Central

Muniyappa, Ranganath; Chen, Hui; Muzumdar, Radhika H.; Einstein, Francine H.; Yan, Xu; Yue, Lilly Q.; Barzilai, Nir

2009-01-01

Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34–0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary

Study on Mine Emergency Mechanism based on TARP and ICS

NASA Astrophysics Data System (ADS)

Xi, Jian; Wu, Zongzhi

2018-01-01

By analyzing the experiences and practices of mine emergency in China and abroad, especially the United States and Australia, normative principle, risk management principle and adaptability principle of constructing mine emergency mechanism based on Trigger Action Response Plans (TARP) and Incident Command System (ICS) are summarized. Classification method, framework, flow and subject of TARP and ICS which are suitable for the actual situation of domestic mine emergency are proposed. The system dynamics model of TARP and ICS is established. The parameters such as evacuation ratio, response rate, per capita emergency capability and entry rate of rescuers are set up. By simulating the operation process of TARP and ICS, the impact of these parameters on the emergency process are analyzed, which could provide a reference and basis for building emergency capacity, formulating emergency plans and setting up action plans in the emergency process.

Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology.

PubMed

Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

2012-01-01

Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.

Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology

PubMed Central

Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

2012-01-01

Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types. PMID:23109809

Surrogate alcohol containing methanol, social deprivation and public health in Novosibirsk, Russia.

PubMed

Neufeld, Maria; Lachenmeier, Dirk; Hausler, Thomas; Rehm, Jürgen

2016-11-01

Surrogate alcohol, i.e. alcohol not intended or not officially intended for human consumption, continues to play an important role in alcohol consumption in Russia, especially for people with alcohol dependence. Among the different types of surrogate alcohol, there are windshield washer antifreeze liquids; these products are the cheapest kinds of non-beverage alcohol available and thus likely to be used by the most deprived and marginalised groups such as homeless people with alcohol dependence. Although it is well known, that non-beverage alcohol is used for consumption by various groups in Russia, and although there are laws to prohibit the use of methanol as part of windshield washer antifreeze liquids for the very reason that such products could be used as surrogate alcohol, we detected products in retail sale which were a mix of water and methanol only. Methanol poses serious health threats including blindness and death, and there had been repeated methanol deaths from surrogate alcohol in Russia over the last years. If law-enforcement does not change for surrogate products, we can expect more methanol-resulting deaths in the most deprived and marginalized groups of people with alcohol dependence in Russia. In addition, ingredients with questionable safety profiles such as formic acid should also be prohibited in non-beverage alcohol products that are likely to be consumed as surrogate alcohol. Copyright © 2016. Published by Elsevier B.V.

Using surrogate species and groups for conservation planning and management

Treesearch

John A. Wiens; Gregory D. Hayward; Richard S. Holthausen; Michael J. Wisdom

2008-01-01

In species management and conservation, surrogate species or groups of species can be used as proxies for broader sets of species when the number of species of concern is too great to allow each to be considered individually. However, these surrogate approaches are not applicable to all situations. In this article we discuss how the nature of the ecological system, the...

ic-cmtp3: 3rd International Conference on Competitive Materials and Technology Processes

NASA Astrophysics Data System (ADS)

2016-04-01

Competitiveness is one of the most important factors in our lives and it plays a key role in the efficiency both of organizations and societies. The more scientifically advanced and prepared organizations develop more competitive materials with better physical, chemical, and biological properties, and the leading companies apply more competitive equipment and technological processes. The aims of the 3rd International Conference on Competitive Materials and Technology Processes (ic-cmtp3), and the 1st International Symposium on Innovative Carbons and Carbon Based Materials (is-icbm1) and the 1st International Symposium on Innovative Construction Materials (is-icm1) organized alongside are the following: —Promote new methods and results of scientific research in the fields of material, biological, environmental and technological sciences; —Exchange information between the theoretical and applied sciences as well as technical and technological implementations; —Promote communication and collaboration between the scientists, researchers and engineers of different nations, countries and continents. Among the major fields of interest are advanced and innovative materials with competitive characteristics, including mechanical, physical, chemical, biological, medical and thermal, properties and extreme dynamic strength. Their crystalline, nano - and micro-structures, phase transformations as well as details of their technological processes, tests and measurements are also in the focus of the ic-cmtp3 conference and the is-scbm1 and is-icm1 symposia. Multidisciplinary applications of material science and the technological problems encountered in sectors like ceramics, glasses, thin films, aerospace, automotive and marine industries, electronics, energy, construction materials, medicine, biosciences and environmental sciences are of particular interest. In accordance with the program of the ic-cmtp3 conference and is-icbm1 and is-icm1 symposia we have received more

Statistical Surrogate Modeling of Atmospheric Dispersion Events Using Bayesian Adaptive Splines

NASA Astrophysics Data System (ADS)

Francom, D.; Sansó, B.; Bulaevskaya, V.; Lucas, D. D.

2016-12-01

Uncertainty in the inputs of complex computer models, including atmospheric dispersion and transport codes, is often assessed via statistical surrogate models. Surrogate models are computationally efficient statistical approximations of expensive computer models that enable uncertainty analysis. We introduce Bayesian adaptive spline methods for producing surrogate models that capture the major spatiotemporal patterns of the parent model, while satisfying all the necessities of flexibility, accuracy and computational feasibility. We present novel methodological and computational approaches motivated by a controlled atmospheric tracer release experiment conducted at the Diablo Canyon nuclear power plant in California. Traditional methods for building statistical surrogate models often do not scale well to experiments with large amounts of data. Our approach is well suited to experiments involving large numbers of model inputs, large numbers of simulations, and functional output for each simulation. Our approach allows us to perform global sensitivity analysis with ease. We also present an approach to calibration of simulators using field data.

Surrogate pregnancy: a guide for Canadian prenatal health care providers

PubMed Central

Reilly, Dan R.

2007-01-01

Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks ofsurrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

Surrogate pregnancy: a guide for Canadian prenatal health care providers.

PubMed

Reilly, Dan R

2007-02-13

Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks of surrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support.

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

NASA Astrophysics Data System (ADS)

Janardhanan, S.; Datta, B.

2011-12-01

Surrogate models are widely used to develop computationally efficient simulation-optimization models to solve complex groundwater management problems. Artificial intelligence based models are most often used for this purpose where they are trained using predictor-predictand data obtained from a numerical simulation model. Most often this is implemented with the assumption that the parameters and boundary conditions used in the numerical simulation model are perfectly known. However, in most practical situations these values are uncertain. Under these circumstances the application of such approximation surrogates becomes limited. In our study we develop a surrogate model based coupled simulation optimization methodology for determining optimal pumping strategies for coastal aquifers considering parameter uncertainty. An ensemble surrogate modeling approach is used along with multiple realization optimization. The methodology is used to solve a multi-objective coastal aquifer management problem considering two conflicting objectives. Hydraulic conductivity and the aquifer recharge are considered as uncertain values. Three dimensional coupled flow and transport simulation model FEMWATER is used to simulate the aquifer responses for a number of scenarios corresponding to Latin hypercube samples of pumping and uncertain parameters to generate input-output patterns for training the surrogate models. Non-parametric bootstrap sampling of this original data set is used to generate multiple data sets which belong to different regions in the multi-dimensional decision and parameter space. These data sets are used to train and test multiple surrogate models based on genetic programming. The ensemble of surrogate models is then linked to a multi-objective genetic algorithm to solve the pumping optimization problem. Two conflicting objectives, viz, maximizing total pumping from beneficial wells and minimizing the total pumping from barrier wells for hydraulic control of

Making the MagIC (Magnetics Information Consortium) Web Application Accessible to New Users and Useful to Experts

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.

2017-12-01

Challenges are faced by both new and experienced users interested in contributing their data to community repositories, in data discovery, or engaged in potentially transformative science. The Magnetics Information Consortium (https://earthref.org/MagIC) has recently simplified its data model and developed a new containerized web application to reduce the friction in contributing, exploring, and combining valuable and complex datasets for the paleo-, geo-, and rock magnetic scientific community. The new data model more closely reflects the hierarchical workflow in paleomagnetic experiments to enable adequate annotation of scientific results and ensure reproducibility. The new open-source (https://github.com/earthref/MagIC) application includes an upload tool that is integrated with the data model to provide early data validation feedback and ease the friction of contributing and updating datasets. The search interface provides a powerful full text search of contributions indexed by ElasticSearch and a wide array of filters, including specific geographic and geological timescale filtering, to support both novice users exploring the database and experts interested in compiling new datasets with specific criteria across thousands of studies and millions of measurements. The datasets are not large, but they are complex, with many results from evolving experimental and analytical approaches. These data are also extremely valuable due to the cost in collecting or creating physical samples and the, often, destructive nature of the experiments. MagIC is heavily invested in encouraging young scientists as well as established labs to cultivate workflows that facilitate contributing their data in a consistent format. This eLightning presentation includes a live demonstration of the MagIC web application, developed as a configurable container hosting an isomorphic Meteor JavaScript application, MongoDB database, and ElasticSearch search engine. Visitors can explore the MagIC

Unveiling the AGN in IC 883: discovery of a parsec-scale radio jet

NASA Astrophysics Data System (ADS)

Romero-Cañizales, C.; Alberdi, A.; Ricci, C.; Arévalo, P.; Pérez-Torres, M. Á.; Conway, J. E.; Beswick, R. J.; Bondi, M.; Muxlow, T. W. B.; Argo, M. K.; Bauer, F. E.; Efstathiou, A.; Herrero-Illana, R.; Mattila, S.; Ryder, S. D.

2017-05-01

IC 883 is a luminous infrared galaxy (LIRG) classified as a starburst-active galactic nucleus (AGN) composite. In a previous study, we detected a low-luminosity AGN (LLAGN) radio candidate. Here, we report on our radio follow-up at three frequencies that provides direct and unequivocal evidence of the AGN activity in IC 883. Our analysis of archival X-ray data, together with the detection of a transient radio source with luminosity typical of bright supernovae, gives further evidence of the ongoing star formation activity, which dominates the energetics of the system. At sub-parsec scales, the radio nucleus has a core-jet morphology with the jet being a newly ejected component showing a subluminal proper motion of 0.6-1 c. The AGN contributes less than 2 per cent of the total IR luminosity of the system. The corresponding Eddington factor is ˜10-3, suggesting this is a low-accretion rate engine, as often found in LLAGNs. However, its high bolometric luminosity (˜1044 erg s-1) agrees better with a normal AGN. This apparent discrepancy may just be an indication of the transition nature of the nucleus from a system dominated by star formation, to an AGN-dominated system. The nucleus has a strongly inverted spectrum and a turnover at ˜4.4 GHz, thus qualifying as a candidate for the least luminous (L5.0 GHz ˜ 6.3 × 1028 erg s-1 Hz-1) and one of the youngest (˜3 × 103 yr) gigahertz-peaked spectrum (GPS) sources. If the GPS origin for the IC 883 nucleus is confirmed, then advanced mergers in the LIRG category are potentially key environments to unveil the evolution of GPS sources into more powerful radio galaxies.

The Use of Surrogate Endpoints in Regulating Medicines for Cardio-Renal Disease: Opinions of Stakeholders

PubMed Central

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

Aim There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. Methods We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Results Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Conclusion Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them. PMID:25268242

The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

PubMed

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

The jet-ISM interactions in IC 5063

NASA Astrophysics Data System (ADS)

Mukherjee, Dipanjan; Wagner, Alexander Y.; Bicknell, Geoffrey V.; Morganti, Raffaella; Oosterloo, Tom; Nesvadba, Nicole; Sutherland, Ralph S.

2018-05-01

The interstellar medium of the radio galaxy IC 5063 is highly perturbed by an AGN jet expanding in the gaseous disc of the galaxy. We model this interaction with relativistic hydrodynamic simulations and multiphase initial conditions for the interstellar medium and compare the results with recent observations. As the jets flood through the intercloud channels of the disc, they ablate, accelerate, and disperse clouds to velocities exceeding 400 km s-1. Clouds are also destroyed or displaced in bulk from the central regions of the galaxy. Our models with jet powers of 1044 and 1045 erg s-1 are capable of reproducing many of the observed features in the position velocity diagram of IC 5063, and confirm the notion that the jet is responsible for the strongly perturbed gas dynamics seen in the ionized, neutral, and molecular gas phases. In our simulations, we also see strong venting of the jet plasma perpendicular to the disc, which entrains clumps and diffuse filaments into the halo of the galaxy. Our simulations are the first 3D hydrodynamic simulations of the jet and interstellar matter of IC 5063.

Low-order nonlinear dynamic model of IC engine-variable pitch propeller system for general aviation aircraft

NASA Technical Reports Server (NTRS)

Richard, Jacques C.

1995-01-01

This paper presents a dynamic model of an internal combustion engine coupled to a variable pitch propeller. The low-order, nonlinear time-dependent model is useful for simulating the propulsion system of general aviation single-engine light aircraft. This model is suitable for investigating engine diagnostics and monitoring and for control design and development. Furthermore, the model may be extended to provide a tool for the study of engine emissions, fuel economy, component effects, alternative fuels, alternative engine cycles, flight simulators, sensors, and actuators. Results show that the model provides a reasonable representation of the propulsion system dynamics from zero to 10 Hertz.

Observation of Burial and Migration of Instrumented Surrogate Munitions Deployed in the Swash Zone

NASA Astrophysics Data System (ADS)

Cristaudo, D.; Puleo, J. A.; Bruder, B. L.

2017-12-01

Munitions (also known as unexploded ordnance; UXO) in the nearshore environment due to past military activities, may be found on the beach, constituting a risk for beach users. Munitions may be transported from offshore to shallower water and/or migrate along the coast. In addition, munitions may bury in place or be exhumed due to hydrodynamic forcing. Observations on munitions mobility have generally been collected offshore, while observations in the swash zone are scarce. The swash zone is the region of the beach alternately covered by wave runup where hydrodynamic processes may be intense. Studies of munitions mobility require the use of realistic surrogates to quantify mobility/burial and hydrodynamic forcing conditions. Four surrogates (BLU-61 Cluster Bomb, 81 mm Mortar, M151-70 Hydra Rocket and M107 155 mm High Explosive Howitzer) were developed and tested during large-scale laboratory and field studies. Surrogates house sensors that measure different components of motion. Errors between real munitions and surrogate parameters (mass, center of gravity and axial moment of inertia) are all within an absolute error of 20%. Internal munitions sensors consist of inertial motion units (for acceleration and angular velocity in and around the three directions and orientation), pressure transducers (for water depth above surrogate), shock recorders (for high frequency acceleration to detect wave impact on the surrogate), and an in-house designed array of optical sensors (for burial/exposure and rolling). An in situ array of sensors to measure hydrodynamics, bed morphology and sediment concentrations, was deployed in the swash zone, aligned with the surrogate deployment. Data collected during the studies will be shown highlighting surrogate sensor capabilities. Sensors response will be compared with GPS measurements and imagery from cameras overlooking the study sites of surrogate position as a function of time. Examples of burial/exposure and migration of surrogates

The Search for Wolf-Rayet Stars in IC10

NASA Astrophysics Data System (ADS)

Tehrani, Katie; Crowther, Paul; Archer, Isabelle

2017-11-01

We present a deep imaging and spectroscopic survey of the Local Group starburst galaxy IC10 using Gemini North/GMOS to unveil the global Wolf-Rayet population. It has previously been suggested that for IC10 to follow the WC/WN versus metallicity dependence seen in other Local Group galaxies, a large WN population must remain undiscovered. Our search revealed 3 new WN stars, and 5 candidates awaiting confirmation, providing little evidence to support this claim. We also compute an updated nebular derived metallicity of log(O/H)+12=8.40 +/- 0.04 for the galaxy using the direct method. Inspection of IC10 WR average line luminosities show these stars are more similar to their LMC, rather than SMC counterparts.

