Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability
NASA Astrophysics Data System (ADS)
Sourbron, S. P.; Buckley, D. L.
2012-01-01
The tracer-kinetic models developed in the early 1990s for dynamic contrast-enhanced MRI (DCE-MRI) have since become a standard in numerous applications. At the same time, the development of MRI hardware has led to increases in image quality and temporal resolution that reveal the limitations of the early models. This in turn has stimulated an interest in the development and application of a second generation of modelling approaches. They are designed to overcome these limitations and produce additional and more accurate information on tissue status. In particular, models of the second generation enable separate estimates of perfusion and capillary permeability rather than a single parameter Ktrans that represents a combination of the two. A variety of such models has been proposed in the literature, and development in the field has been constrained by a lack of transparency regarding terminology, notations and physiological assumptions. In this review, we provide an overview of these models in a manner that is both physically intuitive and mathematically rigourous. All are derived from common first principles, using concepts and notations from general tracer-kinetic theory. Explicit links to their historical origins are included to allow for a transfer of experience obtained in other fields (PET, SPECT, CT). A classification is presented that reveals the links between all models, and with the models of the first generation. Detailed formulae for all solutions are provided to facilitate implementation. Our aim is to encourage the application of these tools to DCE-MRI by offering researchers a clearer understanding of their assumptions and requirements.
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R; La Riviere, Patrick J; Alessio, Adam M
2014-04-01
Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This
NASA Astrophysics Data System (ADS)
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.
2014-04-01
Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)-1, cardiac output = 3, 5, 8 L min-1). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that
Elliott, Jonathan T.; Samkoe, Kimberley S.; Gunn, Jason R.; Stewart, Errol E.; Gardner, Timothy B.; Tichauer, Kenneth M.; Lee, Ting-Yim; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.
2015-01-01
Objectives It was hypothesized that perfusion computed tomography (CT) blood flow (BF), blood volume (BV) and vascular permeability surface-area (PS) product parameters would be predictive of therapeutic anti-cancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of injected photosensitizer, vertepofin. Materials and Methods Nine New Zealand White rabbits underwent direct pancreas implantation of VX2 tumors and CT perfusion or endoscopic ultrasound was performed 10 days post-implantation. Verteporfin was injected during CT imaging and tissue was removed 1 h post-injection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathological staining were performed. Results DCE-CT showed enhanced BF, BV, and PS in the tumor rim, and decreased BF, BV and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. Conclusions The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a non-invasive method of mapping photosensitizer dose. PMID:25683500
Wong, T Z; Mechling, J A; Jones, E L; Strohbehn, J W
1988-01-01
A two-dimensional time-dependent finite element model was developed to evaluate thermal techniques for estimating blood flow and specific absorption rate (SAR). In these computer simulations, homogeneously and nonhomogeneously perfused tumour models were heated by a 915 MHz interstitial microwave antenna array. Representative blood flow values were assigned within the tumour, and the applied SAR distribution was based on a previously developed antenna theory. SAR values were estimated from the power-on transient temperatures, and blood flow values were estimated from thermal clearance data after power was discontinued. These estimated parameters were then compared to the known 'true' blood flow and SAR values throughout the treatment region. SAR values could be predicted with reasonable accuracy throughout most of the heated region independent of local blood flow. For a homogeneous model, thermal clearance was found to yield reasonably accurate blood flow estimates at high perfusion rates and less accurate estimates at lower perfusion rates. However, for the inhomogeneous model, the blood perfusion estimates were generally poor, and an average blood flow value for the tumour was obtained with little ability to resolve the differences in perfusion between regions. Using temperatures observed early in the cool-down curve resulted in improved spatial resolution, but increased the contribution of thermal conduction to the blood flow estimates. A single time-constant exponential thermal decay curve was found to be a necessary but not sufficient condition for reliable blood flow estimates using this technique. PMID:3171254
Gullberg, Grant T.; Huesman, Ronald H.; Reutter, Bryan W.; Qi,Jinyi; Ghosh Roy, Dilip N.
2004-01-01
In dynamic cardiac SPECT estimates of kinetic parameters ofa one-compartment perfusion model are usually obtained in a two stepprocess: 1) first a MAP iterative algorithm, which properly models thePoisson statistics and the physics of the data acquisition, reconstructsa sequence of dynamic reconstructions, 2) then kinetic parameters areestimated from time activity curves generated from the dynamicreconstructions. This paper provides a method for calculating thecovariance matrix of the kinetic parameters, which are determined usingweighted least squares fitting that incorporates the estimated varianceand covariance of the dynamic reconstructions. For each transaxial slicesets of sequential tomographic projections are reconstructed into asequence of transaxial reconstructions usingfor each reconstruction inthe time sequence an iterative MAP reconstruction to calculate themaximum a priori reconstructed estimate. Time-activity curves for a sumof activity in a blood region inside the left ventricle and a sum in acardiac tissue region are generated. Also, curves for the variance of thetwo estimates of the sum and for the covariance between the two ROIestimates are generated as a function of time at convergence using anexpression obtained from the fixed-point solution of the statisticalerror of the reconstruction. A one-compartment model is fit to the tissueactivity curves assuming a noisy blood input function to give weightedleast squares estimates of blood volume fraction, wash-in and wash-outrate constants specifying the kinetics of 99mTc-teboroxime for theleftventricular myocardium. Numerical methods are used to calculate thesecond derivative of the chi-square criterion to obtain estimates of thecovariance matrix for the weighted least square parameter estimates. Eventhough the method requires one matrix inverse for each time interval oftomographic acquisition, efficient estimates of the tissue kineticparameters in a dynamic cardiac SPECT study can be obtained with
Tomographic digital subtraction angiography for lung perfusion estimation in rodents
Badea, Cristian T.; Hedlund, Laurence W.; De Lin, Ming; Boslego Mackel, Julie S.; Samei, Ehsan; Allan Johnson, G.
2007-05-15
In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of {mu}L volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 {mu}m, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.
Estimating a regional ventilation-perfusion index
Muller, P A; Li, T; Isaacson, D; Newell, J C; Saulnier, G J; Kao, Tzu-Jen; Ashe, Jeffrey
2015-01-01
This is a methods paper, where an approximation to the local ventilation-perfusion ratio is derived. This approximation, called the ventilation-perfusion index since it is not exactly the physiological ventilation-perfusion ratio, is calculated using conductivity reconstructions obtained using electrical impedance tomography. Since computation of the ventilation-perfusion index only requires knowledge of the internal conductivity, any conductivity reconstruction method may be used. The method is explained, and results are presented using conductivities obtained from two EIT systems, one using an iterative method and the other a linearization method. PMID:26006279
TISSUE ENGINEERING PERFUSABLE CANCER MODELS
Fong, E.L.; Santoro, M.; Farach-Carson, M.C.; Kasper, F.K.; Mikos, A.G.
2014-01-01
The effect of fluid flow on cancer progression is currently not well understood, highlighting the need for perfused tumor models to close this gap in knowledge. Enabling biological processes at the cellular level to be modeled with high spatiotemporal control, microfluidic tumor models have demonstrated applicability as platforms to study cell-cell interactions, effect of interstitial flow on tumor migration and the role of vascular barrier function. To account for the multi-scale nature of cancer growth and invasion, macroscale models are also necessary. The consideration of fluid dynamics within tumor models at both the micro- and macroscopic levels may greatly improve our ability to more fully mimic the tumor microenvironment. PMID:24634812
Bayesian hemodynamic parameter estimation by bolus tracking perfusion weighted imaging.
Boutelier, Timothé; Kudo, Koshuke; Pautot, Fabrice; Sasaki, Makoto
2012-07-01
A delay-insensitive probabilistic method for estimating hemodynamic parameters, delays, theoretical residue functions, and concentration time curves by computed tomography (CT) and magnetic resonance (MR) perfusion weighted imaging is presented. Only a mild stationarity hypothesis is made beyond the standard perfusion model. New microvascular parameters with simple hemodynamic interpretation are naturally introduced. Simulations on standard digital phantoms show that the method outperforms the oscillating singular value decomposition (oSVD) method in terms of goodness-of-fit, linearity, statistical and systematic errors on all parameters, especially at low signal-to-noise ratios (SNRs). Delay is always estimated sharply with user-supplied resolution and is purely arterial, by contrast to oSVD time-to-maximum TMAX that is very noisy and biased by mean transit time (MTT), blood volume, and SNR. Residue functions and signals estimates do not suffer overfitting anymore. One CT acute stroke case confirms simulation results and highlights the ability of the method to reliably estimate MTT when SNR is low. Delays look promising for delineating the arterial occlusion territory and collateral circulation. PMID:22410325
NASA Astrophysics Data System (ADS)
Dillon, C. R.; Borasi, G.; Payne, A.
2016-01-01
For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one.
Dillon, C R; Borasi, G; Payne, A
2016-01-21
For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one. PMID:26741344
Modelling of temperature and perfusion during scalp cooling
NASA Astrophysics Data System (ADS)
Janssen, F. E. M.; Van Leeuwen, G. M. J.; Van Steenhoven, A. A.
2005-09-01
Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 °C to 18.3 °C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 °C to 21.8 °C, which in turn reduced relative perfusion to 13% and 33%, respectively.
Renal vascular perfusion index in a canine model.
Shau, Yio-Wha; Pao, Sun-Hua; Chou, Nai-Kuan; Chang, King-Jen; Shyu, Jeou-Jong
2009-01-01
Decreased renal perfusion plays an important role in the progression toward renal failure. In this study, a novel measure was proposed to quantify renal perfusion using canine model. Serial renal vascular images at different vascular areas including the whole vascular tree, interlobar, arcuate and interlobular vessels were captured. Image processing software was designed to analyze the changes of power Doppler intensity of colored pixels within regions-of-interest (ROI). For a given ROI, the power Doppler vascular index (PDVI) was found to fluctuate with the cardiac cycle. It was also noted that the power Doppler signals generated by arterial vessels have different fluctuating waveforms and different phase compared with the signal derived from venous vessels. A power Doppler correlation-map was developed to differentiate the arteries and veins in the ROI. Using the serial power Doppler images and the derived flow direction information, the interlobular perfusion can be strongly quantified. The renal vascular perfusion index (RVPI) defined as the ratio of PDVI(max) versus PDVI(min) was significantly higher in the interlobular vessel areas than three other areas for seven healthy dogs. The RVPI resembles the systolic/diastolic (S/D) ratio that commonly reflects arterial hemodynamics. RVPI and power Doppler correlation-map reveal more "dynamic" sense of vascular perfusion and provide a novel approach for the examination of renal function in clinical practice. PMID:18805627
Pancreas tumor model in rabbit imaged by perfusion CT scans
NASA Astrophysics Data System (ADS)
Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.
2013-03-01
The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.
A fast nonlinear regression method for estimating permeability in CT perfusion imaging
Bennink, Edwin; Riordan, Alan J; Horsch, Alexander D; Dankbaar, Jan Willem; Velthuis, Birgitta K; de Jong, Hugo W
2013-01-01
Blood–brain barrier damage, which can be quantified by measuring vascular permeability, is a potential predictor for hemorrhagic transformation in acute ischemic stroke. Permeability is commonly estimated by applying Patlak analysis to computed tomography (CT) perfusion data, but this method lacks precision. Applying more elaborate kinetic models by means of nonlinear regression (NLR) may improve precision, but is more time consuming and therefore less appropriate in an acute stroke setting. We propose a simplified NLR method that may be faster and still precise enough for clinical use. The aim of this study is to evaluate the reliability of in total 12 variations of Patlak analysis and NLR methods, including the simplified NLR method. Confidence intervals for the permeability estimates were evaluated using simulated CT attenuation–time curves with realistic noise, and clinical data from 20 patients. Although fixating the blood volume improved Patlak analysis, the NLR methods yielded significantly more reliable estimates, but took up to 12 × longer to calculate. The simplified NLR method was ∼4 × faster than other NLR methods, while maintaining the same confidence intervals (CIs). In conclusion, the simplified NLR method is a new, reliable way to estimate permeability in stroke, fast enough for clinical application in an acute stroke setting. PMID:23881247
Modelling Brain Temperature and Perfusion for Cerebral Cooling
NASA Astrophysics Data System (ADS)
Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael
2015-11-01
Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.
Lapointe, D.S.; Olson, M.S.
1987-05-01
The multiple indicator dilution technique provides a useful mechanism for the determination of the rates of processes involved in the uptake and subsequent release of substances between an organ, such as the liver, and the vasculature. They have used this technique to investigate the uptake of /sup 45/Ca/sup 2 +/ into the perfused rat liver at a number of different perfusate Ca/sup 2 +/ concentrations. Each perfused liver is calibrated using reference injections of a mixture of /sup 3/H-sucrose and /sup 14/C-urea to determine parameters of a microcirculatory model of the liver, such as the characteristic transit times through vascular spaces and the ratio of tissue volume to extracellular volume. Using a single injection of a mixture of /sup 3/H-sucrose and /sup 45/Ca/sup 2 +/, the profiles of the efflux of the injected tracers are analyzed to estimate the rate constant for uptake of /sup 45/Ca/sup 2 +/. The estimated rate constant for uptake decreases with increasing perfusate Ca/sup 2 +/ concentration (kin = 0.155 +/- 0.036, 0.0896 +/- 0.024, 0.0713 +/- 0.009 for (Ca/sup 2 +/) = 0.05, 0.5, 1.25 mM; n=5). From these data, estimates for the maximum velocity of uptake of Ca/sup 2 +/ and the Ca/sup 2 +/ concentration for half maximal uptake are calculated to be 0.1208 mM/sec and 0.7278 mM respectively.
NASA Astrophysics Data System (ADS)
Mukherjee, Joyeeta Mitra; Pretorius, P. H.; Johnson, K. L.; Hutton, Brian F.; King, Michael A.
2011-03-01
In myocardial perfusion SPECT imaging patient motion during acquisition causes severe artifacts in about 5% of studies. Motion estimation strategies commonly used are a) data-driven, where the motion may be determined by registration and checking consistency with the SPECT acquisition data, and b) external surrogate-based, where the motion is obtained from a dedicated motion-tracking system. In this paper a data-driven strategy similar to a 2D-3D registration scheme with multiple views is investigated, using a partially reconstructed heart for the 3D model. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The goal of this paper is to compare the performance of different cost-functions in quantifying consistency with the SPECT projection data in a registration-based scheme for motion estimation as the image-quality of the 3D model degrades. Six intensity-based metrics- Mean-squared difference (MSD), Mutual information (MI), Normalized Mutual information NMI), Pattern intensity (PI), normalized cross-correlation (NCC) and Entropy of the difference (EDI) were studied. Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and collimator blurring. Further the image quality of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in acquisitions of anthropomorphic phantoms and patient studies in a real clinical setting. Pattern intensity and Normalized Mutual Information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations and anthropomorphic phantom acquisitions. In patient studies
A corneal perfusion device for estimating ocular bioavailability in vitro.
Richman, J B; Tang-Liu, D D
1990-02-01
An in vitro method for investigating drug penetration across the cornea from acute doses has been developed. The donor (epithelial or tear) side of a corneal chamber similar to those used by Edelhauser and co-workers was modified with a reduced-volume insert so that the donor side volume approximated 6% of the receiver (endothelial or aqueous humor) chamber volume. Fluid was pumped through the anterior chamber to simulate the physiologic tear turnover in vivo. The receiver chamber was bubbled with oxygen:carbon dioxide (95%:5%) to aerate and circulate the fluid. We investigated the in vitro ocular bioavailability of several marketed ophthalmic drug formulations using this model (0.03% flurbiprofen, 0.5% levobunolol, 0.1 and 0.25% fluorometholone, and 1% prednisolone acetate). At 1 min after the dose administration, drug was eluted from the donor chamber at a dose turnover rate of 12%/min. In all experiments, a small percentage of the applied dose penetrated the cornea. Using this chamber device, the ocular bioavailability via corneal absorption ranged between 5 and 16% for solution formulations, whereas the ocular bioavailability for the suspension formulations was less than 0.3%. The major portion of the administered dose was recovered from the donor side effluent. This observation was consistent with findings showing low ocular bioavailability of ophthalmic preparations due to the rapid precorneal washout in vivo. The extent of drug penetrating as its corneal metabolite in the model correlated well to in vitro corneal metabolism rate constants. The new model opens several potentially useful areas of research into ocular absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2324964
Estimation of intra-operator variability in perfusion parameter measurements using DCE-US
Gauthier, Marianne; Leguerney, Ingrid; Thalmensi, Jessie; Chebil, Mohamed; Parisot, Sarah; Peronneau, Pierre; Roche, Alain; Lassau, Nathalie
2011-01-01
AIM: To investigate intra-operator variability of semi-quantitative perfusion parameters using dynamic contrast-enhanced ultrasonography (DCE-US), following bolus injections of SonoVue®. METHODS: The in vitro experiments were conducted using three in-house sets up based on pumping a fluid through a phantom placed in a water tank. In the in vivo experiments, B16F10 melanoma cells were xenografted to five nude mice. Both in vitro and in vivo, images were acquired following bolus injections of the ultrasound contrast agent SonoVue® (Bracco, Milan, Italy) and using a Toshiba Aplio® ultrasound scanner connected to a 2.9-5.8 MHz linear transducer (PZT, PLT 604AT probe) (Toshiba, Japan) allowing harmonic imaging (“Vascular Recognition Imaging”) involving linear raw data. A mathematical model based on the dye-dilution theory was developed by the Gustave Roussy Institute, Villejuif, France and used to evaluate seven perfusion parameters from time-intensity curves. Intra-operator variability analyses were based on determining perfusion parameter coefficients of variation (CV). RESULTS: In vitro, different volumes of SonoVue® were tested with the three phantoms: intra-operator variability was found to range from 2.33% to 23.72%. In vivo, experiments were performed on tumor tissues and perfusion parameters exhibited values ranging from 1.48% to 29.97%. In addition, the area under the curve (AUC) and the area under the wash-out (AUWO) were two of the parameters of great interest since throughout in vitro and in vivo experiments their variability was lower than 15.79%. CONCLUSION: AUC and AUWO appear to be the most reliable parameters for assessing tumor perfusion using DCE-US as they exhibited the lowest CV values. PMID:21512654
Cao Yue; Platt, Joel F.; Francis, Isaac R; Balter, James M.; Pan, Charlie; Normolle, Daniel; Ben-Josef, Edgar; Haken, Randall K. ten; Lawrence, Theodore S.
2007-02-15
We have shown that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. The ability to safely deliver higher doses is primarily limited by the development of radiation-induced liver disease, characterized by venous occlusion. In this study, we investigated whether portal venous perfusion measured prior to the end of radiation therapy (RT) together with dose could predict liver venous perfusion dysfunction after treatment. Ten patients with unresectable intrahepatic cancer participated in an IRB-approved computer tomography (CT) perfusion study. Hepatic arterial and portal vein perfusion distributions were estimated by using dynamic contrast enhanced CT and the single compartmental model. Scans were obtained at four time points: prior to treatment, after 15 and 30 fractions of 1.5 Gy treatments, and one month following the completion of RT. Multivariant linear regression was used to determine covariances among the first three time point measurements plus dose for prediction of the post RT measurement. The reduction in the regional venous perfusion one month following RT was predicted by the local accumulated dose and the change in the regional venous perfusion after {approx}30 fractions (F=90.6,p<0.000 01). Each Gy produced an approximately 1.2% of reduction in the venous perfusion. This local dose and venous perfusion model has the potential to predict individual sensitivity to radiation. This is the first step toward developing a method to deliver higher and potentially more curative radiation doses to the patients who can safely receive these higher doses.
Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda
2014-09-01
Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion
Uterine perfusion model for analyzing barriers to transport in fibroids.
Stirland, Darren L; Nichols, Joseph W; Jarboe, Elke; Adelman, Marisa; Dassel, Mark; Janát-Amsbury, Margit-Maria; Bae, You Han
2015-09-28
This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids. Some fibroids exhibited regions with partial methylene blue penetration into the tumor environment. Histological analysis comparing representative sections of fibroids and normal myometrium showed a smaller number of vessels with decreased diameters within the fibroid. Imaging of fluorescently stained vessels exposed a stark contrast between fluorescence within the myometrium and relatively little within the fibroid tissues. Imaging at higher magnification revealed that fibroid blood vessels were indeed perfused and stained with the lipophilic membrane dye; however, the vessels were only the size of small capillaries and the blood vessel coverage was only 12% that of the normal myometrium. The majority of sampled fibroids had a strong negative correlation (Pearson's r=-0.68 or beyond) between collagen and methylene blue staining. As methylene blue was able to passively diffuse into fibroid tissue, the true barrier to transport in these fibroids is likely high interstitial fluid pressure, correlating with high collagen content and solid stress observed in the fibroid tissue. Fibroids had an average elevated interstitial fluid pressure of 4mmHg compared to -1mmHg in normal myometrium. Our findings signify relationships between drug distribution in fibroids and between vasculature characteristics, collagen levels, and interstitial fluid pressure. Understanding these barriers to transport can lead to developments in drug delivery for the treatment of uterine fibroids and tumors of similar composition. PMID:26184049
Dynamic chest image analysis: model-based pulmonary perfusion analysis with pyramid images
NASA Astrophysics Data System (ADS)
Liang, Jianming; Haapanen, Arto; Jaervi, Timo; Kiuru, Aaro J.; Kormano, Martti; Svedstrom, Erkki; Virkki, Raimo
1998-07-01
The aim of the study 'Dynamic Chest Image Analysis' is to develop computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected at different phases of the respiratory/cardiac cycles in a short period of time. We have proposed a framework for ventilation study with an explicit ventilation model based on pyramid images. In this paper, we extend the framework to pulmonary perfusion study. A perfusion model and the truncated pyramid are introduced. The perfusion model aims at extracting accurate, geographic perfusion parameters, and the truncated pyramid helps in understanding perfusion at multiple resolutions and speeding up the convergence process in optimization. Three cases are included to illustrate the experimental results.
Dynamic Chest Image Analysis: Model-Based Perfusion Analysis in Dynamic Pulmonary Imaging
NASA Astrophysics Data System (ADS)
Liang, Jianming; Järvi, Timo; Kiuru, Aaro; Kormano, Martti; Svedström, Erkki
2003-12-01
The "Dynamic Chest Image Analysis" project aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the dynamic pulmonary imaging technique. We have proposed and evaluated a multiresolutional method with an explicit ventilation model for ventilation analysis. This paper presents a new model-based method for pulmonary perfusion analysis. According to perfusion properties, we first devise a novel mathematical function to form a perfusion model. A simple yet accurate approach is further introduced to extract cardiac systolic and diastolic phases from the heart, so that this cardiac information may be utilized to accelerate the perfusion analysis and improve its sensitivity in detecting pulmonary perfusion abnormalities. This makes perfusion analysis not only fast but also robust in computation; consequently, perfusion analysis becomes computationally feasible without using contrast media. Our clinical case studies with 52 patients show that this technique is effective for pulmonary embolism even without using contrast media, demonstrating consistent correlations with computed tomography (CT) and nuclear medicine (NM) studies. This fluoroscopical examination takes only about 2 seconds for perfusion study with only low radiation dose to patient, involving no preparation, no radioactive isotopes, and no contrast media.
Development of an Ex Vivo, Beating Heart Model for CT Myocardial Perfusion
Pelgrim, Gert Jan; Das, Marco; Haberland, Ulrike; Slump, Cees; Handayani, Astri; van Tuijl, Sjoerd; Stijnen, Marco; Klotz, Ernst; Oudkerk, Matthijs; Wildberger, Joachim E.; Vliegenthart, Rozemarijn
2015-01-01
Objective. To test the feasibility of a CT-compatible, ex vivo, perfused porcine heart model for myocardial perfusion CT imaging. Methods. One porcine heart was perfused according to Langendorff. Dynamic perfusion scanning was performed with a second-generation dual source CT scanner. Circulatory parameters like blood flow, aortic pressure, and heart rate were monitored throughout the experiment. Stenosis was induced in the circumflex artery, controlled by a fractional flow reserve (FFR) pressure wire. CT-derived myocardial perfusion parameters were analysed at FFR of 1 to 0.10/0.0. Results. CT images did not show major artefacts due to interference of the model setup. The pacemaker-induced heart rhythm was generally stable at 70 beats per minute. During most of the experiment, blood flow was 0.9–1.0 L/min, and arterial pressure varied between 80 and 95 mm/Hg. Blood flow decreased and arterial pressure increased by approximately 10% after inducing a stenosis with FFR ≤ 0.50. Dynamic perfusion scanning was possible across the range of stenosis grades. Perfusion parameters of circumflex-perfused myocardial segments were affected at increasing stenosis grades. Conclusion. An adapted Langendorff porcine heart model is feasible in a CT environment. This model provides control over physiological parameters and may allow in-depth validation of quantitative CT perfusion techniques. PMID:26185756
NASA Astrophysics Data System (ADS)
Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.
2014-03-01
Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.
Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J
2013-05-01
Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. PMID:22711674
Whole ovine ovaries as a model for human: perfusion with cryoprotectants in vivo and in vitro.
Isachenko, Vladimir; Rahimi, Gohar; Dattena, Maria; Mallmann, Peter; Baikoshkarova, Saltanat; Kellerwessel, Elisabeth; Otarbaev, Marat; Shalakhmetova, Tamara; Isachenko, Evgenia
2014-01-01
These experiments were performed to test the perfusion of ovine as a model for human ovaries by cryoprotectants in vivo at high temperature when the permeability of capillaries is high and when blood is insensibly replaced by the solution of cryoprotectants. By our hypothetical supposition, ovaries could be saturated by cryoprotectants before their surgical removal. The objective was to examine the effectiveness of perfusion of ovine ovaries with vascular pedicle in vivo and in vitro. Arteria ovarica was cannuled and ovaries were perfused by Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink in vivo and in vitro. In the first and second cycle of experiments, ovaries (n = 13 and n = 23) were perfused in vivo and in vitro, respectively, during 60 min with the rate of perfusion 50 mL/h (0.8 mL/min). It was established with in vivo perfusion that only about 10% of ovarian tissues were perfused due to an appearance of multiple anastomoses when the perfusion medium goes from arteria ovarica to arteria uterina without inflow into the ovaries. It was concluded that in vitro perfusion of ovine intact ovaries with vascular pedicle by freezing medium is more effective than this manipulation performed in vivo. PMID:24701576
Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice
Fushima, Tomofumi; Sekimoto, Akiyo; Minato, Takahiro; Ito, Takuya; Oe, Yuji; Kisu, Kiyomi; Sato, Emiko; Funamoto, Kenichi; Hayase, Toshiyuki; Kimura, Yoshitaka; Ito, Sadayoshi; Sato, Hiroshi; Takahashi, Nobuyuki
2016-01-01
Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE. PMID:27187738
Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice.
Fushima, Tomofumi; Sekimoto, Akiyo; Minato, Takahiro; Ito, Takuya; Oe, Yuji; Kisu, Kiyomi; Sato, Emiko; Funamoto, Kenichi; Hayase, Toshiyuki; Kimura, Yoshitaka; Ito, Sadayoshi; Sato, Hiroshi; Takahashi, Nobuyuki
2016-01-01
Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE. PMID:27187738
Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin
2010-01-01
Objective We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. Materials and Methods An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Results Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Conclusion Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans. PMID:20808699
Rajendran, Reshmi; Liang, Jieming; Tang, Mei Yee Annie; Henry, Brian; Chuang, Kai-Hsiang
2015-08-01
Perfusion is an important biomarker of tissue function and has been associated with tumor pathophysiology such as angiogenesis and hypoxia. Arterial spin labeling (ASL) MRI allows noninvasive and quantitative imaging of perfusion; however, the application in mouse xenograft tumor models has been challenging due to the low sensitivity and high perfusion heterogeneity. In this study, flow-sensitive alternating inversion recovery (FAIR) ASL was optimized for a mouse xenograft tumor. To assess the sensitivity and reliability for measuring low perfusion, the lumbar muscle was used as a reference region. By optimizing the number of averages and inversion times, muscle perfusion as low as 32.4 ± 4.8 (mean ± standard deviation) ml/100 g/min could be measured in 20 min at 7 T with a quantification error of 14.4 ± 9.1%. Applying the optimized protocol, heterogeneous perfusion ranging from 49.5 to 211.2 ml/100 g/min in a renal carcinoma was observed. To understand the relationship with tumor pathology, global and regional tumor perfusion was compared with histological staining of blood vessels (CD34), hypoxia (CAIX) and apoptosis (TUNEL). No correlation was observed when the global tumor perfusion was compared with these pathological parameters. Regional analysis shows that areas of high perfusion had low microvessel density, which was due to larger vessel area compared with areas of low perfusion. Nonetheless, these were not correlated with hypoxia or apoptosis. The results suggest that tumor perfusion may reflect certain aspect of angiogenesis, but its relationship with other pathologies needs further investigation. PMID:26104980
Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R
2016-01-01
Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850
Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R
2016-01-01
Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850
Volentine, G.D.; Ogden, K.A.; Tuma, D.J.; Sorrell, M.F.
1987-05-01
The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. /sup 3/H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde.
Fahmi, Rachid; Eck, Brendan L; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G; Wilson, David L
2016-03-21
We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR < 0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR [Formula: see text] 0.65, the anterior-to-lateral flow ratio was 0.29 ± 0.01, over-estimating stenosis severity as compared to 0.42 ± 0.01 (p < 0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50 ± 0.04 falsely indicating an actionable ischemic condition
NASA Astrophysics Data System (ADS)
Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.
2016-03-01
We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR < 0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29 ± 0.01, over-estimating stenosis severity as compared to 0.42 ± 0.01 (p < 0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50 ± 0.04 falsely indicating an actionable ischemic condition in a healthy
Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip.
Shitzer, A; Stroschein, L A; Gonzalez, R R; Pandolf, K B
1996-05-01
A lumped-parameter model of a fingertip is presented. The semispherical model includes the effects of heat storage, heat exchange with the environment, and heat transport by blood perfusion. The thermal insulation on the surface of the fingertip is represented by the overall heat transfer coefficient that is calculated by common engineering formulas. The model is solved analytically for the simple case of constant blood perfusion rate. The general case of variable blood perfusion rates is solved by an Euler finite difference technique. At this stage, the model does not include active control mechanisms of blood perfusion. Thus the effects of cold-induced vasodilatation have to be superimposed and are modeled by symmetrical triangular waveforms because these were found to best depict the behavior of fingers exposed to cold environments. Results of this model were compared with experimental data obtained in two separate studies. One included 60-min infrared thermograms of the dorsal surface of bare hands of sedentary subjects horizontally suspended on a fish net in a 0 degree C environment. Another study, on gloved finger temperatures, involved 0 and -6.7 degrees C environments. Fingertip (nail bed) temperatures of both these studies were compared with model predictions. Blood perfusion rates were assumed and adjusted within physiologically reasonable limits. Comparison of measured and computed temperature records showed very good conformity in both cases studied. PMID:8727573
A microfluidically perfused three dimensional human liver model.
Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S
2015-12-01
Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. PMID:26322723
Radiation risk estimation models
Hoel, D.G.
1987-11-01
Cancer risk models and their relationship to ionizing radiation are discussed. There are many model assumptions and risk factors that have a large quantitative impact on the cancer risk estimates. Other health end points such as mental retardation may be an even more serious risk than cancer for those with in utero exposures. 8 references.
Peters, Kristina; Michel, Maurice Stephan; Matis, Ulrike; Häcker, Axel
2006-01-01
Experiments to develop innovative surgical therapy procedures are conventionally conducted on animals, as crucial aspects like tissue removal and bleeding disposition cannot be investigated in vitro. Extracorporeal organ models however reflect these aspects and could thus reduce the use of animals for this purpose fundamentally in the future. The aim of this work was to validate the isolated perfused porcine kidney model with regard to its use for surgical purposes on the basis of histological and radiological procedures. The results show that neither storage nor artificial perfusion led to any structural or functional damage which would affect the quality of the organ. The kidney model is highly suitable for simulating the main aspects of renal physiology and allows a constant calibration of perfusion pressure and tissue temperature. Thus, with only a moderate amount of work involved, the kidney model provides a cheap and readily available alternative to conventional animal experiments; it allows standardised experimental settings and provides valid results. PMID:17086351
Koning, Nick J; de Lange, Fellery; Vonk, Alexander B A; Ahmed, Yunus; van den Brom, Charissa E; Bogaards, Sylvia; van Meurs, Matijs; Jongman, Rianne M; Schalkwijk, Casper G; Begieneman, Mark P V; Niessen, Hans W; Baufreton, Christophe; Boer, Christa
2016-03-01
Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury. PMID:26747506
Bell, M.R.; Rumberger, J.A.; Lerman, L.O.; Behrenbeck, T.; Sheedy, P.F.; Ritman, E.L. )
1990-02-26
Measurement of myocardial perfusion with fast CT, using venous injections of contrast, underestimates high flow rates. Accounting for intramyocardial blood volume improves the accuracy of such measurements but the additional influence of different contrast injection sites is unknown. To examine this, eight closed chest anesthetized dogs (18-24 kg) underwent fast CT studies of regional myocardial perfusion which were compared to microspheres (M). Dilute iohexol (0.5 mL/kg) was injected over 2.5 seconds, via, in turn, the pulmonary artery (PA), proximal inferior vena cava (IVC) and femoral vein (FV) during CT scans performed at rest and after vasodilation with adenosine (M flow range: 52-399 mL/100 g/minute). Correlations made with M were not significantly different for PA vs IVC (n = 24), PA vs FV (n = 22) and IVC vs FV (n = 44). To determine the relative influence of injection site on accuracy of measurements above normal flow rates (> 150mL/100g/minute), CT flow (mL/100g/minute; mean {+-}SD) was compared to M. Thus, at normal flow, some CT overestimation of myocardial perfusion occurred with PA injections but FV or IVC injections provided for accurate measurements. At higher flow rates only PA and IVC injections enabled accurate CT measurements of perfusion. This may be related to differing transit kinetics of the input bolus of contrast.
Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model
Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.
2016-01-01
Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642
Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos; Schmidt, Taly Gilat
2012-09-15
Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 Degree-Sign through anthropomorphic voxelized female chest and head (0 Degree-Sign and 30 Degree-Sign tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tables of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDI{sub vol} and multiplying by a physical CTDI{sub vol} measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 Degree-Sign relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate
Optical modeling toward optimizing monitoring of intestinal perfusion in trauma patients
Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance; Cote, Gerard L.
2013-01-01
Trauma is the number one cause of death for people between the ages 1 and 44 years in the United States. In addition, according to the Centers of Disease Control and Prevention, injury results in over 31 million emergency department visits annually. Minimizing the resuscitation period in major abdominal injuries increases survival rates by correcting impaired tissue oxygen delivery. Optimization of resuscitation requires a monitoring method to determine sufficient tissue oxygenation. Oxygenation can be assessed by determining the adequacy of tissue perfusion. In this work, we present the design of a wireless perfusion and oxygenation sensor based on photoplethysmography. Through optical modeling, the benefit of using the visible wavelengths 470, 525 and 590nm (around the 525nm hemoglobin isobestic point) for intestinal perfusion monitoring is compared to the typical near infrared (NIR) wavelengths (805nm isobestic point) used in such sensors. Specifically, NIR wavelengths penetrate through the thin intestinal wall (~4mm) leading to high background signals. However, these visible wavelengths have two times shorter penetration depth that the NIR wavelengths. Monte-Carlo simulations show that the transmittance of the three selected wavelengths is lower by 5 orders of magnitude depending on the perfusion state. Due to the high absorbance of hemoglobin in the visible range, the perfusion signal carried by diffusely reflected light is also enhanced by an order of magnitude while oxygenation signal levels are maintained. In addition, short source-detector separations proved to be beneficial for limiting the probing depth to the thickness of the intestinal wall.
A Phantom Tissue System for the Calibration of Perfusion Measurements
Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Scott, Elaine P.; Diller, Thomas E.
2008-01-01
A convenient method for testing and calibrating surface perfusion sensors has been developed. A phantom tissue model is used to simulate the nondirectional blood flow of tissue perfusion. A computational fluid dynamics (CFD) model was constructed in Fluent® to design the phantom tissue and validate the experimental results. The phantom perfusion system was used with a perfusion sensor based on clearance of thermal energy. A heat flux gage measures the heat flux response of tissue when a thermal event (convective cooling) is applied. The blood perfusion and contact resistance are estimated by a parameter estimation code. From the experimental and analytical results, it was concluded that the probe displayed good measurement repeatability and sensitivity. The experimental perfusion measurements in the tissue were in good agreement with those of the CFD models and demonstrated the value of the phantom tissue system. PMID:19045509
NASA Astrophysics Data System (ADS)
Wang, Xueya; Wolf, Marc P.; Keel, Rahel Bänziger; Lehner, Roman; Hunziker, Patrick R.
2012-07-01
Existing mouse artery ex vivo perfusion models have utilized arteries such as carotid, uterine, and mesenteric arteries, but not the aorta. However, the aorta is the principal vessel analyzed for atherosclerosis studies in vivo. We have devised a mouse aorta ex vivo perfusion model that can bridge this gap. Aortas from apoE(-/-) mice are embedded in a transparent, gas-permeable, and elastic polymer matrix [polydimethylsiloxane (PDMS)] and artificially perfused with cell culture medium under cell culture conditions. After 24 h of artificial ex vivo perfusion, no evidence of cellular apoptosis is detected. Utilizing a standard confocal microscope, it is possible to image specific receptor targeting of cells in atherosclerotic plaques during 24 h. Imaging motion artifacts are minimal due to the polymer matrix embedding. Re-embedding of the aorta enables tissue sectioning and immuno-histochemical analysis. The ex vivo data are validated by comparison with in vivo experiments. This model can save animal lives via production of multiple endpoints in a single experiment, is easy to apply, and enables straightforward comparability with pre-existing atherosclerosis in vivo data. It is suited to investigate atherosclerotic disease in particular and vascular biology in general.
Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.
2014-01-01
Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters
Lennernäs, H; Lee, I D; Fagerholm, U; Amidon, G L
1997-07-01
The goal of this study was to determine the most appropriate hydrodynamic model for the Loc-I-Gut in-vivo perfusion system. The general mixing-tank-in-series model, which can approximate single mixing tank and laminar and plug-flow hydrodynamics, was fitted to the observed experimental residence-time distribution curves for the non-absorbable marker [14C]PEG 4000. The residence-time distribution analysis shows that the hydrodynamics of the perfusion solution within the jejunal segment in man is well approximately by a model containing on average between 1-2 mixing tanks in series. The solution is well mixed when using perfusion rates of 2.0, 3.0 and 6.0 mL min-1. The average mean residence time estimates from the fitted residence-time distribution were 12 +/- 7.6, 15 +/- 4.2 and 7.7 +/- 4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25 +/- 15, 45 +/- 12 and 46 +/- 27 mL, respectively. There were no statistical differences between 2.0, 3.0 and 6.0 mL min-1 in respect of the number of mixing tanks (n) and mean residence times. This residence-time distribution analysis indicates that the luminal fluid in the Loc-I-Gut perfusion system is well-mixed, and that permeability calculations based on the well-mixed assumption most closely approximate the actual local (average) membrane permeability within the perfused segment. PMID:9255711
Animal models of ex vivo lung perfusion as a platform for transplantation research
Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Jr, Don Hayes; Black, Sylvester M; Whitson, Bryan A
2014-01-01
Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117
Animal models of ex vivo lung perfusion as a platform for transplantation research.
Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Hayes, Don; Black, Sylvester M; Whitson, Bryan A
2014-05-20
Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117
Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.
2016-01-01
Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293
NASA Astrophysics Data System (ADS)
Le, Hanh N. D.; Opferman, Justin; Decker, Ryan; Cheon, Gyeong W.; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel
2016-04-01
Anastomosis, the connection of two structures, is a critical procedure for reconstructive surgery with over 1 million cases/year for visceral indication alone. However, complication rates such as strictures and leakage affect up to 19% of cases for colorectal anastomoses and up to 30% for visceral transplantation anastomoses. Local ischemia plays a critical role in anastomotic complications, making blood perfusion an important indicator for tissue health and predictor for healing following anastomosis. In this work, we apply a real time multispectral imaging technique to monitor impact on tissue perfusion due to varying interrupted suture spacing and suture tensions. Multispectral tissue images at 470, 540, 560, 580, 670 and 760 nm are analyzed in conjunction with an empirical model based on diffuse reflectance process to quantify the hemoglobin oxygen saturation within the suture site. The investigated tissues for anastomoses include porcine small (jejunum and ileum) and large (transverse colon) intestines. Two experiments using interrupted suturing with suture spacing of 1, 2, and 3 mm and tension levels from 0 N to 2.5 N are conducted. Tissue perfusion at 5, 10, 20 and 30 min after suturing are recorded and compared with the initial normal state. The result indicates the contrast between healthy and ischemic tissue areas and assists the determination of suturing spacing and tension. Therefore, the assessment of tissue perfusion will permit the development and intra-surgical monitoring of an optimal suture protocol during anastomosis with less complications and improved functional outcome.
Modeling laser speckle imaging of perfusion in the skin (Conference Presentation)
NASA Astrophysics Data System (ADS)
Regan, Caitlin; Hayakawa, Carole K.; Choi, Bernard
2016-02-01
Laser speckle imaging (LSI) enables visualization of relative blood flow and perfusion in the skin. It is frequently applied to monitor treatment of vascular malformations such as port wine stain birthmarks, and measure changes in perfusion due to peripheral vascular disease. We developed a computational Monte Carlo simulation of laser speckle contrast imaging to quantify how tissue optical properties, blood vessel depths and speeds, and tissue perfusion affect speckle contrast values originating from coherent excitation. The simulated tissue geometry consisted of multiple layers to simulate the skin, or incorporated an inclusion such as a vessel or tumor at different depths. Our simulation used a 30x30mm uniform flat light source to optically excite the region of interest in our sample to better mimic wide-field imaging. We used our model to simulate how dynamically scattered photons from a buried blood vessel affect speckle contrast at different lateral distances (0-1mm) away from the vessel, and how these speckle contrast changes vary with depth (0-1mm) and flow speed (0-10mm/s). We applied the model to simulate perfusion in the skin, and observed how different optical properties, such as epidermal melanin concentration (1%-50%) affected speckle contrast. We simulated perfusion during a systolic forearm occlusion and found that contrast decreased by 35% (exposure time = 10ms). Monte Carlo simulations of laser speckle contrast give us a tool to quantify what regions of the skin are probed with laser speckle imaging, and measure how the tissue optical properties and blood flow affect the resulting images.
NASA Technical Reports Server (NTRS)
Vidal Melo, M. F.; Loeppky, J. A.; Caprihan, A.; Luft, U. C.
1993-01-01
This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.
Dynamic CT perfusion measurement in a cardiac phantom.
Ziemer, Benjamin P; Hubbard, Logan; Lipinski, Jerry; Molloi, Sabee
2015-10-01
Widespread clinical implementation of dynamic CT myocardial perfusion has been hampered by its limited accuracy and high radiation dose. The purpose of this study was to evaluate the accuracy and radiation dose reduction of a dynamic CT myocardial perfusion technique based on first pass analysis (FPA). To test the FPA technique, a pulsatile pump was used to generate known perfusion rates in a range of 0.96-2.49 mL/min/g. All the known perfusion rates were determined using an ultrasonic flow probe and the known mass of the perfusion volume. FPA and maximum slope model (MSM) perfusion rates were measured using volume scans acquired from a 320-slice CT scanner, and then compared to the known perfusion rates. The measured perfusion using FPA (P(FPA)), with two volume scans, and the maximum slope model (P(MSM)) were related to known perfusion (P(K)) by P(FPA) = 0.91P(K) + 0.06 (r = 0.98) and P(MSM) = 0.25P(K) - 0.02 (r = 0.96), respectively. The standard error of estimate for the FPA technique, using two volume scans, and the MSM was 0.14 and 0.30 mL/min/g, respectively. The estimated radiation dose required for the FPA technique with two volume scans and the MSM was 2.6 and 11.7-17.5 mSv, respectively. Therefore, the FPA technique can yield accurate perfusion measurements using as few as two volume scans, corresponding to approximately a factor of four reductions in radiation dose as compared with the currently available MSM. In conclusion, the results of the study indicate that the FPA technique can make accurate dynamic CT perfusion measurements over a range of clinically relevant perfusion rates, while substantially reducing radiation dose, as compared to currently available dynamic CT perfusion techniques. PMID:26156231
Rosa, Maria J.; Mehta, Mitul A.; Pich, Emilio M.; Risterucci, Celine; Zelaya, Fernando; Reinders, Antje A. T. S.; Williams, Steve C. R.; Dazzan, Paola; Doyle, Orla M.; Marquand, Andre F.
2015-01-01
An increasing number of neuroimaging studies are based on either combining more than one data modality (inter-modal) or combining more than one measurement from the same modality (intra-modal). To date, most intra-modal studies using multivariate statistics have focused on differences between datasets, for instance relying on classifiers to differentiate between effects in the data. However, to fully characterize these effects, multivariate methods able to measure similarities between datasets are needed. One classical technique for estimating the relationship between two datasets is canonical correlation analysis (CCA). However, in the context of high-dimensional data the application of CCA is extremely challenging. A recent extension of CCA, sparse CCA (SCCA), overcomes this limitation, by regularizing the model parameters while yielding a sparse solution. In this work, we modify SCCA with the aim of facilitating its application to high-dimensional neuroimaging data and finding meaningful multivariate image-to-image correspondences in intra-modal studies. In particular, we show how the optimal subset of variables can be estimated independently and we look at the information encoded in more than one set of SCCA transformations. We illustrate our framework using Arterial Spin Labeling data to investigate multivariate similarities between the effects of two antipsychotic drugs on cerebral blood flow. PMID:26528117
Rosa, Maria J; Mehta, Mitul A; Pich, Emilio M; Risterucci, Celine; Zelaya, Fernando; Reinders, Antje A T S; Williams, Steve C R; Dazzan, Paola; Doyle, Orla M; Marquand, Andre F
2015-01-01
An increasing number of neuroimaging studies are based on either combining more than one data modality (inter-modal) or combining more than one measurement from the same modality (intra-modal). To date, most intra-modal studies using multivariate statistics have focused on differences between datasets, for instance relying on classifiers to differentiate between effects in the data. However, to fully characterize these effects, multivariate methods able to measure similarities between datasets are needed. One classical technique for estimating the relationship between two datasets is canonical correlation analysis (CCA). However, in the context of high-dimensional data the application of CCA is extremely challenging. A recent extension of CCA, sparse CCA (SCCA), overcomes this limitation, by regularizing the model parameters while yielding a sparse solution. In this work, we modify SCCA with the aim of facilitating its application to high-dimensional neuroimaging data and finding meaningful multivariate image-to-image correspondences in intra-modal studies. In particular, we show how the optimal subset of variables can be estimated independently and we look at the information encoded in more than one set of SCCA transformations. We illustrate our framework using Arterial Spin Labeling data to investigate multivariate similarities between the effects of two antipsychotic drugs on cerebral blood flow. PMID:26528117
The isolated perfused equine distal limb as an ex vivo model for pharmacokinetic studies.
Friebe, M; Stahl, J; Kietzmann, M
2013-06-01
Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered as BM disodium phosphate intra-articularly to the fetlock joint (4 mg BM/joint), was investigated. The concentration of BM in the venous perfusate of the radial vein was measured by means of high-performance liquid chromatography. The average BM efflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mg BM had left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies. PMID:22913456
NASA Astrophysics Data System (ADS)
Lu, Xiaoguang; Xue, Hui; Jolly, Marie-Pierre; Guetter, Christoph; Kellman, Peter; Hsu, Li-Yueh; Arai, Andrew; Zuehlsdorff, Sven; Littmann, Arne; Georgescu, Bogdan; Guehring, Jens
2011-03-01
Cardiac perfusion magnetic resonance imaging (MRI) has proven clinical significance in diagnosis of heart diseases. However, analysis of perfusion data is time-consuming, where automatic detection of anatomic landmarks and key-frames from perfusion MR sequences is helpful for anchoring structures and functional analysis of the heart, leading toward fully automated perfusion analysis. Learning-based object detection methods have demonstrated their capabilities to handle large variations of the object by exploring a local region, i.e., context. Conventional 2D approaches take into account spatial context only. Temporal signals in perfusion data present a strong cue for anchoring. We propose a joint context model to encode both spatial and temporal evidence. In addition, our spatial context is constructed not only based on the landmark of interest, but also the landmarks that are correlated in the neighboring anatomies. A discriminative model is learned through a probabilistic boosting tree. A marginal space learning strategy is applied to efficiently learn and search in a high dimensional parameter space. A fully automatic system is developed to simultaneously detect anatomic landmarks and key frames in both RV and LV from perfusion sequences. The proposed approach was evaluated on a database of 373 cardiac perfusion MRI sequences from 77 patients. Experimental results of a 4-fold cross validation show superior landmark detection accuracies of the proposed joint spatial-temporal approach to the 2D approach that is based on spatial context only. The key-frame identification results are promising.
Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model
Yang, Kwang Mo; Russell, James; Lupu, Mihaela E.; Cho, HyungJoon; Li, Xiao-Feng; Koutcher, Jason A.; Ling, C. Clifton
2010-01-01
The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone. PMID:19717985
NASA Astrophysics Data System (ADS)
Forkert, Nils Daniel; Kaesemann, Philipp; Fiehler, Jens; Thomalla, Götz
2012-03-01
Acute stroke is a major cause for death and disability among adults in the western hemisphere. Time-resolved perfusion-weighted (PWI) and diffusion-weighted (DWI) MR datasets are typically used for the estimation of tissue-at-risk, which is an important variable for acute stroke therapy decision-making. Although several parameters, which can be estimated based on PWI concentration curves, have been proposed for tissue-at-risk definition in the past, the time-to-peak (TTP) or time-to-max (Tmax) parameter is used most frequently in recent trials. Unfortunately, there is no clear consensus which method should be used for estimation of Tmax or TTP maps. Consequently, tissue-at-risk estimations and following treatment decision might vary considerably with the method used. In this work, 5 PWI datasets of acute stroke patients were used to calculate TTP or Tmax maps using 10 different estimation techniques. The resulting maps were segmented using a typical threshold of +4s and the corresponding PWI-lesions were calculated. The first results suggest that the TTP or Tmax method used has a major impact on the resulting tissue-at-risk volume. Numerically, the calculated volumes differed up to a factor of 3. In general, the deconvolution-based Tmax techniques estimate the ischemic penumbra rather smaller compared to direct TTP based techniques. In conclusion, the comparison of different methods for TTP or Tmax estimation revealed high variations regarding the resulting tissue-at-risk volume, which might lead to different therapy decisions. Therefore, a consensus how TTP or Tmax maps should be calculated seems necessary.
Chung, Wen Yuan; Gravante, Gianpiero; Eltweri, Amar; Sorge, Roberto; Ong, Seok Ling; Pollard, Cristina; Metcalfe, Mathew; Dennison, Ashley
2015-06-01
The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu. PMID:25557139
NASA Astrophysics Data System (ADS)
Storm, Corstiaan J.; Slump, Cornelis H.
2008-03-01
Coronary angiography is the primary technique for diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. However, the clinical relevance of an appearing stenosis is not that easy to assess. In previous work we have analyzed the myocardial perfusion by comparing basal and hyperemic coronary flow. This comparison is the basis of a Relative Coronary Flow Reserve (RCFR) measure. In a Region-of-Interest (ROI) on the angiogram the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In previous work we have presented the results of a small study of 20 patients. In this paper we present an analysis of the sensitivity of the method for variations in X-ray exposure between the two runs due to the Automatic Exposure Control (AEC) unit. The AEC is a system unit with the task to ensure a constant dose rate at the entrance of the detector by making the appropriate adaptations in X-ray factor settings for patients which range from slim to more obese. We have setup a phantom study to reveal the expected exposure variations. We present several of the developed phantoms together with a compensation strategy.
Validation of a two-compartment model of ventilation/perfusion distribution.
Loeppky, Jack A; Caprihan, Arvind; Altobelli, Stephen A; Icenogle, Milton V; Scotto, Pietro; Vidal Melo, Marcos F
2006-03-28
Ventilation (V (A)) to perfusion (Q ) heterogeneity (V (A)/Q ) analyses by a two-compartment lung model (2C), utilizing routine gas exchange measurements and a computer solution to account for O(2) and CO(2) measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V (A)/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V (A)/Q distributions (SD(V (A)/Q )) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(V (A)/Q ) values. SD(V (A)/Q ) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V (A)/Q ) weighted by V (A) was closer to MC at higher values because the V (A)-weighted SD(V (A)/Q ) is related to blood-to-gas PCO(2) differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V (A)/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O(2) diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V (A)/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible. PMID:16024300
Assessment of myocardial blood perfusion improved by CD151 in a pig myocardial infarction model
Zuo, Hou-juan; Liu, Zheng-xiang; Liu, Xiao-chun; Yang, Jun; Liu, Tao; Wen, Sha; Wang, Dao-wen; Zhang, Xin
2009-01-01
Aim: To appraise the efficacy of CD151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model. Methods: CD151 and anti-CD151 were constructed into the recombinant adeno-associated virus (rAAV) vector. All 26 pigs were subjected to coronary artery ligation or no surgery. Eight weeks after coronary artery ligation, the expression of CD151 was measured by Western blot and immunostaining. Capillary density was evaluated using immunostaining for von Willebrand factor (vWF). 13N-labeled NH3 positron emission computed tomography ([13N]NH3 PET) was measured to assess regional myocardial perfusion and the defect area. Results: CD151 gene delivery could increase the expression of CD151 at protein level. Over-expression of CD151 increased the density of total capillaries in the ischemic myocardium, significantly improved the blood perfusion and reduced the defect area percentage. Conclusion: This study demonstrated that the rAAV-mediated CD151 gene delivery promoted efficient neovascularization and increased the blood perfusion after myocardial infarction in pigs. PMID:19079294
Pekor, Christopher; Gerlach, Jörg C.; Nettleship, Ian
2015-01-01
The development of functional engineered tissue constructs depends on high cell densities and appropriate vascularization. In this study we implemented a four-compartment three-dimensional perfusion bioreactor culture model for studying the effects of medium perfusion on endothelial, hepatic, and hematopoietic cell populations of primary human fetal liver in an in vivo-like environment. Human fetal liver cells were cultured in bioreactors configured to provide either perfusion or diffusion conditions. Metabolic activities of the cultures were monitored daily by measuring glucose consumption and lactate production. Cell viability during culture was analyzed by lactate dehydrogenase activity. Hepatic functionality was determined by the release of albumin and alpha-fetoprotein (AFP) in culture medium samples. After 4 days of culture, cells were analyzed for the expression of a variety of endothelial, hepatic, and hematopoietic genes, as well as the surface marker expression of CD31 and CD34 in flow cytometry. We found that medium perfusion increased the gene expression of endothelial markers such as CD31, von Willebrand factor (vWF), CD140b, CD309, and CD144 while decreasing the gene expression of the erythrocyte-surface marker CD235a. Hepatic differentiation was promoted under perfusion conditions as demonstrated by lower AFP and higher albumin secretion compared with cultures not exposed to medium perfusion. Additionally, cultures exposed to medium perfusion gave higher rates of glucose consumption and lactate production, indicating increased metabolic activity. In conclusion, high-density bioreactors configured to provide constant medium perfusion significantly induced hepatic and endothelial cell differentiation and provided improved conditions for the culture of human fetal liver cells compared with cultures without perfusion. PMID:25559936
Pekor, Christopher; Gerlach, Jörg C; Nettleship, Ian; Schmelzer, Eva
2015-07-01
The development of functional engineered tissue constructs depends on high cell densities and appropriate vascularization. In this study we implemented a four-compartment three-dimensional perfusion bioreactor culture model for studying the effects of medium perfusion on endothelial, hepatic, and hematopoietic cell populations of primary human fetal liver in an in vivo-like environment. Human fetal liver cells were cultured in bioreactors configured to provide either perfusion or diffusion conditions. Metabolic activities of the cultures were monitored daily by measuring glucose consumption and lactate production. Cell viability during culture was analyzed by lactate dehydrogenase activity. Hepatic functionality was determined by the release of albumin and alpha-fetoprotein (AFP) in culture medium samples. After 4 days of culture, cells were analyzed for the expression of a variety of endothelial, hepatic, and hematopoietic genes, as well as the surface marker expression of CD31 and CD34 in flow cytometry. We found that medium perfusion increased the gene expression of endothelial markers such as CD31, von Willebrand factor (vWF), CD140b, CD309, and CD144 while decreasing the gene expression of the erythrocyte-surface marker CD235a. Hepatic differentiation was promoted under perfusion conditions as demonstrated by lower AFP and higher albumin secretion compared with cultures not exposed to medium perfusion. Additionally, cultures exposed to medium perfusion gave higher rates of glucose consumption and lactate production, indicating increased metabolic activity. In conclusion, high-density bioreactors configured to provide constant medium perfusion significantly induced hepatic and endothelial cell differentiation and provided improved conditions for the culture of human fetal liver cells compared with cultures without perfusion. PMID:25559936
Decorte, Nicolas; Buehler, Tania; Caldas de Almeida Araujo, Ericky; Vignaud, Alexandre; Carlier, Pierre G
2014-01-01
The objective of this work was to demonstrate the feasibility of measuring muscle O2 consumption (V˙O2) noninvasively with a combination of functional nuclear magnetic resonance (NMR) imaging methods, and to verify that changes in muscle V˙O2 can be detected with a temporal resolution compatible with physiological investigation and patient ease. T2-based oxymetry of arterial and venous blood was combined with the arterial-spin labeling (ASL)-based determination of muscle perfusion. These measurements were performed on 8 healthy volunteers under normoxic and hypoxic conditions in order to assess the sensitivity of measurements over a range of saturation values. Blood samples were drawn simultaneously and used to titrate blood T2 measurements versus hemoglobin O2 saturation (%HbO2) in vitro. The in vitro calibration curve of blood T2 fitted very well with the %HbO2 (r(2): 0.95). The in vivo venous T2 measurements agreed well with the in vitro measurements (intraclass correlation coefficient 0.82, 95% confidence interval 0.61-0.91). Oxygen extraction at rest decreased in the calf muscles subjected to hypoxia (p = 0.031). The combination of unaltered muscle perfusion and pinched arteriovenous O2 difference (p = 0.038) pointed towards a reduced calf muscle V˙O2 during transient hypoxia (p = 0.018). The results of this pilot study confirmed that muscle O2 extraction and V˙O2 can be estimated noninvasively using a combination of functional NMR techniques. Further studies are needed to confirm the usefulness in a larger sample of volunteers and patients. PMID:25531648
Hall, Sheldon K.; Ooi, Ean H.; Payne, Stephen J.
2015-01-01
Abstract Purpose: A sensitivity analysis has been performed on a mathematical model of radiofrequency ablation (RFA) in the liver. The purpose of this is to identify the most important parameters in the model, defined as those that produce the largest changes in the prediction. This is important in understanding the role of uncertainty and when comparing the model predictions to experimental data. Materials and methods: The Morris method was chosen to perform the sensitivity analysis because it is ideal for models with many parameters or that take a significant length of time to obtain solutions. A comprehensive literature review was performed to obtain ranges over which the model parameters are expected to vary, crucial input information. Results: The most important parameters in predicting the ablation zone size in our model of RFA are those representing the blood perfusion, electrical conductivity and the cell death model. The size of the 50 °C isotherm is sensitive to the electrical properties of tissue while the heat source is active, and to the thermal parameters during cooling. Conclusions: The parameter ranges chosen for the sensitivity analysis are believed to represent all that is currently known about their values in combination. The Morris method is able to compute global parameter sensitivities taking into account the interaction of all parameters, something that has not been done before. Research is needed to better understand the uncertainties in the cell death, electrical conductivity and perfusion models, but the other parameters are only of second order, providing a significant simplification. PMID:26000972
Noninvasive Blood Perfusion Measurements of an Isolated Rat Liver and an Anesthetized Rat Kidney
Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Lee, Charles Y.; Diller, Thomas E.; Scott, Elaine P.
