Initialisation of Nonlinearities for PNL and Wiener systems Inversion

This paper proposes a very fast method for blindly initial- izing a nonlinear mapping which transforms a sum of random variables. The method provides a surprisingly good approximation even when the basic assumption is not fully satis¯ed. The method can been used success- fully for initializing nonlinearity in post-nonlinear mixtures or in Wiener system inversion, for improving algorithm speed and convergence.

Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.

OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850 mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered as a continuous 3-day infusion in patients with confirmed or suspected Gram-negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins bind and neutralize endotoxin, and experimental animal studies demonstrate protection from septic death when lipoproteins are administered. Endotoxin neutralization correlates with the amount of phospholipid in the lipoprotein particles. DESIGN: A three-arm, randomized, blinded, placebo-controlled trial. SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006. PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients. MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo. CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.

Development of a Conductometric Test for Frost Resistance of Concrete, HR-272, Phase II, 1986

The purpose of this report is to describe the major research activities during the period of February 1, 1985 - October 30, 1986 for the Iowa Highway Research Board under the research contract entitled "Development of a Conductometric Test for Frost Resistance of Concrete." The objective of this research, as stated in the project proposal, is to develop a test method which can be reasonably rapidly performed in the laboratory and in the field to predict the behavior of concrete subjected to the action of alternate freezing and thawing with a high degree of certainty. In the work plan of the proposal it was stated that the early part of the first year would be devoted to construction of testing equipment and preparation of specimens and the remainder of the year would be devoted to the testing of specimens. It was also stated that the second and third years would be devoted to performance and refinements of tests, data analysis, preparation of suggested specifications, and performance of tests covering variables which need to be studied such as types of aggregates, fly ash replacements and other admixtures. The objective of this report is to describe the progress made during the first 20 months of this project and assess the significance of the results obtained thus far and the expected significance of the results obtainable during the third year of the project.

High-throughput and sensitive quantitation of plasma catecholamines by ultraperformance liquid chromatography-tandem mass spectrometry using a solid phase microwell extraction plate.

Plasma catecholamines provide a reliable biomarker of sympathetic activity. The low circulating concentrations of catecholamines and analytical interferences require tedious sample preparation and long chromatographic runs to ensure their accurate quantification by HPLC with electrochemical detection. Published or commercially available methods relying on solid phase extraction technology lack sensitivity or require derivatization of catecholamine by hazardous reagents prior to tandem mass spectrometry (MS) analysis. Here, we manufactured a novel 96-well microplate device specifically designed to extract plasma catecholamines prior to their quantification by a new and highly sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Processing time, which included sample purification on activated aluminum oxide and elution, is less than 1 h per 96-well microplate. The UPLC-MS/MS analysis run time is 2.0 min per sample. This UPLC-MS/MS method does not require a derivatization step, reduces the turnaround time by 10-fold compared to conventional methods used for routine application, and allows catecholamine quantification in reduced plasma sample volumes (50-250 μL, e.g., from children and mice).

Development of In Situ Detection Methods for Materials-Related Distress (MRD) in Concrete Pavements: Phase 2, HR-1081, 2005

This project utilized information from ground penetrating radar (GPR) and visual inspection via the pavement profile scanner (PPS) in proof-of-concept trials. GPR tests were carried out on a variety of portland cement concrete pavements and laboratory concrete specimens. Results indicated that the higher frequency GPR antennas were capable of detecting subsurface distress in two of the three pavement sites investigated. However, the GPR systems failed to detect distress in one pavement site that exhibited extensive cracking. Laboratory experiments indicated that moisture conditions in the cracked pavement probably explain the failure. Accurate surveys need to account for moisture in the pavement slab. Importantly, however, once the pavement site exhibits severe surface cracking, there is little need for GPR, which is primarily used to detect distress that is not observed visually. Two visual inspections were also conducted for this study by personnel from Mandli Communications, Inc., and the Iowa Department of Transportation (DOT). The surveys were conducted using an Iowa DOT video log van that Mandli had fitted with additional equipment. The first survey was an extended demonstration of the PPS system. The second survey utilized the PPS with a downward imaging system that provided high-resolution pavement images. Experimental difficulties occurred during both studies; however, enough information was extracted to consider both surveys successful in identifying pavement surface distress. The results obtained from both GPR testing and visual inspections were helpful in identifying sites that exhibited materials-related distress, and both were considered to have passed the proof-of-concept trials. However, neither method can currently diagnose materials-related distress. Both techniques only detected the symptoms of materials-related distress; the actual diagnosis still relied on coring and subsequent petrographic examination. Both technologies are currently in rapid development, and the limitations may be overcome as the technologies advance and mature.