Ultrasound and radiology surrogate endpoints in pharmacological studies.

PubMed

Agewall, S; DeGroot, E; Marcos-Alberca, P; Zamorano, J L; Barrero, A A; Badano, L P; Perrone-Filardi, P

2012-09-01

Cardiovascular studies investigating therapeutic intervention with clinical endpoints are costly due to the need for considerable duration and large number of patients, or both. Therefore, for evaluation of novel cardiovascular drug efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have proven their worth. Sometimes the relevance of imaging is questioned and other methods are suggested instead. There is also some confusion about the strengths of imaging endpoints. The aim of the present paper is to review ultrasound and radiology imaging techniques as surrogate endpoints in pharmacological trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Purification, Crystallization And Preliminary X-Ray Analysis of Aminoglycoside-2 ''-Phosphotransferase-Ic [APH(2 '')-Ic] From Enterococcus Gallinarum

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

Byrnes, L.J.; /SLAC, SSRL; Badarau, A.

2009-04-30

Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2{double_prime}-phosphotransferase-Ic [APH(2{double_prime})-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and three mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2{double_prime})-Ic variants were crystallized in the presence of 14-20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris-HClmore » pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 {angstrom}, {beta} = 108.8{sup o}. X-ray diffraction data were collected to approximately 2.15 {angstrom} resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

Effectiveness of Biodiversity Surrogates for Conservation Planning: Different Measures of Effectiveness Generate a Kaleidoscope of Variation

PubMed Central

Grantham, Hedley S.; Pressey, Robert L.; Wells, Jessie A.; Beattie, Andrew J.

2010-01-01

Conservation planners represent many aspects of biodiversity by using surrogates with spatial distributions readily observed or quantified, but tests of their effectiveness have produced varied and conflicting results. We identified four factors likely to have a strong influence on the apparent effectiveness of surrogates: (1) the choice of surrogate; (2) differences among study regions, which might be large and unquantified (3) the test method, that is, how effectiveness is quantified, and (4) the test features that the surrogates are intended to represent. Analysis of an unusually rich dataset enabled us, for the first time, to disentangle these factors and to compare their individual and interacting influences. Using two data-rich regions, we estimated effectiveness using five alternative methods: two forms of incidental representation, two forms of species accumulation index and irreplaceability correlation, to assess the performance of ‘forest ecosystems’ and ‘environmental units’ as surrogates for six groups of threatened species—the test features—mammals, birds, reptiles, frogs, plants and all of these combined. Four methods tested the effectiveness of the surrogates by selecting areas for conservation of the surrogates then estimating how effective those areas were at representing test features. One method measured the spatial match between conservation priorities for surrogates and test features. For methods that selected conservation areas, we measured effectiveness using two analytical approaches: (1) when representation targets for the surrogates were achieved (incidental representation), or (2) progressively as areas were selected (species accumulation index). We estimated the spatial correlation of conservation priorities using an index known as summed irreplaceability. In general, the effectiveness of surrogates for our taxa (mostly threatened species) was low, although environmental units tended to be more effective than forest

Methylene blue as a lignin surrogate in manganese peroxidase reaction systems.

PubMed

Goby, Jeffrey D; Penner, Michael H; Lajoie, Curtis A; Kelly, Christine J

2017-11-15

Manganese peroxidase (MnP) is associated with lignin degradation and is thus relevant to lignocellulosic-utilization technologies. Technological applications require reaction mixture optimization. A surrogate substrate can facilitate this if its susceptibility to degradation is easily monitored and mirrors that of lignin. The dye methylene blue (MB) was evaluated in these respects as a surrogate substrate by testing its reactivity in reaction mixtures containing relevant redox mediators (dicarboxylic acids, fatty acids). Relative rates of MB degradation were compared to available literature reports of lignin degradation under similar conditions, and suggest that MB can be a useful lignin surrogate in MnP systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Adaptive surrogate model based multi-objective transfer trajectory optimization between different libration points

NASA Astrophysics Data System (ADS)

Peng, Haijun; Wang, Wei

2016-10-01

An adaptive surrogate model-based multi-objective optimization strategy that combines the benefits of invariant manifolds and low-thrust control toward developing a low-computational-cost transfer trajectory between libration orbits around the L1 and L2 libration points in the Sun-Earth system has been proposed in this paper. A new structure for a multi-objective transfer trajectory optimization model that divides the transfer trajectory into several segments and gives the dominations for invariant manifolds and low-thrust control in different segments has been established. To reduce the computational cost of multi-objective transfer trajectory optimization, a mixed sampling strategy-based adaptive surrogate model has been proposed. Numerical simulations show that the results obtained from the adaptive surrogate-based multi-objective optimization are in agreement with the results obtained using direct multi-objective optimization methods, and the computational workload of the adaptive surrogate-based multi-objective optimization is only approximately 10% of that of direct multi-objective optimization. Furthermore, the generating efficiency of the Pareto points of the adaptive surrogate-based multi-objective optimization is approximately 8 times that of the direct multi-objective optimization. Therefore, the proposed adaptive surrogate-based multi-objective optimization provides obvious advantages over direct multi-objective optimization methods.

The effect of framing on surrogate optimism bias: A simulation study.

PubMed

Patel, Dev; Cohen, Elan D; Barnato, Amber E

2016-04-01

To explore the effect of emotion priming and physician communication behaviors on optimism bias. We conducted a 5 × 2 between-subject randomized factorial experiment using a Web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age at least 35 years and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with cardiopulmonary resuscitation (CPR) > their recollection of the physician's estimate. Of 373 respondents, 256 (69%) logged in and were randomized and 220 (86%) had nonmissing data for prognosis. Sixty-seven (30%) of 220 overall and 56 of (32%) 173 with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (P < .001). Emotion priming (P = .397), physician attention to emotion (P = .537), and framing of CPR as the social norm (P = .884) did not affect optimism bias. Framing the decision as the patient's vs the surrogate's (25% vs 36%, P = .066) and describing the alternative to CPR as "allow natural death" instead of "do not resuscitate" (25% vs 37%, P = .035) decreased optimism bias. Framing of CPR choice during code status conversations may influence surrogates' optimism bias. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 54940 - Agency Information Collection (IC) Activities; Revision of an Approved IC; Accident Recordkeeping...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... include the Agency name and the docket number for this Notice. Note that DOT posts all comments received... underlying this IC is 49 CFR 390.15, ``Assistance in investigations and special studies.'' It requires motor... Information Technology. [FR Doc. 2010-22456 Filed 9-8-10; 8:45 am] BILLING CODE 4910-EX-P ...

Surrogate Parents and Children with Disabilities: State-Level Approaches. inForum

ERIC Educational Resources Information Center

Muller, Eve

2009-01-01

Based on a survey of states, this document summarizes state-level approaches to using surrogate parents in order to meet the needs of children with disabilities. Most respondents noted that their states had issued policy or formal guidance pertaining to surrogate parents and children with disabilities, and most also described efforts to ensure…

ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

PubMed

Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

2015-02-01

IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

Wide-Field Structure of Local Group Dwarf Irregular Galaxy IC1613

NASA Astrophysics Data System (ADS)

Pucha, Ragadeepika; Carlin, Jeffrey; Willman, Beth; Sand, David J.; Bechtol, Keith

2018-01-01

IC1613 is a typical dwarf irregular galaxy in the Local Group. Being an isolated dwarf, as opposed to the dwarfs around the Milky Way, it is likely to be subjected to fewer strong environmental effects. As a result, it serves as a good prototype for the study of the structure and evolution of dwarf galaxies. We present g- and i- band photometry from deep imaging of four fields around IC1613, that resolved stars up to ~ 4 magnitudes fainter than the tip of the RGB. This photometry was obtained using Hyper-Suprime Cam (HSC) on the Subaru Telescope. The large (1.5o) field-of-view of HSC provides us with a unique opportunity to study the wide-field structure of this dwarf galaxy. This project explores the structure of IC1613 to radii of about ~ 25 kpc using different types of stellar tracers. The aim is to search for evidence of a stellar halo or stellar over-densities around IC1613. The relative contributions of the different stellar populations as a function of position in IC1613 are also shown.

30 CFR 57.22203 - Main fan operation (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation (I-C mines). 57.22203... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22203 Main fan operation (I-C mines). Main fans shall be operated continuously while ore production is in progress. ...

Simultaneous detection of three lily viruses using Triplex IC-RT-PCR.

PubMed

Zhang, Yubao; Wang, Yajun; Xie, Zhongkui; Yang, Guo; Guo, Zhihong; Wang, Le

2017-11-01

Viruses commonly infecting lily (Lilium spp.) include: Lily symptomless virus (LSV), Cucumber mosaic virus (CMV) and Lily mottle virus (LMoV). These viruses usually co-infect lilies causing severe economic losses in terms of quantity and quality of flower and bulb production around the world. Reliable and precise detection systems need to be developed for virus identification. We describe the development of a triplex immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) assay for the simultaneous detection of LSV, CMV and LMoV. The triplex IC-RT-PCR was compared with a quadruplex RT-PCR assay. Relative to the quadruplex RT-PCR, the specificity of the triplex IC-RT-PCR system for LSV, CMV and LMoV was 100% for field samples. The sensitivity of the triplex IC-RT-PCR system was 99.4%, 81.4% and 98.7% for LSV, CMV and LMoV, respectively. Agreement (κ) between the results obtained from the two tests was 0.968, 0.844 and 0.984 for LSV, CMV and LMoV, respectively. This is the first report of the simultaneous detection of LSV, CMV and LMoV in a triplex IC-RT-PCR assay. In particular we believe this convenient and reliable triplex IC-RT-PCR method could be used routinely for large-scale field surveys or crop health monitoring of lily. Copyright © 2017. Published by Elsevier B.V.

Development of teaching material to integrate GT-POWER into combustion courses for IC engine simulations.

DOT National Transportation Integrated Search

2009-02-01

The main objective of this project was to develop instructional engineering projects that utilize the newly-offered PACE software GT-POWER for engine simulations in combustion-related courses at the Missouri University of Science and Technology. Stud...

AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC50).

PubMed

Qureshi, Abid; Tandon, Himani; Kumar, Manoj

2015-11-01

Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc.

Surrogate Motherhood II: Reflections after "Baby M."

ERIC Educational Resources Information Center

Schwartz, Lita Linzer

1988-01-01

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

Illuminating the Depths of the MagIC (Magnetics Information Consortium) Database

NASA Astrophysics Data System (ADS)

Koppers, A. A. P.; Minnett, R.; Jarboe, N.; Jonestrask, L.; Tauxe, L.; Constable, C.

2015-12-01

The Magnetics Information Consortium (http://earthref.org/MagIC/) is a grass-roots cyberinfrastructure effort envisioned by the paleo-, geo-, and rock magnetic scientific community. Its mission is to archive their wealth of peer-reviewed raw data and interpretations from magnetics studies on natural and synthetic samples. Many of these valuable data are legacy datasets that were never published in their entirety, some resided in other databases that are no longer maintained, and others were never digitized from the field notebooks and lab work. Due to the volume of data collected, most studies, modern and legacy, only publish the interpreted results and, occasionally, a subset of the raw data. MagIC is making an extraordinary effort to archive these data in a single data model, including the raw instrument measurements if possible. This facilitates the reproducibility of the interpretations, the re-interpretation of the raw data as the community introduces new techniques, and the compilation of heterogeneous datasets that are otherwise distributed across multiple formats and physical locations. MagIC has developed tools to assist the scientific community in many stages of their workflow. Contributors easily share studies (in a private mode if so desired) in the MagIC Database with colleagues and reviewers prior to publication, publish the data online after the study is peer reviewed, and visualize their data in the context of the rest of the contributions to the MagIC Database. From organizing their data in the MagIC Data Model with an online editable spreadsheet, to validating the integrity of the dataset with automated plots and statistics, MagIC is continually lowering the barriers to transforming dark data into transparent and reproducible datasets. Additionally, this web application generalizes to other databases in MagIC's umbrella website (EarthRef.org) so that the Geochemical Earth Reference Model (http://earthref.org/GERM/) portal, Seamount Biogeosciences

Deconstructing the surrogate species concept: a life history approach to the protection of ecosystem services

USDA-ARS?s Scientific Manuscript database

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 ...

Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View.

PubMed

Wickström, Kerstin; Moseley, Jane

2017-05-01

To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. The key endpoints that have been used in registration studies so far are based on visual acuity, signs, and symptoms, or on surrogate endpoints. In some ocular conditions, established outcome measures such as those based on visual acuity or visual field are not feasible (as with slowly progressing diseases), or lack relevance (e.g., when central visual acuity may be preserved even though the patient is legally blind owing to a severely restricted visual field, or vice versa). There are several ocular conditions for which there is an unmet medical need. In some of these conditions, surrogate endpoints as well as new clinical endpoints are needed to help speed up patient access to new medicines. Interaction with European regulators through the pathway specific for the development of biomarkers or novel methods is encouraged.

Deconstructing the surrogate species concept:a life history approach to the protection of ecosystem services.

USDA-ARS?s Scientific Manuscript database

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...

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…

The beautiful side of IC 335

NASA Image and Video Library

2017-12-08

Hubble sees a galaxy 60 million light-years away This new NASA/ESA Hubble Space Telescope image shows the galaxy IC 335 in front of a backdrop of distant galaxies. IC 335 is part of a galaxy group containing three other galaxies, and located in the Fornax Galaxy Cluster 60 million light-years away. As seen in this image, the disk of IC 335 appears edge-on from the vantage point of Earth. This makes it harder for astronomers to classify it, as most of the characteristics of a galaxy’s morphology — the arms of a spiral or the bar across the center — are only visible on its face. Still, the 45 000 light-year-long galaxy could be classified as an S0 type. These lenticular galaxies are an intermediate state in galaxy morphological classification schemes between true spiral and elliptical galaxies. They have a thin stellar disk and a bulge, like spiral galaxies, but in contrast to typical spiral galaxies they have used up most of the interstellar medium. Only a few new stars can be created out of the material that is left and the star formation rate is very low. Hence, the population of stars in S0 galaxies consists mainly of aging stars, very similar to the star population in elliptical galaxies. As S0 galaxies have only ill-defined spiral arms they are easily mistaken for elliptical galaxies if they are seen inclined face-on or edge-on as IC 335 here. And indeed, despite the morphological differences between S0 and elliptical class galaxies, they share some common characteristics, like typical sizes and spectral features. Both classes are also deemed "early-type" galaxies, because they are evolving passively. However, while elliptical galaxies may be passively evolving when we observe them, they have usually had violent interactions with other galaxies in their past. In contrast, S0 galaxies are either aging and fading spiral galaxies, which never had any interactions with other galaxies, or they are the aging result of a single merger between two spiral galaxies

LVAD patients' and surrogates' perspectives on SPIRIT-HF: An advance care planning discussion.