2008-01-01
A simple, cost effective, and noninvasive blood perfusion system is tested in animal models. The system uses a small sensor to measure the heat transfer response to a thermal event (convective cooling) imposed on the tissue surface. Heat flux data are compared with a mathematical model of the tissue to estimate both blood perfusion and thermal contact resistance between the tissue and the probe. The perfusion system was evaluated for repeatability and sensitivity using isolated rat liver and exposed rat kidney tests. Perfusion in the isolated liver tests was varied by controlling the flow of the perfusate into the liver, and the perfusion in the exposed kidney tests was varied by temporarily occluding blood flow through the renal artery and vein. The perfusion estimated by the convective perfusion probe was in good agreement with that of the metered flow of the perfusate into the liver model. The liver tests indicated that the probe can be used to detect small changes in perfusion (0.005 ml/ml/s). The probe qualitatively tracked the changes in the perfusion in the kidney model due to occlusion of the renal artery and vein. PMID:19045542
Hunter, Kendall S; Fjield, Todd; Heitzmann, Hal; Shandas, Robin; Kahook, Malik Y
2014-01-01
Micro-invasive glaucoma surgery with the Glaukos iStent® or iStent inject® (Glaukos Corporation, Laguna Hills, CA, USA) is intended to create a bypass through the trabecular meshwork to Schlemm’s canal to improve aqueous outflow through the natural physiologic pathway. While the iStent devices have been evaluated in ex vivo anterior segment models, they have not previously been evaluated in whole eye perfusion models nor characterized by computational fluid dynamics. Intraocular pressure (IOP) reduction with the iStent was evaluated in an ex vivo whole human eye perfusion model. Numerical modeling, including computational fluid dynamics, was used to evaluate the flow through the stents over physiologically relevant boundary conditions. In the ex vivo model, a single iStent reduced IOP by 6.0 mmHg from baseline, and addition of a second iStent further lowered IOP by 2.9 mmHg, for a total IOP reduction of 8.9 mmHg. Computational modeling showed that simulated flow through the iStent or iStent inject is smooth and laminar at physiological flow rates. Each stent was computed to have a negligible flow resistance consistent with an expected significant decrease in IOP. The present perfusion results agree with prior clinical and laboratory studies to show that both iStent and iStent inject therapies are potentially titratable, providing clinicians with the opportunity to achieve lower target IOPs by implanting additional stents. PMID:24648713
Donaldson, Stephanie B.; Betts, Guy; Bonington, Suzanne C.; Homer, Jarrod J.; Slevin, Nick J.; Kershaw, Lucy E.; Valentine, Helen; West, Catharine M.L.; Buckley, David L.
2011-11-15
Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. Methods and Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. Results: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). Conclusions: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.
Segmentation of the Left Ventricle in Myocardial Perfusion SPECT Using Active Shape Model
NASA Astrophysics Data System (ADS)
Tan, Wooi-Haw; Besar, Rosli
In the quantification of myocardial perfusion SPECT (MPS), numerous processes are involved. Automation is desired as it will considerably reduce the laboriousness of the underlying tasks. In this paper, we propose a segmentation scheme for the delineation of left ventricle (LV) using the Active Shape Models. Our scheme will reduce the labour-intensiveness in MPS quantification, while still allowing interactive guidance from the medical experts. The proposed scheme has been applied on clinical MPS tomograms in which it has successfully delineated the LV in 94% of the test data. In addition, it has also shown to be more suitable for LV segmentation than the rivaling Active Contour Model.
Blind estimation of compartmental model parameters.
Di Bella, E V; Clackdoyle, R; Gullberg, G T
1999-03-01
Computation of physiologically relevant kinetic parameters from dynamic PET or SPECT imaging requires knowledge of the blood input function. This work is concerned with developing methods to accurately estimate these kinetic parameters blindly; that is, without use of a directly measured blood input function. Instead, only measurements of the output functions--the tissue time-activity curves--are used. The blind estimation method employed here minimizes a set of cross-relation equations, from which the blood term has been factored out, to determine compartmental model parameters. The method was tested with simulated data appropriate for dynamic SPECT cardiac perfusion imaging with 99mTc-teboroxime and for dynamic PET cerebral blood flow imaging with 15O water. The simulations did not model the tomographic process. Noise levels typical of the respective modalities were employed. From three to eight different regions were simulated, each with different time-activity curves. The time-activity curve (24 or 70 time points) for each region was simulated with a compartment model. The simulation used a biexponential blood input function and washin rates between 0.2 and 1.3 min(-1) and washout rates between 0.2 and 1.0 min(-1). The system of equations was solved numerically and included constraints to bound the range of possible solutions. From the cardiac simulations, washin was determined to within a scale factor of the true washin parameters with less than 6% bias and 12% variability. 99mTc-teboroxime washout results had less than 5% bias, but variability ranged from 14% to 43%. The cerebral blood flow washin parameters were determined with less than 5% bias and 4% variability. The washout parameters were determined with less than 4% bias, but had 15-30% variability. Since washin is often the parameter of most use in clinical studies, the blind estimation approach may eliminate the current necessity of measuring the input function when performing certain dynamic studies
NASA Astrophysics Data System (ADS)
Miyazaki, Shohei; Yamazaki, Youichi; Murase, Kenya
2008-11-01
We performed an error analysis of the quantification of liver perfusion from dynamic contrast-enhanced computed tomography (DCE-CT) data using a dual-input single-compartment model for various disease severities, based on computer simulations. In the simulations, the time-density curves (TDCs) in the liver were generated from an actually measured arterial input function using a theoretical equation describing the kinetic behavior of the contrast agent (CA) in the liver. The rate constants for the transfer of CA from the hepatic artery to the liver (K1a), from the portal vein to the liver (K1p), and from the liver to the plasma (k2) were estimated from simulated TDCs with various plasma volumes (V0s). To investigate the effect of the shapes of input functions, the original arterial and portal-venous input functions were stretched in the time direction by factors of 2, 3 and 4 (stretching factors). The above parameters were estimated with the linear least-squares (LLSQ) and nonlinear least-squares (NLSQ) methods, and the root mean square errors (RMSEs) between the true and estimated values were calculated. Sensitivity and identifiability analyses were also performed. The RMSE of V0 was the smallest, followed by those of K1a, k2 and K1p in an increasing order. The RMSEs of K1a, K1p and k2 increased with increasing V0, while that of V0 tended to decrease. The stretching factor also affected parameter estimation in both methods. The LLSQ method estimated the above parameters faster and with smaller variations than the NLSQ method. Sensitivity analysis showed that the magnitude of the sensitivity function of V0 was the greatest, followed by those of K1a, K1p and k2 in a decreasing order, while the variance of V0 obtained from the covariance matrices was the smallest, followed by those of K1a, K1p and k2 in an increasing order. The magnitude of the sensitivity function and the variance increased and decreased, respectively, with increasing disease severity and decreased
Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival
2015-09-01
Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. PMID:25891783
NASA Astrophysics Data System (ADS)
Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration
2015-11-01
Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.
Jonas, Jost B.; Wang, Ningli; Nangia, Vinay
2015-01-01
Purpose: To test the hypothesis that taking translamina pressure difference into consideration changes associations between ocular perfusion pressure and glaucomatous optic neuropathy. Methods: The population-based Central India Eye and Medical Study included 4711 subjects. Ocular perfusion pressure was calculated as follows: ⅔ [diastolic blood pressure + ⅓ × (systolic blood pressure – diastolic blood pressure)] – IOP. Cerebrospinal fluid pressure (mm Hg) was estimated as follows: 0.44 body mass index (kg/m2) + 0.16 diastolic blood pressure (mm Hg) − 0.18 × age (years) − 1.91. Translamina pressure difference was IOP minus cerebrospinal fluid pressure. Results: In multivariate analysis, higher open-angle glaucoma prevalence was associaed with higher IOP (P<.001; odds ratio [OR], 1.19; 95% CI, 1.15, 1.24) or with higher translamina pressure difference (P<.001; OR, 1.15; 95% CI, 1.10, 1.19), but not with ocular perfusion pressure (P<.37). A smaller neuroretinal rim area was correlated with higher IOP (P<.001; standardized coefficient beta −0.09) or larger translamina pressure difference (P<.001; β −0.10), but not with ocular perfusion pressure (P=.26). Greater prevalence of angle-closure glaucoma was associated with higher IOP (P<.001; OR, 1.22; 95% CI, 1.15, 1.28) or higher translamina pressure difference (P<.001; OR, 1.19; 95% CI, 1.13, 1.25) or lower ocular perfusion pressure (P<.04; OR, 0.95; 95% CI, 0.90, 0.996). Correlation coefficients were highest for the association with IOP and lowest for ocular perfusion pressure. A smaller rim area was correlated with higher IOP (P<.001; beta −0.08) and higher translamina pressure difference (P<.001; beta −0.08); rim area and ocular perfusion pressure were not significantly associated (P=.25). Conclusions: The present study provides information on the relationship of translamina pressure difference to the development of optic nerve damage in what is presently called glaucoma. It does not provide
NASA Astrophysics Data System (ADS)
Stantz, Keith M.; Liang, Yun; Meyer, Cristopher A.; Teague, Shawn; Stecker, Michael; Hutchins, Gary; McLennan, Gordon; Persohn, Scott
2003-05-01
Purpose: To evaluate whether functional multi-slice computed tomography (MSCT) can identify regional areas of normally perfused and ischemic myocardium in a porcine model. Material and Methods: Three out bred pigs, two of which had ameroids surgically implanted to constrict flow within the LAD and LCx coronary arteries, were injected with 25 mL of iopromide (Isovue) at a rate of 5 mL/second via the femoral or jugular vein. Sixty axial scans along the short axis of the heart was acquired on a 16-slice CT scanner (Philips MX8000-IDT) triggered at end-diastole of the cardiac cycle and acquiring an image within 270 msec. A second series of scans were taken after an intravenous injection of a vasodilator, 150 μg/kg/min of adenosine. ROIs were drawn around the myocardial tissue and the resulting time-density curves were used to extract perfusion values. Results: Determination of the myocardial perfusion and fractional blood volume implementing three different perfusion models. A 5-point averaging or 'smoothing' algorithm was employed to effectively filter the data due to its noisy nature. The (preliminary) average perfusion and fractional blood volume values over selected axial slices for the pig without an artificially induced stenosis were measured to be 84 +/- 22 mL/min/100g-tissue and 0.17 +/- 0.04 mL/g-tissue, the former is consistent with PET scan and EBCT results. The pig with a stenosis in the left LAD coronary artery showed a reduced global perfusion value -- 45 mL/min/100g-tissue. Correlations in regional perfusion values relative to the stenosis were weak. During the infusion of adenosine, averaged perfusion values for the three subjects increased by 46 (+/-45) percent, comparable to increases measured with PET. Conclusion: Quantifying global perfusion values using MDCT appear encouraging. Future work will focus resolving the systematic effects from noise due to signal fluctuation from the porcine tachyardia (80-93 BPM) and provide a more robust measurement
NASA Astrophysics Data System (ADS)
Ghaly, Michael; Links, Jonathan M.; Frey, Eric C.
2016-03-01
The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel-hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators
Ghaly, Michael; Links, Jonathan M; Frey, Eric C
2016-03-01
The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel-hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators
NASA Astrophysics Data System (ADS)
Deán-Ben, Xosé Luís.; Ermolayev, Vladimir; Mandal, Subhamoy; Ntziachristos, Vasilis; Razansky, Daniel
2016-03-01
Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.
NASA Astrophysics Data System (ADS)
Diana, Michele
2016-03-01
Pre-anastomotic bowel perfusion is a key factor for a successful healing process. Clinical judgment has limited accuracy to evaluate intestinal microperfusion. Fluorescence videography is a promising tool for image-guided intraoperative assessment of the bowel perfusion at the future anastomotic site in the setting of minimally invasive procedures. The standard configuration for fluorescence videography includes a Near-Infrared endoscope able to detect the signal emitted by a fluorescent dye, more frequently Indocyanine Green (ICG), which is administered by intravenous injection. Fluorescence intensity is proportional to the amount of fluorescent dye diffusing in the tissue and consequently is a surrogate marker of tissue perfusion. However, fluorescence intensity alone remains a subjective approach and an integrated computer-based analysis of the over-time evolution of the fluorescence signal is required to obtain quantitative data. We have developed a solution integrating computer-based analysis for intra-operative evaluation of the optimal resection site, based on the bowel perfusion as determined by the dynamic fluorescence intensity. The software can generate a "virtual perfusion cartography", based on the "fluorescence time-to-peak". The virtual perfusion cartography can be overlapped onto real-time laparoscopic images to obtain the Enhanced Reality effect. We have defined this approach FLuorescence-based Enhanced Reality (FLER). This manuscript describes the stepwise development of the FLER concept.
Piiper, J; Meyer, M
1984-01-01
In order to study the dependence of blood-tissue gas exchange upon diffusion, the simultaneous washout of two inert gases of differing diffusivity was investigated in isolated-perfused dog gastrocnemius preparations. The muscles were equilibrated with CH4 and SF6 via arterial blood. The washout kinetics were determined from venous blood samples analyzed by gas chromatography. The results revealed the following features: The washout of the test gases was pronouncedly multi-exponential, and could be described by three exponential components when analyzed to 5% of the initial value. The non-exponential washout was attributed to unequal distribution of capillary blood flow to tissue volume. The mean ratio of washout rate constants CH4/SF6 was within 1.10-1.25 and was even smaller than the ratio expected for pure perfusion limitation (1.46). Therefore, no evidence for effective tissue-blood diffusion limitation was obtained. The observed washout rate constant ratio could be explained by a model with veno-arterial back diffusion which more strongly retards washout kinetics of the better diffusible gas (CH4) as compared to the less diffusible gas (SF6). PMID:6731103
Single-pass intestinal perfusion to establish the intestinal permeability of model drugs in mouse.
Escribano, Elvira; Sala, Xavier García; Salamanca, Jorge; Navarro, Claudia Roig; Regué, Josep Queralt
2012-10-15
The aim of the present work was to study the intestinal permeabilities (P(eff)) of five model drugs: furosemide, piroxicam, naproxen, ranitidine and amoxicillin in the in situ intestinal perfusion technique in mice and compare them with corresponding rat and human in vivo P(eff) values. The main experimental conditions were: mice CD1 30-35 g, test drug concentrations in perfusion experiments (the highest dose strength dissolved in 250 mL of PBS pH 6.2) and flow rate of 0.2 mL/min. The test compounds were assayed following a validated HPLC method. The effective permeability coefficients at steady-state were calculated after correcting the outlet concentration following the gravimetric correction method proposed by Sutton et al. (2001). The permeability coefficient values ranged from 0.1751±0.0756×10(-4) cm/s for ranitidine to 17.19±4.16×10(-4) cm/s for naproxen. The mouse method correctly assigned the BCS permeability classification of a given drug and a correlation between mouse permeability data and the fraction of an oral dose absorbed in humans was achieved (FA=1-exp(-34,745·P(eff(mouse))); R=0.9631). Based on the results obtained, we conclude that mouse can be considered a valuable tool in the evaluation of intestinal permeability in order to predict the extent of human gastrointestinal absorption following oral administration of a drug. PMID:22814225
Medeiros, Israel L.; Pêgo-Fernandes, Paulo M.; Mariani, Alessandro W.; Fernandes, Flávio G.; Unterpertinger, Fernando V.; Canzian, Mauro; Jatene, Fabio B.
2012-01-01
OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex® was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p = 0.035). The mean pulmonary compliance was 46.8 cm H2O in Group 1 and 49.3 ml/cm H2O in Group 2 (p = 0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p = 0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm2 and 137.50/mm2, respectively (p = 0.71). CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation. PMID:23018310
NASA Astrophysics Data System (ADS)
Stiukhina, Elena S.; Kurochkin, Maxim A.; Klochkov, Victor A.; Fedosov, Ivan V.; Postnov, Dmitry E.
2015-03-01
A method is presented to obtain information on tissue perfusability from capillary velocimetry experiments coupled with venous occlusion probe. The method based on data fitting to developed mathematical model describing the blood flow redistribution caused by the introduced occlusion. Using mathematical modeling, we identify the segment of velocity time courses that corresponds to tissue swelling process and thus allows ones quantify it. We also compared the results of direct measurement of red blood cells (RBCs) velocity with time courses obtained from finger-placed sensors of two types: (i) photoplethysmographic sensor used in pulsometry and (ii) piezoelectric sensor for sphygmography. The obtained results suggest the measurable contribution of RBCs aggregation process in optical pulse signal formation.
2013-01-01
Background The first crucial step in transplantation appears to be the effective rinsing of the graft during organ procurement. Even though there is strong suspicion that ex situ perfusion results in better rinsing of the graft, there is no proof for this hypothesis. The aim of this study was to analyse the differences of in situ and ex situ kidney perfusion in a porcine model. Methods Standardised multiorgan procurement was performed in 15 German landrace pigs. Perfusion was carried out using histidine–tryptophan–ketoglutarate solution (HTK) under the application of pressure. In one kidney, in situ perfusion via the aorta was carried out while the second kidney received ex situ perfusion via the renal artery (RA). Perfusate flow inside the aorta and the RA was recorded at different pressure steps. In order to visualise the effect on the microcirculation, different coloured microparticles (MPs; 10 μm) were administered via the aorta or RA. Subsequently, frozen sections of the explanted kidneys were analysed histologically and MPs were evaluated quantitatively. Results Ex situ kidney perfusion resulted in significantly improved flow rates (P<0.0001) compared with in situ perfusion. By applying ex situ perfusion it was even possible to attain physiological flow levels on the RA under the application of external pressure of 150 to 200 mmHg. The amount of MPs was able to highlight the positive impact of ex situ perfusion on microcirculation of the kidney graft (P<0.0001). Conclusions The use of MPs represents a valuable tool for quantitative investigation and illustration of kidney perfusion in experimental setups. Additional ex situ perfusion is able to improve the quality of kidney perfusion. PMID:23837545
Borst, Jordi; Marquering, Henk A.; Beenen, Ludo F. M.; Berkhemer, Olvert A.; Dankbaar, Jan Willem; Riordan, Alan J.; Majoie, Charles B. L. M.
2015-01-01
Background and Purpose It has been suggested that CT Perfusion acquisition times <60 seconds are too short to capture the complete in and out-wash of contrast in the tissue, resulting in incomplete time attenuation curves. Yet, these short acquisitions times are not uncommon in clinical practice. The purpose of this study was to investigate the occurrence of time attenuation curve truncation in 48 seconds CT Perfusion acquisition and to quantify its effect on ischemic core and penumbra estimation in patients with acute ischemic stroke due to a proximal intracranial arterial occlusion of the anterior circulation. Materials and Methods We analyzed CT Perfusion data with 48 seconds and extended acquisition times, assuring full time attenuation curves, of 36 patients. Time attenuation curves were classified as complete or truncated. Ischemic core and penumbra volumes resulting from both data sets were compared by median paired differences and interquartile ranges. Controlled experiments were performed using a digital CT Perfusion phantom to investigate the effect of time attenuation curve truncation on ischemic core and penumbra estimation. Results In 48 seconds acquisition data, truncation was observed in 24 (67%) cases for the time attenuation curves in the ischemic core, in 2 cases for the arterial input function and in 5 cases for the venous output function. Analysis of extended data resulted in smaller ischemic cores and larger penumbras with a median difference of 13.2 (IQR: 4.3–26.0)ml (P<0.001) and; 12.4 (IQR: 4.1–25.7)ml (P<0.001), respectively. The phantom data showed increasing ischemic core overestimation with increasing tissue time attenuation curve truncation. Conclusions Truncation is common in patients with large vessel occlusion and results in repartitioning of the area of hypoperfusion into larger ischemic core and smaller penumbra estimations. Phantom experiments confirmed that truncation results in overestimation of the ischemic core. PMID
Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus
2016-01-01
Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications. PMID:26253243
Debbaut, Charlotte; Vierendeels, Jan; Siggers, Jennifer H; Repetto, Rodolfo; Monbaliu, Diethard; Segers, Patrick
2014-01-01
The hepatic blood circulation is complex, particularly at the microcirculatory level. Previously, 2D liver lobule models using porous media and a 3D model using real sinusoidal geometries have been developed. We extended these models to investigate the role of vascular septa (VS) and anisotropic permeability. The lobule was modelled as a hexagonal prism (with or without VS) and the tissue was treated as a porous medium (isotropic or anisotropic permeability). Models were solved using computational fluid dynamics. VS inclusion resulted in more spatially homogeneous perfusion. Anisotropic permeability resulted in a larger axial velocity component than isotropic permeability. A parameter study revealed that results are most sensitive to the lobule size and radial pressure drop. Our model provides insight into hepatic microhaemodynamics, and suggests that inclusion of VS in the model leads to perfusion patterns that are likely to reflect physiological reality. The model has potential for applications to unphysiological and pathological conditions. PMID:23237543
HIFU Therapy Compared with Other Thermal Ablation Methods in a Perfused Organ Model
NASA Astrophysics Data System (ADS)
Jenne, Jürgen W.; Risse, Frank; Häcker, Axel; Peters, Kristina; Siegler, Peter; Divkovic, Gabriela Wilzbach; Huber, Peter E.
2007-05-01
Therapy with high intensity focused ultrasound (HIFU) has been shown to be both safe and clinically practical in a growing number of patient studies for a variety of different target organs. Especially in cancer therapy there are comparable ablation methods like radio frequency (RFA) or laser (LITT) ablation, which are clinically more accepted. In an ongoing study we compare HIFU with RF- and laser ablation under MRI guidance in a perfused organ model. All evaluated techniques were appropriate to induce defined and localized ablation necrosis in the renal cortex. Our HIFU system and the laser system were completely MRI compatible. The tested RF- system showed local needle artefacts and disturbed the MR images during operation. The ablation rate of HIFU using a spot scanning technique was clearly lower compared to the other ablation techniques. However, advanced HIFU scanning methods might overcome this limitation. In addition HIFU is the only complete non-invasive ablation technique.
Handayani, A.; Dijkstra, H.; Prakken, N. H. J.; Slart, R. H. J. A.; Oudkerk, M.; Van Ooijen, P. M. A.; Vliegenthart, R.; Sijens, P. E.
2016-01-01
Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings. PMID:27088083
Pelgrim, G J; Handayani, A; Dijkstra, H; Prakken, N H J; Slart, R H J A; Oudkerk, M; Van Ooijen, P M A; Vliegenthart, R; Sijens, P E
2016-01-01
Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings. PMID:27088083
Lofthouse, E. M.; Perazzolo, S.; Brooks, S.; Crocker, I. P.; Glazier, J. D.; Johnstone, E. D.; Panitchob, N.; Sibley, C. P.; Widdows, K. L.; Sengers, B. G.
2015-01-01
Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID:26676251
GPU-accelerated voxelwise hepatic perfusion quantification.
Wang, H; Cao, Y
2012-09-01
Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10(-6). The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645
Yoda, Shunichi; Nakanishi, Kanae; Tano, Ayako; Hori, Yusuke; Hayase, Misa; Mineki, Takashi; Suzuki, Yasuyuki; Matsumoto, Naoya; Hirayama, Atsushi
2016-07-27
We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with ≥ 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for ≥ 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 ± 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease. PMID:27357436
Pallarès, Jordi; Senan, Oriol; Guimerà, Roger; Vernet, Anton; Aguilar-Mogas, Antoni; Vilahur, Gemma; Badimon, Lina; Sales-Pardo, Marta; Cito, Salvatore
2015-01-01
Thrombus formation is a multiscale phenomenon triggered by platelet deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict platelet deposition. Specifically, we consider measurements of platelet deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s−1, 1390 s−1 and 1690 s−1. Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables. PMID:26391513
NASA Astrophysics Data System (ADS)
Peladeau-Pigeon, M.; Coolens, C.
2013-09-01
Dynamic contrast-enhanced computed tomography (DCE-CT) is an imaging tool that aids in evaluating functional characteristics of tissue at different stages of disease management: diagnostic, radiation treatment planning, treatment effectiveness, and monitoring. Clinical validation of DCE-derived perfusion parameters remains an outstanding problem to address prior to perfusion imaging becoming a widespread standard as a non-invasive quantitative measurement tool. One approach to this validation process has been the development of quality assurance phantoms in order to facilitate controlled perfusion ex vivo. However, most of these systems fail to establish and accurately replicate physiologically relevant capillary permeability and exchange performance. The current work presents the first step in the development of a prospective suite of physics-based perfusion simulations based on coupled fluid flow and particle transport phenomena with the goal of enhancing the understanding of clinical contrast agent kinetics. Existing knowledge about a controllable, two-compartmental fluid exchange phantom was used to validate the computational fluid dynamics (CFD) simulation model presented herein. The sensitivity of CFD-derived contrast uptake curves to contrast injection parameters, including injection duration and flow rate, were quantified and found to be within 10% accuracy. The CFD model was employed to evaluate two commonly used clinical kinetic algorithms used to derive perfusion parameters: Fick's principle and the modified Tofts model. Neither kinetic model was able to capture the true transport phenomena it aimed to represent but if the overall contrast concentration after injection remained identical, then successive DCE-CT evaluations could be compared and could indeed reflect differences in regional tissue flow. This study sets the groundwork for future explorations in phantom development and pharmaco-kinetic modelling, as well as the development of novel contrast
Modeling of landslide volume estimation
NASA Astrophysics Data System (ADS)
Amirahmadi, Abolghasem; Pourhashemi, Sima; Karami, Mokhtar; Akbari, Elahe
2016-06-01
Mass displacement of materials such as landslide is considered among problematic phenomena in Baqi Basin located at southern slopes of Binaloud, Iran; since, it destroys agricultural lands and pastures and also increases deposits at the basin exit. Therefore, it is necessary to identify areas which are sensitive to landslide and estimate the significant volume. In the present study, in order to estimate the volume of landslide, information about depth and area of slides was collected; then, considering regression assumptions, a power regression model was given which was compared with 17 suggested models in various regions in different countries. The results showed that values of estimated mass obtained from the suggested model were consistent with observed data (P value= 0.000 and R = 0.692) and some of the existing relations which implies on efficiency of the suggested model. Also, relations that were created in small-area landslides were more suitable rather than the ones created in large-area landslides for using in Baqi Basin. According to the suggested relation, average depth value of landslides was estimated 3.314 meters in Baqi Basin which was close to the observed value, 4.609 m.
Sawyer, R T; Horst, M N; Garner, R E; Hudson, J; Jenkins, P R; Richardson, A L
1990-01-01
The adherence of Candida albicans was studied in situ by using the perfused mouse liver model. After exhaustive washing, 10(6) C. albicans were infused into mouse livers. At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C. albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4%. This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver. Chemical pretreatment of C. albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C. albicans to hepatic tissue. By contrast, pepsin pretreatment significantly decreased hepatic trapping. Simultaneous perfusion with either 100 mg of C. albicans glycoprotein per liter or 100 mg of C. albicans mannan per liter also decreased trapping. Furthermore, both substances eluted previously trapped C. albicans from hepatic tissue. Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C. albicans three- to fivefold within hepatic tissue. The data suggest that mannose-containing structures on the surface of C. albicans, for example. mannans or glucomannoproteins, mediate adherence of C. albicans within the liver. Indirectly, chemical and enzymatic pretreatment renders C. albicans more susceptible to hepatic killing. PMID:2117571
Duncan, K R; Gowland, P; Francis, S; Moore, R; Baker, P N; Johnson, I R
1998-09-01
Echo-planar imaging (EPI) is a form of magnetic resonance imaging (MRI) which acquires images in milliseconds rather than minutes as with conventional MRI. The images produced using EPI are affected by the physiological environment in which the hydrogen atoms producing the signals are found, a process referred to as relaxation. Also by producing images a matter of milliseconds apart, quantification of perfusion within the tissue being imaged is feasible. The objective of this study was to investigate T1 and T2 relaxation times along with perfusion in placentae from normal pregnancies at different gestations and also to compare these to pregnancies complicated by abnormal placental function. A cross-sectional study of normal and compromised pregnancies from 20 weeks to term and a longitudinal study of normal pregnancy were performed. Placental T1, T2 relaxation times, and perfusion were measured using echo-planar magnetic resonance imaging. Placental T1 and T2 relaxation times decreased in normal pregnancy (P<0.001). Relaxation times in pregnancies associated with placental pathology appeared to be reduced for that gestation although the numbers were too small to allow any statistical validation. No differences in placental perfusion with gestation or between normal and compromised pregnancy were demonstrated using this technique. This is the first demonstration of placental magnetic resonance relaxation and perfusion measurements in normal pregnancy using echo-planar magnetic resonance imaging. In the future it may be possible to identify compromised pregnancies by differences in placental T1 and T2 relaxation times, using this novel non-invasive technique. PMID:9778128
Estimation of pharmacokinetic model parameters.
Timcenko, A; Reich, D L; Trunfio, G
1995-01-01
This paper addresses the problem of estimating the depth of anesthesia in clinical practice where many drugs are used in combination. The aim of the project is to use pharmacokinetically-derived data to predict episodes of light anesthesia. The weighted linear combination of anesthetic drug concentrations was computed using a stochastic pharmacokinetic model. The clinical definition of light anesthesia was based on the hemodynamic consequences of autonomic nervous system responses to surgical stimuli. A rule-based expert system was used to review anesthesia records to determine instances of light anesthesia using hemodynamic criteria. It was assumed that light anesthesia was a direct consequence of the weighted linear combination of drug concentrations in the patient's body that decreased below a certain threshold. We augmented traditional two-compartment models with a stochastic component of anesthetics' concentrations to compensate for interpatient pharmacokinetic and pharmacodynamic variability. A cohort of 532 clinical anesthesia cases was examined and parameters of two compartment pharmacokinetic models for 6 intravenously administered anesthetic drugs (fentanyl, thiopenthal, morphine, propofol, midazolam, ketamine) were estimated, as well as the parameters for 2 inhalational anesthetics (N2O and isoflurane). These parameters were then prospectively applied to 22 cases that were not used for parameter estimation, and the predictive ability of the pharmacokinetic model was determined. The goal of the study is the development of a pharmacokinetic model that will be useful in predicting light anesthesia in the clinically relevant circumstance where many drugs are used concurrently. PMID:8563327
Estimating proportions of materials using mixture models
NASA Technical Reports Server (NTRS)
Heydorn, R. P.; Basu, R.
1983-01-01
An approach to proportion estimation based on the notion of a mixture model, appropriate parametric forms for a mixture model that appears to fit observed remotely sensed data, methods for estimating the parameters in these models, methods for labelling proportion determination from the mixture model, and methods which use the mixture model estimates as auxiliary variable values in some proportion estimation schemes are addressed.