Portland Cement Concrete Curing Compound Performance Phase I and Phase II, MLR-02-03, 2003

Testing the efficiency of Portland Cement Concrete (PCC) curing compounds is currently done following Test Method Iowa 901-D, May 2002. Concrete test specimens are prepared from mortar materials and are wet cured 5 hours before the curing compound is applied. All brands of curing compound submitted to the Iowa Department of Transportation are laboratory tested for comparative performance under the same test conditions. These conditions are different than field PCC paving conditions. Phase I tests followed Test Method Iowa 901-D, but modified the application amounts of the curing compound. Test results showed that the application of two coats of one-half thickness each increased efficiency compared to one full thickness coat. Phase II tests also used the modified application amounts, used a concrete mix (instead of a mortar mix) and applied curing compound a few minutes after molding. Measurements of losses, during spraying of the curing compound, were noted and were found to be significant. Test results showed that application amounts, testing techniques, concrete specimen mix design and spray losses do influence the curing compound efficiency. The significance of the spray losses indicates that the conventional test method being used (Iowa 901 D) should be revised.

Stabilization Procedures to Mitigate Edge Rutting for Granular Shoulders - Phase II, TR-591, 2011

A multifaceted investigation was undertaken to develop recommendations for methods to stabilize granular road shoulders with the goal of mitigating edge ruts. Included was reconnaissance of problematic shoulder locations, a laboratory study to develop a method to test for changes in granular material stability when stabilizing agents are used, and the construction of three sets of test sections under traffic at locations with problematic granular shoulders. Full results of this investigation are included in this report and its appendices. This report also presents conclusions and recommendations based on the study results.

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

BACKGROUND: Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. METHODS: In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. FINDINGS: 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). INTERPRETATION: Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. FUNDING: Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