PubMed

Metzger, Maureen; Song, Mi-Kyung; Devane-Johnson, Stephanie

2016-01-01

To describe LVAD patients' and surrogates' experiences with, and perspectives on SPIRIT-HF, an advance care planning (ACP) intervention. ACP is important for patients with LVAD, yet little is known about their experiences or those of their surrogates who have participated in ACP discussions. We used qualitative content analysis techniques to conduct a secondary analysis of 28 interviews with patients with LVAD (n = 14) and their surrogates (n = 14) who had participated in an RCT pilot study of SPIRIT-HF. Main themes from the data include: 1) sharing their HF stories was very beneficial; 2) participating in SPIRIT-HF led to greater peace of mind for patients and surrogates; 3) "one size does not fit all" when it comes to timing of ACP discussions. An understanding patient and surrogate perspectives may inform clinicians' approach to ACP discussions. Copyright © 2016 Elsevier Inc. All rights reserved.

Surrogate safety measures from traffic simulation models

DOT National Transportation Integrated Search

2003-01-01

This project investigates the potential for deriving surrogate measures of safety from existing microscopic traffic simulation models for intersections. The process of computing the measures in the simulation, extracting the required data, and summar...

International Space Agency CIO Forum Industrial Control System (ICS) and Cyber

NASA Technical Reports Server (NTRS)

Powell, Robert

2017-01-01

This briefing covers Industrial Control System (ICS) best practices for enhancing cyber protection. The briefing provides a very high-level overview of best practices currently being pursued by NASA as well as by other US government agencies such as NIST and DHS ICS-CERT. All information presented in this slide deck is publicly available and no sensitive information is provided in these slides. These slides will be used to generate discussion around best practices within the international community in the area of ICS cyber protections.

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

PubMed Central

Petkau, J; Reingold, SC; Held, U; Cutter, GR; Fleming, TR; Hughes, MD; Miller, DH; McFarland, HF; Wolinsky, JS

2009-01-01

Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy. PMID:18535021

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

PubMed

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

2011-06-01

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

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

PubMed Central

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

2015-01-01

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. PMID:26271918

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

PubMed

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

2017-10-01

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.

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. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

AGB stars as tracers to IC 1613 evolution.

NASA Astrophysics Data System (ADS)

Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

First imaging Fourier-transform spectral measurements of detonation in an internal combustion engine

NASA Astrophysics Data System (ADS)

Gross, Kevin C.; Borel, Chris; White, Allen; Sakai, Stephen; DeVasher, Rebecca; Perram, Glen P.

2010-08-01

The Telops Hyper-Cam midwave (InSb 1.5-5.5μm) imaging Fourier-transformspectrometer (IFTS) observed repeated detonations in an ethanol-powered internal combustion (IC) engine. The IC engine is aMegatech Corporation MEG 150 with a 1in. bore, 4in. stroke, and a compression ratio of 3 : 1. The IC combustion cylinder is made from sapphire permitting observation in the visible and infrared. From a distance of 3m, the IFTS imaged the combustion cylinder on a 64×32 pixel array with each pixel covering a 0.1×0.1cm2 area. More than 14,000 interferograms were collected at a rate of 16Hz. The maximum optical path difference of the interferograms was 0.017cm corresponding to an unapodized spectral resolution of 36cm-1. Engine speed was varied between 600-1200RPM to de-correlate the observation time scale from the occurrence of detonations. A method is devised to process the ensemble of interferograms which takes advantage of the DC component so that the time history of the combustion spectrum can be recovered at each pixel location. Preliminary results of this analysis will be presented.

Use of optical technique for inspection of warpage of IC packages

NASA Astrophysics Data System (ADS)

Toh, Siew-Lok; Chau, Fook S.; Ong, Sim Heng

2001-06-01

The packaging of IC packages has changed over the years, form dual-in-line, wire-bond, and pin-through-hole in printed wiring board technologies in the 1970s to ball grid array, chip scale and surface mount technologies in the 1990s. Reliability has been a big problem for manufacturers for some moisture-sensitive packages. One of the potential problems in plastic IC packages is moisture-induced popcorn effect which can arise during the reflow process. Shearography is a non-destructive inspection technique that may be used to detect the delamination and warpage of IC packages. It is non-contacting and permits a full-field observation of surface displacement derivatives. Another advantage of this technique is that it is able to give the real-time formation of the fringes which indicate flaws in the IC package under real-time simulation condition of Surface Mount Technology (SMT) IR reflow profile. It is extremely fast and convenient to study the true behavior of the packaging deformation during the SMT process. It can be concluded that shearography has the potential for the real- time detection, in situ and non-destructive inspection of IC packages during the surface mount process.

Student Definitions of Intercultural Competence (IC)--Are They Context-Specific?

ERIC Educational Resources Information Center

Binder, Nadine; Odag, Ozen; Leiser, Anne; Ludders, Lisa; Kedzior, Karina Karolina

2018-01-01

Higher education institutions increasingly seek to promote students' intercultural competence (IC), yet its conceptualization remains a challenge. The first aim of this study was to explore how a purposive sample of n = 77 domestic, undergraduate students at a public university in Germany define IC. The second aim was to assess to what extent such…

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

Narrative Interest Standard: A Novel Approach to Surrogate Decision-Making for People With Dementia.

PubMed

Wilkins, James M

2017-06-17

Dementia is a common neurodegenerative process that can significantly impair decision-making capacity as the disease progresses. When a person is found to lack capacity to make a decision, a surrogate decision-maker is generally sought to aid in decision-making. Typical bases for surrogate decision-making include the substituted judgment standard and the best interest standard. Given the heterogeneous and progressive course of dementia, however, these standards for surrogate decision-making are often insufficient in providing guidance for the decision-making for a person with dementia, escalating the likelihood of conflict in these decisions. In this article, the narrative interest standard is presented as a novel and more appropriate approach to surrogate decision-making for people with dementia. Through case presentation and ethical analysis, the standard mechanisms for surrogate decision-making for people with dementia are reviewed and critiqued. The narrative interest standard is then introduced and discussed as a dementia-specific model for surrogate decision-making. Through incorporation of elements of a best interest standard in focusing on the current benefit-burden ratio and elements of narrative to provide context, history, and flexibility for values and preferences that may change over time, the narrative interest standard allows for elaboration of an enriched context for surrogate decision-making for people with dementia. More importantly, however, a narrative approach encourages the direct contribution from people with dementia in authoring the story of what matters to them in their lives.

Related Progenitor Models for Long-duration Gamma-Ray Bursts and Type Ic Superluminous Supernovae

NASA Astrophysics Data System (ADS)

Aguilera-Dena, David R.; Langer, Norbert; Moriya, Takashi J.; Schootemeijer, Abel

2018-05-01

We model the late evolution and mass loss history of rapidly rotating Wolf–Rayet stars in the mass range 5 M ⊙…100 M ⊙). We find that quasi-chemically homogeneously evolving single stars computed with enhanced mixing retain very little or no helium and are compatible with Type Ic supernovae. The more efficient removal of core angular momentum and the expected smaller compact object mass in our lower-mass models lead to core spins in the range suggested for magnetar-driven superluminous supernovae. Our higher-mass models retain larger specific core angular momenta, expected for long-duration gamma-ray bursts in the collapsar scenario. Due to the absence of a significant He envelope, the rapidly increasing neutrino emission after core helium exhaustion leads to an accelerated contraction of the whole star, inducing a strong spin-up and centrifugally driven mass loss at rates of up to {10}-2 {M}ȯ {yr}}-1 in the last years to decades before core collapse. Because the angular momentum transport in our lower-mass models enhances the envelope spin-up, they show the largest relative amounts of centrifugally enforced mass loss, i.e., up to 25% of the expected ejecta mass. Our most massive models evolve into the pulsational pair-instability regime. We would thus expect signatures of interaction with a C/O-rich circumstellar medium for Type Ic superluminous supernovae with ejecta masses below ∼10 M ⊙ as well as for the most massive engine-driven explosions with ejecta masses above ∼30 M ⊙. Signs of such interaction should be observable at early epochs of the supernova explosion; they may be related to bumps observed in the light curves of superluminous supernovae, or to the massive circumstellar CO-shell proposed for Type Ic superluminous supernova Gaia16apd.

Development of Intake Swirl Generators for Turbo Jet Engine Testing

DTIC Science & Technology

1987-03-01

As a test object a Larxac 04 turbofan engine was chosen which is used as propulsion in the Alpha Jet aircraft . This twospool engine features a two...a__ OPI: !’fIC-TID N .18.1 DEVELOPMENT OF NAR 8WZRL GENERATORS FOR TURBO JET ENGINE TU TING by H.P. Gensmlor*, W. Meyer**, L. Fottner*** Dipl.-Ing...at the Universitit der Bundeswehr MUnchen. The test facility is designed for turbo jet engines up to an maximum thrust of 30kN and a maximum mass

Surrogate endpoints and competing risk of death in cardiac arrest research.

PubMed

McCredie, Victoria A; Scales, Damon C

2016-06-29

We urgently need new therapies to improve outcomes after cardiac arrest. Initial studies typically target surrogate endpoints, and these studies help to inform subsequent larger trials that are powered to measure more patient-orientated clinical outcomes such as survival. The competing risk of death and premature assessment of neurological prognosis pose significant challenges to measuring these surrogate endpoints after cardiac arrest.

An entropy-based nonparametric test for the validation of surrogate endpoints.

PubMed

Miao, Xiaopeng; Wang, Yong-Cheng; Gangopadhyay, Ashis

2012-06-30

We present a nonparametric test to validate surrogate endpoints based on measure of divergence and random permutation. This test is a proposal to directly verify the Prentice statistical definition of surrogacy. The test does not impose distributional assumptions on the endpoints, and it is robust to model misspecification. Our simulation study shows that the proposed nonparametric test outperforms the practical test of the Prentice criterion in terms of both robustness of size and power. We also evaluate the performance of three leading methods that attempt to quantify the effect of surrogate endpoints. The proposed method is applied to validate magnetic resonance imaging lesions as the surrogate endpoint for clinical relapses in a multiple sclerosis trial. Copyright © 2012 John Wiley & Sons, Ltd.

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Boreholes shall be drilled in such a manner to insure that the advancing face will not accidently break into... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass.

PubMed

Bojsen-Møller, Kirstine N; Dirksen, Carsten; Svane, Maria S; Jørgensen, Nils B; Holst, Jens J; Richter, Erik A; Madsbad, Sten

2017-05-01

Roux-en-Y gastric bypass (RYGB) induces weight loss and improves insulin sensitivity when evaluated by the hyperinsulinemic-euglycemic clamp (HEC). Surrogate indices of insulin sensitivity calculated from insulin and glucose concentrations at fasting or after an oral glucose tolerance test (OGTT) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting surrogates (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared with HEC-estimated peripheral insulin sensitivity ( R d or R d /I, depending on how the index was originally validated) and the tracer-determined hepatic insulin sensitivity index (HISI) in patients with preoperative type 2 diabetes ( n = 10) and normal glucose tolerance ( n = 10) 1 wk, 3 mo, and 1 yr postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in R d at any visit, but were comparable to changes in HISI at 1 wk. Changes in QUICKI and revised-QUICKI correlated with R d /I after surgery. Changes in the Matsuda and Gutt indices did not correlate with changes in R d /I and R d , respectively, whereas OGIS changes correlated with R d changes at 1 yr post-RYGB. In conclusion, surrogate measures of insulin sensitivity may not reflect results obtained with gold standard methodology after RYGB, underscoring the importance of critical reflection when surrogate endpoints are used. Fasting surrogate indices may be particularly affected by post-RYGB changes in insulin clearance, whereas the validity of OGTT-derived surrogates may be compromised by surgical rearrangements of the gut. Copyright © 2017 the American Physiological Society.

Mapping people's views regarding the acceptability of surrogate motherhood.

PubMed

Petitfils, Charlotte; Munoz Sastre, Maria Teresa; Sorum, Paul Clay; Mullet, Etienne

2017-02-01

The aims of the present study were to map French laypersons' views regarding the acceptability of maternal surrogacy and to delineate the circumstances under which surrogacy is considered, by different groups of people, as especially problematic. Participants (N = 236) were presented with a number of scenarios depicting the circumstances in which a couple has contracted with a surrogate mother and were asked to indicate the extent to which such a contract may present a moral problem. The scenarios were created by varying four factors: the type of surrogacy (traditional or gestational), the surrogate mother's level of autonomy, the family context in which the surrogate mother lives, and whether surrogacy was commercial or altruistic. Three qualitatively different personal positions were found: (a) a majority group for which surrogacy always (30%) or often (34%) presents a moral problem, (b) a minority group (14%) for which maternal surrogacy does not systematically present a moral problem, and (c) another minority group (22%) for which circumstances - mainly the mother's level of autonomy and the family context in which she lives - were completely determining.

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. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of countermeasures for red light running by traffic simulator-based surrogate safety measures.

PubMed

Lee, Changju; So, Jaehyun Jason; Ma, Jiaqi

2018-01-02

The conflicts among motorists entering a signalized intersection with the red light indication have become a national safety issue. Because of its sensitivity, efforts have been made to investigate the possible causes and effectiveness of countermeasures using comparison sites and/or before-and-after studies. Nevertheless, these approaches are ineffective when comparison sites cannot be found, or crash data sets are not readily available or not reliable for statistical analysis. Considering the random nature of red light running (RLR) crashes, an inventive approach regardless of data availability is necessary to evaluate the effectiveness of each countermeasure face to face. The aims of this research are to (1) review erstwhile literature related to red light running and traffic safety models; (2) propose a practical methodology for evaluation of RLR countermeasures with a microscopic traffic simulation model and surrogate safety assessment model (SSAM); (3) apply the proposed methodology to actual signalized intersection in Virginia, with the most prevalent scenarios-increasing the yellow signal interval duration, installing an advance warning sign, and an RLR camera; and (4) analyze the relative effectiveness by RLR frequency and the number of conflicts (rear-end and crossing). All scenarios show a reduction in RLR frequency (-7.8, -45.5, and -52.4%, respectively), but only increasing the yellow signal interval duration results in a reduced total number of conflicts (-11.3%; a surrogate safety measure of possible RLR-related crashes). An RLR camera makes the greatest reduction (-60.9%) in crossing conflicts (a surrogate safety measure of possible angle crashes), whereas increasing the yellow signal interval duration results in only a 12.8% reduction of rear-end conflicts (a surrogate safety measure of possible rear-end crash). Although increasing the yellow signal interval duration is advantageous because this reduces the total conflicts (a possibility of total

Overview of selected surrogate technologies for continuous suspended-sediment monitoring

USGS Publications Warehouse

Gray, J.R.; Gartner, J.W.

2006-01-01

Surrogate technologies for inferring selected characteristics of suspended sediments in surface waters are being tested by the U.S. Geological Survey and several partners with the ultimate goal of augmenting or replacing traditional monitoring methods. Optical properties of water such as turbidity and optical backscatter are the most commonly used surrogates for suspended-sediment concentration, but use of other techniques such as those based on acoustic backscatter, laser diffraction, digital photo-optic, and pressure-difference principles is increasing for concentration and, in some cases, particle-size distribution and flux determinations. The potential benefits of these technologies include acquisition of automated, continuous, quantifiably accurate data obtained with increased safety and at less expense. When suspended-sediment surrogate data meet consensus accuracy criteria and appropriate sediment-record computation techniques are applied, these technologies have the potential to revolutionize the way fluvial-sediment data are collected, analyzed, and disseminated.

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

Post-test analysis of PIPER-ONE PO-IC-2 experiment by RELAP5/MOD3 codes

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

Bovalini, R.; D`Auria, F.; Galassi, G.M.