2014-01-01
Background Exact drug dosing in isolated limb perfusion (ILP) and infusion (ILI) is essential. We developed and evaluated a model for calculating the volume of extremities and compared this model with body weight- and height-dependent parameters. Methods The extremity was modeled by a row of coupled truncated cones. The sizes of the truncated cone bases were derived from the circumference measurements of the extremity at predefined levels (5 cm). The resulting volumes were added. This extremity volume model was correlated to the computed tomography (CT) volume data of the extremity (total limb volume). The extremity volume was also correlated with the patient’s body weight, body mass index (BMI) and ideal body weight (IBW). The no-fat CT limb volume was correlated with the circumference-measured limb volume corrected by the ideal-body-weight to actual-body-weight ratio (IBW corrected-limb-volume). Results The correlation between the CT volume and the volume measured by the circumference was high and significant. There was no correlation between the limb volume and the bare body weight, BMI or IBW. The correlation between the no-fat CT volume and IBW-corrected limb volume was high and significant. Conclusions An appropriate drug dosing in ILP can be achieved by combining the limb volume with the simple circumference measurements and the IBW to body-weight ratio. PMID:24684972
Parameter estimation for transformer modeling
NASA Astrophysics Data System (ADS)
Cho, Sung Don
Large Power transformers, an aging and vulnerable part of our energy infrastructure, are at choke points in the grid and are key to reliability and security. Damage or destruction due to vandalism, misoperation, or other unexpected events is of great concern, given replacement costs upward of $2M and lead time of 12 months. Transient overvoltages can cause great damage and there is much interest in improving computer simulation models to correctly predict and avoid the consequences. EMTP (the Electromagnetic Transients Program) has been developed for computer simulation of power system transients. Component models for most equipment have been developed and benchmarked. Power transformers would appear to be simple. However, due to their nonlinear and frequency-dependent behaviors, they can be one of the most complex system components to model. It is imperative that the applied models be appropriate for the range of frequencies and excitation levels that the system experiences. Thus, transformer modeling is not a mature field and newer improved models must be made available. In this work, improved topologically-correct duality-based models are developed for three-phase autotransformers having five-legged, three-legged, and shell-form cores. The main problem in the implementation of detailed models is the lack of complete and reliable data, as no international standard suggests how to measure and calculate parameters. Therefore, parameter estimation methods are developed here to determine the parameters of a given model in cases where available information is incomplete. The transformer nameplate data is required and relative physical dimensions of the core are estimated. The models include a separate representation of each segment of the core, including hysteresis of the core, lambda-i saturation characteristic, capacitive effects, and frequency dependency of winding resistance and core loss. Steady-state excitation, and de-energization and re-energization transients
Eikefjord, Eli; Andersen, Erling; Hodneland, Erlend; Zöllner, Frank; Lundervold, Arvid; Svarstad, Einar; Rørvik, Jarle
2015-03-01
OBJECTIVE. The purpose of this article is to compare two 3D dynamic contrast-enhanced (DCE) MRI measurement techniques for MR renography, a radial k-space weighted image contrast (KWIC) sequence and a cartesian FLASH sequence, in terms of intrasubject differences in estimates of renal functional parameters and image quality characteristics. SUBJECTS AND METHODS. Ten healthy volunteers underwent repeated breath-hold KWIC and FLASH sequence examinations with temporal resolutions of 2.5 and 2.8 seconds, respectively. A two-compartment model was used to estimate MRI-derived perfusion parameters and glomerular filtration rate (GFR). The latter was compared with the iohexol GFR and the estimated GFR. Image quality was assessed using a visual grading characteristic analysis of relevant image quality criteria and signal-to-noise ratio calculations. RESULTS. Perfusion estimates from FLASH were closer to literature reference values than were the KWIC sequences. In relation to the iohexol GFR (mean [± SD], 103 ± 11 mL/min/1.73 m(2)), KWIC produced significant underestimations and larger bias in GFR values (mean, 70 ± 30 mL/min/1.73 m(2); bias = -33.2 mL/min/1.73 m(2)) compared with the FLASH GFR (110 ± 29 mL/min/1.73 m(2); bias = 6.4 mL/min/1.73 m(2)). KWIC was statistically significantly (p < 0.005) more impaired by artifacts than was FLASH (AUC = 0.18). The average signal-enhancement ratio (delta ratio) in the cortex was significantly lower for KWIC (delta ratio = 0.99) than for FLASH (delta ratio = 1.40). Other visually graded image quality characteristics and signal-to-noise ratio measurements were not statistically significantly different. CONCLUSION. Using the same postprocessing scheme and pharmacokinetic model, FLASH produced more accurate perfusion and filtration parameters than did KWIC compared with clinical reference methods. Our data suggest an apparent relationship between image quality characteristics and the degree of stability in the numeric model
Apostolova, Ivayla; Niedzielska, Dagmara; Derlin, Thorsten; Koziolek, Eva J; Amthauer, Holger; Salmen, Benedikt; Pahnke, Jens; Brenner, Winfried; Mautner, Victor F; Buchert, Ralph
2015-08-01
Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/- mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/- mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1. PMID:25785829
Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption (VO2), vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase (ALT) leakage, and meta...
Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model.
Wang, Jian; Zhou, DA-Qing; He, Meng; Li, Wen-Gang; Pang, Xiang; Yu, Xiao-Xiang; Jiang, Bo
2013-05-01
The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886
Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model
WANG, JIAN; ZHOU, DA-QING; HE, MENG; LI, WEN-GANG; PANG, XIANG; YU, XIAO-XIANG; JIANG, BO
2013-01-01
The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886
A Mathematical Model of the Metabolic and Perfusion Effects on Cortical Spreading Depression
Chang, Joshua C.; Brennan, Kevin C.; He, Dongdong; Huang, Huaxiong; Miura, Robert M.; Wilson, Phillip L.; Wylie, Jonathan J.
2013-01-01
Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism—aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium–ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD—vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization—found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease. PMID:23967075
Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.
Boyle, Erin C; Dombrowsky, Heike; Sarau, Jürgen; Braun, Janin; Aepfelbacher, Martin; Lautenschläger, Ingmar; Grassl, Guntram A
2016-01-15
Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine. PMID:26564721
Tompkins, D T; Vanderby, R; Klein, S A; Beckman, W A; Steeves, R A; Frye, D M; Paliwal, B R
1994-01-01
Finite-element solutions to the Pennes bioheat equation are obtained with a model of a tumour-containing, human prostate and surrounding normal tissues. Simulations of ferromagnetic hyperthermia treatments are conducted on the tissue model in which the prostate is implanted with an irregularly spaced array of thermoseeds. Several combinations of thermoseed temperatures with different Curie points are investigated. Non-uniform, constant-rate blood perfusion models are studied and compared with temperature-dependent descriptions of blood perfusion. Blood perfusions in the temperature-dependent models initially increase with tissue temperature and then decrease at higher temperatures. Simulations with temperature-dependent versus constant-rate blood perfusion models reveal significant differences in temperature distributions in and surrounding the tumour-containing prostate. Results from the simulations include differences (between temperature-dependent and constant-rate models) in (1) the percentage of normal tissue volume and tumour volume at temperatures > 42 degrees C, and (2) temperature descriptors in the tumour (subscript t) and normal (subscript n) tissues including Tmax.t, Tmin.t and Tmax.n. Isotherms and grey-scale contours in the tumour and surrounding normal tissues are presented for four simulations that model a combination of high-temperature thermoseeds. Several simulations show that Tmin.t is between 1.7 and 2.6 degrees C higher and Tmax.n is between 2.1 and 3.3 degrees C higher with a temperature-dependent versus a comparable constant-rate blood perfusion model. The same simulations reveal that the percentages of tumour volume at temperatures > 42 degrees C are between 0 and 68% higher with the temperature-dependent versus the constant-rate perfusion model over all seed combinations studied. In summary, a numerical method is presented which makes it possible to investigate temperature-dependent, continuous functions of blood perfusion in simulations
An integrated in vitro model of perfused tumor and cardiac tissue
2013-01-01
Cancer and cardiovascular disease remain the two leading causes of death in the United States. Progress in treatment to reduce morbidity and mortality will include the development of new drugs. Recent advances in induced pluripotent stem cell technology, tissue engineering, and microfabrication techniques have created a unique opportunity to develop three-dimensional (3D) microphysiological systems that more accurately reflect in vivo human biology when compared with two-dimensional flat systems or animal models. Our group is working to develop 3D microphysiological systems using induced pluripotent stem cell technology that simulates the microcirculation, the cardiac muscle, and the solid tumor, and then to combine these systems into an integrated microphysiological system that simulates perfused cardiac muscle and solid tumor on a single platform. The platform will be initially validated to predict anti-cancer efficacy while minimizing cardiac muscle toxicity. A critical feature will be blood flow through a human microcirculation (capillaries and larger microvessels), which is necessary to overcome diffusion limitations of nutrients and waste products in realistic 3D cultures, and serves to integrate multiple organ systems. This is a necessary and critical feature of any platform that seeks to simulate integrated human organ systems. The results of our project should produce a new paradigm for efficient and accurate drug and toxicity screening, initially for anti-cancer drugs with minimal cardiac side effects, and a platform technology that can be eventually used to integrate multiple major organ systems of the human body. PMID:24565445
Ikegami, Akira; Ueshima, Keiichiro; Saito, Masazumi; Ikoma, Kazuya; Fujioka, Mikihiro; Hayashi, Shigeki; Ishida, Masashi; Fujiwara, Hiroyoshi; Mazda, Osam; Kubo, Toshikazu
2015-07-01
This study was designed to evaluate femoral perfusion after pulsed electromagnetic field (PEMF) stimulation in a steroid-induced osteonecrosis rabbit model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Steroid-induced osteonecrosis was produced by single intramuscular injection of methylprednisolone in 15 rabbits. Eight rabbits underwent PEMF stimulation (PEMF group) and seven did not (control group). DCE-MRI was performed before PEMF stimulation, immediately before steroid administration, and 1, 5, 10, and 14 days after steroid administration. Regions of interest were set in the bilateral proximal femora. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were analyzed. ER, IS, and AUC in the control group significantly decreased after steroid administration compared with before administration (P<0.05). In PEMF group, IS significantly decreased; however, ER and AUC showed no significant differences after steroid administration compared with before. ER and IS in PEMF group were higher than in control group until 10th day, and AUC was higher until 5th day after steroid administration (P<0.05). PEMF stimulation restrains the decrease in blood flow after steroid administration. PMID:25808585
Lee, Ho Yun; Kim, Namkug; Goo, Jin Mo; Chie, Eui Kyu; Song, Hye Jong
2016-01-01
PURPOSE We aimed to compare various tumor-related radiologic morphometric changes and computed tomography (CT) perfusion parameters before and after treatment, and to determine the optimal imaging assessment technique for the prediction of early response in a rat tumor model treated with radiotherapy. METHODS Among paired tumors of FN13762 murine breast cancer cells implanted bilaterally in the necks of eight Fischer rats, tumors on the right side were treated with a single 20 Gy dose of radiotherapy. Perfusion CT studies were performed on day 0 before radiotherapy, and on days 1 and 5 after radiotherapy. Variables based on the size, including the longest diameter, tumor area, and volume, were measured. Quantitative perfusion analysis was performed for the whole tumor volume and permeabilities and blood volumes (BVs) were obtained. The area under the curve (AUC) difference in the histograms of perfusion parameters and texture analyses of uniformity and entropy were quantified. Apoptotic cell density was measured on pathology specimens immediately after perfusion imaging on day 5. RESULTS On day 1 after radiotherapy, differences in size between the irradiated and nonirradiated tumors were not significant. In terms of percent changes in the uniformity of permeabilities between tumors before irradiation and on day 1 after radiotherapy, the changes were significantly higher in the irradiated tumors than in the nonirradiated tumors (0.085 [−0.417, 0.331] vs. −0.131 [−0.536, 0.261], respectively; P = 0.042). The differences in AUCs of the histogram of voxel-by-voxel vascular permeability and BV in tumors between day 0 and day 1 were significantly higher in treated tumors compared with the control group (permeability, 21.4 [−2.2, 37.5] vs. 9.5 [−8.9, 33.8], respectively, P = 0.030; BV, 52.9 [−6186.0, 419.2] vs. 11.9 [−198.3, 346.7], respectively, P = 0.049). Apoptotic cell density showed a significantly positive correlation with the AUC difference of BV, the
Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging
Cao Yue; Wang Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary
2013-01-01
Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which
Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging
Cao, Yue; Wang, Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary
2013-01-01
Purpose To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which
NASA Astrophysics Data System (ADS)
Parages, Felipe M.; O'Connor, J. Michael; Pretorius, P. Hendrik; Brankov, Jovan G.
2014-03-01
Model observers (MO) are widely used in medical imaging to act as surrogates of human observers in task-based image quality evaluation, frequently towards optimization of reconstruction algorithms. In SPECT myocardial perfusion imaging (MPI), a realistic task-based approach involves detection and localization of perfusion defects, as well as a subsequent assessment of defect severity. In this paper we explore a machine-learning MO based on Naive- Bayes classification (NB-MO). NB-MO uses a set of polar-map image features to predict lesion detection, localization and severity scores given by five human readers for a set of simulated 3D SPECT-MPI patients. The simulated dataset included lesions with different sizes, perfusion-reduction ratios, and locations. Simulated projections were reconstructed using two readily used methods namely: FBP and OSEM. For validation, a multireader multi-case (MRMC) analysis of alternative free-response ROC (AFROC) curve was performed for NB-MO and human observers. For comparison, we also report performances of a statistical Hotelling Observer applied on polar-map images. Results show excellent agreement between NB-MO and humans, as well as model's good generalization between different reconstruction treatments.
Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel
2014-01-01
Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092
Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel
2014-10-01
Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092
Kaufman, Christopher L.; Baetiong, Alvin; Radhakrishnan, Jeejabai
2016-01-01
Background Several characteristics of the ventricular fibrillation (VF) waveform have been found predictive of successful defibrillation and hypothesized to reflect the myocardial energy state. In an open-chest swine model of VF, we modeled “average CPR” using extracorporeal circulation (ECC) and assessed the time course of coronary blood flow, myocardial metabolism, and myocardial structure in relation to the amplitude spectral area (AMSA) of the VF waveform without artifacts related to chest compression. Methods VF was induced and left untreated for 8 minutes in 16 swine. ECC was then started adjusting its flow to maintain a coronary perfusion pressure of 10 mmHg for 10 minutes. AMSA was calculated in the frequency domain and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. Results AMSA progressively declined during untreated VF. With ECC, AMSA increased from 7.0 ± 1.9 mV·Hz (at minute 8) to 12.8 ± 3.3 mV·Hz (at minute 14) (p < 0.05) without subsequent increase and showing a modest correlation with coronary blood flow of borderline statistical significance (r = 0.489, p = 0.0547). Myocardial energy measurements showed marked reduction in phosphocreatine and moderate reduction in ATP with increases in ADP, AMP, and adenosine along with myocardial lactate, all indicative of ischemia. Yet, ischemia did not resolve during ECC despite a coronary blood flow of ~ 30% of baseline. Conclusion AMSA increased upon return of coronary blood flow during ECC. However, the maximal level was reached after ~ 6 minutes without further change. The significance of the findings for determining the optimal timing for delivering an electrical shock during resuscitation from VF remains to be further explored. PMID:27536996
NASA Astrophysics Data System (ADS)
Paltiel, H. J.; Padua, H. M.; Gargollo, P. C.; Cannon, G. M., Jr.; Alomari, A. I.; Yu, R.; Clement, G. T.
2011-04-01
Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.
Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study
NASA Astrophysics Data System (ADS)
Stewart, Errol E.; Chen, Xiaogang; Hadway, Jennifer; Lee, Ting-Yim
2008-08-01
In the current study we investigate the accuracy and precision of hepatic perfusion measurements based on the Johnson and Wilson model with the adiabatic approximation. VX2 carcinoma cells were implanted into the livers of New Zealand white rabbits. Simultaneous dynamic contrast-enhanced computed tomography (DCE-CT) and radiolabeled microsphere studies were performed under steady-state normo-, hyper- and hypo-capnia. The hepatic arterial blood flows (HABF) obtained using both techniques were compared with ANOVA. The precision was assessed by the coefficient of variation (CV). Under normo-capnia the microsphere HABF were 51.9 ± 4.2, 40.7 ± 4.9 and 99.7 ± 6.0 ml min-1 (100 g)-1 while DCE-CT HABF were 50.0 ± 5.7, 37.1 ± 4.5 and 99.8 ± 6.8 ml min-1 (100 g)-1 in normal tissue, tumor core and rim, respectively. There were no significant differences between HABF measurements obtained with both techniques (P > 0.05). Furthermore, a strong correlation was observed between HABF values from both techniques: slope of 0.92 ± 0.05, intercept of 4.62 ± 2.69 ml min-1 (100 g)-1 and R2 = 0.81 ± 0.05 (P < 0.05). The Bland-Altman plot comparing DCE-CT and microsphere HABF measurements gives a mean difference of -0.13 ml min-1 (100 g)-1, which is not significantly different from zero. DCE-CT HABF is precise, with CV of 5.7, 24.9 and 1.4% in the normal tissue, tumor core and rim, respectively. Non-invasive measurement of HABF with DCE-CT is accurate and precise. DCE-CT can be an important extension of CT to assess hepatic function besides morphology in liver diseases.
Eichten, Alexandra; Adler, Alexander P; Cooper, Blerta; Griffith, Jennifer; Wei, Yi; Yancopoulos, George D; Lin, Hsin Chieh; Thurston, Gavin
2013-04-01
Vascular endothelial growth factor (VEGF) is a key upstream mediator of tumor angiogenesis, and blockade of VEGF can inhibit tumor angiogenesis and decrease tumor growth. However, not all tumors respond well to anti-VEGF therapy. Despite much effort, identification of early response biomarkers that correlate with long-term efficacy of anti-VEGF therapy has been difficult. These difficulties arise in part because the functional effects of VEGF inhibition on tumor vessels are still unclear. We therefore assessed rapid molecular, morphologic and functional vascular responses following treatment with aflibercept (also known as VEGF Trap or ziv-aflibercept in the United States) in preclinical tumor models with a range of responses to anti-VEGF therapy, including Colo205 human colorectal carcinoma (highly sensitive), C6 rat glioblastoma (moderately sensitive), and HT1080 human fibrosarcoma (resistant), and correlated these changes to long-term tumor growth inhibition. We found that an overall decrease in tumor vessel perfusion, assessed by dynamic contrast-enhanced ultrasound (DCE-US), and increases in tumor hypoxia correlated well with long-term tumor growth inhibition, whereas changes in vascular gene expression and microvessel density did not. Our findings support previous clinical studies showing that decreased tumor perfusion after anti-VEGF therapy (measured by DCE-US) correlated with response. Thus, measuring tumor perfusion changes shortly after treatment with VEGF inhibitors, or possibly other anti-angiogenic therapies, may be useful to predict treatment efficacy. PMID:23238831
Graham, M.M.
1987-01-01
This meeting provided an excellent overview of the state-of-the-art in perfusion imaging from the viewpoints of mathematical data analysis, radiochemical synthesis and evaluation, and instrumentation physics. The participants and audience had an opportunity to see how each of these aspects is essential for continued progress in this field.
Kawamoto, M.; Ikegami, T.
1994-05-01
Matsuda reported a non-invasive, simple method for the quantitative measurements of brain perfusion using radionuclide angiography with Tc-99m. HMPAO and showed graphical analysis of the ratio of brain activity to aortic arch activity gave two parameters, which are the slope of the fitted line (Ku:unidirectional influx constant) and its intercept with the yards (Vn:initial volume of distribution). Brain perfusion index (BPI),which is a connected Ku value, showed good correlation with cerebral blood flow determined with Xe-133 SPECT. The aim of our study is to elucidate the clinical significance of another parameter, Vn value, determined inpatients with cerebral vessel disease. Eighty-nine cases were studied and classified into three groups on the basis of clinical history and images of CT and/or MR: Group A, normal, 36 cases; Group B, infarction, 44 cases; Group C, subarachnoid hemorrhage, 9 cases. The average age of each group were not different statistically (63.3, 67.4 and 59.8, respectively). The average BPI values for group B and C were significantly lower than that of group A(7.7, 6. 8 and 9.5, respectively ). On the other hand, Vn for group C(0.23) was significantly lower than that for group A(0.45); however that for group B(0.49) was not. These findings indicate that cerebral blood flow in both infarction and subarachnoid hemorrhage decrease but their circumstances near vessels differ from the aspect of initial volume of tracer distribution. This might help to understand or diagnose cerebral vessel diseases.
Saad, S; Hewett, K; Greenman, J
2012-03-01
An in vitro matrix biofilm perfusion model of tongue-derived microcosms for studying volatile sulfur compound (VSC) biogenesis has been previously described. The model was modified in order to monitor H(2)S in situ by use of a specialized electrode assembly based on microbial fuel cell technology. This system was designed to give real-time measurements expressed as electrode power output, which were proportional to H(2)S levels, measured by other means. In addition to the model modifications, the aim of this study was to demonstrate the biofilm responses following single or multiple exposure to biocidal, biostatic or VSC-inhibiting active compounds used in products. Tongue-derived biofilms (n = 6 per experiment) were perfused with one-fifth strength BHI at 20 ml h(-1) pH 7.2 and pulsed with putative treatment agent, placebo and controls including Zn(2+) ions and chlorhexidine (CHX). Compared with their pre-treatment conditions, all biofilms responded to the treatments in terms of reductions in hydrogen sulfide generation (as detected by the biofilm-electrode response) and other microbial volatile organic compounds (VOCs) as detected using a selected ion flow tube mass spectrometry analyser. The microbiological analysis of the treated and control biofilms show that test products (formulations with active agents) all gave reduced cell populations compared to the control biofilm. An order of effects (magnitude and duration) suggests that both the test agent and CHX produced the strongest reductions, distinct from the responses obtained for the placebo and water controls, which were largely similar. It is concluded that the in vitro perfusion model may be used to replicate many of the activities and reactions believed to be occurring by the tongue biofilm microflora within a real mouth, including H(2)S and VOC biogenesis and their inhibition by exposure to active agents. PMID:22234955
La Manna, Gaetano; Conte, Diletta; Cappuccilli, Maria Laura; Nardo, Bruno; D'Addio, Francesca; Puviani, Lorenza; Comai, Giorgia; Bianchi, Francesca; Bertelli, Riccardo; Lanci, Nicole; Donati, Gabriele; Scolari, Maria Piera; Faenza, Alessandro; Stefoni, Sergio
2009-07-01
There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation. Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion (n = 6) or cold storage (n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation. The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys. The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage. PMID:19566736
Distributed estimation and joint probabilities estimation by entropy model
NASA Astrophysics Data System (ADS)
Fassinut-Mombot, B.; Zribi, M.; Choquel, J. B.
2001-05-01
This paper proposes the use of Entropy Model for distributed estimation system. Entropy Model is an entropic technique based on the minimization of conditional entropy and developed for Multi-Source/Sensor Information Fusion (MSIF) problem. We address the problem of distributed estimation from independent observations involving multiple sources, i.e., the problem of estimating or selecting one of several identity declaration, or hypothesis concerning an observed object. Two problems are considered in Entropy Model. In order to fuse observations using Entropy Model, it is necessary to know or estimate the conditional probabilities and by equivalent the joint probabilities. A common practice for estimating probability distributions from data when nothing is known (without a priori knowledge), one should prefer distributions that are as uniform as possible, that is, have maximal entropy. Next, the problem of combining (or ``fusing'') observations relating to identity hypotheses and selecting the most appropriate hypothesis about the object's identity is addressed. Much future work remains, but the results indicate that Entropy Model is a promising technique for distributed estimation. .
Chung, Johnathan C.; Wang, Dingxin; Lewandowski, Robert J.; Tang, Richard; Chrisman, Howard B.; Vogelzang, Robert L.; Woloschak, Gayle E.; Larson, Andrew C.; Omary, Reed A.; Ryu, Robert K.
2010-01-01
Purpose To test the hypothesis that four-dimensional (4D) transcatheter intra-arterial perfusion (TRIP) MR imaging can measure uterine fibroid perfusion changes immediately before and after uterine artery embolization (UAE) in the rabbit VX2 tumor model. Materials and Methods Eight VX2 uterine tumors were grown in 6 rabbits. After positioning a catheter within the uterine artery, we performed 4D TRIP-MRI measurements with 3 mL injections of 2.5% gadopentetate dimeglumine. We used a dynamic 3D spoiled-GRE sequence with in vivo B1-field correction for improved accuracy during perfusion quantification. We performed UAE using 1 mL of gelatin microspheres (2×106 particles; diameter 40-120 μm). Two regions-of-interest were drawn within each tumor upon perfusion maps. Functional embolic endpoints were reported as the mean percent reduction in fibroid tumor perfusion. Measurements before and after UAE were compared using paired t-tests (α = 0.05). Results VX2 uterine tumor perfusion decreased significantly from 27.1 at baseline to 7.09 after UAE (mL/min/100 mL tissue, p < 0.0001). Overall perfusion reduction was 76.3% (95% CI: 66.3%-86.3%). Conclusion 4D TRIP MRI can objectively quantify uterine fibroid perfusion reductions during UAE in VX2 rabbits. This technique could be used clinically to potentially determine an optimal embolic endpoint with the long-term goals of improving UAE success rates and minimizing procedure-related ischemic pain. PMID:20432349
Sheibley, R.W.; Jackman, A.P.; Duff, J.H.; Triska, F.J.
2003-01-01
Nitrification and denitrification kinetics in sediment perfusion cores were numerically modeled and compared to experiments on cores from the Shingobee River MN, USA. The experimental design incorporated mixing groundwater discharge with stream water penetration into the cores, which provided a well-defined, one-dimensional simulation of in situ hydrologic conditions. Ammonium (NH+4) and nitrate (NO-3) concentration gradients suggested the upper region of the cores supported coupled nitrification-denitrification, where groundwater-derived NH+4 was first oxidized to NO-3 then subsequently reduced via denitrification to N2. Nitrification and denitrification were modeled using a Crank-Nicolson finite difference approximation to a one-dimensional advection-dispersion equation. Both processes were modeled using first-order reaction kinetics because substrate concentrations (NH+4 and NO-3) were much smaller than published Michaelis constants. Rate coefficients for nitrification and denitrification ranged from 0.2 to 15.8 h-1 and 0.02 to 8.0 h-1, respectively. The rate constants followed an Arrhenius relationship between 7.5 and 22 ??C. Activation energies for nitrification and denitrification were 162 and 97.3 kJ/mol, respectively. Seasonal NH+4 concentration patterns in the Shingobee River were accurately simulated from the relationship between perfusion core temperature and NH+4 flux to the overlying water. The simulations suggest that NH+4 in groundwater discharge is controlled by sediment nitrification that, consistent with its activation energy, is strongly temperature dependent. ?? 2003 Elsevier Ltd. All rights reserved.
Robust parameter estimation method for bilinear model
NASA Astrophysics Data System (ADS)
Ismail, Mohd Isfahani; Ali, Hazlina; Yahaya, Sharipah Soaad S.
2015-12-01
This paper proposed the method of parameter estimation for bilinear model, especially on BL(1,0,1,1) model without and with the presence of additive outlier (AO). In this study, the estimated parameters for BL(1,0,1,1) model are using nonlinear least squares (LS) method and also through robust approaches. The LS method employs the Newton-Raphson (NR) iterative procedure in estimating the parameters of bilinear model, but, using LS in estimating the parameters can be affected with the occurrence of outliers. As a solution, this study proposed robust approaches in dealing with the problem of outliers specifically on AO in BL(1,0,1,1) model. In robust estimation method, for improvement, we proposed to modify the NR procedure with robust scale estimators. We introduced two robust scale estimators namely median absolute deviation (MADn) and Tn in linear autoregressive model, AR(1) that be adequate and suitable for bilinear BL(1,0,1,1) model. We used the estimated parameter value in AR(1) model as an initial value in estimating the parameter values of BL(1,0,1,1) model. The investigation of the performance of LS and robust estimation methods in estimating the coefficients of BL(1,0,1,1) model is carried out through simulation study. The achievement of performance for both methods will be assessed in terms of bias values. Numerical results present that, the robust estimation method performs better than LS method in estimating the parameters without and with the presence of AO.
Shi, Haifeng; Li, Ruokun; Qiang, Jinwei; Li, Ying; Wang, Li; Sun, Rongxun
2016-01-01
Objective To evaluate multi-slice computed tomography (CT) perfusion imaging (CTPI) for identifying microcirculatory dysfunction in small intestinal ischemia−reperfusion (IR) injury in a porcine model. Materials and Methods Fifty-two pigs were randomly divided into 4 groups: (1) the IR group (n = 24), where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA) for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively); (2) the sham-operated (SO) group (n = 20), where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively); (3) the ischemia group (n = 4), where the SMA was separated and clamped for 2 h, without reperfusion, and (4) baseline group (n = 4), an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) and for histopathological examination. Results The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia). The blood flow (BF), blood volume (BV), and permeability surface (PS) among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion. Conclusion CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury. PMID:27458696
NASA Astrophysics Data System (ADS)
Kim, Minji; Quan, Yuhua; Han, Kook Nam; Choi, Byeong Hyun; Choi, Yeonho; Kim, Hyun Koo; Kim, Beop-Min
2016-03-01
This study was to evaluate the feasibility of near infrared (NIR) fluorescent images as a tool for evaluating the perfusion of the gastric tube after esophagectomy. In addition, we investigated the time required to acquire enough signal to confirm the presence of ischemia in gastric tube after injection of indocyanine green (ICG) through peripheral versus and central venous route. 4 porcine underwent esophagogastrostomy and their right gastric arteries were ligated to mimic ischemic condition of gastric tube. ICG (0.6mg/kg) was intravenously injected and the fluorescence signal-to-background ratios (SBR) were measured by using the custom-built intraoperative color and fluorescence imaging system (ICFIS). We evaluated perfusion of gastric tubes by comparing their SBR with esophageal SBR. In ischemic models, SBR of esophagus was higher than that of gastric tube (2.8+/-0.54 vs. 1.7+/-0.37, p<0.05). It showed high esophagus-stomach signal to signal ratio. (SSR, 1.8+/-0.76). We also could observe recovery of blood perfusion in few minutes after releasing the ligation of right gastric artery. In addition, in comparison study according to the injection route of ICG, The time to acquire signal stabilization was faster in central than in peripheral route (119 +/- 65.1 seconds in central route vs. 295+/-130.4 in peripheral route, p<0.05). NIR fluorescent images could provide the real-time information if there was ischemia or not in gastric tube during operation. And, central injection of ICG might give that information faster than peripheral route.