Pore-scale modeling of two-phase flow instabilities in porous media

Les problèmes d'écoulements multiphasiques en média poreux sont d'un grand intérêt pour de nombreuses applications scientifiques et techniques ; comme la séquestration de C02, l'extraction de pétrole et la dépollution des aquifères. La complexité intrinsèque des systèmes multiphasiques et l'hétérogénéité des formations géologiques sur des échelles multiples représentent un challenge majeur pour comprendre et modéliser les déplacements immiscibles dans les milieux poreux. Les descriptions à l'échelle supérieure basées sur la généralisation de l'équation de Darcy sont largement utilisées, mais ces méthodes sont sujettes à limitations pour les écoulements présentant de l'hystérèse. Les avancées récentes en terme de performances computationnelles et le développement de méthodes précises pour caractériser l'espace interstitiel ainsi que la distribution des phases ont favorisé l'utilisation de modèles qui permettent une résolution fine à l'échelle du pore. Ces modèles offrent un aperçu des caractéristiques de l'écoulement qui ne peuvent pas être facilement observées en laboratoire et peuvent être utilisé pour expliquer la différence entre les processus physiques et les modèles à l'échelle macroscopique existants. L'objet premier de la thèse se porte sur la simulation numérique directe : les équations de Navier-Stokes sont résolues dans l'espace interstitiel et la méthode du volume de fluide (VOF) est employée pour suivre l'évolution de l'interface. Dans VOF, la distribution des phases est décrite par une fonction fluide pour l'ensemble du domaine et des conditions aux bords particulières permettent la prise en compte des propriétés de mouillage du milieu poreux. Dans la première partie de la thèse, nous simulons le drainage dans une cellule Hele-Shaw 2D avec des obstacles cylindriques. Nous montrons que l'approche proposée est applicable même pour des ratios de densité et de viscosité très importants et permet de modéliser la transition entre déplacement stable et digitation visqueuse. Nous intéressons ensuite à l'interprétation de la pression capillaire à l'échelle macroscopique. Nous montrons que les techniques basées sur la moyenne spatiale de la pression présentent plusieurs limitations et sont imprécises en présence d'effets visqueux et de piégeage. Au contraire, une définition basée sur l'énergie permet de séparer les contributions capillaires des effets visqueux. La seconde partie de la thèse est consacrée à l'investigation des effets d'inertie associés aux reconfigurations irréversibles du ménisque causé par l'interface des instabilités. Comme prototype pour ces phénomènes, nous étudions d'abord la dynamique d'un ménisque dans un pore angulaire. Nous montrons que, dans un réseau de pores cubiques, les sauts et reconfigurations sont si fréquents que les effets d'inertie mènent à différentes configurations des fluides. A cause de la non-linéarité du problème, la distribution des fluides influence le travail des forces de pression, qui, à son tour, provoque une chute de pression dans la loi de Darcy. Cela suggère que ces phénomènes devraient être pris en compte lorsque que l'on décrit l'écoulement multiphasique en média poreux à l'échelle macroscopique. La dernière partie de la thèse s'attache à démontrer la validité de notre approche par une comparaison avec des expériences en laboratoire : un drainage instable dans un milieu poreux quasi 2D (une cellule Hele-Shaw avec des obstacles cylindriques). Plusieurs simulations sont tournées sous différentes conditions aux bords et en utilisant différents modèles (modèle intégré 2D et modèle 3D) afin de comparer certaines quantités macroscopiques avec les observations au laboratoire correspondantes. Malgré le challenge de modéliser des déplacements instables, où, par définition, de petites perturbations peuvent grandir sans fin, notre approche numérique apporte de résultats satisfaisants pour tous les cas étudiés. - Problems involving multiphase flow in porous media are of great interest in many scientific and engineering applications including Carbon Capture and Storage, oil recovery and groundwater remediation. The intrinsic complexity of multiphase systems and the multi scale heterogeneity of geological formations represent the major challenges to understand and model immiscible displacement in porous media. Upscaled descriptions based on generalization of Darcy's law are widely used, but they are subject to several limitations for flow that exhibit hysteric and history- dependent behaviors. Recent advances in high performance computing and the development of accurate methods to characterize pore space and phase distribution have fostered the use of models that allow sub-pore resolution. These models provide an insight on flow characteristics that cannot be easily achieved by laboratory experiments and can be used to explain the gap between physical processes and existing macro-scale models. We focus on direct numerical simulations: we solve the Navier-Stokes equations for mass and momentum conservation in the pore space and employ the Volume Of Fluid (VOF) method to track the evolution of the interface. In the VOF the distribution of the phases is described by a fluid function (whole-domain formulation) and special boundary conditions account for the wetting properties of the porous medium. In the first part of this thesis we simulate drainage in a 2-D Hele-Shaw cell filled with cylindrical obstacles. We show that the proposed approach can handle very large density and viscosity ratios and it is able to model the transition from stable displacement to viscous fingering. We then focus on the interpretation of the macroscopic capillary pressure showing that pressure average techniques are subject to several limitations and they are not accurate in presence of viscous effects and trapping. On the contrary an energy-based definition allows separating viscous and capillary contributions. In the second part of the thesis we investigate inertia effects associated with abrupt and irreversible reconfigurations of the menisci caused by interface instabilities. As a prototype of these phenomena we first consider the dynamics of a meniscus in an angular pore. We show that in a network of cubic pores, jumps and reconfigurations are so frequent that inertia effects lead to different fluid configurations. Due to the non-linearity of the problem, the distribution of the fluids influences the work done by pressure forces, which is in turn related to the pressure drop in Darcy's law. This suggests that these phenomena should be taken into account when upscaling multiphase flow in porous media. The last part of the thesis is devoted to proving the accuracy of the numerical approach by validation with experiments of unstable primary drainage in a quasi-2D porous medium (i.e., Hele-Shaw cell filled with cylindrical obstacles). We perform simulations under different boundary conditions and using different models (2-D integrated and full 3-D) and we compare several macroscopic quantities with the corresponding experiment. Despite the intrinsic challenges of modeling unstable displacement, where by definition small perturbations can grow without bounds, the numerical method gives satisfactory results for all the cases studied.