1996-11-01

RELAP5/MOD3.1 was applied to the PO-IC-2 experiment performed in PIPER-ONE facility, which has been modified to reproduce typical isolation condenser thermal-hydraulic conditions. RELAP5 is a well known code widely used at the University of Pisa during the past seven years. RELAP5/MOD3.1 was the latest version of the code made available by the Idaho National Engineering Laboratory at the time of the reported study. PIPER-ONE is an experimental facility simulating a General Electric BWR-6 with volume and height scaling ratios of 1/2,200 and 1./1, respectively. In the frame of the present activity a once-through heat exchanger immersed in a pool ofmore » ambient temperature water, installed approximately 10 m above the core, was utilized to reproduce qualitatively the phenomenologies expected for the Isolation Condenser in the simplified BWR (SBWR). The PO-IC-2 experiment is the flood up of the PO-SD-8 and has been designed to solve some of the problems encountered in the analysis of the PO-SD-8 experiment. A very wide analysis is presented hereafter including the use of different code versions.« less

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

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

Theiler, J.; Galdrikian, B.; Longtin, A.

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 themore » 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.« less

Reduced-order surrogate models for Green's functions in black hole spacetimes

NASA Astrophysics Data System (ADS)

Galley, Chad; Wardell, Barry

2016-03-01

The fundamental nature of linear wave propagation in curved spacetime is encoded in the retarded Green's function (or propagator). Green's functions are useful tools because almost any field quantity of interest can be computed via convolution integrals with a source. In addition, perturbation theories involving nonlinear wave propagation can be expressed in terms of multiple convolutions of the Green's function. Recently, numerical solutions for propagators in black hole spacetimes have been found that are globally valid and accurate for computing physical quantities. However, the data generated is too large for practical use because the propagator depends on two spacetime points that must be sampled finely to yield accurate convolutions. I describe how to build a reduced-order model that can be evaluated as a substitute, or surrogate, for solutions of the curved spacetime Green's function equation. The resulting surrogate accurately and quickly models the original and out-of-sample data. I discuss applications of the surrogate, including self-consistent evolutions and waveforms of extreme mass ratio binaries. Green's function surrogate models provide a new and practical way to handle many old problems involving wave propagation and motion in curved spacetimes.

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

PubMed

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

2016-05-10

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

The Family Navigator: A Pilot Intervention to Support Intensive Care Unit Family Surrogates.

PubMed

Torke, Alexia M; Wocial, Lucia D; Johns, Shelley A; Sachs, Greg A; Callahan, Christopher M; Bosslet, Gabriel T; Slaven, James E; Perkins, Susan M; Hickman, Susan E; Montz, Kianna; Burke, Emily S

2016-11-01

Communication problems between family surrogates and intensive care unit (ICU) clinicians have been documented, but few interventions are effective. Nurses have the potential to play an expanded role in ICU communication and decision making. To conduct a pilot randomized controlled trial of the family navigator (FN), a distinct nursing role to address family members' unmet communication needs early in an ICU stay. An interprofessional team developed the FN protocol. A randomized controlled pilot intervention trial of the FN was performed in a tertiary referral hospital's ICU to test the feasibility and acceptability of the intervention. The intervention addressed informational and emotional communication needs through daily contact by using structured clinical updates, emotional and informational support modules, family meeting support, and follow-up phone calls. Twenty-six surrogate/patient pairs (13 per study arm) were enrolled. Surrogates randomized to the intervention had contact with the FN on 90% or more of eligible patient days. All surrogates agreed that they would recom mend the FN to other families. Open-ended comments from both surrogates and clinicians were uniformly positive. Having a fully integrated nurse empowered to facilitate decision making is a feasible intervention in an ICU and is well-received by ICU families and staff. A larger randomized controlled trial is needed to demonstrate impact on important outcomes, such as surrogates' well-being and decision quality. ©2016 American Association of Critical-Care Nurses.

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.

Global Parameter Optimization of CLM4.5 Using Sparse-Grid Based Surrogates

NASA Astrophysics Data System (ADS)

Lu, D.; Ricciuto, D. M.; Gu, L.

2016-12-01

Calibration of the Community Land Model (CLM) is challenging because of its model complexity, large parameter sets, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time. The goal of this study is to calibrate some of the CLM parameters in order to improve model projection of carbon fluxes. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first use advanced sparse grid (SG) interpolation to construct a surrogate system of the actual CLM model, and then we calibrate the surrogate model in the optimization process. As the surrogate model is a polynomial whose evaluation is fast, it can be efficiently evaluated with sufficiently large number of times in the optimization, which facilitates the global search. We calibrate five parameters against 12 months of GPP, NEP, and TLAI data from the U.S. Missouri Ozark (US-MOz) tower. The results indicate that an accurate surrogate model can be created for the CLM4.5 with a relatively small number of SG points (i.e., CLM4.5 simulations), and the application of the optimized parameters leads to a higher predictive capacity than the default parameter values in the CLM4.5 for the US-MOz site.

How Social Network Size and Quality Affect End-of-Life Surrogate Preferences.

PubMed

Moorman, Sara M; Boerner, Kathrin

2018-04-16

Older adults typically choose their next-of-kin to serve as surrogate on their behalf should they become decisionally incapacitated at the end of life. However, some older adults do not choose their closest relative, even if they are married or parents. We compared the social networks of these latter persons to their peers who prefer a next-of-kin surrogate, anticipating differences in relationship quality and network size. We used multinomial logistic regressions to investigate the quality and size of the social networks of 1,245 persons whose next of kin was a spouse and 723 persons whose next-of-kin was an adult child, and who participated in the 2005 National Social Life, Health and Aging Project. Twenty percent of those whose next-of-kin was a spouse and 32% of those whose next-of-kin was an adult child either bypassed that person in favor of a different surrogate, or preferred no surrogate at all. Low-quality next-of-kin relationships pushed older adults away from next-of-kin, and a greater number of high-quality relationships outside the immediate family pulled older adults toward a surrogate who was not next-of-kin. We discuss what is distinctive about the social networks of each group, and the implications for end-of-life support.

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

PubMed

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

2012-07-10

Although the benefits of the use of less lethal kinetic energy munitions are numerous, there is a need to evaluate the munitions prior to deployment to ensure their intended effect. The objective of the current research was to validate a surrogate that could be used to predict the risk of penetration of these devices. Existing data from biomechanical testing with post-mortem human specimens (PMHS) served as the foundation for this research. Development of the surrogate involved simulating the various layers of the skin and underlying soft tissues using a combination of materials. A standardized 12-gauge impactor was used to assess each combination. The energy density that resulted in a 50% risk of penetration for the anterior thorax region (23.99 J/cm(2)) from the previous research was matched using a specific combination of layers. Twelve various combinations of materials were tested with the 50% risk of penetration determined. The final validated surrogate consisted of a Laceration Assessment Layer (LAL) of natural chamois and .6 cm of closed-cell foam over a Penetration Assessment Layer (PAL) of 20% ordnance gelatin. This surrogate predicted a 50% risk of penetration at 23.88 J/cm(2). Injury risk curves for the PMHS and surrogate development work are presented. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

NURSE-LED INTERVENTION TO IMPROVE SURROGATE DECISION MAKING FOR PATIENTS WITH ADVANCED CRITICAL ILLNESS

PubMed Central

White, Douglas B.; Cua, Sarah Martin; Walk, Roberta; Pollice, Laura; Weissfeld, Lisa; Hong, Seoyeon; Landefeld, C. Seth; Arnold, Robert M.

2013-01-01

Background Problems persist with surrogate decision making in intensive care units, leading to distress for surrogates and treatment that may not reflect patients’ values. Objectives To assess the feasibility, acceptability, and perceived effectiveness of a multifaceted, nurse-led intervention to improve surrogate decision making in intensive care units. Study Design A single-center, single-arm, interventional study in which 35 surrogates and 15 physicians received the Four Supports Intervention, which involved incorporating a family support specialist into the intensive care team. That specialist maintained a longitudinal relationship with surrogates and provided emotional support, communication support, decision support, and anticipatory grief support. A mixed-methods approach was used to evaluate the intervention. Results The intervention was implemented successfully in all 15 patients, with a high level of completion of each component of the intervention. The family support specialist devoted a mean of 48 (SD 36) minutes per day to each clinician-patient-family triad. All participants reported that they would recommend the intervention to others. At least 90% of physicians and surrogates reported that the intervention (1) improved the quality and timeliness of communication, (2) facilitated discussion of the patient’s values and treatment preferences, and (3) improved the patient-centeredness of care. Conclusions The Four Supports Intervention is feasible, acceptable, and was perceived by physicians and surrogates to improve the quality of decision making and the patient-centeredness of care. A randomized trial is warranted to determine whether the intervention improves patient, family, and health system outcomes. PMID:23117903

The scaling of performance and losses in miniature internal combustion engines

NASA Astrophysics Data System (ADS)

Menon, Shyam Kumar

Miniature glow ignition internal combustion (IC) piston engines are an off--the--shelf technology that could dramatically increase the endurance of miniature electric power supplies and the range and endurance of small unmanned air vehicles provided their overall thermodynamic efficiencies can be increased to 15% or better. This thesis presents the first comprehensive analysis of small (<500 g) piston engine performance. A unique dynamometer system is developed that is capable of making reliable measurements of engine performance and losses in these small engines. Methodologies are also developed for measuring volumetric, heat transfer, exhaust, mechanical, and combustion losses. These instruments and techniques are used to investigate the performance of seven single-cylinder, two-stroke, glow fueled engines ranging in size from 15 to 450 g (0.16 to 7.5 cm3 displacement). Scaling rules for power output, overall efficiency, and normalized power are developed from the data. These will be useful to developers of micro-air vehicles and miniature power systems. The data show that the minimum length scale of a thermodynamically viable piston engine based on present technology is approximately 3 mm. Incomplete combustion is the most important challenge as it accounts for 60-70% of total energy losses. Combustion losses are followed in order of importance by heat transfer, sensible enthalpy, and friction. A net heat release analysis based on in-cylinder pressure measurements suggest that a two--stage combustion process occurs at low engine speeds and equivalence ratios close to 1. Different theories based on burning mode and reaction kinetics are proposed to explain the observed results. High speed imaging of the combustion chamber suggests that a turbulent premixed flame with its origin in the vicinity of the glow plug is the primary driver of combustion. Placing miniature IC engines on a turbulent combustion regime diagram shows that they operate in the 'flamelet in eddy

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

Using Video Images to Improve the Accuracy of Surrogate Decision-Making: A Randomized Controlled Trial

PubMed Central

Volandes, Angelo E.; Mitchell, Susan L.; Gillick, Muriel R.; Chang, Yuchiao; Paasche-Orlow, Michael K.

2009-01-01

Introduction When patients are unable to make important end-of-life decisions, doctors ask surrogate decision makers to provide insight into patients’ preferences. Unfortunately, multiple studies have shown that surrogates’ knowledge of patient preferences is poor. We hypothesized that a video decision tool would improve concordance between patients and their surrogates for end-of-life preferences. Objective To compare the concordance of preferences among elderly patients and their surrogates listening to only a verbal description of advanced dementia or viewing a video decision support tool of the disease after hearing the verbal description. Methods This was a randomized controlled trial of a convenience sample of community-dwelling elderly subjects (≥65 years) and their surrogates, and was conducted at 2 geriatric clinics affiliated with 2 academic medical centers in Boston. The study was conducted between September 1, 2007, and May 30, 2008. Random assignment of patient and surrogate dyads was to either a verbal narrative or a video decision support tool after the verbal narrative. End points were goals of care chosen by the patient and predicted goals of care by the surrogate. Goals of care included life-prolonging care (CPR, mechanical ventilation), limited care (hospitalization, antibiotics, but not CPR), and comfort care (only treatment to relieve symptoms). The primary outcome measure was the concordance rate of preferences between patients and their surrogates. Results A total of 14 pairs of patients and their surrogates were randomized to verbal narrative (n = 6) or video after verbal narrative (n = 8). Among the 6 patients receiving only the verbal narrative, 3 (50%) preferred comfort care, 1 (17%) chose limited care, and 2 (33%) desired life-prolonging care. Among the surrogates for these patients, only 2 correctly chose what their loved one would want if in a state of advanced dementia, yielding a concordance rate of 33%. Among the 8 patients

The Limits of Surrogates' Moral Authority and Physician Professionalism: Can the Paradigm of Palliative Sedation Be Instructive?

PubMed

Berger, Jeffrey T

2017-01-01

With narrow exception, physicians' treatment of incapacitated patients requires the consent of health surrogates. Although the decision-making authority of surrogates is appropriately broad, their moral authority is not without limits. Discerning these bounds is particularly germane to ethically complex treatments and has important implications for the welfare of patients, for the professional integrity of clinicians, and, in fact, for the welfare of surrogates. Palliative sedation is one such complex treatment; as such, it provides a valuable model for analyzing the scope of surrogates' moral authority. Guidelines for palliative sedation that present it as a "last-resort" treatment for severe and intractable suffering yet require surrogate consent in order to offer it are ethically untenable, precisely because the moral limits of surrogate authority have not been considered. © 2017 The Hastings Center.

The Stirling engine as a low cost tool to educate mechanical engineers

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

Gros, J.; Munoz, M.; Moreno, F.

1995-12-31

The University of Zaragoza through CIRCE, the New Enterprise foundation, an Opel foundation and the local Government of Aragon have been developed a program to introduce the Stirling Engine as a low cost tool to educate students in mechanical engineering. The promotion of a prize like GNAT Power organized by the magazine Model Engineer in London, has improved the practical education of students in the field of mechanical devices and thermal engines. Two editions of the contest, 1993 and 1994, awarded the greatest power Stirling engine made by only using a little candle of paraffin as a heat source. Fourmore » engines were presented in the first edition, with an average power of about 100 mW, and seven engines in the second one, achieving a power of about 230 mW. Presentations in Technical Schools and the University have been carried out. Also low cost tools have been made for measuring an electronic device to draw the real internal pressure volume diagram using a PC. A very didactic software to design classic kinematic alpha, beta and gamma engines plus Ringbom beta and gamma engines has been created. A book is going to be published (in Spanish) explaining the design of small Stirling engines as a way to start with low cost research in thermal engines, a very difficult target with IC engines.« less

Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?

PubMed

Kemp, Robert; Prasad, Vinay

2017-07-21

Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies. In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked. We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm. The use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.

3D-ICs created using oblique processing

NASA Astrophysics Data System (ADS)

Burckel, D. Bruce

2016-03-01

This paper demonstrates that another class of three-dimensional integrated circuits (3D-ICs) exists, distinct from through silicon via centric and monolithic 3D-ICs. Furthermore, it is possible to create devices that are 3D at the device level (i.e. with active channels oriented in each of the three coordinate axes), by performing standard CMOS fabrication operations at an angle with respect to the wafer surface into high aspect ratio silicon substrates using membrane projection lithography (MPL). MPL requires only minimal fixturing changes to standard CMOS equipment, and no change to current state-of-the-art lithography. Eliminating the constraint of 2D planar device architecture enables a wide range of new interconnect topologies which could help reduce interconnect resistance/capacitance, and potentially improve performance.

IC [Interior Communications] Electrician 3 and 2: Rate Training Manual. Revised.

ERIC Educational Resources Information Center

Naval Education and Training Command, Pensacola, FL.