Deep space network software cost estimation model
NASA Technical Reports Server (NTRS)
Tausworthe, R. C.
1981-01-01
A parametric software cost estimation model prepared for Deep Space Network (DSN) Data Systems implementation tasks is presented. The resource estimation model incorporates principles and data from a number of existing models. The model calibrates task magnitude and difficulty, development environment, and software technology effects through prompted responses to a set of approximately 50 questions. Parameters in the model are adjusted to fit DSN software life cycle statistics. The estimation model output scales a standard DSN Work Breakdown Structure skeleton, which is then input into a PERT/CPM system, producing a detailed schedule and resource budget for the project being planned.
NASA Astrophysics Data System (ADS)
Fahmi, Rachid; Eck, Brendan L.; Fares, Anas; Levi, Jacob; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.
2015-03-01
Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow
Estimating Canopy Dark Respiration for Crop Models
NASA Technical Reports Server (NTRS)
Monje Mejia, Oscar Alberto
2014-01-01
Crop production is obtained from accurate estimates of daily carbon gain.Canopy gross photosynthesis (Pgross) can be estimated from biochemical models of photosynthesis using sun and shaded leaf portions and the amount of intercepted photosyntheticallyactive radiation (PAR).In turn, canopy daily net carbon gain can be estimated from canopy daily gross photosynthesis when canopy dark respiration (Rd) is known.
NASA Astrophysics Data System (ADS)
Karki, Kishor; Hugo, Geoffrey D.; Ford, John C.; Olsen, Kathryn M.; Saraiya, Siddharth; Groves, Robert; Weiss, Elisabeth
2015-10-01
The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with \\text{TR}≈ 4500 ms, TE = 74 ms, eight b-values of 0-1000 μs μm-2, pixel size = 1.98× 1.98 mm2, slice thickness = 6 mm, interslice gap = 1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm-2 from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm-2 were not significantly different from ADCIVIM values (p>0.05 , paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets—0-1000 50-1000 100-1000 500-1000 and 250 and 800 μs μm-2 were significantly different from the ADCIVIM values. From Rician noise simulation
Kietzmann, M; Löscher, W; Arens, D; Maass, P; Lubach, D
1993-10-01
Using udders from slaughtered cows as a new in vitro model of percutaneous drug absorption, the tissue viability and the percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by a histological examination. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetration of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic acid, ointment without salicylic acid, and acetone solution. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. In conclusion, the isolated perfused bovine udder is a new in vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to compare the dermal penetration, metabolism, and absorption of substances after topical administration of different drug formulations. PMID:8298184
Placental Transfer of Rilpivirine in an Ex Vivo Human Cotyledon Perfusion Model
Duro, Dominique; Belissa, Emilie; Peytavin, Gilles
2015-01-01
Placental transfers of the HIV nonnucleoside reverse transcriptase inhibitor rilpivirine were investigated in 8 term human cotyledons perfused with rilpivirine (400 ng/ml) in the maternal-to-fetal direction. The mean fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 15 to 90 min) was 26% ± 8% (mean ± standard deviation), and the clearance index (rilpivirine FTR/antipyrine FTR) was 61% ± 20%. This shows that rilpivirine crosses the placenta at a relatively high rate, suggesting that the fetus is exposed to the compound during treatment of the mother. PMID:25691637
Laemmel, Elisabeth; Segal, Nicolas; Mirshahi, Massoud; Azzazene, Dalel; Le Marchand, Sylvie; Wybier, Marc; Vicaut, Eric; Laredo, Jean-Denis
2016-06-01
Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the
Ecposure Related Dose Estimating Model
ERDEM is a physiologically based pharmacokinetic (PBPK) modeling system consisting of a general model and an associated front end. An actual model is defined when the user prepares an input command file. Such a command file defines the chemicals, compartments and processes that...
Control by model error estimation
NASA Technical Reports Server (NTRS)
Likins, P. W.; Skelton, R. E.
1976-01-01
Modern control theory relies upon the fidelity of the mathematical model of the system. Truncated modes, external disturbances, and parameter errors in linear system models are corrected by augmenting to the original system of equations an 'error system' which is designed to approximate the effects of such model errors. A Chebyshev error system is developed for application to the Large Space Telescope (LST).
Karki, K; Hugo, G; Ford, J; Saraiya, S; Weiss, E; Olsen, K; Groves, R
2014-06-15
Purpose: Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADC_{IVIM}) in nonsmall cell lung cancer. Methods: Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98X1.98mm{sub 2}, slice thickness=4–6mm and 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0–1000μs/μm{sup 2}. Monoexponential model ADC values using various b-value sets were compared to ADC_{IVIM} using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. Results: ADC_{IVIM}, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm{sup 2}/s, 8119-33834 μm{sup 2}/s and 0.104–0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250–1000μs/μm{sup 2} only were not significantly different from ADC_{IVIM}(p>0.05, paired t-test). Error in ADC values for 0–1000, 50–1000, 100–1000, 250–1000, 500–1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2} were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADC_{IVIM}, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADC_{IVIM} was 23.3%. Conclusion: ADC values of two 3 b-value sets
Deep space network software cost estimation model
NASA Technical Reports Server (NTRS)
Tausworthe, R. C.
1981-01-01
A parametric software cost estimation model prepared for Jet PRopulsion Laboratory (JPL) Deep Space Network (DSN) Data System implementation tasks is described. The resource estimation mdel modifies and combines a number of existing models. The model calibrates the task magnitude and difficulty, development environment, and software technology effects through prompted responses to a set of approximately 50 questions. Parameters in the model are adjusted to fit JPL software life-cycle statistics.
Maximum Likelihood Estimation in Generalized Rasch Models.
ERIC Educational Resources Information Center
de Leeuw, Jan; Verhelst, Norman
1986-01-01
Maximum likelihood procedures are presented for a general model to unify the various models and techniques that have been proposed for item analysis. Unconditional maximum likelihood estimation, proposed by Wright and Haberman, and conditional maximum likelihood estimation, proposed by Rasch and Andersen, are shown as important special cases. (JAZ)
RECURSIVE PARAMETER ESTIMATION OF HYDROLOGIC MODELS
Proposed is a nonlinear filtering approach to recursive parameter estimation of conceptual watershed response models in state-space form. he conceptual model state is augmented by the vector of free parameters which are to be estimated from input-output data, and the extended Kal...
Lozoya, X; Becerril, G; Martínez, M
1990-01-01
An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts. PMID:2103704
Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N
2015-05-01
The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. PMID:25777770
Tuzun, Egemen; Chorpenning, Katherine; Liu, Maxine Qun; Bonugli, Katherine; Tamez, Dan; Lenox, Mark; Miller, Matthew W; Fossum, Theresa W
2014-01-01
The effects of the continuous-flow output on renal and intestinal microcirculation have not been extensively studied. To address this, the Heartware HVAD pump loaded with continuous and intermittent reduced speed (IRS) modes was implanted in four sheep and then operated at low and high speeds to mimic partial and complete unloading of the left ventricle. Then microsphere and positron emission tomography/computed tomography (PET/CT) studies were used to assess renal and intestinal tissue perfusion at various pump speeds and flow modes as compared with baseline (pump off). Arterial and venous oxygen (T02) and carbon dioxide (TCO2) contents were measured to assess changes in intestinal metabolism. Renal and intestinal regional blood flows did not produce any significant changes compared with baseline values in either continuous or IRS modes and speeds. The venous TO2 and TCO2 significantly increased in continuous and IRS modes and speeds compared with baseline. Our data suggested that renal and intestinal tissue perfusions were not adversely affected by continuous and IRS modes either in partial or complete unloading. Intestinal venous hyperoxia and increased TCO2 may be the evidence of intestinal arteriovenous shunting along with increased intestinal tissue metabolism. Longer-term studies are warranted in chronic heart failure models. PMID:24299973
Modeling [15O] oxygen tracer data for estimating oxygen consumption
Deussen, Andreas; Bassingthwaighte, James B.
2010-01-01
The most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water via mitochondrial respiration. To calculate oxygen consumption from the analysis of tissue residue curves or outflow dilution curves after injection of labeled oxygen one needs realistic mathematical models that account for convection, diffusion, and transformation in the tissue. A linear, three-region, axially distributed model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers (with the use of appropriate binding spaces to account for oxygen binding to hemoglobin and myoglobin), the metabolism to [15O]water in parenchymal cells, and [15O]water transport into the venous effluent. Model solutions fit residue and outflow dilution data obtained in an isolated, red blood cell-perfused rabbit heart preparation and give estimates of the rate of oxygen consumption similar to those obtained experimentally from the flow times the arteriovenous differences in oxygen contents. The proposed application is for the assessment of regional oxidative metabolism in vivo from tissue 15O-residue curves obtained by positron emission tomography. PMID:8780210
On Estimation of Partially Linear Transformation Models.
Lu, Wenbin; Zhang, Hao Helen
2010-06-01
We study a general class of partially linear transformation models, which extend linear transformation models by incorporating nonlinear covariate effects in survival data analysis. A new martingale-based estimating equation approach, consisting of both global and kernel-weighted local estimation equations, is developed for estimating the parametric and nonparametric covariate effects in a unified manner. We show that with a proper choice of the kernel bandwidth parameter, one can obtain the consistent and asymptotically normal parameter estimates for the linear effects. Asymptotic properties of the estimated nonlinear effects are established as well. We further suggest a simple resampling method to estimate the asymptotic variance of the linear estimates and show its effectiveness. To facilitate the implementation of the new procedure, an iterative algorithm is developed. Numerical examples are given to illustrate the finite-sample performance of the procedure. PMID:20802823
On Estimation of Partially Linear Transformation Models
Lu, Wenbin; Zhang, Hao Helen
2010-01-01
We study a general class of partially linear transformation models, which extend linear transformation models by incorporating nonlinear covariate effects in survival data analysis. A new martingale-based estimating equation approach, consisting of both global and kernel-weighted local estimation equations, is developed for estimating the parametric and nonparametric covariate effects in a unified manner. We show that with a proper choice of the kernel bandwidth parameter, one can obtain the consistent and asymptotically normal parameter estimates for the linear effects. Asymptotic properties of the estimated nonlinear effects are established as well. We further suggest a simple resampling method to estimate the asymptotic variance of the linear estimates and show its effectiveness. To facilitate the implementation of the new procedure, an iterative algorithm is developed. Numerical examples are given to illustrate the finite-sample performance of the procedure. PMID:20802823
Zhou, Wei; Di, Liu-qing; Wang, Juan; Shan, Jin-jun; Liu, Shi-jia; Ju, Wen-zheng; Cai, Bao-chang
2012-01-01
Aim: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. Methods: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. Results: In the in vitro Caco-2 cell model, the mean apparent permeability value (Papp-value) was 4.15×10-7 cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6–10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The Papp-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the Papp-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the Papp-values. In the in situ intestinal perfusion model, both the absorption rate constant (Ka) and the effective permeability (Peff-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the Peff-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the Peff-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the
Parameter Estimation of Partial Differential Equation Models
Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J.; Maity, Arnab
2013-01-01
Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data. PMID:24363476
Parameter Estimation of Partial Differential Equation Models.
Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J; Maity, Arnab
2013-01-01
Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data. PMID:24363476
Robich, Michael P.; Osipov, Robert M.; Nezafat, Reza; Feng, Jun; Clements, Richard T.; Bianchi, Cesario; Boodhwani, Munir; Coady, Michael A.; Laham, Roger J.; Sellke, Frank W.
2010-01-01
Introduction Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Methods and Results Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac magnetic resonance imaging and coronary angiography 7 weeks later, prior to sacrifice and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (p<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (p=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (p=0.32). Tissue blood flow during stress was 2.8 fold greater in HCRV swine when compared to HCC swine (p=0.04). Endothelial dependent microvascular relaxation response to Substance P was diminished in HCC swine which was rescued by resveratrol treatment (p=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine v. control swine (p=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV v. HCC swine of the following markers of angiogenesis: VEGF (p=0.002), peNOS(ser1177)(p=0.04), NFkB (p=0.004), and pAkt(thr308)(p=0.001). Conclusion Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelial dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway. PMID:20837905
Mineral resources estimation based on block modeling
NASA Astrophysics Data System (ADS)
Bargawa, Waterman Sulistyana; Amri, Nur Ali
2016-02-01
The estimation in this paper uses three kinds of block models of nearest neighbor polygon, inverse distance squared and ordinary kriging. The techniques are weighting scheme which is based on the principle that block content is a linear combination of the grade data or the sample around the block being estimated. The case study in Pongkor area, here is gold-silver resource modeling that allegedly shaped of quartz vein as a hydrothermal process of epithermal type. Resources modeling includes of data entry, statistical and variography analysis of topography and geological model, the block model construction, estimation parameter, presentation model and tabulation of mineral resources. Skewed distribution, here isolated by robust semivariogram. The mineral resources classification generated in this model based on an analysis of the kriging standard deviation and number of samples which are used in the estimation of each block. Research results are used to evaluate the performance of OK and IDS estimator. Based on the visual and statistical analysis, concluded that the model of OK gives the estimation closer to the data used for modeling.
Ultrasound perfusion signal processing for tumor detection
NASA Astrophysics Data System (ADS)
Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.
2016-04-01
Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.
Veress, Alexander I; Fung, George S K; Lee, Taek-Soo; Tsui, Benjamin M W; Kicska, Gregory A; Paul Segars, W; Gullberg, Grant T
2015-05-01
This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59 ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54 ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R
Dombrowsky, Heike; Zitta, Karina; Bein, Berthold; Krause, Thorsten; Goldmann, Torsten; Frerichs, Inez; Steinfath, Markus; Weiler, Norbert; Albrecht, Martin
2015-01-01
Background The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine. Methods An isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups. Results Compared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces. Conclusion A vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small
NASA Astrophysics Data System (ADS)
Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter
2015-08-01
Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.
Model feedback in Bayesian propensity score estimation.
Zigler, Corwin M; Watts, Krista; Yeh, Robert W; Wang, Yun; Coull, Brent A; Dominici, Francesca
2013-03-01
Methods based on the propensity score comprise one set of valuable tools for comparative effectiveness research and for estimating causal effects more generally. These methods typically consist of two distinct stages: (1) a propensity score stage where a model is fit to predict the propensity to receive treatment (the propensity score), and (2) an outcome stage where responses are compared in treated and untreated units having similar values of the estimated propensity score. Traditional techniques conduct estimation in these two stages separately; estimates from the first stage are treated as fixed and known for use in the second stage. Bayesian methods have natural appeal in these settings because separate likelihoods for the two stages can be combined into a single joint likelihood, with estimation of the two stages carried out simultaneously. One key feature of joint estimation in this context is "feedback" between the outcome stage and the propensity score stage, meaning that quantities in a model for the outcome contribute information to posterior distributions of quantities in the model for the propensity score. We provide a rigorous assessment of Bayesian propensity score estimation to show that model feedback can produce poor estimates of causal effects absent strategies that augment propensity score adjustment with adjustment for individual covariates. We illustrate this phenomenon with a simulation study and with a comparative effectiveness investigation of carotid artery stenting versus carotid endarterectomy among 123,286 Medicare beneficiaries hospitlized for stroke in 2006 and 2007. PMID:23379793
Challenges for non-invasive brain perfusion quantification using arterial spin labeling.
Sousa, I; Santos, N; Sanches, J; Figueiredo, P
2011-03-29
Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed. PMID:24059574
NASA Astrophysics Data System (ADS)
Lee, Taek-Soo; Frey, Eric C.; Tsui, Benjamin M. W.
2015-04-01
This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of 99mTc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman’s rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the
Lee, Taek-Soo; Frey, Eric C; Tsui, Benjamin M W
2015-04-01
This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of (99m)Tc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman's rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the
Maslov, Mikhail Y.; Edelman, Elazer R.; Pezone, Matthew J.; Wei, Abraham E.; Wakim, Matthew G.; Murray, Michael R.; Tsukada, Hisashi; Gerogiannis, Iraklis S.; Groothuis, Adam; Lovich, Mark A.
2014-01-01
the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821
Joint estimation of multiple graphical models
Guo, Jian; Levina, Elizaveta; Michailidis, George; Zhu, Ji
2011-01-01
Summary Gaussian graphical models explore dependence relationships between random variables, through the estimation of the corresponding inverse covariance matrices. In this paper we develop an estimator for such models appropriate for data from several graphical models that share the same variables and some of the dependence structure. In this setting, estimating a single graphical model would mask the underlying heterogeneity, while estimating separate models for each category does not take advantage of the common structure. We propose a method that jointly estimates the graphical models corresponding to the different categories present in the data, aiming to preserve the common structure, while allowing for differences between the categories. This is achieved through a hierarchical penalty that targets the removal of common zeros in the inverse covariance matrices across categories. We establish the asymptotic consistency and sparsity of the proposed estimator in the high-dimensional case, and illustrate its performance on a number of simulated networks. An application to learning semantic connections between terms from webpages collected from computer science departments is included. PMID:23049124
Vinot, C.; Gavard, L.; Tréluyer, J. M.; Manceau, S.; Courbon, E.; Scherrmann, J. M.; Declèves, X.; Duro, D.; Peytavin, G.; Mandelbrot, L.
2013-01-01
Nowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfused ex vivo for 90 min with maraviroc (600 ng/ml) either in the maternal-to-fetal (n = 10 placentas) or fetal-to-maternal (n = 6 placentas) direction. Plasma concentrations were determined by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fetal transfer rates (FTR) and clearance indexes (CLI) were calculated as ratios of fetal to maternal concentrations at steady state (mean values between 30 and 90 min) and ratios of FTR of maraviroc to that of antipyrine, respectively. ABC transporter gene expression levels were determined by quantitative reverse transcription (RT)-PCR and ABCB1 protein expression by Western blotting. For the maternal-to-fetal direction, the mean FTR and CLI were 8.0% ± 3.0 and 0.26 ± 0.07, respectively, whereas the mean CLI was 0.52 ± 0.23 for the fetal-to-maternal direction. We showed a significant inverse correlation between maraviroc CLI and ABCC2, ABCC10, and ABCC11 placental gene expression levels (P < 0.05). To conclude, we report a low maraviroc placental transfer probably involving ABC efflux transporters and thus in all likelihood associated with a limited fetal exposition. Nevertheless, these results would need to be supported by in vivo data obtained from paired maternal and cord blood samples. PMID:23295922
Density Estimation Framework for Model Error Assessment
NASA Astrophysics Data System (ADS)
Sargsyan, K.; Liu, Z.; Najm, H. N.; Safta, C.; VanBloemenWaanders, B.; Michelsen, H. A.; Bambha, R.
2014-12-01
In this work we highlight the importance of model error assessment in physical model calibration studies. Conventional calibration methods often assume the model is perfect and account for data noise only. Consequently, the estimated parameters typically have biased values that implicitly compensate for model deficiencies. Moreover, improving the amount and the quality of data may not improve the parameter estimates since the model discrepancy is not accounted for. In state-of-the-art methods model discrepancy is explicitly accounted for by enhancing the physical model with a synthetic statistical additive term, which allows appropriate parameter estimates. However, these statistical additive terms do not increase the predictive capability of the model because they are tuned for particular output observables and may even violate physical constraints. We introduce a framework in which model errors are captured by allowing variability in specific model components and parameterizations for the purpose of achieving meaningful predictions that are both consistent with the data spread and appropriately disambiguate model and data errors. Here we cast model parameters as random variables, embedding the calibration problem within a density estimation framework. Further, we calibrate for the parameters of the joint input density. The likelihood function for the associated inverse problem is degenerate, therefore we use Approximate Bayesian Computation (ABC) to build prediction-constraining likelihoods and illustrate the strengths of the method on synthetic cases. We also apply the ABC-enhanced density estimation to the TransCom 3 CO2 intercomparison study (Gurney, K. R., et al., Tellus, 55B, pp. 555-579, 2003) and calibrate 15 transport models for regional carbon sources and sinks given atmospheric CO2 concentration measurements.
Robust estimation for ordinary differential equation models.
Cao, J; Wang, L; Xu, J
2011-12-01
Applied scientists often like to use ordinary differential equations (ODEs) to model complex dynamic processes that arise in biology, engineering, medicine, and many other areas. It is interesting but challenging to estimate ODE parameters from noisy data, especially when the data have some outliers. We propose a robust method to address this problem. The dynamic process is represented with a nonparametric function, which is a linear combination of basis functions. The nonparametric function is estimated by a robust penalized smoothing method. The penalty term is defined with the parametric ODE model, which controls the roughness of the nonparametric function and maintains the fidelity of the nonparametric function to the ODE model. The basis coefficients and ODE parameters are estimated in two nested levels of optimization. The coefficient estimates are treated as an implicit function of ODE parameters, which enables one to derive the analytic gradients for optimization using the implicit function theorem. Simulation studies show that the robust method gives satisfactory estimates for the ODE parameters from noisy data with outliers. The robust method is demonstrated by estimating a predator-prey ODE model from real ecological data. PMID:21401565
EXPOSURE RELATED DOSE ESTIMATING MODEL (ERDEM)
ERDEM is a physiologically-based pharmacokinetic (PBPK) model with a graphical user interface (GUI) front end. Such a mathematical model was needed to make reliable estimates of the chemical dose to organs of animals or humans because of uncertainties of making route-to route, lo...
Systematic Error Modeling and Bias Estimation
Zhang, Feihu; Knoll, Alois
2016-01-01
This paper analyzes the statistic properties of the systematic error in terms of range and bearing during the transformation process. Furthermore, we rely on a weighted nonlinear least square method to calculate the biases based on the proposed models. The results show the high performance of the proposed approach for error modeling and bias estimation. PMID:27213386
Systematic Error Modeling and Bias Estimation.
Zhang, Feihu; Knoll, Alois
2016-01-01
This paper analyzes the statistic properties of the systematic error in terms of range and bearing during the transformation process. Furthermore, we rely on a weighted nonlinear least square method to calculate the biases based on the proposed models. The results show the high performance of the proposed approach for error modeling and bias estimation. PMID:27213386
Estimating solar radiation for plant simulation models
NASA Technical Reports Server (NTRS)
Hodges, T.; French, V.; Leduc, S.
1985-01-01
Five algorithms producing daily solar radiation surrogates using daily temperatures and rainfall were evaluated using measured solar radiation data for seven U.S. locations. The algorithms were compared both in terms of accuracy of daily solar radiation estimates and terms of response when used in a plant growth simulation model (CERES-wheat). Requirements for accuracy of solar radiation for plant growth simulation models are discussed. One algorithm is recommended as being best suited for use in these models when neither measured nor satellite estimated solar radiation values are available.
Hydrograph estimation with fuzzy chain model
NASA Astrophysics Data System (ADS)
Güçlü, Yavuz Selim; Şen, Zekai
2016-07-01
Hydrograph peak discharge estimation is gaining more significance with unprecedented urbanization developments. Most of the existing models do not yield reliable peak discharge estimations for small basins although they provide acceptable results for medium and large ones. In this study, fuzzy chain model (FCM) is suggested by considering the necessary adjustments based on some measurements over a small basin, Ayamama basin, within Istanbul City, Turkey. FCM is based on Mamdani and the Adaptive Neuro Fuzzy Inference Systems (ANFIS) methodologies, which yield peak discharge estimation. The suggested model is compared with two well-known approaches, namely, Soil Conservation Service (SCS)-Snyder and SCS-Clark methodologies. In all the methods, the hydrographs are obtained through the use of dimensionless unit hydrograph concept. After the necessary modeling, computation, verification and adaptation stages comparatively better hydrographs are obtained by FCM. The mean square error for the FCM is many folds smaller than the other methodologies, which proves outperformance of the suggested methodology.
NASA Astrophysics Data System (ADS)
Ibey, Bennett L.; Lee, Seungjoon; Ericson, M. Nance; Wilson, Mark A.; Cote, Gerard L.
2004-06-01
A Multi-Layer Monte Carlo (MLMC) model was developed to predict the results of in vivo blood perfusion and oxygenation measurement of transplanted organs as measured by an indwelling optical sensor. A sensor has been developed which uses three-source excitation in the red and infrared ranges (660, 810, 940 nm). In vitro data was taken using this sensor by changing the oxygenation state of whole blood and passing it through a single-tube pump system wrapped in bovine liver tissue. The collected data showed that the red signal increased as blood oxygenation increased and infrared signal decreased. The center wavelength of 810 nanometers was shown to be quite indifferent to blood oxygenation change. A model was developed using MLMC code that sampled the wavelength range from 600-1000 nanometers every 6 nanometers. Using scattering and absorption data for blood and liver tissue within this wavelength range, a five-layer model was developed (tissue, clear tubing, blood, clear tubing, tissue). The theoretical data generated from this model was compared to the in vitro data and showed good correlation with changing blood oxygenation.
Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes,, Don; Black, Sylvester M.
2015-01-01
The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and “pearls of wisdom”/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794
Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes, Don; Black, Sylvester M; Ghadiali, Samir; Whitson, Bryan A
2015-01-01
The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and "pearls of wisdom"/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794
Mullani, N.A.
1984-11-01
The relation between the quantitative perfusion deficit, as measured by emission computerized tomography, and the severity of coronary artery stenosis is important for the noninvasive clinical evaluation of coronary artery disease in man. Positron emission tomography allows direct noninvasive measurement of myocardial perfusion and quantification of the size of the perfusion defect. Given this important imformation, a mathematical model has been derived to gauge the severity of a coronary stenosis from quantitative perfusion measurements in the normal and poststenotic regions of the heart. The theoretical basis is presented for relating regional myocardial perfusion and regional perfusion resistance to total, coronary blood flow and resistance at normal resting flow and during maximal coronary vasodilation. The concept of perfusion reserve is presented as a clinical measure of the severity of a stenosis.
McCommis, Kyle S.; Zhang, Haosen; Herrero, Pilar; Gropler, Robert J.; Zheng, Jie
2008-01-01
The purpose of this study was to examine the feasibility of quantifying myocardial blood flow (MBF) and rate of myocardial oxygen consumption (MVO2) during pharmacologically induced stress without using a contrast agent. The former was measured by the arterial spin labeling (ASL) method and the later was obtained by measuring the oxygen extraction fraction (OEF) with the magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) effect and Fick's law. The MRI results were compared with the established positron emission tomography (PET) methods. Six mongrel dogs with induced acute moderate left coronary artery stenosis were scanned using a clinical PET and a 1.5T MRI system, in the same day. Regional MBF, myocardial OEF, and MVO2 were measured with both imaging modalities. Correlation coefficients (R2) of the three myocardial indexes (MBF, OEF, and MVO2) between MRI and PET methods ranged from 0.70 to 0.93. Bland-Altman statistics demonstrated that the estimated precision of the limits of agreement between MRI and PET measurements varied from 18% (OEF), to 37% (MBF), and 45% (MVO2). The detected changes in these indexes, at rest and during dobutamine stress, were similar between two image modalities. The proposed non-contrast MRI technique is a promising method to quantitatively assess myocardial perfusion and oxygenation. PMID:17566684
Optimal estimator model for human spatial orientation
NASA Technical Reports Server (NTRS)
Borah, J.; Young, L. R.; Curry, R. E.
1979-01-01
A model is being developed to predict pilot dynamic spatial orientation in response to multisensory stimuli. Motion stimuli are first processed by dynamic models of the visual, vestibular, tactile, and proprioceptive sensors. Central nervous system function is then modeled as a steady-state Kalman filter which blends information from the various sensors to form an estimate of spatial orientation. Where necessary, this linear central estimator has been augmented with nonlinear elements to reflect more accurately some highly nonlinear human response characteristics. Computer implementation of the model has shown agreement with several important qualitative characteristics of human spatial orientation, and it is felt that with further modification and additional experimental data the model can be improved and extended. Possible means are described for extending the model to better represent the active pilot with varying skill and work load levels.
Winer, Jesse L; Kramer, Daniel R; Robison, Richard A; Ohiorhenuan, Ifije; Minneti, Michael; Giannotta, Steven; Zada, Gabriel
2015-11-01
Cadaveric surgical simulation carries the advantage of realistic anatomy and haptic feedback but has been historically difficult to model for intraventricular approaches given the need for active flow of CSF. This feasibility study was designed to simulate intraventricular neuroendoscopic approaches and techniques by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human cadavers, a simple cervical laminectomy and dural opening were made, and a 12-gauge arterial catheter was introduced. Saline was continuously perfused at physiological CSF pressures to reconstitute the subarachnoid space and ventricles. A neuroendoscope was subsequently inserted via a standard right frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic access of the lateral and third ventricles were achieved. In 2 cadavers, ventricular access was not feasible, perhaps because of a small ventricle size and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow reconstitution and endoscopic access, identifying the foramen of Monro was possible, as was performing septum pellucidotomy and endoscopic third ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis was possible, providing a complementary educational paradigm for resident education that cannot typically be performed in live surgery. Surgical simulation plays a critical and increasingly prominent role in surgical education, particularly for techniques with steep learning curves including intraventricular neuroendoscopic procedures. This novel model provides feasible and realistic surgical simulation of neuroendoscopic intraventricular procedures and approaches. PMID:25859805
Estimation and uncertainty of reversible Markov models
NASA Astrophysics Data System (ADS)
Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank
2015-11-01
Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software — http://pyemma.org — as of version 2.0.
Pulmonary ventilation/perfusion scan
V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health ...
Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi
2016-01-01
We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [(11)C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO. PMID:27116932
Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi
2016-01-01
We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [11C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO. PMID:27116932
Robust estimation procedure in panel data model
NASA Astrophysics Data System (ADS)
Shariff, Nurul Sima Mohamad; Hamzah, Nor Aishah
2014-06-01
The panel data modeling has received a great attention in econometric research recently. This is due to the availability of data sources and the interest to study cross sections of individuals observed over time. However, the problems may arise in modeling the panel in the presence of cross sectional dependence and outliers. Even though there are few methods that take into consideration the presence of cross sectional dependence in the panel, the methods may provide inconsistent parameter estimates and inferences when outliers occur in the panel. As such, an alternative method that is robust to outliers and cross sectional dependence is introduced in this paper. The properties and construction of the confidence interval for the parameter estimates are also considered in this paper. The robustness of the procedure is investigated and comparisons are made to the existing method via simulation studies. Our results have shown that robust approach is able to produce an accurate and reliable parameter estimates under the condition considered.