Field Evaluation of Compaction Monitoring Technology: Phase I, 2004

This Phase I report describes a preliminary evaluation of a new compaction monitoring system developed by Caterpillar, Inc. (CAT), for use as a quality control and quality assurance (QC/QA) tool during earthwork construction operations. The CAT compaction monitoring system consists of an instrumented roller with sensors to monitor machine power output in response to changes in soil machine interaction and is fitted with a global positioning system (GPS) to monitor roller location in real time. Three pilot tests were conducted using CAT’s compaction monitoring technology. Two of the sites were located in Peoria, Illinois, at the Caterpillar facilities. The third project was an actual earthwork grading project in West Des Moines, Iowa. Typical construction operations for all tests included the following steps: (1) aerate/till existing soil; (2) moisture condition soil with water truck (if too dry); (3) remix; (4) blade to level surface; and (5) compact soil using the CAT CP-533E roller instrumented with the compaction monitoring sensors and display screen. Test strips varied in loose lift thickness, water content, and length. The results of the study show that it is possible to evaluate soil compaction with relatively good accuracy using machine energy as an indicator, with the advantage of 100% coverage with results in real time. Additional field trials are necessary, however, to expand the range of correlations to other soil types, different roller configurations, roller speeds, lift thicknesses, and water contents. Further, with increased use of this technology, new QC/QA guidelines will need to be developed with a framework in statistical analysis. Results from Phase I revealed that the CAT compaction monitoring method has a high level of promise for use as a QC/QA tool but that additional testing is necessary in order to prove its validity under a wide range of field conditions. The Phase II work plan involves establishing a Technical Advisor Committee, developing a better understanding of the algorithms used, performing further testing in a controlled environment, testing on project sites in the Midwest, and developing QC/QA procedures.

Study of OSEM with different subsets in grating-based X-ray differential phase-contrast imaging.

Impressive developments in X-ray imaging are associated with X-ray phase contrast computed tomography based on grating interferometry, a technique that provides increased contrast compared with conventional absorption-based imaging. A new "single-step" method capable of separating phase information from other contributions has been recently proposed. This approach not only simplifies data-acquisition procedures, but, compared with the existing phase step approach, significantly reduces the dose delivered to a sample. However, the image reconstruction procedure is more demanding than for traditional methods and new algorithms have to be developed to take advantage of the "single-step" method. In the work discussed in this paper, a fast iterative image reconstruction method named OSEM (ordered subsets expectation maximization) was applied to experimental data to evaluate its performance and range of applicability. The OSEM algorithm with different subsets was also characterized by comparison of reconstruction image quality and convergence speed. Computer simulations and experimental results confirm the reliability of this new algorithm for phase-contrast computed tomography applications. Compared with the traditional filtered back projection algorithm, in particular in the presence of a noisy acquisition, it furnishes better images at a higher spatial resolution and with lower noise. We emphasize that the method is highly compatible with future X-ray phase contrast imaging clinical applications.

On-line desorption of dried blood spots coupled to hydrophilic interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites.