The rate training manual provides information related to the tasks assigned to the Interior Communications (IC) Electricians Third and Second Class who operate and maintain the interior communications systems and associated equipment. Chapter one discusses career challenges for the IC Electrician in terms of responsibilities, advancement…

Numerical investigation of spray ignition of a multi-component fuel surrogate

NASA Astrophysics Data System (ADS)

Backer, Lara; Narayanaswamy, Krithika; Pepiot, Perrine

2014-11-01

Simulating turbulent spray ignition, an important process in engine combustion, is challenging, since it combines the complexity of multi-scale, multiphase turbulent flow modeling with the need for an accurate description of chemical kinetics. In this work, we use direct numerical simulation to investigate the role of the evaporation model on the ignition characteristics of a multi-component fuel surrogate, injected as droplets in a turbulent environment. The fuel is represented as a mixture of several components, each one being representative of a different chemical class. A reduced kinetic scheme for the mixture is extracted from a well-validated detailed chemical mechanism, and integrated into the multiphase turbulent reactive flow solver NGA. Comparisons are made between a single-component evaporation model, in which the evaporating gas has the same composition as the liquid droplet, and a multi-component model, where component segregation does occur. In particular, the corresponding production of radical species, which are characteristic of the ignition of individual fuel components, is thoroughly analyzed.

Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

DOE PAGES

Xi, Maolong; Lu, Dan; Gui, Dongwei; ...

2016-11-27

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so asmore » to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO 3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.« less

Coral reef habitats as surrogates of species, ecological functions, and ecosystem services.

PubMed

Mumby, Peter J; Broad, Kenneth; Brumbaugh, Daniel R; Dahlgren, Craig P; Harborne, Alastair R; Hastings, Alan; Holmes, Katherine E; Kappel, Carrie V; Micheli, Fiorenza; Sanchirico, James N

2008-08-01

Habitat maps are often the core spatially consistent data set on which marine reserve networks are designed, but their efficacy as surrogates for species richness and applicability to other conservation measures is poorly understood. Combining an analysis of field survey data, literature review, and expert assessment by a multidisciplinary working group, we examined the degree to which Caribbean coastal habitats provide useful planning information on 4 conservation measures: species richness, the ecological functions of fish species, ecosystem processes, and ecosystem services. Approximately one-quarter to one-third of benthic invertebrate species and fish species (disaggregated by life phase; hereafter fish species) occurred in a single habitat, and Montastraea-dominated forereefs consistently had the highest richness of all species, processes, and services. All 11 habitats were needed to represent all 277 fish species in the seascape, although reducing the conservation target to 95% of species approximately halved the number of habitats required to ensure representation. Species accumulation indices (SAIs) were used to compare the efficacy of surrogates and revealed that fish species were a more appropriate surrogate of benthic species (SAI = 71%) than benthic species were for fishes (SAI = 42%). Species of reef fishes were also distributed more widely across the seascape than invertebrates and therefore their use as a surrogate simultaneously included mangroves, sea grass, and coral reef habitats. Functional classes of fishes served as effective surrogates of fish and benthic species which, given their ease to survey, makes them a particularly useful measure for conservation planning. Ecosystem processes and services exhibited great redundancy among habitats and were ineffective as surrogates of species. Therefore, processes and services in this case were generally unsuitable for a complementarity-based approach to reserve design. In contrast, the representation

Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

NASA Astrophysics Data System (ADS)

Xi, Maolong; Lu, Dan; Gui, Dongwei; Qi, Zhiming; Zhang, Guannan

2017-01-01

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so as to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.

Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

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

Xi, Maolong; Lu, Dan; Gui, Dongwei

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so asmore » to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO 3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.« less

First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy.

PubMed

Myer, Emily; Hill, James

2015-10-01

Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed uncontrolled hypertension requiring hospitalization. She was expectantly managed until her condition deteriorated. At 16 weeks and 1 day she developed hemolysis, elevated liver enzymes, thrombocytopenia, and fetal demise. Conclusions HELLP syndrome is rare and carries a significant morbidity and mortality for the mother and fetus. Clinicians should encourage the surrogate to share her medical history with the embryo donor for appropriate counseling on pregnancy risks.

Surrogate end points in women's health research: science, protoscience, and pseudoscience.

PubMed

Grimes, David A; Schulz, Kenneth F; Raymond, Elizabeth G

2010-04-01

A surrogate end point (e.g., a laboratory test or image) serves as a proxy for a clinical end point of importance (e.g., fracture, thrombosis, or death). Adoption and use of surrogate end points lacking validation, especially in cardiovascular medicine, have caused thousands of patients' deaths, a serious violation of the ethical principle of beneficence. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Committee-Based Active Learning for Surrogate-Assisted Particle Swarm Optimization of Expensive Problems.

PubMed

Wang, Handing; Jin, Yaochu; Doherty, John

2017-09-01

Function evaluations (FEs) of many real-world optimization problems are time or resource consuming, posing a serious challenge to the application of evolutionary algorithms (EAs) to solve these problems. To address this challenge, the research on surrogate-assisted EAs has attracted increasing attention from both academia and industry over the past decades. However, most existing surrogate-assisted EAs (SAEAs) either still require thousands of expensive FEs to obtain acceptable solutions, or are only applied to very low-dimensional problems. In this paper, a novel surrogate-assisted particle swarm optimization (PSO) inspired from committee-based active learning (CAL) is proposed. In the proposed algorithm, a global model management strategy inspired from CAL is developed, which searches for the best and most uncertain solutions according to a surrogate ensemble using a PSO algorithm and evaluates these solutions using the expensive objective function. In addition, a local surrogate model is built around the best solution obtained so far. Then, a PSO algorithm searches on the local surrogate to find its optimum and evaluates it. The evolutionary search using the global model management strategy switches to the local search once no further improvement can be observed, and vice versa. This iterative search process continues until the computational budget is exhausted. Experimental results comparing the proposed algorithm with a few state-of-the-art SAEAs on both benchmark problems up to 30 decision variables as well as an airfoil design problem demonstrate that the proposed algorithm is able to achieve better or competitive solutions with a limited budget of hundreds of exact FEs.

Counterfactual reasoning in surrogate decision making -- another look.

PubMed

Johansson, Mats; Broström, Linus

2011-06-01

Incompetent patients need to have someone else make decisions on their behalf. According to the Substituted Judgment Standard the surrogate decision maker ought to make the decision that the patient would have made, had he or she been competent. Objections have been raised against this traditional construal of the standard on the grounds that it involves flawed counterfactual reasoning, and amendments have been suggested within the framework of possible worlds semantics. The paper shows that while this approach may circumvent the alleged problem, the way it has so far been elaborated reflects insufficient understanding of the moral underpinnings of the idea of substituted judgment. Proper recognition of these moral underpinnings has potentially far-reaching implications for our normative assumptions about accuracy and objectivity in surrogate decision making.

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

PubMed

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

2016-01-01

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

USE OF SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK TO ENDANGERED AND THREATENED FISHES

EPA Science Inventory

Surrogate species used in toxicity assessments must be carefully selected in order to be protective of listed species. At present, the rainbow trout is considered to be an acceptable surrogate for coldwater fishes. Similarly, the fathead minnow is considered to be an acceptable s...

A microbiological surrogate for evaluating treatment efficiency

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

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 ellipsoidalmore » 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.« less

Decision conflict and regret among surrogate decision makers in the medical intensive care unit.

PubMed

Miller, Jesse J; Morris, Peter; Files, D Clark; Gower, Emily; Young, Michael

2016-04-01

Family members of critically ill patients in the intensive care unit face significant morbidity. It may be the decision-making process that plays a significant role in the psychological morbidity associated with being a surrogate in the ICU. We hypothesize that family members facing end-of-life decisions will have more decisional conflict and decisional regret than those facing non-end-of-life decisions. We enrolled a sample of adult patients and their surrogates in a tertiary care, academic medical intensive care unit. We queried the surrogates regarding decisions they had made on behalf of the patient and assessed decision conflict. We then contacted the family member again to assess decision regret. Forty (95%) of 42 surrogates were able to identify at least 1 decision they had made on behalf of the patient. End-of-life decisions (defined as do not resuscitate [DNR]/do not intubate [DNI] or continuation of life support) accounted for 19 of 40 decisions (47.5%). Overall, the average Decision Conflict Scale (DCS) score was 21.9 of 100 (range 0-100, with 0 being little decisional conflict and 100 being great decisional conflict). The average DCS score for families facing end-of-life decisions was 25.5 compared with 18.7 for all other decisions. Those facing end-of-life decisions scored higher on the uncertainty subscale (subset of DCS questions that indicates level of certainty regarding decision) with a mean score of 43.4 compared with all other decisions with a mean score of 27.0. Overall, very few surrogates experienced decisional regret with an average DRS score of 13.4 of 100. Nearly all surrogates enrolled were faced with decision-making responsibilities on behalf of his or her critically ill family member. In our small pilot study, we found more decisional conflict in those surrogates facing end-of-life decisions, specifically on the subset of questions dealing with uncertainty. Surrogates report low levels of decisional regret. Copyright © 2015 Elsevier

Edwards nXDS15iC Vacuum Scroll Pump Pressure Testing

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

Sessions, H.; Morgan, G. A.

2013-07-17

The SRNL High Pressure Laboratory performed testing on an Edwards Model nXDS15iC Vacuum Scroll Pump on July 10th and 11th of 2013 at 723-A. This testing was done in an attempt to obtain initial compression ratio information for the nXDS15iC pump, with compression ratio defined as discharge pressure of the pump divided by suction pressure. Pressure burst testing was also done on the pump to determine its design pressure for pressure safety reasons. The Edwards nXDS15iC pump is being evaluated by SRNL for use part of the SHINE project being executed by SRNL.

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

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

Malinowski, Kathleen T.; Fischell Department of Bioengineering, University of Maryland, College Park, MD; McAvoy, Thomas J.

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 precisionmore » 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.« less

Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

ERIC Educational Resources Information Center

Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

2010-01-01

This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

Uncertainty propagation through an aeroelastic wind turbine model using polynomial surrogates

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

Murcia, Juan Pablo; Réthoré, Pierre-Elouan; Dimitrov, Nikolay

Polynomial surrogates are used to characterize the energy production and lifetime equivalent fatigue loads for different components of the DTU 10 MW reference wind turbine under realistic atmospheric conditions. The variability caused by different turbulent inflow fields are captured by creating independent surrogates for the mean and standard deviation of each output with respect to the inflow realizations. A global sensitivity analysis shows that the turbulent inflow realization has a bigger impact on the total distribution of equivalent fatigue loads than the shear coefficient or yaw miss-alignment. The methodology presented extends the deterministic power and thrust coefficient curves to uncertaintymore » models and adds new variables like damage equivalent fatigue loads in different components of the turbine. These surrogate models can then be implemented inside other work-flows such as: estimation of the uncertainty in annual energy production due to wind resource variability and/or robust wind power plant layout optimization. It can be concluded that it is possible to capture the global behavior of a modern wind turbine and its uncertainty under realistic inflow conditions using polynomial response surfaces. In conclusion, the surrogates are a way to obtain power and load estimation under site specific characteristics without sharing the proprietary aeroelastic design.« less

Uncertainty propagation through an aeroelastic wind turbine model using polynomial surrogates

DOE PAGES

Murcia, Juan Pablo; Réthoré, Pierre-Elouan; Dimitrov, Nikolay; ...

2017-07-17

Polynomial surrogates are used to characterize the energy production and lifetime equivalent fatigue loads for different components of the DTU 10 MW reference wind turbine under realistic atmospheric conditions. The variability caused by different turbulent inflow fields are captured by creating independent surrogates for the mean and standard deviation of each output with respect to the inflow realizations. A global sensitivity analysis shows that the turbulent inflow realization has a bigger impact on the total distribution of equivalent fatigue loads than the shear coefficient or yaw miss-alignment. The methodology presented extends the deterministic power and thrust coefficient curves to uncertaintymore » models and adds new variables like damage equivalent fatigue loads in different components of the turbine. These surrogate models can then be implemented inside other work-flows such as: estimation of the uncertainty in annual energy production due to wind resource variability and/or robust wind power plant layout optimization. It can be concluded that it is possible to capture the global behavior of a modern wind turbine and its uncertainty under realistic inflow conditions using polynomial response surfaces. In conclusion, the surrogates are a way to obtain power and load estimation under site specific characteristics without sharing the proprietary aeroelastic design.« less

ICS classification system of infected osteosynthesis: Long-term results.

PubMed

Romanò, Carlo L; Morelli, Ilaria; Romanò, Delia; Meani, Enzo; Drago, Lorenzo

2018-03-01

The best treatment strategy for infected osteosyntheses is still debated. While hardware removal or eventually early device exchange may be necessary in most of the cases, temporary hardware retention until fracture healing can be a valid alternative option in others. Aim of the present study is to report the long-term results of 215 patients with infected osteosyntheses, treated according to the ICS (Infection, Callus, Stability) classification in two Italian hospitals. Patients classified as ICS Type 1 (N = 83) feature callus progression and hardware stability, in spite of the presence of infection; these patients were treated with suppressive antibiotic therapy coupled with local debridement in 18.1% of the cases, and no hardware removal until bone healing. Type 2 patients (N = 75) are characterized by the presence of infection and hardware stability, but no callus progression; these patients were treated as Type 1 patients, but with additional callus stimulation therapies. Type 3 patients (N = 57), showing infection, no callus progression and loss of hardware stability, underwent removal and exchange of the fixation device. Considering only the initial treatment, performed according to the ICS classification, at a minimum 5 years follow up, 89.3% achieved bone healing and 93.5% did not show infection recurrence. The ICS classification appears as a useful and reliable tool to help standardizing the decision-making process in treating infected osteosynthesis with the most conservative approach. Copyright © 2018 Elsevier Ltd. All rights reserved.

Establishing a Numerical Modeling Framework for Hydrologic Engineering Analyses of Extreme Storm Events

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

Chen, Xiaodong; Hossain, Faisal; Leung, L. Ruby

In this study a numerical modeling framework for simulating extreme storm events was established using the Weather Research and Forecasting (WRF) model. Such a framework is necessary for the derivation of engineering parameters such as probable maximum precipitation that are the cornerstone of large water management infrastructure design. Here this framework was built based on a heavy storm that occurred in Nashville (USA) in 2010, and verified using two other extreme storms. To achieve the optimal setup, several combinations of model resolutions, initial/boundary conditions (IC/BC), cloud microphysics and cumulus parameterization schemes were evaluated using multiple metrics of precipitation characteristics. Themore » evaluation suggests that WRF is most sensitive to IC/BC option. Simulation generally benefits from finer resolutions up to 5 km. At the 15km level, NCEP2 IC/BC produces better results, while NAM IC/BC performs best at the 5km level. Recommended model configuration from this study is: NAM or NCEP2 IC/BC (depending on data availability), 15km or 15km-5km nested grids, Morrison microphysics and Kain-Fritsch cumulus schemes. Validation of the optimal framework suggests that these options are good starting choices for modeling extreme events similar to the test cases. This optimal framework is proposed in response to emerging engineering demands of extreme storm events forecasting and analyses for design, operations and risk assessment of large water infrastructures.« less

Incapacitated Surrogates: A New and Increasing Dilemma in Hospital Care.