Robust estimation procedure in panel data model
Shariff, Nurul Sima Mohamad; Hamzah, Nor Aishah
2014-06-19
The panel data modeling has received a great attention in econometric research recently. This is due to the availability of data sources and the interest to study cross sections of individuals observed over time. However, the problems may arise in modeling the panel in the presence of cross sectional dependence and outliers. Even though there are few methods that take into consideration the presence of cross sectional dependence in the panel, the methods may provide inconsistent parameter estimates and inferences when outliers occur in the panel. As such, an alternative method that is robust to outliers and cross sectional dependence is introduced in this paper. The properties and construction of the confidence interval for the parameter estimates are also considered in this paper. The robustness of the procedure is investigated and comparisons are made to the existing method via simulation studies. Our results have shown that robust approach is able to produce an accurate and reliable parameter estimates under the condition considered.
Long term perfusion system supporting adipogenesis
Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.
2015-01-01
Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606
Mariotti, E; Orton, M R; Eerbeek, O; Ashruf, J F; Zuurbier, C J; Southworth, R; Eykyn, T R
2016-04-01
Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-(13)C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. PMID:26777799
Mariotti, E.; Orton, M. R.; Eerbeek, O.; Ashruf, J. F.; Zuurbier, C. J.; Southworth, R.
2016-01-01
Hyperpolarized 13C MR measurements have the potential to display non‐linear kinetics. We have developed an approach to describe possible non‐first‐order kinetics of hyperpolarized [1‐13C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second‐order model for conversion of [1‐13C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second‐order modeling yielded significantly improved fits of pyruvate–bicarbonate kinetics compared with the more traditionally used first‐order model and suggested time‐dependent decreases in pyruvate–bicarbonate flux. Second‐order modeling gave time‐dependent changes in forward and reverse reaction kinetics of pyruvate–lactate exchange and pyruvate–alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first‐order model. The mechanism giving rise to second‐order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD+ (the cofactor for PDH), consistent with the non‐linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:26777799
Generalized Mixture Models for Molecular Phylogenetic Estimation
Evans, Jason; Sullivan, Jack
2012-01-01
The rapidly growing availability of multigene sequence data during the past decade has enabled phylogeny estimation at phylogenomic scales. However, dealing with evolutionary process heterogeneity across the genome becomes increasingly challenging. Here we develop a mixture model approach that uses reversible jump Markov chain Monte Carlo (MCMC) estimation to permit as many distinct models as the data require. Each additional model considered may be a fully parametrized general time-reversible model or any of its special cases. Furthermore, we expand the usual proposal mechanisms for topology changes to permit hard polytomies (i.e., zero-length internal branches). This new approach is implemented in the Crux software toolkit. We demonstrate the feasibility of using reversible jump MCMC on mixture models by reexamining a well-known 44-taxon mammalian data set comprising 22 concatenated genes. We are able to reproduce the results of the original analysis (with respect to bipartition support) when we make identical assumptions, but when we allow for polytomies and/or use data-driven mixture model estimation, we infer much lower bipartition support values for several key bipartitions. PMID:21873377
Waller, Helen L; Harper, Simon J F; Hosgood, Sarah A; Bagul, Atul; Kay, Mark D; Kaushik, Monika; Yang, Bin; Bicknell, Gareth R; Nicholson, Michael L
2007-07-01
The optimal kidney preservation system and methods to ameliorate reperfusion injury are major factors in accomplishing successful graft function following transplantation. Ischaemia and reperfusion lead to cellular stress and the adaptive response may include the activation of genes involved in cellular protection and/or cell death by apoptosis. We investigated the expression of cytoprotective heme oxygenase-1 (HO-1), anti-apoptotic Bcl-2 and pro-apoptotic Bax after 6 h isolated organ perfusion in porcine kidneys that had been given 10 and 40 min warm ischaemic time. The level of HO-1 was shown to be significantly higher in the 10-min warm ischaemic group compared with 40-min group (0.90 +/- 0.03 vs. 0.83 +/- 0.03; P = 0.002). The levels of HO-1 showed a significant positive correlated with parameters of renal function, creatinine clearance, and renal blood flow and urine output (AUC; r = 0.8042, P = 0.03; r = 0.6028, P = 0.04; r = 0.6055, P = 0.04), demonstrating a possible protective role of this gene in this model of renal transplantation. PMID:17639610
Extreme Earthquake Risk Estimation by Hybrid Modeling
NASA Astrophysics Data System (ADS)
Chavez, M.; Cabrera, E.; Ashworth, M.; Garcia, S.; Emerson, D.; Perea, N.; Salazar, A.; Moulinec, C.
2012-12-01
The estimation of the hazard and the economical consequences i.e. the risk associated to the occurrence of extreme magnitude earthquakes in the neighborhood of urban or lifeline infrastructure, such as the 11 March 2011 Mw 9, Tohoku, Japan, represents a complex challenge as it involves the propagation of seismic waves in large volumes of the earth crust, from unusually large seismic source ruptures up to the infrastructure location. The large number of casualties and huge economic losses observed for those earthquakes, some of which have a frequency of occurrence of hundreds or thousands of years, calls for the development of new paradigms and methodologies in order to generate better estimates, both of the seismic hazard, as well as of its consequences, and if possible, to estimate the probability distributions of their ground intensities and of their economical impacts (direct and indirect losses), this in order to implement technological and economical policies to mitigate and reduce, as much as possible, the mentioned consequences. Herewith, we propose a hybrid modeling which uses 3D seismic wave propagation (3DWP) and neural network (NN) modeling in order to estimate the seismic risk of extreme earthquakes. The 3DWP modeling is achieved by using a 3D finite difference code run in the ~100 thousands cores Blue Gene Q supercomputer of the STFC Daresbury Laboratory of UK, combined with empirical Green function (EGF) techniques and NN algorithms. In particular the 3DWP is used to generate broadband samples of the 3D wave propagation of extreme earthquakes (plausible) scenarios corresponding to synthetic seismic sources and to enlarge those samples by using feed-forward NN. We present the results of the validation of the proposed hybrid modeling for Mw 8 subduction events, and show examples of its application for the estimation of the hazard and the economical consequences, for extreme Mw 8.5 subduction earthquake scenarios with seismic sources in the Mexican
The venous equilibrium model is widely used to describe hepatic clearance (CLH) of chemicals metabolized by the liver. If chemical delivery to the tissue does not limit CLH, this model predicts that CLH will approximately equal the product of intrinsic metabolic clearance and a t...
Pan, Youmin; Krueger, T; Tran, Nam; Yan, Hua; Ris, H-B; McKee, T A
2005-01-01
Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature. PMID:15905614
Estimating population trends with a linear model
Bart, J.; Collins, B.; Morrison, R.I.G.
2003-01-01
We describe a simple and robust method for estimating trends in population size. The method may be used with Breeding Bird Survey data, aerial surveys, point counts, or any other program of repeated surveys at permanent locations. Surveys need not be made at each location during each survey period. The method differs from most existing methods in being design based, rather than model based. The only assumptions are that the nominal sampling plan is followed and that sample size is large enough for use of the t-distribution. Simulations based on two bird data sets from natural populations showed that the point estimate produced by the linear model was essentially unbiased even when counts varied substantially and 25% of the complete data set was missing. The estimating-equation approach, often used to analyze Breeding Bird Survey data, performed similarly on one data set but had substantial bias on the second data set, in which counts were highly variable. The advantages of the linear model are its simplicity, flexibility, and that it is self-weighting. A user-friendly computer program to carry out the calculations is available from the senior author.
Entropy Based Modelling for Estimating Demographic Trends.
Li, Guoqi; Zhao, Daxuan; Xu, Yi; Kuo, Shyh-Hao; Xu, Hai-Yan; Hu, Nan; Zhao, Guangshe; Monterola, Christopher
2015-01-01
In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely: 1) Prediction of the age distribution of a country's population based on an "age-structured population model"; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an "individual household size model"; and 3) Estimation the number of each household size based on a "total household size model". The last stage is achieved by projecting the age distribution of the country's population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables. PMID:26382594
Model-based estimation of individual fitness
Link, W.A.; Cooch, E.G.; Cam, E.
2002-01-01
Fitness is the currency of natural selection, a measure of the propagation rate of genotypes into future generations. Its various definitions have the common feature that they are functions of survival and fertility rates. At the individual level, the operative level for natural selection, these rates must be understood as latent features, genetically determined propensities existing at birth. This conception of rates requires that individual fitness be defined and estimated by consideration of the individual in a modelled relation to a group of similar individuals; the only alternative is to consider a sample of size one, unless a clone of identical individuals is available. We present hierarchical models describing individual heterogeneity in survival and fertility rates and allowing for associations between these rates at the individual level. We apply these models to an analysis of life histories of Kittiwakes (Rissa tridactyla) observed at several colonies on the Brittany coast of France. We compare Bayesian estimation of the population distribution of individual fitness with estimation based on treating individual life histories in isolation, as samples of size one (e.g. McGraw and Caswell, 1996).
Model-based estimation of individual fitness
Link, W.A.; Cooch, E.G.; Cam, E.
2002-01-01
Fitness is the currency of natural selection, a measure of the propagation rate of genotypes into future generations. Its various definitions have the common feature that they are functions of survival and fertility rates. At the individual level, the operative level for natural selection, these rates must be understood as latent features, genetically determined propensities existing at birth. This conception of rates requires that individual fitness be defined and estimated by consideration of the individual in a modelled relation to a group of similar individuals; the only alternative is to consider a sample of size one, unless a clone of identical individuals is available. We present hierarchical models describing individual heterogeneity in survival and fertility rates and allowing for associations between these rates at the individual level. We apply these models to an analysis of life histories of Kittiwakes (Rissa tridactyla ) observed at several colonies on the Brittany coast of France. We compare Bayesian estimation of the population distribution of individual fitness with estimation based on treating individual life histories in isolation, as samples of size one (e.g. McGraw & Caswell, 1996).
Taeger, Christian D; Müller-Seubert, Wibke; Horch, Raymund E; Präbst, Konstantin; Münch, Frank; Geppert, Carol I; Birkholz, Torsten; Dragu, Adrian
2014-01-01
Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia-related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)-1-α as marker for hypoxia and of the pro-apoptotic protein Caspase-3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty-four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase-3 and HIF-1-α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase-3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF-1-α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase-3 and HIF-1-α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air. PMID:24636195
Heritability Estimation using Regression Models for Correlation
Lee, Hye-Seung; Paik, Myunghee Cho; Rundek, Tatjana; Sacco, Ralph L; Dong, Chuanhui; Krischer, Jeffrey P
2012-01-01
Heritability estimates a polygenic effect on a trait for a population. Reliable interpretation of heritability is critical in planning further genetic studies to locate a gene responsible for the trait. This study accommodates both single and multiple trait cases by employing regression models for correlation parameter to infer the heritability. Sharing the properties of regression approach, the proposed methods are exible to incorporate non-genetic and/or non-additive genetic information in the analysis. The performances of the proposed model are compared with those using the likelihood approach through simulations and carotid Intima Media Thickness analysis from Northern Manhattan family Study. PMID:22457844
Uncertainty estimation in reconstructed deformable models
Hanson, K.M.; Cunningham, G.S.; McKee, R.
1996-12-31
One of the hallmarks of the Bayesian approach to modeling is the posterior probability, which summarizes all uncertainties regarding the analysis. Using a Markov Chain Monte Carlo (MCMC) technique, it is possible to generate a sequence of objects that represent random samples drawn from the posterior distribution. We demonstrate this technique for reconstructions of two-dimensional objects from noisy projections taken from two directions. The reconstructed object is modeled in terms of a deformable geometrically-defined boundary with a constant interior density yielding a nonlinear reconstruction problem. We show how an MCMC sequence can be used to estimate uncertainties in the location of the edge of the reconstructed object.
A new estimator method for GARCH models
NASA Astrophysics Data System (ADS)
Onody, R. N.; Favaro, G. M.; Cazaroto, E. R.
2007-06-01
The GARCH (p, q) model is a very interesting stochastic process with widespread applications and a central role in empirical finance. The Markovian GARCH (1, 1) model has only 3 control parameters and a much discussed question is how to estimate them when a series of some financial asset is given. Besides the maximum likelihood estimator technique, there is another method which uses the variance, the kurtosis and the autocorrelation time to determine them. We propose here to use the standardized 6th moment. The set of parameters obtained in this way produces a very good probability density function and a much better time autocorrelation function. This is true for both studied indexes: NYSE Composite and FTSE 100. The probability of return to the origin is investigated at different time horizons for both Gaussian and Laplacian GARCH models. In spite of the fact that these models show almost identical performances with respect to the final probability density function and to the time autocorrelation function, their scaling properties are, however, very different. The Laplacian GARCH model gives a better scaling exponent for the NYSE time series, whereas the Gaussian dynamics fits better the FTSE scaling exponent.
Shitzer, Avraham; Arens, Edward; Zhang, Hui
2016-07-01
The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and
NASA Astrophysics Data System (ADS)
Shitzer, Avraham; Arens, Edward; Zhang, Hui
2015-11-01
The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.
NASA Astrophysics Data System (ADS)
Shitzer, Avraham; Arens, Edward; Zhang, Hui
2016-07-01
The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.
On Bayesian estimation of marginal structural models.
Saarela, Olli; Stephens, David A; Moodie, Erica E M; Klein, Marina B
2015-06-01
The purpose of inverse probability of treatment (IPT) weighting in estimation of marginal treatment effects is to construct a pseudo-population without imbalances in measured covariates, thus removing the effects of confounding and informative censoring when performing inference. In this article, we formalize the notion of such a pseudo-population as a data generating mechanism with particular characteristics, and show that this leads to a natural Bayesian interpretation of IPT weighted estimation. Using this interpretation, we are able to propose the first fully Bayesian procedure for estimating parameters of marginal structural models using an IPT weighting. Our approach suggests that the weights should be derived from the posterior predictive treatment assignment and censoring probabilities, answering the question of whether and how the uncertainty in the estimation of the weights should be incorporated in Bayesian inference of marginal treatment effects. The proposed approach is compared to existing methods in simulated data, and applied to an analysis of the Canadian Co-infection Cohort. PMID:25677103
Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion.
Bell, Robert M; Mocanu, Mihaela M; Yellon, Derek M
2011-06-01
In the late 19th century, a number of investigators were working on perfecting isolated heart model, but it was Oscar Langendorff who, in 1895, pioneered the isolated perfused mammalian heart. Since that time, the Langendorff preparation has evolved and provided a wealth of data underpinning our understanding of the fundamental physiology of the heart: its contractile function, coronary blood flow regulation and cardiac metabolism. In more recent times, the procedure has been used to probe pathophysiology of ischaemia/reperfusion and disease states, and with the dawn of molecular biology and genetic manipulation, the Langendorff perfused heart has remained a stalwart tool in the study of the impact upon the physiology of the heart by pharmacological inhibitors and targeted deletion or up-regulation of genes and their impact upon intracellular signalling and adaption to clinically relevant stressful stimuli. We present here the basic structure of the Langendorff system and the fundamental experimental rules which warrant a viable heart preparation. In addition, we discuss the use of the isolated retrograde perfused heart in the model of ischaemia-reperfusion injury ex-vivo, and its applicability to other areas of study. The Langendorff perfusion apparatus is highly adaptable and this is reflected not only in the procedure's longevity but also in the number of different applications to which it has been turned. PMID:21385587
Parameter Estimation of Spacecraft Fuel Slosh Model
NASA Technical Reports Server (NTRS)
Gangadharan, Sathya; Sudermann, James; Marlowe, Andrea; Njengam Charles
2004-01-01
Fuel slosh in the upper stages of a spinning spacecraft during launch has been a long standing concern for the success of a space mission. Energy loss through the movement of the liquid fuel in the fuel tank affects the gyroscopic stability of the spacecraft and leads to nutation (wobble) which can cause devastating control issues. The rate at which nutation develops (defined by Nutation Time Constant (NTC can be tedious to calculate and largely inaccurate if done during the early stages of spacecraft design. Pure analytical means of predicting the influence of onboard liquids have generally failed. A strong need exists to identify and model the conditions of resonance between nutation motion and liquid modes and to understand the general characteristics of the liquid motion that causes the problem in spinning spacecraft. A 3-D computerized model of the fuel slosh that accounts for any resonant modes found in the experimental testing will allow for increased accuracy in the overall modeling process. Development of a more accurate model of the fuel slosh currently lies in a more generalized 3-D computerized model incorporating masses, springs and dampers. Parameters describing the model include the inertia tensor of the fuel, spring constants, and damper coefficients. Refinement and understanding the effects of these parameters allow for a more accurate simulation of fuel slosh. The current research will focus on developing models of different complexity and estimating the model parameters that will ultimately provide a more realistic prediction of Nutation Time Constant obtained through simulation.
NASA Astrophysics Data System (ADS)
Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.
2014-03-01
We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.
Mak, K H; Eisenberg, M J; Shaw, J
1999-12-01
The objective of this study was to perform a theoretical cost-efficacy analysis on the use of routine functional testing with perfusion imaging to identify patients with asymptomatic restenosis following percutaneous transluminal coronary angioplasty (PTCA) procedures. Approximately 50% of patients with restenosis following PTCA are asymptomatic. Routine functional testing is commonly performed at 3 to 6 months to identify these patients. The cost-efficacy associated with this strategy is unknown. Theoretical models were constructed based on assumed costs for functional testing (U.S. $1,300) and coronary angiography (U.S. $3,000). Restenosis rates were assumed to be 40%, and half of patients with restenosis were assumed to be asymptomatic. To provide a range of costs to identify a patient with asymptomatic restenosis, three scenarios were constructed based on the diagnostic test characteristics of functional testing. Sensitivity analyses were performed using a range of costs for functional testing, restenosis rates, and proportion of patients with restenosis who are asymptomatic. Depending on the diagnostic accuracy of functional testing, it costs $8,200 to $22,400 to identify an asymptomatic patient with restenosis following PTCA. The cost to identify a patient with asymptomatic restenosis varies inversely with the rates of restenosis. When restenosis rates are < 20%, the cost to identify a patient with asymptomatic restenosis exceeds $10,000. Similarly, the cost to identify a patient with asymptomatic restenosis increases when the proportion of patients with asymptomatic restenosis decreases. The cost, associated with the use of routine functional testing for the identification of asymptomatic patients with restenosis appears exorbitant. However, a formal study is warranted to determine the cost-efficacy of such a strategy. Cathet. Cardiovasc. Intervent. 48:352-356, 1999. PMID:10559811
Guyot, Y; Luyten, F P; Schrooten, J; Papantoniou, I; Geris, L
2015-12-01
Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. Biotechnol. Bioeng. 2015;112: 2591-2600. © 2015 Wiley Periodicals, Inc. PMID:26059101
Dyke, Jonathan P; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K
2015-03-01
This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523
Dyke, Jonathan P.; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K.
2014-01-01
Purpose This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. Methods We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Results Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. Discussion MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523
Gardel, Ls; Afonso, M; Frias, C; Gomes, Me; Reis, Rl
2014-01-01
This work evaluated in vivo performance of a tissue-engineered bone-like matrix obtained by culturing cell-scaffold constructs in a flow perfusion bioreactor, designed to enable culture of large constructs, envisioning the regeneration of critical-sized defects. A blend of starch with polycaprolactone scaffolds was seeded with goat bone marrow stromal cells (GBMSCs) cultured in the perfusion bioreactor for 14 days using osteogenic medium. Cell seeded scaffolds cultured in static conditions acted as controls. After 14 days, constructs (42 mm length and 16 mm in diameter) were implanted in critical size defects performed in the tibial bone of six adult goats from which the bone marrow had been collected previously. Explants were retrieved after six and 12 weeks of implantation and characterized using scanning electron microscopy, energy-dispersive spectroscopy, micro-computed tomography and radiographic analysis to assess tissue morphology and calcification. Explants were histologically analyzed, using Hematoxylin & Eosin and Masson Trichrome staining. Results provided relevant information about the performance and functionality of starch with polycaprolactone-goat bone marrow stromal cell constructs in a critical size orthotopic defect performed in a large animal model and demonstrated that culture of the starch with polycaprolactone scaffolds with the autologous cells in perfusion culture provide a good therapy for the healing and regenerative process of bone defects. PMID:24413026
Pardon, Nicolas A; Vicario, Maria; Vanheel, Hanne; Vanuytsel, Tim; Ceulemans, Laurens J; Vieth, Michael; Jimenez, Marcel; Tack, Jan; Farré, Ricard
2016-04-01
Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure. PMID:26797397
Brunner, Stefan; Huber, Bruno C; Weinberger, Tobias; Vallaster, Marcus; Wollenweber, Tim; Gerbitz, Armin; Hacker, Marcus; Franz, Wolfgang-Michael
2012-01-01
Abstract Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor-dependent mechanisms, mobilization and homing of bone marrow-derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO-treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c-kit, CXCR-4 and Sca-1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single-photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO-treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO-treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR-4+ (4.3-fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively. PMID:21362129
Selection and estimation for mixed graphical models
Chen, Shizhe; Witten, Daniela M.; shojaie, Ali
2016-01-01
Summary We consider the problem of estimating the parameters in a pairwise graphical model in which the distribution of each node, conditioned on the others, may have a different exponential family form. We identify restrictions on the parameter space required for the existence of a well-defined joint density, and establish the consistency of the neighbourhood selection approach for graph reconstruction in high dimensions when the true underlying graph is sparse. Motivated by our theoretical results, we investigate the selection of edges between nodes whose conditional distributions take different parametric forms, and show that efficiency can be gained if edge estimates obtained from the regressions of particular nodes are used to reconstruct the graph. These results are illustrated with examples of Gaussian, Bernoulli, Poisson and exponential distributions. Our theoretical findings are corroborated by evidence from simulation studies.
Model estimates hurricane wind speed probabilities
NASA Astrophysics Data System (ADS)
Mumane, Richard J.; Barton, Chris; Collins, Eric; Donnelly, Jeffrey; Eisner, James; Emanuel, Kerry; Ginis, Isaac; Howard, Susan; Landsea, Chris; Liu, Kam-biu; Malmquist, David; McKay, Megan; Michaels, Anthony; Nelson, Norm; O Brien, James; Scott, David; Webb, Thompson, III
In the United States, intense hurricanes (category 3, 4, and 5 on the Saffir/Simpson scale) with winds greater than 50 m s -1 have caused more damage than any other natural disaster [Pielke and Pielke, 1997]. Accurate estimates of wind speed exceedance probabilities (WSEP) due to intense hurricanes are therefore of great interest to (re)insurers, emergency planners, government officials, and populations in vulnerable coastal areas.The historical record of U.S. hurricane landfall is relatively complete only from about 1900, and most model estimates of WSEP are derived from this record. During the 1899-1998 period, only two category-5 and 16 category-4 hurricanes made landfall in the United States. The historical record therefore provides only a limited sample of the most intense hurricanes.
Validation of Kp Estimation and Prediction Models
NASA Astrophysics Data System (ADS)
McCollough, J. P., II; Young, S. L.; Frey, W.
2014-12-01
Specifification and forecast of geomagnetic indices is an important capability for space weather operations. The University Partnering for Operational Support (UPOS) effort at the Applied Physics Laboratory of Johns Hopkins University (JHU/APL) produced many space weather models, including the Kp Predictor and Kp Estimator. We perform a validation of index forecast products against definitive indices computed by the Deutches GeoForschungsZentstrum Potsdam (GFZ). We compute continuous predictant skill scores, as well as 2x2 contingency tables and associated scalar quantities for different index thresholds. We also compute a skill score against a nowcast persistence model. We discuss various sources of error for the models and how they may potentially be improved.
Parameter Estimation for Viscoplastic Material Modeling
NASA Technical Reports Server (NTRS)
Saleeb, Atef F.; Gendy, Atef S.; Wilt, Thomas E.
1997-01-01
A key ingredient in the design of engineering components and structures under general thermomechanical loading is the use of mathematical constitutive models (e.g. in finite element analysis) capable of accurate representation of short and long term stress/deformation responses. In addition to the ever-increasing complexity of recent viscoplastic models of this type, they often also require a large number of material constants to describe a host of (anticipated) physical phenomena and complicated deformation mechanisms. In turn, the experimental characterization of these material parameters constitutes the major factor in the successful and effective utilization of any given constitutive model; i.e., the problem of constitutive parameter estimation from experimental measurements.
3D functional and perfusable microvascular networks for organotypic microfluidic models.
Bersini, Simone; Moretti, Matteo
2015-05-01
The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases. PMID:25893395
Reeder, Scott B.; Atalay, Michael K.; McVeigh, Elliot R.; Zerhouni, Elias A.; Forder, John R.
2007-01-01
PURPOSE: To quantitate myocardial arterial perfusion with a noninvasive magnetic resonance (MR) imaging technique that exploits the geometry of coronary vessel anatomy. MATERIALS AND METHODS: MR imaging was performed with a spinlabeling method in six arrested rabbit hearts at 4.7 T. Selective inversion of magnetization in the short-axis imaging section along with all myocardium apical to that section produces signal enhancement from arterial perfusion. A linescan protocol was used for validation of flow enhancement. Flow was quantitated from two images and validated with spin-echo (SE) imaging. Regional perfusion defects were created by means of coronary artery ligation and delineated with gadolinium-enhanced imaging. RESULTS: Linescan estimates of T1 obtained at physiologic flows agreed with model predictions. Flow-induced signal enhancement measured on SE images also agreed with expected values. Finally, perfusion abnormalities created by means of coronary artery ligation were detected. CONCLUSION: This spin-labeling method provides quantitative estimates of myocardial arterial perfusion in this model and may hold promise for clinical applications. PMID:8657907
Solar sails: Modeling, estimation, and trajectory control
NASA Astrophysics Data System (ADS)
Rios-Reyes, Leonel
There has been great interest in developing solar sail technology and missions by several international space agencies in recent years. However, at present there is no consensus on how one can mathematically model forces and moments acting on a solar sail. Traditional analytical models and finite element methods are not feasible for integration into a precise navigation system. This dissertation takes a step toward resolving this issue by developing tools and concepts that can be integrated into a precise solar sail navigation system. These steps are the derivation of a generalized sail model, a linear estimation method for estimating and predicting forces and moments acting on a solar sail, and a new trajectory control methodology for tracking a nominal trajectory when the sail performance exceeds the nominal design performance. The main contributions of this dissertation follow. First, the generalized sail model (GSM) is defined to analytically describe the forces and moments acting on a solar sail of arbitrary shape. The GSM is derived by performing an integration, of all the differential forces and moments acting on the sail, over the sail surface. Next, the GSM is applied to several examples to illustrate the use of the GSM's analytic equations. These examples allow comparisons of forces and moments generated by different solar sails, the computation of force derivatives, and the application of the model to orbital mechanics problems. Since it is difficult to model the sail geometry based on ground measurements; errors in the sail model are expected once the sail is deployed in space. Due to this difficulty; a least-squares estimation method for the force and moment coefficients of the GSM is derived. For realistic implementation of a sail trajectory, the deployed sail must have an excess thrust capacity. We develop and implement a control methodology for flying a nominal mission profile with such an excess capacity. Control laws for maintaining a flat, ideal
Regression models for estimating coseismic landslide displacement
Jibson, R.W.
2007-01-01
Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived from a collection of 2270 strong-motion records from 30 worldwide earthquakes. The regression equations predict Newmark displacement in terms of (1) critical acceleration ratio, (2) critical acceleration ratio and earthquake magnitude, (3) Arias intensity and critical acceleration, and (4) Arias intensity and critical acceleration ratio. These equations are well constrained and fit the data well (71% < R2 < 88%), but they have standard deviations of about 0.5 log units, such that the range defined by the mean ?? one standard deviation spans about an order of magnitude. These regression models, therefore, are not recommended for use in site-specific design, but rather for regional-scale seismic landslide hazard mapping or for rapid preliminary screening of sites. ?? 2007 Elsevier B.V. All rights reserved.
Quantification of myocardial perfusion based on signal intensity of flow sensitized MRI
NASA Astrophysics Data System (ADS)
Abeykoon, Sumeda B.
maximum percentage deviation is about 5%. Then the SI-method was used in comparison to a delayed enhanced method to qualitatively and quantitatively assess perfusion deficits in an ischemia-reperfusion (IR) mouse model. The infarcted region of the perfusion map is comparable to the hyper intense region of the delayed enhanced image of the IR mouse. The SI method also used to record a chronological comparison of perfusion on delta sarcoglycan null (DSG) mice. Perfusion of DSG and wild-type (WT) mice at ages of 12 weeks and 32 weeks were compared and percentage change of perfusion was estimated. The result shows that in DSG mice perfusion changes considerably. Finally, the SI method was implemented on a 3 Tesla Philip scanner by modifying to data acquisition method. The perfusion obtained in this is consistent with literature values but further adjustment of pulse sequence and modification of numerical solution is needed. The most important benefit of the SI method is that it reduces scan time 30%--40% and lessens motion artifacts of images compared to the T1 method. This study demonstrates that the signal intensity-based ASL method is a robust alternative to the conventional T1-method.
Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling
Chapman, Lloyd A. C.; Shipley, Rebecca J.; Whiteley, Jonathan P.; Ellis, Marianne J.; Byrne, Helen M.; Waters, Sarah L.
2014-01-01
The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges to (equivalent to to ) and to (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells. PMID:25157635
Nonlinear models for estimating GSFC travel requirements
NASA Technical Reports Server (NTRS)
Buffalano, C.; Hagan, F. J.
1974-01-01
A methodology is presented for estimating travel requirements for a particular period of time. Travel models were generated using nonlinear regression analysis techniques on a data base of FY-72 and FY-73 information from 79 GSFC projects. Although the subject matter relates to GSFX activities, the type of analysis used and the manner of selecting the relevant variables would be of interest to other NASA centers, government agencies, private corporations and, in general, any organization with a significant travel budget. Models were developed for each of six types of activity: flight projects (in-house and out-of-house), experiments on non-GSFC projects, international projects, ART/SRT, data analysis, advanced studies, tracking and data, and indirects.