An assay for the simultaneous analysis of pharmaceutical compounds and their metabolites from micro-whole blood samples (i.e. 5 microL) was developed using an on-line dried blood spot (on-line DBS) device coupled with hydrophilic interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly integrated to the LC device using a homemade inox desorption cell. Without any sample pretreatment, analytes are desorbed from the paper towards an automated system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the same run, the polar fraction is separated by the zwitterionic-HILIC column while the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT-MS operating in full scan mode for the survey scan and in product ion mode for the dependant scan using an ESI source. The procedure was evaluated by the simultaneous qualitative analysis of four probes and their relative phase I and II metabolites spiked in whole blood. In addition, the method was successfully applied to the in vivo monitoring of buprenorphine metabolism after the administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar rat.

Spatiotemporal adaptive multiscale multiphysics simulations of two-phase flow

We present a spatiotemporal adaptive multiscale algorithm, which is based on the Multiscale Finite Volume method. The algorithm offers a very efficient framework to deal with multiphysics problems and to couple regions with different spatial resolution. We employ the method to simulate two-phase flow through porous media. At the fine scale, we consider a pore-scale description of the flow based on the Volume Of Fluid method. In order to construct a global problem that describes the coarse-scale behavior, the equations are averaged numerically with respect to auxiliary control volumes, and a Darcy-like coarse-scale model is obtained. The space adaptivity is based on the idea that a fine-scale description is only required in the front region, whereas the resolution can be coarsened elsewhere. Temporal adaptivity relies on the fact that the fine-scale and the coarse-scale problems can be solved with different temporal resolution (longer time steps can be used at the coarse scale). By simulating drainage under unstable flow conditions, we show that the method is able to capture the coarse-scale behavior outside the front region and to reproduce complex fluid patterns in the front region.

Bayesian Markov-chain-Monte-Carlo inversion of time-lapse cross hole ground-penetrating radar data to characterize the vadose zone at the Arrenaes field site, Denmark

The ground-penetrating radar (GPR) geophysical method has the potential to provide valuable information on the hydraulic properties of the vadose zone because of its strong sensitivity to soil water content. In particular, recent evidence has suggested that the stochastic inversion of crosshole GPR traveltime data can allow for a significant reduction in uncertainty regarding subsurface van Genuchten-Mualem (VGM) parameters. Much of the previous work on the stochastic estimation of VGM parameters from crosshole GPR data has considered the case of steady-state infiltration conditions, which represent only a small fraction of practically relevant scenarios. We explored in detail the dynamic infiltration case, specifically examining to what extent time-lapse crosshole GPR traveltimes, measured during a forced infiltration experiment at the Arreneas field site in Denmark, could help to quantify VGM parameters and their uncertainties in a layered medium, as well as the corresponding soil hydraulic properties. We used a Bayesian Markov-chain-Monte-Carlo inversion approach. We first explored the advantages and limitations of this approach with regard to a realistic synthetic example before applying it to field measurements. In our analysis, we also considered different degrees of prior information. Our findings indicate that the stochastic inversion of the time-lapse GPR data does indeed allow for a substantial refinement in the inferred posterior VGM parameter distributions compared with the corresponding priors, which in turn significantly improves knowledge of soil hydraulic properties. Overall, the results obtained clearly demonstrate the value of the information contained in time-lapse GPR data for characterizing vadose zone dynamics.

Image Analysis for the Characterization of Materials for Highway Construction : Phase I, Progress Report, HR-346, 1992

The major objective of this project is to evaluate image analysis for characterizing air voids in Portland cement contract (PCC) and asphalt concrete (AC) and aggregate gradation in asphalt concrete. Phase 1 of this project has concentrated on evaluation and refinement of sample preparation techniques, evaluation of methods and instruments for conducting image analysis, and finally, analysis and comparison of a select portion of samples. Preliminary results suggest a strong correlation between the results obtained from the linear traverse method and image analysis methods for determining percent air voids in concrete. Preliminary work with asphalt samples has shown that damage caused by a high vacuum of the conventional scanning electron microscope (SEM) may too disruptive. Alternative solutions have been explored, including confocal microscopy and low vacuum electron microscopy. Additionally, a conventional high vacuum SEM operating at a marginal operating vacuum may suffice.