PubMed

Smith, Karen L; Fedel, Patrice; Heitman, Jay

2017-01-01

A power of attorney for healthcare (POAHC) form gives designated individuals legal status to make healthcare decisions when patients are unable to convey their decisions to medical staff. Completion of a POAHC form is crucial in the provision of comprehensive healthcare, since it helps to ensure that patients' interests, values, and preferences are represented in decisions about their medical treatment. Because increasing numbers of people suffer from debilitating illness and cognitive deficits, healthcare systems may be called upon to navigate the complexities of patients' care without clear directives from the patients themselves. Hence, the healthcare industry encourages all individuals to complete a POAHC form to ensure that persons who have the patients' trust are able to act as their surrogate decision makers. However, sometimes POAHC agents, even when they are patients' trusted agents, lack the capacity to make fully informed decisions that are in the patients' best interests. We describe designated surrogate decision makers who have impaired or diminished judgment capacity as incapacitated surrogates. Decision making that is obviously flawed or questionable is a significant impediment to providing timely and appropriate care to patients. Moreover, failure to redress these issues in a timely and efficient manner can result in significant costs to an institution and a diminished quality of patient care. The authors offer a legal, ethical, and interdisciplinary framework to help navigate cases of incapacitated surrogates. Copyright 2017 The Journal of Clinical Ethics. All rights reserved.

Convergence analysis of surrogate-based methods for Bayesian inverse problems

NASA Astrophysics Data System (ADS)

Yan, Liang; Zhang, Yuan-Xiang

2017-12-01

The major challenges in the Bayesian inverse problems arise from the need for repeated evaluations of the forward model, as required by Markov chain Monte Carlo (MCMC) methods for posterior sampling. Many attempts at accelerating Bayesian inference have relied on surrogates for the forward model, typically constructed through repeated forward simulations that are performed in an offline phase. Although such approaches can be quite effective at reducing computation cost, there has been little analysis of the approximation on posterior inference. In this work, we prove error bounds on the Kullback-Leibler (KL) distance between the true posterior distribution and the approximation based on surrogate models. Our rigorous error analysis show that if the forward model approximation converges at certain rate in the prior-weighted L 2 norm, then the posterior distribution generated by the approximation converges to the true posterior at least two times faster in the KL sense. The error bound on the Hellinger distance is also provided. To provide concrete examples focusing on the use of the surrogate model based methods, we present an efficient technique for constructing stochastic surrogate models to accelerate the Bayesian inference approach. The Christoffel least squares algorithms, based on generalized polynomial chaos, are used to construct a polynomial approximation of the forward solution over the support of the prior distribution. The numerical strategy and the predicted convergence rates are then demonstrated on the nonlinear inverse problems, involving the inference of parameters appearing in partial differential equations.

Surrogate Decision Makers and Proxy Ownership: Challenges of Privacy Management in Health Care Decision Making

PubMed Central

Bute, Jennifer J.; Petronio, Sandra; Torke, Alexia M.

2016-01-01

This study explored the communicative experiences of surrogates who served as decision makers for patients who were unable to convey health information and choices about treatment options. Drawing on assumptions from communication privacy management theory (Petronio, 2002), 35 surrogates were interviewed to explore how they navigated the role of guardian of patients’ private health information while the patient was hospitalized. This research determined that surrogates are not only guardians and thereby co-owners of the patients’ private health information, they actually served in a “proxy ownership” role. Surrogates described obstacles to both obtaining and sharing private health information about the patient, suggesting that their rights as legitimate co-owners of the patients’ information were not fully acknowledged by the medical teams. Surrogates also described challenges in performing the proxy ownership role when they were not fully aware of the patient's wishes. Theoretical and practical implications of these challenges are discussed. PMID:25175060

Doubt and belief in physicians' ability to prognosticate during critical illness: The perspective of surrogate decision makers

PubMed Central

Zier, Lucas S.; Burack, Jeffrey H.; Micco, Guy; Chipman, Anne K.; Frank, James A.; Luce, John M.; White, Douglas B.

2009-01-01

Objectives: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Design, Setting, and Patients: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Measurements and Main Results: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic

ICS-II USA research design and methodology.

PubMed

Rana, H; Andersen, R M; Nakazono, T T; Davidson, P L

1997-05-01

The purpose of the WHO-sponsored International Collaborative Study of Oral Health Outcomes (ICS-II) was to provide policy-markers and researchers with detailed, reliable, and valid data on the oral health situation in their countries or regions, together with comparative data from other dental care delivery systems. ICS-II used a cross-sectional design with no explicit control groups or experimental interventions. A standardized methodology was developed and tested for collecting and analyzing epidemiological, sociocultural, economic, and delivery system data. Respondent information was obtained by household interviews, and clinical examinations were conducted by calibrated oral epidemiologists. Discussed are the sampling design characteristics for the USA research locations, response rates, samples size for interview and oral examination data, weighting procedures, and statistical methods. SUDAAN was used to adjust variance calculations, since complex sampling designs were used.

Multicolor CCD Photometry of the Open Cluster IC361

DTIC Science & Technology

2010-01-01

journal Volume 19 Numbers 1/2 2010 Contents V. Straizys, A. Kazlauskas. Young stars in the Camelopardalis dust and molecular clouds. VI. YSOs...Vilnius + I system for 7250 stars down to 1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog...1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog of 1420 stars down to V ~ 18.5 mag

Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers.

PubMed

De Martino, Federico; Gentile, Francesco; Esposito, Fabrizio; Balsi, Marco; Di Salle, Francesco; Goebel, Rainer; Formisano, Elia

2007-01-01

We present a general method for the classification of independent components (ICs) extracted from functional MRI (fMRI) data sets. The method consists of two steps. In the first step, each fMRI-IC is associated with an IC-fingerprint, i.e., a representation of the component in a multidimensional space of parameters. These parameters are post hoc estimates of global properties of the ICs and are largely independent of a specific experimental design and stimulus timing. In the second step a machine learning algorithm automatically separates the IC-fingerprints into six general classes after preliminary training performed on a small subset of expert-labeled components. We illustrate this approach in a multisubject fMRI study employing visual structure-from-motion stimuli encoding faces and control random shapes. We show that: (1) IC-fingerprints are a valuable tool for the inspection, characterization and selection of fMRI-ICs and (2) automatic classifications of fMRI-ICs in new subjects present a high correspondence with those obtained by expert visual inspection of the components. Importantly, our classification procedure highlights several neurophysiologically interesting processes. The most intriguing of which is reflected, with high intra- and inter-subject reproducibility, in one IC exhibiting a transiently task-related activation in the 'face' region of the primary sensorimotor cortex. This suggests that in addition to or as part of the mirror system, somatotopic regions of the sensorimotor cortex are involved in disambiguating the perception of a moving body part. Finally, we show that the same classification algorithm can be successfully applied, without re-training, to fMRI collected using acquisition parameters, stimulation modality and timing considerably different from those used for training.

Fast neural network surrogates for very high dimensional physics-based models in computational oceanography.

PubMed

van der Merwe, Rudolph; Leen, Todd K; Lu, Zhengdong; Frolov, Sergey; Baptista, Antonio M

2007-05-01

We present neural network surrogates that provide extremely fast and accurate emulation of a large-scale circulation model for the coupled Columbia River, its estuary and near ocean regions. The circulation model has O(10(7)) degrees of freedom, is highly nonlinear and is driven by ocean, atmospheric and river influences at its boundaries. The surrogates provide accurate emulation of the full circulation code and run over 1000 times faster. Such fast dynamic surrogates will enable significant advances in ensemble forecasts in oceanography and weather.

The long-term experiences of surrogates: relationships and contact with surrogacy families in genetic and gestational surrogacy arrangements.

PubMed

Imrie, Susan; Jadva, Vasanti

2014-10-01

This study examined the contact arrangements and relationships between surrogates and surrogacy families and whether these outcomes differed according to the type of surrogacy undertaken. Surrogates' motivations for carrying out multiple surrogacy arrangements were also examined, and surrogates' psychological health was assessed. Semi-structured interviews were administered to 34 women who had given birth to a child conceived through surrogacy approximately 7 years prior to interview. Some surrogates had carried out multiple surrogacy arrangements, and data were collected on the frequency, type of contact, and surrogate's feelings about the level of contact in each surrogacy arrangement, the surrogate's relationship with each child and parent, and her experience of, and motivation for, each surrogacy. Questionnaire measures of psychological health were administered. Surrogates had completed a total of 102 surrogacy arrangements and remained in contact with the majority of families, and reported positive relationships in most cases. Surrogates were happy with their level of contact in the majority of arrangements and most were viewed as positive experiences. Few differences were found according to surrogacy type. The primary motivation given for multiple surrogacy arrangements was to help couples have a sibling for an existing child. Most surrogates showed no psychological health problems at the time of data collection. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Galaxy IC 3639 with Obscured Active Galactic Nucleus

NASA Image and Video Library

2017-01-07

IC 3639, a galaxy with an active galactic nucleus, is seen in this image combining data from the Hubble Space Telescope and the European Southern Observatory. This galaxy contains an example of a supermassive black hole hidden by gas and dust. Researchers analyzed NuSTAR data from this object and compared them with previous observations from NASA's Chandra X-Ray Observatory and the Japanese-led Suzaku satellite. The findings from NuSTAR, which is more sensitive to higher energy X-rays than these observatories, confirm the nature of IC 3639 as an active galactic nucleus that is heavily obscured, and intrinsically much brighter than observed. http://photojournal.jpl.nasa.gov/catalog/PIA21087

A Conceptual Model of the Role of Communication in Surrogate Decision Making for Hospitalized Adults

PubMed Central

Torke, Alexia M.; Petronio, Sandra; Sachs, Greg A.; Helft, Paul R.; Purnell, Christianna

2011-01-01

Objective To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. Methods We propose a model and describe each construct in detail. We review what is known about interpersonal and patient-physician communication, describe literature about surrogate-clinician communication, and discuss implications for our developing model. Results The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Conclusion Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication–focused interventions. More research is needed to test the relationships proposed in the model. Practice Implications Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate. PMID:21889865

A conceptual model of the role of communication in surrogate decision making for hospitalized adults.

PubMed

Torke, Alexia M; Petronio, Sandra; Sachs, Greg A; Helft, Paul R; Purnell, Christianna

2012-04-01

To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. We proposed a model and described each construct in detail. We review what is known about interpersonal and patient-physician communication, described literature about surrogate-clinician communication, and discussed implications for our developing model. The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication-focused interventions. More research is needed to test the relationships proposed in the model. Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Observing Migration and Burial of Unexploded Ordnance in the Nearshore Environment with Instrumented Surrogates

NASA Astrophysics Data System (ADS)

Bruder, B. L.; Cristaudo, D.; Puleo, J. A.

2016-12-01

Prior to 1972, it was legal and common practice to unload unexploded ordnance (UXO) into the ocean. Only 60-100 miles off the US coast alone there are 72 dumping sites where it is estimated 31 million pounds of UXO lie. As recently as 2015, UXO have been found not only in the nearshore environment, but on populated beaches. Thus, understanding the migration and burial of these objects is not only of oceanographic interest, but a matter of public safety. The presented project evaluates the efficacy of instrumented UXO surrogates for observing munition migration and burial. Instrumented surrogates were exposed to near prototype scale wave conditions over a mobile bed at the Littoral Warfare Environment at Aberdeen Test Center, MD. Surrogates were deployed in the swash zone, inner and outer surf zones. Dependent on munition size, surrogates housed multiple suites of self-logging sensors. Sensor suites included different combinations of inertial motion units, ultra-wideband tracking tags, pressure transducers, shock recorders, and photocells. Preliminary results show sensor suites can resolve various types of surrogate movement. Pressure transducers accurately record ambient wave conditions as well as changes in mean depth due to surrogate migration. Inertial motion units resolve munition accelerations for rolling and translational motion. Inertial motion unit data is used to estimate trajectory as well when coupled with mean depth and bathymetric data. Photocells, which measure ambient light, resolve munition burial as well as serve as proxies for surrounding environmental conditions such as suspended sediment and water depth. The presented project will continue to utilize and couple surrogate sensor data to resolve munition movement and burial under different conditions. Knowledge of munition migration helps focus UXO detection and recovery, conserving US military and coastal resources.

LES on unstructured deforming meshes: Towards reciprocating IC engines

NASA Technical Reports Server (NTRS)

Haworth, D. C.; Jansen, K.

1996-01-01

A variable explicit/implicit characteristics-based advection scheme that is second-order accurate in space and time has been developed recently for unstructured deforming meshes (O'Rourke & Sahota 1996a). To explore the suitability of this methodology for Large-Eddy Simulation (LES), three subgrid-scale turbulence models have been implemented in the CHAD CFD code (O'Rourke & Sahota 1996b): a constant-coefficient Smagorinsky model, a dynamic Smagorinsky model for flows having one or more directions of statistical homogeneity, and a Lagrangian dynamic Smagorinsky model for flows having no spatial or temporal homogeneity (Meneveau et al. 1996). Computations have been made for three canonical flows, progressing towards the intended application of in-cylinder flow in a reciprocating engine. Grid sizes were selected to be comparable to the coarsest meshes used in earlier spectral LES studies. Quantitative results are reported for decaying homogeneous isotropic turbulence, and for a planar channel flow. Computations are compared to experimental measurements, to Direct-Numerical Simulation (DNS) data, and to Rapid-Distortion Theory (RDT) where appropriate. Generally satisfactory evolution of first and second moments is found on these coarse meshes; deviations are attributed to insufficient mesh resolution. Issues include mesh resolution and computational requirements for a specified level of accuracy, analytic characterization of the filtering implied by the numerical method, wall treatment, and inflow boundary conditions. To resolve these issues, finer-mesh simulations and computations of a simplified axisymmetric reciprocating piston-cylinder assembly are in progress.

Statistical Validation of Surrogate Endpoints: Another Look at the Prentice Criterion and Other Criteria.

PubMed

Saraf, Sanatan; Mathew, Thomas; Roy, Anindya

2015-01-01

For the statistical validation of surrogate endpoints, an alternative formulation is proposed for testing Prentice's fourth criterion, under a bivariate normal model. In such a setup, the criterion involves inference concerning an appropriate regression parameter, and the criterion holds if the regression parameter is zero. Testing such a null hypothesis has been criticized in the literature since it can only be used to reject a poor surrogate, and not to validate a good surrogate. In order to circumvent this, an equivalence hypothesis is formulated for the regression parameter, namely the hypothesis that the parameter is equivalent to zero. Such an equivalence hypothesis is formulated as an alternative hypothesis, so that the surrogate endpoint is statistically validated when the null hypothesis is rejected. Confidence intervals for the regression parameter and tests for the equivalence hypothesis are proposed using bootstrap methods and small sample asymptotics, and their performances are numerically evaluated and recommendations are made. The choice of the equivalence margin is a regulatory issue that needs to be addressed. The proposed equivalence testing formulation is also adopted for other parameters that have been proposed in the literature on surrogate endpoint validation, namely, the relative effect and proportion explained.

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

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.

Biomarkers and surrogate endpoints in clinical trials.

PubMed

Fleming, Thomas R; Powers, John H

2012-11-10

One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function, and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures, and radiological tests, often are considered as replacement endpoints or 'surrogates' for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. Copyright © 2012 John Wiley & Sons, Ltd.

[Selection of "surrogate" and "endpoints" evaluation of the efficacy of medical interventions].