Shakhawath Hossain, Md; Bergstrom, D J; Chen, X B
2015-12-01
The in vitro chondrocyte cell culture for cartilage tissue regeneration in a perfusion bioreactor is a complex process. Mathematical modeling and computational simulation can provide important insights into the culture process, which would be helpful for selecting culture conditions to improve the quality of the developed tissue constructs. However, simulation of the cell culture process is a challenging task due to the complicated interaction between the cells and local fluid flow and nutrient transport inside the complex porous scaffolds. In this study, a mathematical model and computational framework has been developed to simulate the three-dimensional (3D) cell growth in a porous scaffold placed inside a bi-directional flow perfusion bioreactor. The model was developed by taking into account the two-way coupling between the cell growth and local flow field and associated glucose concentration, and then used to perform a resolved-scale simulation based on the lattice Boltzmann method (LBM). The simulation predicts the local shear stress, glucose concentration, and 3D cell growth inside the porous scaffold for a period of 30 days of cell culture. The predicted cell growth rate was in good overall agreement with the experimental results available in the literature. This study demonstrates that the bi-directional flow perfusion culture system can enhance the homogeneity of the cell growth inside the scaffold. The model and computational framework developed is capable of providing significant insight into the culture process, thus providing a powerful tool for the design and optimization of the cell culture process. PMID:26061385
Comparisons of Four Methods for Estimating a Dynamic Factor Model
ERIC Educational Resources Information Center
Zhang, Zhiyong; Hamaker, Ellen L.; Nesselroade, John R.
2008-01-01
Four methods for estimating a dynamic factor model, the direct autoregressive factor score (DAFS) model, are evaluated and compared. The first method estimates the DAFS model using a Kalman filter algorithm based on its state space model representation. The second one employs the maximum likelihood estimation method based on the construction of a…
Jungreuthmayer, C; Jaasma, M J; Al-Munajjed, A A; Zanghellini, J; Kelly, D J; O'Brien, F J
2009-05-01
Tissue-engineered bone shows promise in meeting the huge demand for bone grafts caused by up to 4 million bone replacement procedures per year, worldwide. State-of-the-art bone tissue engineering strategies use flow perfusion bioreactors to apply biophysical stimuli to cells seeded on scaffolds and to grow tissue suitable for implantation into the patient's body. The aim of this study was to quantify the deformation of cells seeded on a collagen-GAG scaffold which was perfused by culture medium inside a flow perfusion bioreactor. Using a microCT scan of an unseeded collagen-GAG scaffold, a sequential 3D CFD-deformation model was developed. The wall shear stress and the hydrostatic wall pressure acting on the cells were computed through the use of a CFD simulation and fed into a linear elastostatics model in order to calculate the deformation of the cells. The model used numerically seeded cells of two common morphologies where cells are either attached flatly on the scaffold wall or bridging two struts of the scaffold. Our study showed that the displacement of the cells is primarily determined by the cell morphology. Although cells of both attachment profiles were subjected to the same mechanical load, cells bridging two struts experienced a deformation up to 500 times higher than cells only attached to one strut. As the scaffold's pore size determines both the mechanical load and the type of attachment, the design of an optimal scaffold must take into account the interplay of these two features and requires a design process that optimizes both parameters at the same time. PMID:19109048
Estimating Resolution Lengths of Hybrid Turbulence Models
NASA Technical Reports Server (NTRS)
Abdol-Hamid, Khaled S.; Girimaji, Sharath S.
2006-01-01
A two-stage procedure has been devised for estimating the spatial resolution achievable in the simulation of a given flow on a given computational grid by a computational fluid dynamics (CFD) code that incorporates a hybrid model of turbulence. The hybrid models to which this procedure is especially relevant are those of the Reynolds-averaged Navier-Stokes (RANS) and the partial-averaged Navier-Stokes (PANS) approaches. This procedure represents the first step toward adding variable-resolution turbulence-modeling capabilities to CFD codes as part of a continuing effort to increase the accuracy and robustness of CFD simulations of unsteady flows. Some background information is prerequisite to a meaningful summary of the procedure. Among experts in CFD, it is well known that combination of the Reynolds-averaged Navier-Stokes (RANS) approach and eddy-viscosity turbulence models offers limited capability for simulating unsteady and complex flows. The RANS approach includes an assumption that most of the energy in a given flow is modeled through turbulence-transport equations and is resolved in a computational grid used to simulate the flow. RANS also overpredicts eddy viscosity, thereby yielding excessive damping of unsteady motion. The eddy viscosity attains an unphysically large value because of unresolved scales, and suppresses most temporal and spatial fluctuations in the resolved flow field. One approach used to overcome this deficiency is to provide a mechanism for the RANS equations to resolve motion only on the largest scales and to use a hybrid model to represent effects at smaller scales. The RANS approach involves the use of a standard two-equation turbulence model in which the effect of turbulence is summarized by a viscosity that is a function of (1) the time-averaged kinetic- energy density (k) associated with the local fluctuating (turbulent) component of flow and (2) the time-averaged rate of dissipation of the turbulent-kinetic- energy density ( ). In
The Mayfield method of estimating nesting success: A model, estimators and simulation results
Hensler, G.L.; Nichols, J.D.
1981-01-01
Using a nesting model proposed by Mayfield we show that the estimator he proposes is a maximum likelihood estimator (m.l.e.). M.l.e. theory allows us to calculate the asymptotic distribution of this estimator, and we propose an estimator of the asymptotic variance. Using these estimators we give approximate confidence intervals and tests of significance for daily survival. Monte Carlo simulation results show the performance of our estimators and tests under many sets of conditions. A traditional estimator of nesting success is shown to be quite inferior to the Mayfield estimator. We give sample sizes required for a given accuracy under several sets of conditions.
Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S
2010-09-01
Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285
Estimation Methods for One-Parameter Testlet Models
ERIC Educational Resources Information Center
Jiao, Hong; Wang, Shudong; He, Wei
2013-01-01
This study demonstrated the equivalence between the Rasch testlet model and the three-level one-parameter testlet model and explored the Markov Chain Monte Carlo (MCMC) method for model parameter estimation in WINBUGS. The estimation accuracy from the MCMC method was compared with those from the marginalized maximum likelihood estimation (MMLE)…
Benefit Estimation Model for Tourist Spaceflights
NASA Astrophysics Data System (ADS)
Goehlich, Robert A.
2003-01-01
It is believed that the only potential means for significant reduction of the recurrent launch cost, which results in a stimulation of human space colonization, is to make the launcher reusable, to increase its reliability, and to make it suitable for new markets such as mass space tourism. But such space projects, that have long range aspects are very difficult to finance, because even politicians would like to see a reasonable benefit during their term in office, because they want to be able to explain this investment to the taxpayer. This forces planners to use benefit models instead of intuitive judgement to convince sceptical decision-makers to support new investments in space. Benefit models provide insights into complex relationships and force a better definition of goals. A new approach is introduced in the paper that allows to estimate the benefits to be expected from a new space venture. The main objective why humans should explore space is determined in this study to ``improve the quality of life''. This main objective is broken down in sub objectives, which can be analysed with respect to different interest groups. Such interest groups are the operator of a space transportation system, the passenger, and the government. For example, the operator is strongly interested in profit, while the passenger is mainly interested in amusement, while the government is primarily interested in self-esteem and prestige. This leads to different individual satisfactory levels, which are usable for the optimisation process of reusable launch vehicles.
ARM Climate Modeling Best Estimate Data
Xie, S.; Jensen, M.; McCoy, R. B.; Klein, S. A.; Cederwall, R. T.; Wiscombe, W. J.; Clothiaux, E. E.; Gaustad, K. L.; Golaz, J.-C.; Hall, S.; Johnson, K. L.; Lin, Y.; Long, C. N.; Mather, J. H.; McCord, R. A.; McFarlane, S. A.; Palanisamy, G.; Shi, Y.; Turner, D. D.
2010-01-01
can hamper the use of ACRF data by the climate community. To make ACRF data better serve the needs of climate studies and model development, ARM has developed a data product specifically tailored for use by the climate community. The new data product, named the Climate Modeling Best Estimate (CMBE) dataset, assembles those quantities that are both well observed by ACRF over many years and are often used in model evaluation into one single dataset. The CMBE product consists of hourly averages and thus has temporal resolution comparable to a typical resolution used in climate model output. It also includes standard deviations within the averaged hour and quality control flags for the selected quantities to indicate the temporal variability and data quality. Since its initial release in February 2008, the new data product has quickly drawn the attention of the climate modeling community. It is being used for model evaluation by two major U.S. climate modeling centers, the National Center for Atmospheric Research (NCAR) and the Geophysical Fluid Dynamics Laboratory (GFDL). The purpose of this paper is to provide an overview of CMBE data and a few examples that demonstrate the potential value of CMBE data for climate modeling and in studies of cloud processes and climate variability and change.
Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona
2015-01-01
The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202
Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona
2015-04-01
The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202
Eckert, Saskia; Eyer, Peter; Mückter, Harald; Worek, Franz
2006-07-28
Quantitative predictions of the course of acetylcholinesterase (AChE) activity, following interference of inhibitors and reactivators, are usually obscured by the time-dependent changes of all reaction partners. To mimic these dynamics we developed an in vitro model. Immobilized human erythrocyte ghosts in a bioreactor were continuously perfused while AChE activity was monitored by a modified Ellman method. The perfusion system consisted of two HPLC pumps with integrated quaternary low-pressure gradient formers that were programmed by a computer using commercial HPLC software. The combined eluates passed a particle filter (Millex-GS, 0.22 microm) containing a thin layer of erythrocytes that was immersed in a temperature-controlled water bath. The effluent passed a flow cell in a UV-vis detector, the signal of which was digitized, written to disc and calculated with curve fitting programs. AChE activity decreased by 3.4% within 2.5 h. The day-to-day variation of the freshly prepared bioreactor using the same enzyme source was +/-3.3%. Residual activity of 0.2% marked the limit of quantification. Following perfusion with paraoxon, pseudo first-order rate constants of inhibition were established that did not differ from results obtained in conventional assays. The same holds true for reactivation with obidoxime. The set-up presented allows freely programmable time-dependent changes of up to eight solvents to mimic pharmacokinetic profiles without accumulation of products. Due to some hysteresis in the system, reaction half-lives should be >3 min and concentration changes in critical compounds should exceed half-lives of 5 min. Otherwise, the system offers much flexibility and operates with high precision. PMID:16725113
Bayram-Weston, Zubeyde; Olsen, Elliott; Harrison, David J.; Dunnett, Stephen B.; Brooks, Simon P.
2016-01-01
Background The Golgi–Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. New methods Conventional rapid Golgi and Golgi–Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24 h. Results Tissue perfused with 4% PFA and post fixed for 24 h remained viable for the modified Golgi–Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi–Cox method yielded consistently reliable high-quality staining. Comparison with existing methods The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. Conclusions The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment. PMID:26459195
Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank
2010-08-01
Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.
On population size estimators in the Poisson mixture model.
Mao, Chang Xuan; Yang, Nan; Zhong, Jinhua
2013-09-01
Estimating population sizes via capture-recapture experiments has enormous applications. The Poisson mixture model can be adopted for those applications with a single list in which individuals appear one or more times. We compare several nonparametric estimators, including the Chao estimator, the Zelterman estimator, two jackknife estimators and the bootstrap estimator. The target parameter of the Chao estimator is a lower bound of the population size. Those of the other four estimators are not lower bounds, and they may produce lower confidence limits for the population size with poor coverage probabilities. A simulation study is reported and two examples are investigated. PMID:23865502
Intestinal perfusion monitoring using photoplethysmography
NASA Astrophysics Data System (ADS)
Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.
2013-08-01
In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.
A Note on Structural Equation Modeling Estimates of Reliability
ERIC Educational Resources Information Center
Yang, Yanyun; Green, Samuel B.
2010-01-01
Reliability can be estimated using structural equation modeling (SEM). Two potential problems with this approach are that estimates may be unstable with small sample sizes and biased with misspecified models. A Monte Carlo study was conducted to investigate the quality of SEM estimates of reliability by themselves and relative to coefficient…
The Mapping Model: A Cognitive Theory of Quantitative Estimation
ERIC Educational Resources Information Center
von Helversen, Bettina; Rieskamp, Jorg
2008-01-01
How do people make quantitative estimations, such as estimating a car's selling price? Traditionally, linear-regression-type models have been used to answer this question. These models assume that people weight and integrate all information available to estimate a criterion. The authors propose an alternative cognitive theory for quantitative…
Infrasound Propagation Modeling for Explosive Yield Estimation
NASA Astrophysics Data System (ADS)
Howard, J. E.; Golden, P.; Negraru, P.
2013-12-01
This study focuses on developing methods of estimating the size or yield of HE surface explosions from local and regional infrasound measurements in the southwestern United States. A munitions disposal facility near Mina, Nevada provides a repeating ground-truth source for this study, with charge weights ranging from 870 - 3800 lbs. Detonation logs and GPS synchronized videos were obtained for a sample of shots representing the full range of weights. These are used to calibrate a relationship between charge weight and spectral level from seismic waveforms recorded at the Nevada Seismic Array (NVAR) at a distance of 36 km. Origin times and yields for the remaining shots are inferred from the seismic recordings at NVAR. Infrasound arrivals from the detonations have been continuously recorded on three four-element, small aperture infrasound arrays since late 2009. NVIAR is collocated with NVAR at a range of approximately 36 km to the northeast. FALN and DNIAR are located at ranges of 154 km to the north, and 293 km to the southeast respectively. Travel times and amplitudes for stratospheric arrivals at DNIAR show strong seasonal variability with the largest amplitudes and celerities occurring during the winter months when the stratospheric winds are favorable. Stratospheric celerities for FNIAR to the north are more consistent as they are not strongly affected by the predominantly meridional stratospheric winds. Tropospheric arrivals at all three arrays show considerable variability that does not appear to be a seasonal effect. Naval Research Laboratory Ground to Space (NRL-G2S) Mesoscale models are used to specify the atmosphere along the propagation path for each detonation. Ray-tracing is performed for each source/receiver pair to identify events for which the models closely match the travel-time observations. This subset of events is used to establish preliminary wind correction formulas using wind values from the G2S profile for the entire propagation path. These
Cano, I; Roca, J; Wagner, P D
2015-01-01
Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017
Parameter Estimates in Differential Equation Models for Chemical Kinetics
ERIC Educational Resources Information Center
Winkel, Brian
2011-01-01
We discuss the need for devoting time in differential equations courses to modelling and the completion of the modelling process with efforts to estimate the parameters in the models using data. We estimate the parameters present in several differential equation models of chemical reactions of order n, where n = 0, 1, 2, and apply more general…
Sutton, S C; Rinaldi, M T; Vukovinsky, K E
2001-01-01
This study was undertaken to determine whether the gravimetric method provided an accurate measure of water flux correction and to compare the gravimetric method with methods that employ nonabsorbed markers (eg, phenol red and 14C-PEG-3350). Phenol red,14C-PEG-3350, and 4-[2-[[2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethoxy]-, methyl ester, (R)-benzene acetic acid (Compound I) were co-perfused in situ through the jejunum of 9 anesthetized rats (single-pass intestinal perfusion [SPIP]). Water absorption was determined from the phenol red,14C-PEG-3350, and gravimetric methods. The absorption rate constant (ka) for Compound I was calculated. Both phenol red and 14C-PEG-3350 were appreciably absorbed, underestimating the extent of water flux in the SPIP model. The average +/- SD water flux microg/h/cm) for the 3 methods were 68.9 +/- 28.2 (gravimetric), 26.8 +/- 49.2 (phenol red), and 34.9 +/- 21.9 (14C-PEG-3350). The (average +/- SD) ka for Compound I (uncorrected for water flux) was 0.024 +/- 0.005 min(-1). For the corrected, gravimetric method, the average +/- SD was 0.031 +/- 0.001 min(-1). The gravimetric method for correcting water flux was as accurate as the 2 "nonabsorbed" marker methods. PMID:11741276
[Ocular perfusion pressure and its relevance for glaucoma].
Schmidl, D; Werkmeister, R; Garhöfer, G; Schmetterer, L
2015-02-01
Ocular perfusion pressure is defined as the difference between arterial and venous pressure in ocular vessels. In practice, mean arterial pressure is used to substitute for arterial pressure in ocular vessels while intraocular pressure gives an estimate for ocular venous pressure. This results in a value that is easy to calculate and which is of importance since several studies have shown that it is correlated to the prevalence, incidence and progression of primary open angle glaucoma. Today, ocular perfusion pressure is used to estimate individual risks. Since no target value for ocular perfusion pressure can be defined, direct therapeutic intervention is difficult. Still, it has to be kept in mind that lowering intraocular pressure automatically leads to an increase in ocular perfusion pressure. The present article also points out problems and limitations in the concept of ocular perfusion pressure and suggests possible solutions for these problems in the future. PMID:25700252
Estimators for variance components in structured stair nesting models
NASA Astrophysics Data System (ADS)
Monteiro, Sandra; Fonseca, Miguel; Carvalho, Francisco
2016-06-01
The purpose of this paper is to present the estimation of the components of variance in structured stair nesting models. The relationship between the canonical variance components and the original ones, will be very important in obtaining that estimators.
Multi-Cone Model for Estimating GPS Ionospheric Delays
NASA Technical Reports Server (NTRS)
Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony
2009-01-01
The multi-cone model is a computational model for estimating ionospheric delays of Global Positioning System (GPS) signals. It is a direct descendant of the conical-domain model. A primary motivation for the development of this model is the need to find alternatives for modeling slant delays at low latitudes, where ionospheric behavior poses an acute challenge for GPS signal-delay estimates based upon the thin-shell model of the ionosphere.
Estimates of Acausal Joint Impedance Models
Perreault, Eric J.
2013-01-01
Estimates of joint or limb impedance are commonly used in the study of how the nervous system controls posture and movement, and how that control is altered by injury to the neural or musculoskeletal systems. Impedance characterizes the dynamic relationship between an imposed perturbation of joint position and the torques generated in response. While there are many practical reasons for estimating impedance rather than its inverse, admittance, it is an acausal representation of the limb mechanics that can lead to difficulties in interpretation or use. The purpose of this study was to explore the acausal nature of nonparametric estimates of joint impedance representations to determine how they are influenced by common experimental and computational choices. This was accomplished by deriving discrete-time realizations of first-and second-order derivatives to illustrate two key difficulties in the physical interpretation of impedance impulse response functions. These illustrations were provided using both simulated and experimental data. It was found that the shape of the impedance impulse response depends critically on the selected sampling rate, and on the bandwidth and noise characteristics of the position perturbation used during the estimation process. These results provide important guidelines for designing experiments in which nonparametric estimates of impedance will be obtained, especially when those estimates are to be used in a multistep identification process. PMID:22907963
Estimates of acausal joint impedance models.
Westwick, David T; Perreault, Eric J
2012-10-01
Estimates of joint or limb impedance are commonly used in the study of how the nervous system controls posture and movement, and how that control is altered by injury to the neural or musculoskeletal systems. Impedance characterizes the dynamic relationship between an imposed perturbation of joint position and the torques generated in response. While there are many practical reasons for estimating impedance rather than its inverse, admittance, it is an acausal representation of the limb mechanics that can lead to difficulties in interpretation or use. The purpose of this study was to explore the acausal nature of nonparametric estimates of joint impedance representations to determine how they are influenced by common experimental and computational choices. This was accomplished by deriving discrete-time realizations of first- and second-order derivatives to illustrate two key difficulties in the physical interpretation of impedance impulse response functions. These illustrations were provided using both simulated and experimental data. It was found that the shape of the impedance impulse response depends critically on the selected sampling rate, and on the bandwidth and noise characteristics of the position perturbation used during the estimation process. These results provide important guidelines for designing experiments in which nonparametric estimates of impedance will be obtained, especially when those estimates are to be used in a multistep identification process. PMID:22907963
Sorace, Anna G; Quarles, C Chad; Whisenant, Jennifer G; Hanker, Ariella B; McIntyre, J Oliver; Sanchez, Violeta M; Yankeelov, Thomas E
2016-01-01
To employ in vivo imaging and histological techniques to identify and quantify vascular changes early in the course of treatment with trastuzumab in a murine model of HER2+ breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively characterize vessel perfusion/permeability (via the parameter K (trans) ) and the extravascular extracellular volume fraction (v e ) in the BT474 mouse model of HER2+ breast cancer (N = 20) at baseline, day one, and day four following trastuzumab treatment (10 mg/kg). Additional cohorts of mice were used to quantify proliferation (Ki67), microvessel density (CD31), pericyte coverage (α-SMA) by immunohistochemistry (N = 44), and to quantify human VEGF-A expression (N = 29) throughout the course of therapy. Longitudinal assessment of combination doxorubicin ± trastuzumab (N = 42) tested the hypothesis that prior treatment with trastuzumab will increase the efficacy of subsequent doxorubicin therapy. Compared to control tumors, trastuzumab-treated tumors exhibited a significant increase in K (trans) (P = 0.035) on day four, indicating increased perfusion and/or vessel permeability and a simultaneous significant increase in v e (P = 0.01), indicating increased cell death. Immunohistochemical and ELISA analyses revealed that by day four the trastuzumab-treated tumors had a significant increase in vessel maturation index (i.e., the ratio of α-SMA to CD31 staining) compared to controls (P < 0.001) and a significant decrease in VEGF-A (P = 0.03). Additionally, trastuzumab dosing prior to doxorubicin improved the overall effectiveness of the therapies (P < 0.001). This study identifies and validates improved perfusion characteristics following trastuzumab therapy, resulting in an improvement in trastuzumab-doxorubicin combination therapy in a murine model of HER2+ breast cancer. This data suggests properties of vessel maturation. In particular, the use of DCE-MRI, a clinically
Simultaneous estimation of parameters in the bivariate Emax model.
Magnusdottir, Bergrun T; Nyquist, Hans
2015-12-10
In this paper, we explore inference in multi-response, nonlinear models. By multi-response, we mean models with m > 1 response variables and accordingly m relations. Each parameter/explanatory variable may appear in one or more of the relations. We study a system estimation approach for simultaneous computation and inference of the model and (co)variance parameters. For illustration, we fit a bivariate Emax model to diabetes dose-response data. Further, the bivariate Emax model is used in a simulation study that compares the system estimation approach to equation-by-equation estimation. We conclude that overall, the system estimation approach performs better for the bivariate Emax model when there are dependencies among relations. The stronger the dependencies, the more we gain in precision by using system estimation rather than equation-by-equation estimation. PMID:26190048
Equating Parameter Estimates from the Generalized Graded Unfolding Model.
ERIC Educational Resources Information Center
Roberts, James S.
Three common methods for equating parameter estimates from binary item response theory models are extended to the generalized grading unfolding model (GGUM). The GGUM is an item response model in which single-peaked, nonmonotonic expected value functions are implemented for polytomous responses. GGUM parameter estimates are equated using extended…
Yifat, Jonathan; Gannot, Israel
2015-03-01
Early detection of malignant tumors plays a crucial role in the survivability chances of the patient. Therefore, new and innovative tumor detection methods are constantly searched for. Tumor-specific magnetic-core nano-particles can be used with an alternating magnetic field to detect and treat tumors by hyperthermia. For the analysis of the method effectiveness, the bio-heat transfer between the nanoparticles and the tissue must be carefully studied. Heat diffusion in biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where blood perfusion plays an important role. Malignant tumors are known to initiate an angiogenesis process, where endothelial cell migration from neighboring vasculature eventually leads to the formation of a thick blood capillary network around them. This process allows the tumor to receive its extensive nutrition demands and evolve into a more progressive and potentially fatal tumor. In order to assess the effect of angiogenesis on the bio-heat transfer problem, we have developed a discrete stochastic 3D model & simulation of tumor-induced angiogenesis. The model elaborates other angiogenesis models by providing high resolution 3D stochastic simulation, capturing of fine angiogenesis morphological features, effects of dynamic sprout thickness functions, and stochastic parent vessel generator. We show that the angiogenesis realizations produced are well suited for numerical bio-heat transfer analysis. Statistical study on the angiogenesis characteristics was derived using Monte Carlo simulations. According to the statistical analysis, we provide analytical expression for the blood perfusion coefficient in the Pennes equation, as a function of several parameters. This updated form of the Pennes equation could be used for numerical and analytical analyses of the proposed detection and treatment method. PMID:24462603
Parameter estimation and error analysis in environmental modeling and computation
NASA Technical Reports Server (NTRS)
Kalmaz, E. E.
1986-01-01
A method for the estimation of parameters and error analysis in the development of nonlinear modeling for environmental impact assessment studies is presented. The modular computer program can interactively fit different nonlinear models to the same set of data, dynamically changing the error structure associated with observed values. Parameter estimation techniques and sequential estimation algorithms employed in parameter identification and model selection are first discussed. Then, least-square parameter estimation procedures are formulated, utilizing differential or integrated equations, and are used to define a model for association of error with experimentally observed data.
Performance of Random Effects Model Estimators under Complex Sampling Designs
ERIC Educational Resources Information Center
Jia, Yue; Stokes, Lynne; Harris, Ian; Wang, Yan
2011-01-01
In this article, we consider estimation of parameters of random effects models from samples collected via complex multistage designs. Incorporation of sampling weights is one way to reduce estimation bias due to unequal probabilities of selection. Several weighting methods have been proposed in the literature for estimating the parameters of…
A model for the cost of doing a cost estimate
NASA Technical Reports Server (NTRS)
Remer, D. S.; Buchanan, H. R.
1992-01-01
A model for estimating the cost required to do a cost estimate for Deep Space Network (DSN) projects that range from $0.1 to $100 million is presented. The cost of the cost estimate in thousands of dollars, C(sub E), is found to be approximately given by C(sub E) = K((C(sub p))(sup 0.35)) where C(sub p) is the cost of the project being estimated in millions of dollars and K is a constant depending on the accuracy of the estimate. For an order-of-magnitude estimate, K = 24; for a budget estimate, K = 60; and for a definitive estimate, K = 115. That is, for a specific project, the cost of doing a budget estimate is about 2.5 times as much as that for an order-of-magnitude estimate, and a definitive estimate costs about twice as much as a budget estimate. Use of this model should help provide the level of resources required for doing cost estimates and, as a result, provide insights towards more accurate estimates with less potential for cost overruns.
Maximum likelihood estimation of finite mixture model for economic data
NASA Astrophysics Data System (ADS)
Phoong, Seuk-Yen; Ismail, Mohd Tahir
2014-06-01
Finite mixture model is a mixture model with finite-dimension. This models are provides a natural representation of heterogeneity in a finite number of latent classes. In addition, finite mixture models also known as latent class models or unsupervised learning models. Recently, maximum likelihood estimation fitted finite mixture models has greatly drawn statistician's attention. The main reason is because maximum likelihood estimation is a powerful statistical method which provides consistent findings as the sample sizes increases to infinity. Thus, the application of maximum likelihood estimation is used to fit finite mixture model in the present paper in order to explore the relationship between nonlinear economic data. In this paper, a two-component normal mixture model is fitted by maximum likelihood estimation in order to investigate the relationship among stock market price and rubber price for sampled countries. Results described that there is a negative effect among rubber price and stock market price for Malaysia, Thailand, Philippines and Indonesia.
Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.
2016-01-01
Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This
Pencavel, Tim D; Wilkinson, Michelle J; Mansfield, David C; Khan, Aadil A; Seth, Rohit; Karapanagiotou, Eleni M; Roulstone, Victoria; Aguilar, Richard J; Chen, Nanhai G; Szalay, Aladar A; Hayes, Andrew J; Harrington, Kevin J
2015-02-15
Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells. An orthotopic model of advanced extremity sarcoma was used to evaluate survival of animals after ILP with combinations of TNF-α, melphalan and GLV-1h68. We investigated the efficiency of viral tumour delivery by ILP compared to intravenous therapy, the locoregional and systemic biodistribution of virus after ILP, and the effect of mode of administration on antibody response. The combination of melphalan and GLV-1h68 was synergistic in vitro. The addition of virus to standard ILP regimens was well tolerated and demonstrated superior tumour targeting compared to intravenous administration. Triple therapy (melphalan/TNF-α/GLV-1h68) resulted in increased tumour growth delay and enhanced survival compared to other treatment regimens. Live virus was recovered in large amounts from perfused regions, but in smaller amounts from systemic organs. The addition of oncolytic vaccinia virus to existing TNF-α/melphalan-based ILP strategies results in survival advantage in an immunocompetent rat model of advanced extremity sarcoma. Virus administered by ILP has superior tumour targeting compared to intravenous delivery. Further evaluation and clinical translation of this approach is warranted. PMID:24978211
Distributed Damage Estimation for Prognostics based on Structural Model Decomposition
NASA Technical Reports Server (NTRS)
Daigle, Matthew; Bregon, Anibal; Roychoudhury, Indranil
2011-01-01
Model-based prognostics approaches capture system knowledge in the form of physics-based models of components, and how they fail. These methods consist of a damage estimation phase, in which the health state of a component is estimated, and a prediction phase, in which the health state is projected forward in time to determine end of life. However, the damage estimation problem is often multi-dimensional and computationally intensive. We propose a model decomposition approach adapted from the diagnosis community, called possible conflicts, in order to both improve the computational efficiency of damage estimation, and formulate a damage estimation approach that is inherently distributed. Local state estimates are combined into a global state estimate from which prediction is performed. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the approach.