PubMed

Lazebnik, L B; Gusein-Zade, M G; Efremov, L I

2011-01-01

With the advent of new medical technologies and medicines, as well as due to changes in disease patterns and demographic problems rises the need for continued increases in health spending. Increased costs can be totally inadequate, if it has been done without studying the effectiveness of medical interventions, based on the results of evidence-based medicine and economic of their feasibility. To evaluate the clinical effectiveness of medical interventions have been recently used specific criteria, so called points of clinical efficacy (surrogate and endpoints), that allow to conclude feasibility or harmfulness of the introduction or application of the intervention in clinical practice. The endpoint is reliable indicator the effectiveness of medical intervention. Surrogate point--is a biomarker that is intended to replace the endpoint and is a predictor of the effectiveness of medical intervention. The use of surrogate points has several advantages such as simple in identification and measurement, as well as more higher in compare with endpoints the vents frequency, that can significantly reduce the size of the selection and duration and cost of clinical trials, respectively. Finally, the surrogate points allow to evaluate treatment effect in situations where the use of endpoints is difficult or is unethical.

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

Surrogate assisted multidisciplinary design optimization for an all-electric GEO satellite

NASA Astrophysics Data System (ADS)

Shi, Renhe; Liu, Li; Long, Teng; Liu, Jian; Yuan, Bin

2017-09-01

State-of-the-art all-electric geostationary earth orbit (GEO) satellites use electric thrusters to execute all propulsive duties, which significantly differ from the traditional all-chemical ones in orbit-raising, station-keeping, radiation damage protection, and power budget, etc. Design optimization task of an all-electric GEO satellite is therefore a complex multidisciplinary design optimization (MDO) problem involving unique design considerations. However, solving the all-electric GEO satellite MDO problem faces big challenges in disciplinary modeling techniques and efficient optimization strategy. To address these challenges, we presents a surrogate assisted MDO framework consisting of several modules, i.e., MDO problem definition, multidisciplinary modeling, multidisciplinary analysis (MDA), and surrogate assisted optimizer. Based on the proposed framework, the all-electric GEO satellite MDO problem is formulated to minimize the total mass of the satellite system under a number of practical constraints. Then considerable efforts are spent on multidisciplinary modeling involving geosynchronous transfer, GEO station-keeping, power, thermal control, attitude control, and structure disciplines. Since orbit dynamics models and finite element structural model are computationally expensive, an adaptive response surface surrogate based optimizer is incorporated in the proposed framework to solve the satellite MDO problem with moderate computational cost, where a response surface surrogate is gradually refined to represent the computationally expensive MDA process. After optimization, the total mass of the studied GEO satellite is decreased by 185.3 kg (i.e., 7.3% of the total mass). Finally, the optimal design is further discussed to demonstrate the effectiveness of our proposed framework to cope with the all-electric GEO satellite system design optimization problems. This proposed surrogate assisted MDO framework can also provide valuable references for other all

Surrogate Based Uni/Multi-Objective Optimization and Distribution Estimation Methods

NASA Astrophysics Data System (ADS)

Gong, W.; Duan, Q.; Huo, X.

2017-12-01

Parameter calibration has been demonstrated as an effective way to improve the performance of dynamic models, such as hydrological models, land surface models, weather and climate models etc. Traditional optimization algorithms usually cost a huge number of model evaluations, making dynamic model calibration very difficult, or even computationally prohibitive. With the help of a serious of recently developed adaptive surrogate-modelling based optimization methods: uni-objective optimization method ASMO, multi-objective optimization method MO-ASMO, and probability distribution estimation method ASMO-PODE, the number of model evaluations can be significantly reduced to several hundreds, making it possible to calibrate very expensive dynamic models, such as regional high resolution land surface models, weather forecast models such as WRF, and intermediate complexity earth system models such as LOVECLIM. This presentation provides a brief introduction to the common framework of adaptive surrogate-based optimization algorithms of ASMO, MO-ASMO and ASMO-PODE, a case study of Common Land Model (CoLM) calibration in Heihe river basin in Northwest China, and an outlook of the potential applications of the surrogate-based optimization methods.

Productivity improvement through industrial engineering in the semiconductor industry

NASA Astrophysics Data System (ADS)

Meyersdorf, Doron

1996-09-01

Industrial Engineering is fairly new to the semiconductor industry, though the awareness to its importance has increased in recent years. The US semiconductor industry in particular has come to the realization that in order to remain competitive in the global market it must take the lead not only in product development but also in manufacturing. Industrial engineering techniques offer one ofthe most effective strategies for achieving manufacturing excellence. Industrial engineers play an important role in the success of the manufacturing facility. This paper defines the Industrial engineers role in the IC facility, set the visions of excellence in semiconductor manufacturing and highlights 10 roadblocks on the journey towards manufacturing excellence.

A new proportion measure of the treatment effect captured by candidate surrogate endpoints.

PubMed

Kobayashi, Fumiaki; Kuroki, Manabu

2014-08-30

The use of surrogate endpoints is expected to play an important role in the development of new drugs, as they can be used to reduce the sample size and/or duration of randomized clinical trials. Biostatistical researchers and practitioners have proposed various surrogacy measures; however, (i) most of these surrogacy measures often fall outside the range [0,1] without any assumptions, (ii) these surrogacy measures do not provide a cut-off value for judging a surrogacy level of candidate surrogate endpoints, and (iii) most surrogacy measures are highly variable; thus, the confidence intervals are often unacceptably wide. In order to solve problems (i) and (ii), we propose a new surrogacy measure, a proportion of the treatment effect captured by candidate surrogate endpoints (PCS), on the basis of the decomposition of the treatment effect into parts captured and non-captured by the candidate surrogate endpoints. In order to solve problem (iii), we propose an estimation method based on the half-range mode method with the bootstrap distribution of the estimated surrogacy measures. Finally, through numerical experiments and two empirical examples, we show that the PCS with the proposed estimation method overcomes these difficulties. The results of this paper contribute to the reliable evaluation of how much of the treatment effect is captured by candidate surrogate endpoints. Copyright © 2014 John Wiley & Sons, Ltd.

EVALUATING HABITAT AS A SURROGATE FOR POPULATION VIABILITY USING A SPATIALLY EXPLICIT POPULATION MODEL

EPA Science Inventory

Because data for conservation planning are always limited, surrogates are often substituted for intractable measurements such as species richness or population viability. We examined the ability of habitat quality to act as a surrogate for population performance for both Red-sho...

Purification, crystallization and preliminary X-ray analysis of aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum

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

Byrnes, Laura J.; Badarau, Adriana; Vakulenko, Sergei B.

2008-02-01

APH(2′′)-Ic is an enzyme that is responsible for high-level gentamicin resistance in E. gallinarum isolates. Crystals of the wild-type enzyme and three mutants have been prepared and a complete X-ray diffraction data set was collected to 2.15 Å resolution from an F108L crystal. Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and threemore » mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2′′)-Ic variants were crystallized in the presence of 14–20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris–HCl pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 Å, β = 108.8°. X-ray diffraction data were collected to approximately 2.15 Å resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

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.

Surrogate Safety Assessment Model (SSAM)--software user manual

DOT National Transportation Integrated Search

2008-05-01

This document presents guidelines for the installation and use of the Surrogate Safety Assessment Model (SSAM) software. For more information regarding the SSAM application, including discussion of theoretical background and the results of a series o...

The Effect of Framing on Surrogate Optimism Bias: A Simulation Study

PubMed Central

Patel, Dev; Cohen, Elan D.; Barnato, Amber E.

2016-01-01

Purpose To explore the effect of emotion priming and physician communication behaviors on optimism bias. Materials and Methods We conducted a 5 × 2 between-subject randomized factorial experiment using a web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age ≥ 35 and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with CPR > their recollection of the physician's estimate. Results 256/373 respondents (69%) logged-in and were randomized and 220 (86%) had non-missing data for prognosis. 67/220 (30%) overall, and 56/173 (32%) of those with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (p<.001). Emotion priming (p=.397), physician attention to emotion (p=.537), and framing of CPR as the social norm (p=.884) did not affect optimism bias. Framing the decision as the patient's vs. the surrogate's (25% vs. 36%, p=.066) and describing the alternative to CPR as “allow natural death” instead of “do not resuscitate” (25% vs. 37%, p =.035) decreased optimism bias. Conclusions Framing of CPR choice during code status conversations may influence surrogates’ optimism bias. PMID:26796950

A rapid situation assessment of the market for surrogate and illegal alcohols in Tallinn, Estonia.

PubMed

Pärna, Kersti; Lang, Katrin; Raju, Kadi; Väli, Marika; McKee, Martin

2007-01-01

To understand the phenomenon of consumption of surrogate and illegal alcohols in Tallinn, capital of Estonia. This study, conducted in Tallinn in May 2006, used rapid situation assessment. Interviews with key informants in relevant settings such as emergency departments of hospitals, accommodation for the homeless, police etc. (n = 22), with alcohol abusers (n = 33), natural observations of surrogate sale and consumption venues (n = 46), and tracking of trade data were carried out. Key informants confirmed that consumption of illegal and surrogate alcohols are widely used by alcohol abusers, a finding confirmed by the alcohol abusers. Availability of surrogates varied by area of the city, mainly sold from street kiosks. Illegally produced spirits were also easily available. Sales of surrogates appear to have increased in recent years. A range of alcohol-containing substances that appear to be easily available at low cost, and that have high concentration of ethanol or contaminants known to be toxic, were identified in Tallinn. Alcohol policies in Estonia should address the consumption and availability of these substances.

Surrogacy families 10 years on: relationship with the surrogate, decisions over disclosure and children's understanding of their surrogacy origins

PubMed Central

Jadva, V.; Blake, L.; Casey, P.; Golombok, S.

2012-01-01

BACKGROUND This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. METHODS Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. RESULTS Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P < 0.001) (i.e. where they had met through a third party and the surrogate mother's egg was used to conceive the child). Most families reported harmonious relationships with their surrogate mother. At age 10 years, 19 (90%) children who had been informed of the nature of their conception had a good understanding of this and 13 of the 14 children who were in contact with their surrogate reported that they liked her. CONCLUSIONS Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn. PMID:22814484

Surrogacy families 10 years on: relationship with the surrogate, decisions over disclosure and children's understanding of their surrogacy origins.

PubMed

Jadva, V; Blake, L; Casey, P; Golombok, S

2012-10-01

This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P < 0.001) (i.e. where they had met through a third party and the surrogate mother's egg was used to conceive the child). Most families reported harmonious relationships with their surrogate mother. At age 10 years, 19 (90%) children who had been informed of the nature of their conception had a good understanding of this and 13 of the 14 children who were in contact with their surrogate reported that they liked her. Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn.

Module comprising IC memory stack dedicated to and structurally combined with an IC microprocessor chip

NASA Technical Reports Server (NTRS)

Carson, John C. (Inventor); Indin, Ronald J. (Inventor); Shanken, Stuart N. (Inventor)

1994-01-01

A computer module is disclosed in which a stack of glued together IC memory chips is structurally integrated with a microprocessor chip. The memory provided by the stack is dedicated to the microprocessor chip. The microprocessor and its memory stack may be connected either by glue and/or by solder bumps. The solder bumps can perform three functions--electrical interconnection, mechanical connection, and heat transfer. The electrical connections in some versions are provided by wire bonding.

Simultaneous tumor and surrogate motion tracking with dynamic MRI for radiation therapy planning

NASA Astrophysics Data System (ADS)

Park, Seyoun; Farah, Rana; Shea, Steven M.; Tryggestad, Erik; Hales, Russell; Lee, Junghoon

2018-01-01

Respiration-induced tumor motion is a major obstacle for achieving high-precision radiotherapy of cancers in the thoracic and abdominal regions. Surrogate-based estimation and tracking methods are commonly used in radiotherapy, but with limited understanding of quantified correlation to tumor motion. In this study, we propose a method to simultaneously track the lung tumor and external surrogates to evaluate their spatial correlation in a quantitative way using dynamic MRI, which allows real-time acquisition without ionizing radiation exposure. To capture the lung and whole tumor, four MRI-compatible fiducials are placed on the patient’s chest and upper abdomen. Two different types of acquisitions are performed in the sagittal orientation including multi-slice 2D cine MRIs to reconstruct 4D-MRI and two-slice 2D cine MRIs to simultaneously track the tumor and fiducials. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and groupwise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in the 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model of the fiducials to their segmentations on the 2D cine MRIs. We tested our method on ten lung cancer patients. Using a correlation analysis, the 3D tumor trajectory demonstrates a noticeable phase mismatch and significant cycle-to-cycle motion variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from the fiducials at different locations.

Meta-analyses evaluating surrogate endpoints for overall survival in cancer randomized trials: A critical review.

PubMed

Savina, Marion; Gourgou, Sophie; Italiano, Antoine; Dinart, Derek; Rondeau, Virginie; Penel, Nicolas; Mathoulin-Pelissier, Simone; Bellera, Carine

2018-03-01

In cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. Our aim was to identify meta-analyses that evaluated surrogate endpoints for OS and assess the strength of evidence for each meta-analysis (MA). We performed a systematic review to identify MA of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the German Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema. Fifty-three publications reported on 164 MA, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival (PFS) showed good surrogacy properties for OS in colorectal, lung and head and neck cancers. DFS was highly correlated to OS in gastric cancer. The statistical methodology used to evaluate surrogate endpoints requires consistency in order to facilitate the accurate interpretation of the results. Despite the limited number of clinical settings with validated surrogate endpoints for OS, there is evidence of good surrogacy for DFS and PFS in tumor types that account for a large proportion of cancer cases. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Tuberculosis vaccine candidate: Characterization of H4-IC31 formulation and H4 antigen conformation.

PubMed

Deshmukh, Sasmit S; Magcalas, Federico Webster; Kalbfleisch, Kristen N; Carpick, Bruce W; Kirkitadze, Marina D

2018-08-05

Tuberculosis (TB) is one of the leading causes of death worldwide, making the development of effective TB vaccines a global priority. A TB vaccine consisting of a recombinant fusion protein, H4, combined with a novel synthetic cationic adjuvant, IC31 ® , is currently being developed. The H4 fusion protein consists of two immunogenic mycobacterial antigens, Ag85 B and TB10.4, and the IC31 ® adjuvant is a mixture of KLK, a leucine-rich peptide (KLKL5KLK), and the oligodeoxynucleotide ODN1a, a TLR9 ligand. However, efficient and robust methods for assessing these formulated components are lacking. Here, we developed and optimized phase analysis light scattering (PALS), electrical sensing zone (ESZ), and Raman, FTIR, and CD spectroscopy methods to characterize the H4-IC31 vaccine formulation. PALS-measured conductivity and zeta potential values could differentiate between the similarly sized particles of IC31 ® adjuvant and the H4-IC31 vaccine candidate and could thereby serve as a control during vaccine formulation. In addition, zeta potential is indicative of the adjuvant to antigen ratio which is the key in the immunomodulatory response of the vaccine. ESZ was used as an orthogonal method to measure IC31 ® and H4-IC31 particle sizes. Raman, FTIR, and CD spectroscopy revealed structural changes in H4 protein and IC31 ® adjuvant, inducing an increase in both the β-sheet and random coil content as a result of adsorption. Furthermore, nanoDSF showed changes in the tertiary structure of H4 protein as a result of adjuvantation to IC31 ® . Our findings demonstrate the applicability of biophysical methods to characterize vaccine components in the final H4-IC31 drug product without the requirement for desorption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Multi-Wavelength Views of Protostars in IC 1396

NASA Image and Video Library

2003-12-18

This archival image from 2003 captured by NASA Spitzer Space Telescope captured the Elephant Trunk Nebula, an elongated dark globule within the emission nebula IC 1396 in the constellation of Cepheus.

Surrogacy assessment using principal stratification when surrogate and outcome measures are multivariate normal.

PubMed

Conlon, Anna S C; Taylor, Jeremy M G; Elliott, Michael R

2014-04-01

In clinical trials, a surrogate outcome variable (S) can be measured before the outcome of interest (T) and may provide early information regarding the treatment (Z) effect on T. Using the principal surrogacy framework introduced by Frangakis and Rubin (2002. Principal stratification in causal inference. Biometrics 58, 21-29), we consider an approach that has a causal interpretation and develop a Bayesian estimation strategy for surrogate validation when the joint distribution of potential surrogate and outcome measures is multivariate normal. From the joint conditional distribution of the potential outcomes of T, given the potential outcomes of S, we propose surrogacy validation measures from this model. As the model is not fully identifiable from the data, we propose some reasonable prior distributions and assumptions that can be placed on weakly identified parameters to aid in estimation. We explore the relationship between our surrogacy measures and the surrogacy measures proposed by Prentice (1989. Surrogate endpoints in clinical trials: definition and operational criteria. Statistics in Medicine 8, 431-440). The method is applied to data from a macular degeneration study and an ovarian cancer study.

Comparative study of surrogate models for groundwater contamination source identification at DNAPL-contaminated sites

NASA Astrophysics Data System (ADS)

Hou, Zeyu; Lu, Wenxi

2018-05-01

Knowledge of groundwater contamination sources is critical for effectively protecting groundwater resources, estimating risks, mitigating disaster, and designing remediation strategies. Many methods for groundwater contamination source identification (GCSI) have been developed in recent years, including the simulation-optimization technique. This study proposes utilizing a support vector regression (SVR) model and a kernel extreme learning machine (KELM) model to enrich the content of the surrogate model. The surrogate model was itself key in replacing the simulation model, reducing the huge computational burden of iterations in the simulation-optimization technique to solve GCSI problems, especially in GCSI problems of aquifers contaminated by dense nonaqueous phase liquids (DNAPLs). A comparative study between the Kriging, SVR, and KELM models is reported. Additionally, there is analysis of the influence of parameter optimization and the structure of the training sample dataset on the approximation accuracy of the surrogate model. It was found that the KELM model was the most accurate surrogate model, and its performance was significantly improved after parameter optimization. The approximation accuracy of the surrogate model to the simulation model did not always improve with increasing numbers of training samples. Using the appropriate number of training samples was critical for improving the performance of the surrogate model and avoiding unnecessary computational workload. It was concluded that the KELM model developed in this work could reasonably predict system responses in given operation conditions. Replacing the simulation model with a KELM model considerably reduced the computational burden of the simulation-optimization process and also maintained high computation accuracy.

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

PubMed

Richards, Gary P

2012-03-01

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

Validating the Implementation Climate Scale (ICS) in Child Welfare Organizations

PubMed Central

Ehrhart, Mark G.; Torres, Elisa M.; Wright, Lisa A.; Martinez, Sandra Y.; Aarons, Gregory A.

2015-01-01

There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization’s climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. PMID:26563643

Validating the Implementation Climate Scale (ICS) in child welfare organizations.

PubMed

Ehrhart, Mark G; Torres, Elisa M; Wright, Lisa A; Martinez, Sandra Y; Aarons, Gregory A

2016-03-01

There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

PubMed Central

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

2008-01-01

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 showed less of a stress response, spending less time near their surrogates in the first five minutes of the test session than RS infants (p=.05) and exhibiting a significantly lower rise in salivary cortisol after the test than RS infants (p=.018). 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. PMID:19810188

The ethics of commercial surrogate mothering: a response to Casey Humbyrd.

PubMed

Omonzejele, Peter F

2011-01-01

This article critically examines the argument advanced by Casey Humbyrd in support of international commercial surrogate mothering. It finds her arguments unconvincing especially at the point of implementation. This is because the author was unable to demonstrate how regulation and her notion offair compensation would not lead to undue inducement and exploitation in resource-poor settings where urgent needs often exist. In fact, the argument advanced in this article is that commercial surrogate mothering cannot but be exploitative in so far as urgent and compelling needs exist. To logically drive home this point, the elements of exploitation were discussed in order to show that regulation and fair compensation cannot prevent exploitative transaction in commercial surrogate mothering arrangements. This may happen in the same way as regulation and compensation framework have not been successful in preventing the allegations of exploitation in the research context especially where studies are conducted in resource-poor countries.

[Ants’ higher taxa as surrogates of species richness in a chronosequence of fallows, old-grown forests and agroforestry systems in the Eastern Amazon, Brazil].

PubMed

Muñoz Gutiérrez, Jhonatan Andrés; Roussea, Guillaume Xavier; Andrade-Silva, Joudellys; Delabie, Jacques Hubert Charles

2017-03-01

Deforestation in Amazon forests is one of the main causes for biodiversity loss worldwide. Ants are key into the ecosystem because act like engineers; hence, the loss of ants’ biodiversity may be a guide to measure the loss of essential functions into the ecosystems. The aim of this study was to evaluate soil ant’s richness and to estimate whether higher taxa levels (Subfamily and Genus) can be used as surrogates of species richness in different vegetation types (fallows, old-growth forests and agroforestry systems) in Eastern Amazon. The samples were taken in 65 areas in the Maranhão and Pará States in the period 2011-2014. The sampling scheme followed the procedure of Tropical Soil Biology and Fertility (TSBF). Initially, the vegetation types were characterized according to their age and estimated species richness. Linear and exponential functions were applied to evaluate if higher taxa can be used as surrogates and correlated with the Pearson coefficient. In total, 180 species distributed in 60 genera were identified. The results showed that ant species richness was higher in intermediate fallows (88) and old secondary forest (76), and was lower in agroforestry systems (38) and mature riparian forest (35). The genus level was the best surrogate to estimate the ant’s species richness across the different vegetation types, and explained 72-97 % (P < 0.001) of the total species variability. The results confirmed that the genus level is an excellent surrogate to estimate the ant’s species richness in the region and that both fallows and agroforestry systems may contribute in the conservation of Eastern Amazon ant community.

Someone to Lean on: Assessment and Implications of Social Surrogate Use in Childhood

ERIC Educational Resources Information Center

Arbeau, Kimberley A.; Coplan, Robert J.; Matheson, Adrienne

2012-01-01

A social surrogate is a person who helps a shy individual deal with the stresses of a social situation. Previous research has only investigated social surrogate use in adults. The purpose of the current study was to develop and evaluate a new self-report measure of social surrogacy in middle childhood and to explore the implications of this…

Gay father surrogacy families: relationships with surrogates and egg donors and parental disclosure of children's origins.

PubMed

Blake, Lucy; Carone, Nicola; Slutsky, Jenna; Raffanello, Elizabeth; Ehrhardt, Anke A; Golombok, Susan

2016-11-01

To study the nature and quality of relationships between gay father families and their surrogates and egg donors and parental disclosure of children's origins. Cross-sectional study. Family homes. Parents in 40 gay father families with 3-9-year-old children born through surrogacy. Administration of a semistructured interview. Relationships between parents, children, surrogates, and egg donors and parental disclosure of children's origins were examined using a semistructured interview. The majority of fathers were content with the level of contact they had with the surrogate, with those who were discontent wanting more contact. Fathers were more likely to maintain relationships with surrogates than egg donors, and almost all families had started the process of talking to their children about their origins, with the level of detail and children's understanding increasing with the age of the child. In gay father surrogacy families with young children, relationships between parents, children, surrogates, and egg donors are generally positive. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

PubMed Central

Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

2009-01-01

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

SN2005da: A Spectroscopic and Photometric Analysis of a Peculiar Type Ic Supernova

NASA Astrophysics Data System (ADS)

Williamson, Jacob

2017-12-01

Core collapse supernovae are an important class of objects in stellar evolution research as they are the final life stage of high mass stars. Supernovae in general are classified into several spectral types; this paper explores SN 2005da, classified as a Type Ic, meaning it lacks hydrogen and helium lines. The supernova was originally classified as a broad-lined Type Ic (Type Ic-BL), with expansion velocities near maximum light greater than or approximately equal to 15000 km/s. However, some of the elements present in the spectrum, namely carbon and oxygen, have narrower lines (FWHM approximately equal to 2300 km/s) than other elements, indicating an interaction with a previously ejected envelope. The supernova is also found to have a decay time, with a change in magnitude over 15 days following maximum light of about 1.4 magnitudes, that is significantly faster than typical Type Ic or Ic-BL. This is more akin to a rarer object type known as a Type Ibn, although it lacks the characteristic narrow helium lines of this type. Therefore, SN 2005da appears to be unlike known examples of Type Ic supernovae.

A Solder Based Self Assembly Project in an Introductory IC Fabrication Course

ERIC Educational Resources Information Center

Rao, Madhav; Lusth, John C.; Burkett, Susan L.

2015-01-01

Integrated circuit (IC) fabrication principles is an elective course in a senior undergraduate and early graduate student's curriculum. Over the years, the semiconductor industry relies heavily on students with developed expertise in the area of fabrication techniques, learned in an IC fabrication theory and laboratory course. The theory course…

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-09-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

Pulsed laser ablation of IC packages for device failure analyses

NASA Astrophysics Data System (ADS)

Hong, Ming Hui; Mai, ZhiHong; Chen, G. X.; Thiam, Thomas; Song, Wen D.; Lu, Yongfeng; Soh, Chye E.; Chong, Tow Chong

2002-06-01

Pulsed laser ablation of mold compounds for IC packaging in air and with steam assistance is investigated. It is applied to decap IC packages and expose computer CPU dies for the device failure analyses. Compared with chemical decapping, the laser ablation has advantages of being fast speed, non- contact and dry processing. Laser ablation with the steam assistance results in higher ablation rate and wider ablated crater with much smoother surface morphology. It implies that the steam assisted laser ablation can achieve a faster and better quality laser processing. Audible acoustic wave and plasma optical signal diagnostics are also carried out to have a better understanding of the mechanisms behind. Light wavelength and laser fluence applied in the decapping are two important parameters. The 532 nm Nd:YAG laser decapping at a low laser fluence can achieve a large decapping area with a fine ablation profile. IC packages decapped by the laser ablation show good quality for the device failure analyses.

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

USDA-ARS?s Scientific Manuscript database

The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles have led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicate...

Black-footed ferrets and Siberian polecats as ecological surrogates and ecological equivalents

USGS Publications Warehouse

Biggins, D.E.; Hanebury, L.R.; Miller, B.J.; Powell, R.A.

2011-01-01

Ecologically equivalent species serve similar functions in different communities, and an ecological surrogate species can be used as a substitute for an equivalent species in a community. Siberian polecats (Mustela eversmanii) and black-footed ferrets (M. nigripes) have long been considered ecological equivalents. Polecats also have been used as investigational surrogates for black-footed ferrets, yet the similarities and differences between the 2 species are poorly understood. We contrasted activity patterns of radiotagged polecats and ferrets released onto ferret habitat. Ferrets tended to be nocturnal and most active after midnight. Polecats were not highly selective for any period of the day or night. Ferrets and polecats moved most during brightly moonlit nights. The diel activity pattern of ferrets was consistent with avoidance of coyotes (Canis latrans) and diurnal birds of prey. Similarly, polecat activity was consistent with avoidance of red foxes (Vulpes vulpes) in their natural range. Intraguild predation (including interference competition) is inferred as a selective force influencing behaviors of these mustelines. Examination of our data suggests that black-footed ferrets and Siberian polecats might be ecological equivalents but are not perfect surrogates. Nonetheless, polecats as surrogates for black-footed ferrets have provided critical insight needed, especially related to predation, to improve the success of ferret reintroductions. ?? 2011 American Society of Mammalogists.

Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

PubMed

Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua

2015-01-01

Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05). And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05). Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05). In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture, not

Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning

PubMed Central

Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua

2015-01-01

Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101–150, 151–200 or 201–250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05). And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05). Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05). In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture

A Taylor Expansion-Based Adaptive Design Strategy for Global Surrogate Modeling With Applications in Groundwater Modeling

NASA Astrophysics Data System (ADS)

Mo, Shaoxing; Lu, Dan; Shi, Xiaoqing; Zhang, Guannan; Ye, Ming; Wu, Jianfeng; Wu, Jichun

2017-12-01

Global sensitivity analysis (GSA) and uncertainty quantification (UQ) for groundwater modeling are challenging because of the model complexity and significant computational requirements. To reduce the massive computational cost, a cheap-to-evaluate surrogate model is usually constructed to approximate and replace the expensive groundwater models in the GSA and UQ. Constructing an accurate surrogate requires actual model simulations on a number of parameter samples. Thus, a robust experimental design strategy is desired to locate informative samples so as to reduce the computational cost in surrogate construction and consequently to improve the efficiency in the GSA and UQ. In this study, we develop a Taylor expansion-based adaptive design (TEAD) that aims to build an accurate global surrogate model with a small training sample size. TEAD defines a novel hybrid score function to search informative samples, and a robust stopping criterion to terminate the sample search that guarantees the resulted approximation errors satisfy the desired accuracy. The good performance of TEAD in building global surrogate models is demonstrated in seven analytical functions with different dimensionality and complexity in comparison to two widely used experimental design methods. The application of the TEAD-based surrogate method in two groundwater models shows that the TEAD design can effectively improve the computational efficiency of GSA and UQ for groundwater modeling.

Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis.

PubMed

Ni, Songshi; Fu, Zhenxue; Zhao, Jing; Liu, Hua

2014-07-01

Studies have indicated that therapy with inhaled corticosteroids (ICS) can be associated with a higher risk of pneumonia. However, it is not known whether ICS increases the risk of mycobacterium. Most of these published studies were small, and the conclusions were inconsistent. A meta-analysis was conducted into whether ICS increases the risk of mycobacterium in patients with chronic respiratory diseases. PubMed, OVID, EMBASE and Cochrane Library databases were searched. Five studies involving 4,851 cases and 28,477 controls were considered in the meta-analysis. From the pooled analyses, there was significant association between ICS and risk of mycobacterium in all patients with chronic respiratory diseases [risk ratio (RR) =1.81; 95% confidence interval (CI), 1.23-2.68; P=0.003]. Among patients with chronic respiratory diseases, the relationship between ICS and risk of tuberculosis (TB) was also significant (RR =1.34; 95% CI, 1.15-1.55; P=0.0001). And meta-analysis of four studies in patients with chronic obstructive pulmonary disease (COPD) (RR =1.42; 95% CI, 1.18-1.72; P=0.0003) or two studies in patients who have prior pulmonary TB (RR =1.61; 95% CI, 1.35-1.92; P<0.00001) or three studies in patients with high-dose ICS (RR =1.60; 95% CI, 1.28-1.99; P<0.0001) showed a relationship between ICS and risk of mycobacterium. Significant relationship has been shown between ICS use and risk of mycobacterium in all patients with chronic respiratory diseases. ICS use also increases the risk of TB among the patients with chronic respiratory diseases. Use of ICS increases the risk of mycobacterium in patients with COPD or patients with prior pulmonary TB or patients inhaling high-dose corticosteroids. Further research is required to establish the potential adverse effect of ICS as a therapy for chronic respiratory diseases.

The German Intelligibility in Context Scale (ICS-G): Reliability and Validity Evidence

ERIC Educational Resources Information Center