DINA Model and Parameter Estimation: A Didactic
ERIC Educational Resources Information Center
de la Torre, Jimmy
2009-01-01
Cognitive and skills diagnosis models are psychometric models that have immense potential to provide rich information relevant for instruction and learning. However, wider applications of these models have been hampered by their novelty and the lack of commercially available software that can be used to analyze data from this psychometric…
Obtaining Diagnostic Classification Model Estimates Using Mplus
ERIC Educational Resources Information Center
Templin, Jonathan; Hoffman, Lesa
2013-01-01
Diagnostic classification models (aka cognitive or skills diagnosis models) have shown great promise for evaluating mastery on a multidimensional profile of skills as assessed through examinee responses, but continued development and application of these models has been hindered by a lack of readily available software. In this article we…
Student Models for Prior Knowledge Estimation
ERIC Educational Resources Information Center
Nižnan, Juraj; Pelánek, Radek; Rihák, Jirí
2015-01-01
Intelligent behavior of adaptive educational systems is based on student models. Most research in student modeling focuses on student learning (acquisition of skills). We focus on prior knowledge, which gets much less attention in modeling and yet can be highly varied and have important consequences for the use of educational systems. We describe…
Chen, Ying; Liu, Xinmin; Pan, Ruile; Zhu, Xiaoxin; Steinmetz, André; Liao, Yonghong; Wang, Ning; Peng, Bo; Chang, Qi
2013-10-01
3,6'-Disinapoylsucrose is a major active component of the herb Polygala tenuifolia which has long been used for relieving tranquilization, uneasiness of the mind, and improving learning and memory. Our previous study found that 3,6'-disinapoylsucrose had a very low oral bioavailability. Its mechanisms of absorption in the small intestine have so far been unclear. In the present study, the absorption mechanisms of 3,6'-disinapoylsucrose were investigated by using the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6'-disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2 cell transport study, the results showed that 3,6'-disinapoylsucrose had very limited intestinal permeability with average apparent permeability coefficient values around (1.11-1.34) × 10(-7) cm/s from the apical (A) to the basolateral (B) side and (1.37-1.42) × 10(-7) cm/s from B to A, at concentrations of 5, 20, and 33 µM. No concentration dependence in the 3,6'-disinapoylsucrose transport was observed. The apparent permeability coefficient value of 3,6'-disinapoylsucrose (5 µM) from A to B greatly increased to 4.49 × 10(-7) and 1.81 × 10(-7) cm/s, respectively, when the cells were preincubated with EDTA (17 mM) and sodium caprate (5.14 mM). No significant effect on the 3,6'-disinapoylsucrose transport by the inhibitors including verapamil, cyclosporine A, and sodium azide was observed. Similar results were found in the small intestinal perfusion study. The apparent permeability coefficient value of 3,6'-disinapoylsucrose greatly increased from 3.97 × 10(-6) to 23.4 × 10(-6) and 20.0 × 10(-6) cm/s in the presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion buffer. An in vitro stability evaluation of 3,6'-disinapoylsucrose in the gastrointestinal tract showed that it was relatively stable both in the stomach and small intestine contents, while it was found to be more instable in the colon contents. All of the
Reeb, Jeremie; Cypel, Marcelo
2016-03-01
Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. PMID:26700566
Entropy Based Modelling for Estimating Demographic Trends
Kuo, Shyh-Hao; Xu, Hai-Yan; Hu, Nan; Zhao, Guangshe; Monterola, Christopher
2015-01-01
In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely: 1) Prediction of the age distribution of a country’s population based on an “age-structured population model”; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an “individual household size model”; and 3) Estimation the number of each household size based on a “total household size model”. The last stage is achieved by projecting the age distribution of the country’s population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables. PMID:26382594
A simulation of water pollution model parameter estimation
NASA Technical Reports Server (NTRS)
Kibler, J. F.
1976-01-01
A parameter estimation procedure for a water pollution transport model is elaborated. A two-dimensional instantaneous-release shear-diffusion model serves as representative of a simple transport process. Pollution concentration levels are arrived at via modeling of a remote-sensing system. The remote-sensed data are simulated by adding Gaussian noise to the concentration level values generated via the transport model. Model parameters are estimated from the simulated data using a least-squares batch processor. Resolution, sensor array size, and number and location of sensor readings can be found from the accuracies of the parameter estimates.
Assessing Uncertainty of Interspecies Correlation Estimation Models for Aromatic Compounds
We developed Interspecies Correlation Estimation (ICE) models for aromatic compounds containing 1 to 4 benzene rings to assess uncertainty in toxicity extrapolation in two data compilation approaches. ICE models are mathematical relationships between surrogate and predicted test ...
Mixture Rasch Models with Joint Maximum Likelihood Estimation
ERIC Educational Resources Information Center
Willse, John T.
2011-01-01
This research provides a demonstration of the utility of mixture Rasch models. Specifically, a model capable of estimating a mixture partial credit model using joint maximum likelihood is presented. Like the partial credit model, the mixture partial credit model has the beneficial feature of being appropriate for analysis of assessment data…
Estimation of Unsteady Aerodynamic Models from Flight Test Data
NASA Technical Reports Server (NTRS)
Lan, C. Edward
2003-01-01
This report summarizes the activities in aerodynamic model estimation from flight data. In addition to public presentations at the AIAA Atmospheric Flight Mechanics Conferences, two presentations at Boeing-Seattle were made during personal trips. These are discussed in the following: 1. Methodology of Aerodynamic Model Estimation from Flight Data. 2. Applications of F-16XL aerodynamic modeling. 3. Modeling of turbulence response. 5. Presentations at Boeing-Seattle. 6. Recommendations. and 7. References.
Estimating Lead (Pb) Bioavailability In A Mouse Model
Children are exposed to Pb through ingestion of Pb-contaminated soil. Soil Pb bioavailability is estimated using animal models or with chemically defined in vitro assays that measure bioaccessibility. However, bioavailability estimates in a large animal model (e.g., swine) can be...
Estimating a Noncompensatory IRT Model Using Metropolis within Gibbs Sampling
ERIC Educational Resources Information Center
Babcock, Ben
2011-01-01
Relatively little research has been conducted with the noncompensatory class of multidimensional item response theory (MIRT) models. A Monte Carlo simulation study was conducted exploring the estimation of a two-parameter noncompensatory item response theory (IRT) model. The estimation method used was a Metropolis-Hastings within Gibbs algorithm…
Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C
2013-05-01
Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422
Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.
2014-01-01
Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422
Cardiac tissue engineering using perfusion bioreactor systems
Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana
2009-01-01
This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955
Perfusion Electronic Record Documentation Using Epic Systems Software.
Riley, Jeffrey B; Justison, George A
2015-12-01
The authors comment on Steffens and Gunser's article describing the University of Wisconsin adoption of the Epic anesthesia record to include perfusion information from the cardiopulmonary bypass patient experience. We highlight the current-day lessons and the valuable quality and safety principles the Wisconsin-Epic model anesthesia-perfusion record provides. PMID:26834289
Error Estimation for Reduced Order Models of Dynamical Systems
Homescu, C; Petzold, L; Serban, R
2004-01-22
The use of reduced order models to describe a dynamical system is pervasive in science and engineering. Often these models are used without an estimate of their error or range of validity. In this paper we consider dynamical systems and reduced models built using proper orthogonal decomposition. We show how to compute estimates and bounds for these errors, by a combination of small sample statistical condition estimation and error estimation using the adjoint method. Most importantly, the proposed approach allows the assessment of regions of validity for reduced models, i.e., ranges of perturbations in the original system over which the reduced model is still appropriate. Numerical examples validate our approach: the error norm estimates approximate well the forward error while the derived bounds are within an order of magnitude.
Chian, Chih-Feng; Chiang, Chi-Huei; Chuang, Chiao-Hui; Liu, Shiou-Ling; Tsai, Chen-Liang
2016-08-01
High tidal volume (VT) ventilation causes the release of various mediators and results in ventilator-induced lung injury (VILI). SN50, a cell-permeable nuclear factor-κB (NF-κB) inhibitory peptide, attenuates inflammation and acute respiratory distress syndrome. However, the mechanisms associated with the effects of SN50 in VILI have not been fully elucidated. We investigated the cellular and molecular mechanisms for the effects of SN50 treatment in VILI. An isolated and perfused rat lung model was exposed to low (5 mL/kg) or high (15 mL/kg) VT ventilation for 6 h. SN50 was administered in the perfusate at the onset of the high-stretch mechanical ventilation. The hemodynamics, lung histological changes, inflammatory responses, and activation of apoptotic pathways were evaluated. VILI was demonstrated by increased pulmonary vascular permeability and lung weight gain, as well as by increased levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), hydrogen peroxide, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid. The lung tissue expression of TNF-α, IL-1β, mitogen-activated protein kinases (MAPKs), caspase-3, and phosphorylation of serine/threonine-specific protein kinase (p-AKT) was greater in the high VT group than in the low VT group. Upregulation and activation of NF-κB was associated with increased lung injury in VILI. SN50 attenuated the inflammatory responses, including the expression of IL-1β, TNF-α, MPO, MAPKs, and NF-κB. In addition, the downregulation of apoptosis was evaluated using caspase-3 and p-AKT expression. Furthermore, SN50 mitigated the increases in the lung weights, pulmonary vascular permeability, and lung injury. In conclusion, VILI is associated with inflammatory responses and activation of NF-κB. SN50 inhibits the activation of NF-κB and attenuates VILI. PMID:26780513
Estimates of current debris from flux models
Canavan, G.H.
1997-01-01
Flux models that balance accuracy and simplicity are used to predict the growth of space debris to the present. Known and projected launch rates, decay models, and numerical integrations are used to predict distributions that closely resemble the current catalog-particularly in the regions containing most of the debris.
ESTIMATING UNCERTAINITIES IN FACTOR ANALYTIC MODELS
When interpreting results from factor analytic models as used in receptor modeling, it is important to quantify the uncertainties in those results. For example, if the presence of a species on one of the factors is necessary to interpret the factor as originating from a certain ...
Meteorological models for estimating phenology of corn
NASA Technical Reports Server (NTRS)
Daughtry, C. S. T.; Cochran, J. C.; Hollinger, S. E.
1984-01-01
Knowledge of when critical crop stages occur and how the environment affects them should provide useful information for crop management decisions and crop production models. Two sources of data were evaluated for predicting dates of silking and physiological maturity of corn (Zea mays L.). Initial evaluations were conducted using data of an adapted corn hybrid grown on a Typic Agriaquoll at the Purdue University Agronomy Farm. The second phase extended the analyses to large areas using data acquired by the Statistical Reporting Service of USDA for crop reporting districts (CRD) in Indiana and Iowa. Several thermal models were compared to calendar days for predicting dates of silking and physiological maturity. Mixed models which used a combination of thermal units to predict silking and days after silking to predict physiological maturity were also evaluated. At the Agronomy Farm the models were calibrated and tested on the same data. The thermal models were significantly less biased and more accurate than calendar days for predicting dates of silking. Differences among the thermal models were small. Significant improvements in both bias and accuracy were observed when the mixed models were used to predict dates of physiological maturity. The results indicate that statistical data for CRD can be used to evaluate models developed at agricultural experiment stations.
Liu, Q; Nassar, A; Farias, K; Buccini, L; Mangino, M J; Baldwin, W; Bennett, A; O'Rourke, C; Iuppa, G; Soliman, B G; Urcuyo-Llanes, D; Okamoto, T; Uso, T D; Fung, J; Abu-Elmagd, K; Miller, C; Quintini, C
2016-03-01
The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs. PMID:26663737
Estimation of population size using open capture-recapture models
McDonald, T.L.; Amstrup, Steven C.
2001-01-01
One of the most important needs for wildlife managers is an accurate estimate of population size. Yet, for many species, including most marine species and large mammals, accurate and precise estimation of numbers is one of the most difficult of all research challenges. Open-population capture-recapture models have proven useful in many situations to estimate survival probabilities but typically have not been used to estimate population size. We show that open-population models can be used to estimate population size by developing a Horvitz-Thompson-type estimate of population size and an estimator of its variance. Our population size estimate keys on the probability of capture at each trap occasion and therefore is quite general and can be made a function of external covariates measured during the study. Here we define the estimator and investigate its bias, variance, and variance estimator via computer simulation. Computer simulations make extensive use of real data taken from a study of polar bears (Ursus maritimus) in the Beaufort Sea. The population size estimator is shown to be useful because it was negligibly biased in all situations studied. The variance estimator is shown to be useful in all situations, but caution is warranted in cases of extreme capture heterogeneity.
Comparison of Estimation Procedures for Multilevel AR(1) Models.
Krone, Tanja; Albers, Casper J; Timmerman, Marieke E
2016-01-01
To estimate a time series model for multiple individuals, a multilevel model may be used. In this paper we compare two estimation methods for the autocorrelation in Multilevel AR(1) models, namely Maximum Likelihood Estimation (MLE) and Bayesian Markov Chain Monte Carlo. Furthermore, we examine the difference between modeling fixed and random individual parameters. To this end, we perform a simulation study with a fully crossed design, in which we vary the length of the time series (10 or 25), the number of individuals per sample (10 or 25), the mean of the autocorrelation (-0.6 to 0.6 inclusive, in steps of 0.3) and the standard deviation of the autocorrelation (0.25 or 0.40). We found that the random estimators of the population autocorrelation show less bias and higher power, compared to the fixed estimators. As expected, the random estimators profit strongly from a higher number of individuals, while this effect is small for the fixed estimators. The fixed estimators profit slightly more from a higher number of time points than the random estimators. When possible, random estimation is preferred to fixed estimation. The difference between MLE and Bayesian estimation is nearly negligible. The Bayesian estimation shows a smaller bias, but MLE shows a smaller variability (i.e., standard deviation of the parameter estimates). Finally, better results are found for a higher number of individuals and time points, and for a lower individual variability of the autocorrelation. The effect of the size of the autocorrelation differs between outcome measures. PMID:27242559
Comparison of Estimation Procedures for Multilevel AR(1) Models
Krone, Tanja; Albers, Casper J.; Timmerman, Marieke E.
2016-01-01
To estimate a time series model for multiple individuals, a multilevel model may be used. In this paper we compare two estimation methods for the autocorrelation in Multilevel AR(1) models, namely Maximum Likelihood Estimation (MLE) and Bayesian Markov Chain Monte Carlo. Furthermore, we examine the difference between modeling fixed and random individual parameters. To this end, we perform a simulation study with a fully crossed design, in which we vary the length of the time series (10 or 25), the number of individuals per sample (10 or 25), the mean of the autocorrelation (−0.6 to 0.6 inclusive, in steps of 0.3) and the standard deviation of the autocorrelation (0.25 or 0.40). We found that the random estimators of the population autocorrelation show less bias and higher power, compared to the fixed estimators. As expected, the random estimators profit strongly from a higher number of individuals, while this effect is small for the fixed estimators. The fixed estimators profit slightly more from a higher number of time points than the random estimators. When possible, random estimation is preferred to fixed estimation. The difference between MLE and Bayesian estimation is nearly negligible. The Bayesian estimation shows a smaller bias, but MLE shows a smaller variability (i.e., standard deviation of the parameter estimates). Finally, better results are found for a higher number of individuals and time points, and for a lower individual variability of the autocorrelation. The effect of the size of the autocorrelation differs between outcome measures. PMID:27242559
Wu, Z Y; Smithers, B M; Parsons, P G; Roberts, M S
1997-01-01
An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min(-1)) resulted in higher tissue blood flow (determined with 51Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour. PMID:9099965
Estimating Neuronal Ageing with Hidden Markov Models
NASA Astrophysics Data System (ADS)
Wang, Bing; Pham, Tuan D.
2011-06-01
Neuronal degeneration is widely observed in normal ageing, meanwhile the neurode-generative disease like Alzheimer's disease effects neuronal degeneration in a faster way which is considered as faster ageing. Early intervention of such disease could benefit subjects with potentials of positive clinical outcome, therefore, early detection of disease related brain structural alteration is required. In this paper, we propose a computational approach for modelling the MRI-based structure alteration with ageing using hidden Markov model. The proposed hidden Markov model based brain structural model encodes intracortical tissue/fluid distribution using discrete wavelet transformation and vector quantization. Further, it captures gray matter volume loss, which is capable of reflecting subtle intracortical changes with ageing. Experiments were carried out on healthy subjects to validate its accuracy and robustness. Results have shown its ability of predicting the brain age with prediction error of 1.98 years without training data, which shows better result than other age predition methods.
A regression model to estimate regional ground water recharge.
Lorenz, David L; Delin, Geoffrey N
2007-01-01
A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin-wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0- to 5-cm/year range. In sand-plain areas where SY is greatest, recharge estimates were in the 15- to 29-cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available. PMID:17335484
A regression model to estimate regional ground water recharge
Lorenz, D.L.; Delin, G.N.
2007-01-01
A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin-wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0- to 5-cm/year range. In sand-plain areas where SY is greatest, recharge estimates were in the 15- to 29-cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available.
Iterative blind deconvolution in magnetic resonance brain perfusion imaging.
Grüner, Renate; Taxt, Torfinn
2006-04-01
In first pass magnetic resonance brain perfusion imaging, arterial input functions are used in the deconvolution of the observed contrast concentrations to obtain quantitative hemodynamic parameters. Ideally, arterial input functions should be measured in each imaged voxel to eliminate the effects of delay and dispersion of the contrast agent from the injection site. An approach based on iterative blind deconvolution with the Richardson-Lucy algorithm is proposed for the simultaneous estimation of voxel-specific arterial input functions and voxel-specific tissue residue functions. An extended contrast concentration model was used to separate the first pass bolus from additional recirculation and leakage signals. The extended model was evaluated using in vivo data. Computer simulations examined the feasibility of iterative blind deconvolution in perfusion imaging. Preliminary in vivo results from a patient with fibromuscular dysplasia showed territories with delayed/dispersed arterial input functions that coincided with the location of territories supplied by collateral circulation as described from the complete radiologic examination. Higher flow values and shorter mean transit times compared to conventional methods were obtained in these areas, suggesting that the effects of dispersion were minimized. The in vivo estimated arterial input functions visualized the patient's blood supply patterns as a function of time. PMID:16526016
Glenny, Robb; Robertson, H Thomas
2011-01-01
Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. PMID:23737171
Importance of capillary perfusion.
Hardaway, R M
1979-11-01
Perfusion is more critical than oxygen in the maintenance of cell viability. A high hematocrit or high fibrinogen level increases blood viscosity and predisposes to disseminated intravascular coagulation. It is recommended that a hematocrit of about 30 be maintained in periods of circulatory stress such as shock or extracorporeal circulation. PMID:495856
Estimating neugebauer primaries for multi-channel spectral printing modeling
NASA Astrophysics Data System (ADS)
Slavuj, Radovan; Coppel, Ludovic G.; Olen, Melissa; Hardeberg, Jon Yngve
2014-02-01
Multichannel printer modeling has been an active area of research in the field of spectral printing. The most commonly used models for characterization of such systems are the spectral Neugebauer (SN) and its extensions. This work addresses issues that can arise during calibration and testing of the SN model when modelling a 7-colorant printer. Since most substrates are limited in their capacity to take in large amount of ink, it is not always possible to print all colorant combinations necessary to determine the Neugebauer primaries (NP). A common solution is to estimate the nonprintable Neugebauer primaries from the single colorant primaries using the Kubelka-Munk (KM) optical model. In this work we test whether a better estimate can be obtained using general radiative transfer theory, which better represents the angular variation of the reflectance from highly absorbing media, and takes surface scattering into account. For this purpose we use the DORT2002 model. We conclude DORT2002 does not offer significant improvements over KM in the estimation of the NPs, but a significant improvement is obtained when using a simple surface scattering model. When the estimated primaries are used as inputs to the SN model instead of measured ones, it is found the SN model performs the same or better in terms of color difference and spectral error. If the mixed measured and estimated primaries are used as inputs to the SN model, it performs better than using either measured or estimated.
Satellite servicing mission preliminary cost estimation model
NASA Technical Reports Server (NTRS)
1987-01-01
The cost model presented is a preliminary methodology for determining a rough order-of-magnitude cost for implementing a satellite servicing mission. Mission implementation, in this context, encompassess all activities associated with mission design and planning, including both flight and ground crew training and systems integration (payload processing) of servicing hardward with the Shuttle. A basic assumption made in developing this cost model is that a generic set of servicing hardware was developed and flight tested, is inventoried, and is maintained by NASA. This implies that all hardware physical and functional interfaces are well known and therefore recurring CITE testing is not required. The development of the cost model algorithms and examples of their use are discussed.
A universal model for estimating wheat yields
NASA Technical Reports Server (NTRS)
Feyerherm, A. M.; Paulsen, G. M. (Principal Investigator)
1979-01-01
A universal wheat yield model applicable to both fall- and spring-planted wheat was developed to show separate and joint effects of weather and culture on yields. Data from state experiment stations in a wide range of climates in the U.S. Great Plains were used to build basic relationships among yields, weather, and culture. The application of the model on a macroclimatic scale in the U.S., the U.S.S.R., and India is discussed along with potential improvements.
DEVELOPMENT OF RESIDENTIAL WOOD COMSUMPTION ESTIMATION MODELS
The report gives data on the distribution and usage of firewood, obtained from a pool of household wood use surveys. ased on a series of regression models developed using the STEPWISE procedure in the SAS statistical package, two variables appear to be most predictive of wood use...
Hanna, T P; Shafiq, J
2015-02-01
The measurement of population benefits is important for priority setting, economic evaluation and quality improvement. It also informs advocacy. In this article, the use of demand models to estimate the achievable benefit of cancer therapy is reviewed. Achievable benefit refers to the treatment benefit achievable under optimal conditions. The population benefit of radiotherapy has been used as an example. Demand models provide a means of estimating the optimal proportion of patients with treatment indications when guidelines are followed. They may be used to estimate achievable benefit. The choice of end point should reflect the range of benefits associated with the treatment of interest. In some cases, further model development is needed if a pre-existing demand model is used. The benefit of treatment for each indication is estimated using a systematic review process. The highest level of evidence is used to define the benefit for each indication. In cases where multiple sources of the same level and quality of evidence exist, a meta-analysis is carried out. Population-based effectiveness data sources are considered, but three major challenges to their use are: (i) generalisability of the observed outcomes, (ii) data resolution and (iii) confounding and bias. The population benefit determined from this process describes the population proportion achieving a benefit due to the use of guideline-based treatment, compared with no use of that treatment. Sensitivity analysis provides a means for modelling the effect of model uncertainties. The predominant uncertainty is most often due to uncertainty in indication proportion. Preference-sensitive treatment decisions are a common example. The described approach to estimating the achievable benefit of cancer therapy is robust to model uncertainties, rapidly adaptable and is transparent. However, estimates rely on the quality of model data sources and may be affected by model assumptions. Models should be developed for a
Gaussian estimation for discretely observed Cox-Ingersoll-Ross model
NASA Astrophysics Data System (ADS)
Wei, Chao; Shu, Huisheng; Liu, Yurong
2016-07-01
This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.
Myocardial perfusion scintigraphy: the evidence.
Underwood, S R; Anagnostopoulos, C; Cerqueira, M; Ell, P J; Flint, E J; Harbinson, M; Kelion, A D; Al-Mohammad, A; Prvulovich, E M; Shaw, L J; Tweddel, A C
2004-02-01
This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by
Battery Calendar Life Estimator Manual Modeling and Simulation
Jon P. Christophersen; Ira Bloom; Ed Thomas; Vince Battaglia
2012-10-01
The Battery Life Estimator (BLE) Manual has been prepared to assist developers in their efforts to estimate the calendar life of advanced batteries for automotive applications. Testing requirements and procedures are defined by the various manuals previously published under the United States Advanced Battery Consortium (USABC). The purpose of this manual is to describe and standardize a method for estimating calendar life based on statistical models and degradation data acquired from typical USABC battery testing.
Battery Life Estimator Manual Linear Modeling and Simulation
Jon P. Christophersen; Ira Bloom; Ed Thomas; Vince Battaglia
2009-08-01
The Battery Life Estimator (BLE) Manual has been prepared to assist developers in their efforts to estimate the calendar life of advanced batteries for automotive applications. Testing requirements and procedures are defined by the various manuals previously published under the United States Advanced Battery Consortium (USABC). The purpose of this manual is to describe and standardize a method for estimating calendar life based on statistical models and degradation data acquired from typical USABC battery testing.
Stochastic Wireless Channel Modeling, Estimation and Identification from Measurements
Olama, Mohammed M; Djouadi, Seddik M; Li, Yanyan
2008-07-01
This paper is concerned with stochastic modeling of wireless fading channels, parameter estimation, and system identification from measurement data. Wireless channels are represented by stochastic state-space form, whose parameters and state variables are estimated using the expectation maximization algorithm and Kalman filtering, respectively. The latter are carried out solely from received signal measurements. These algorithms estimate the channel inphase and quadrature components and identify the channel parameters recursively. The proposed algorithm is tested using measurement data, and the results are presented.
Experimental glomerulonephritis in the isolated perfused rat kidney.
Couser, W G; Steinmuller, D R; Stilmant, M M; Salant, D J; Lowenstein, L M
1978-01-01
The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition. Images PMID:372233
On Latent Trait Estimation in Multidimensional Compensatory Item Response Models.
Wang, Chun
2015-06-01
Making inferences from IRT-based test scores requires accurate and reliable methods of person parameter estimation. Given an already calibrated set of item parameters, the latent trait could be estimated either via maximum likelihood estimation (MLE) or using Bayesian methods such as maximum a posteriori (MAP) estimation or expected a posteriori (EAP) estimation. In addition, Warm's (Psychometrika 54:427-450, 1989) weighted likelihood estimation method was proposed to reduce the bias of the latent trait estimate in unidimensional models. In this paper, we extend the weighted MLE method to multidimensional models. This new method, denoted as multivariate weighted MLE (MWLE), is proposed to reduce the bias of the MLE even for short tests. MWLE is compared to alternative estimators (i.e., MLE, MAP and EAP) and shown, both analytically and through simulations studies, to be more accurate in terms of bias than MLE while maintaining a similar variance. In contrast, Bayesian estimators (i.e., MAP and EAP) result in biased estimates with smaller variability. PMID:24604245
Estimating restricted mean treatment effects with stacked survival models.
Wey, Andrew; Vock, David M; Connett, John; Rudser, Kyle
2016-08-30
The difference in restricted mean survival times between two groups is a clinically relevant summary measure. With observational data, there may be imbalances in confounding variables between the two groups. One approach to account for such imbalances is estimating a covariate-adjusted restricted mean difference by modeling the covariate-adjusted survival distribution and then marginalizing over the covariate distribution. Because the estimator for the restricted mean difference is defined by the estimator for the covariate-adjusted survival distribution, it is natural to expect that a better estimator of the covariate-adjusted survival distribution is associated with a better estimator of the restricted mean difference. We therefore propose estimating restricted mean differences with stacked survival models. Stacked survival models estimate a weighted average of several survival models by minimizing predicted error. By including a range of parametric, semi-parametric, and non-parametric models, stacked survival models can robustly estimate a covariate-adjusted survival distribution and, therefore, the restricted mean treatment effect in a wide range of scenarios. We demonstrate through a simulation study that better performance of the covariate-adjusted survival distribution often leads to better mean squared error of the restricted mean difference although there are notable exceptions. In addition, we demonstrate that the proposed estimator can perform nearly as well as Cox regression when the proportional hazards assumption is satisfied and significantly better when proportional hazards is violated. Finally, the proposed estimator is illustrated with data from the United Network for Organ Sharing to evaluate post-lung transplant survival between large-volume and small-volume centers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26934835
NASA Astrophysics Data System (ADS)
Biagi, L.; Caldera, S.; Carcano, L.; Lucchese, A.; Negretti, M.; Sansò, F.; Triglione, D.; Visconti, M. G.
2014-04-01
Global DEMs are fundamental for global applications and are necessary also at the local scale, in regions where local models are not available. Local DEMs are preferred when they are available and if are characterized by better accuracies and resolutions. In general, two problems arise. Firstly, an interest region could be patched by several partly overlapping DEMs that present similar accuracies and spatial resolutions: they should be merged in a unified model. Moreover, even when the interest region is covered by one unified DEM, local DEMs with better accuracy could be available and should be used to locally improve it. All these problems have been addressed within HELI-DEM project. HELI-DEM (HELvetia-Italy Digital Elevation Model) is a project that has been funded by the European Regional Development Fund (ERDF) within the Italy-Switzerland cooperation program. It started in 2010 and finished at the end of 2013. The involved institutions in the project were Fondazione Politecnico di Milano, Politecnico di Milano, Politecnico di Torino, Regione Lombardia, Regione Piemonte and Scuola Universitaria della Svizzera Italiana. One specific aim of the project was the creation and the publication of a unified Digital Elevation Model for the part of the Alps between Italy and Switzerland. The interest area is prevalently mountainous, with heights that range from about 200 m to 4600 m. Three low Resolution DTMs (20-25-50 m of resolution) are available that partly overlap and patch the whole project area: they are characterized by accuracies of some meters. Also High Resolution DTMs (1-5 m) are available: they have accuracies of some decimeters but cover limited areas of the project. The various models are available in different reference frames (the European ETRF89 and the Italian Roma40) and are gridded either in cartographic or geographic coordinates. Before merging them, a validation of the input data has been performed in three steps: cross validation of LR DTMs
Identification of linear system models and state estimators for controls
NASA Technical Reports Server (NTRS)
Chen, Chung-Wen
1992-01-01
The following paper is presented in viewgraph format and covers topics including: (1) linear state feedback control system; (2) Kalman filter state estimation; (3) relation between residual and stochastic part of output; (4) obtaining Kalman filter gain; (5) state estimation under unknown system model and unknown noises; and (6) relationship between filter Markov parameters and system Markov parameters.
Estimation of Graded Response Model Parameters Using MULTILOG.
ERIC Educational Resources Information Center
Baker, Frank B.
1997-01-01
Describes an idiosyncracy of the MULTILOG (D. Thissen, 1991) parameter estimation process discovered during a simulation study involving the graded response model. A misordering reflected in boundary function location parameter estimates resulted in a large negative contribution to the true score followed by a large positive contribution. These…
A Fully Conditional Estimation Procedure for Rasch Model Parameters.
ERIC Educational Resources Information Center
Choppin, Bruce
A strategy for overcoming problems with the Rasch model's inability to handle missing data involves a pairwise algorithm which manipulates the data matrix to separate out the information needed for the estimation of item difficulty parameters in a test. The method of estimation compares two or three items at a time, separating out the ability…
Burdío, Fernando; Navarro, Ana; Sousa, Ramón; Burdío, José M; Güemes, Antonio; Gonzalez, Ana; Cruz, Ignacio; Castiella, Tomás; Lozano, Ricardo; Berjano, Enrique; Figueras, Joan; de Gregorio, Miguel A
2006-08-01
Bipolar radiofrequency (RF) ablation, especially with perfusion of saline, has been shown to increase volume over monopolar conventional methods. The aims of this study are to study whether this method is linked to too flattened thermal lesions and premature rise of impedance and to elucidate some safety concerns. Eighteen RF ablations were performed using a 1.8-mm-diameter bipolar applicator in the liver of nine healthy pigs through laparotomy with or without temporary vascular occlusion [the Pringle maneuver (PGM)]: group A (n=9), without PGM; group B (n=9), with PGM. Hypertonic saline solutions (3% and 20 %) were injected through the applicator at a rate of 400 ml/h during the procedure. The pigs were followed up and they were euthanased on the 15th day. Impedance, current, power output, energy output, temperatures, diameters of thermal lesion, volume, sphericity ratio of thermal lesion were correlated among groups. Impedance at the end of the procedure (50.00 Omega+/-28.39 and 52.88 Omega+/-26.77, for groups A and B, respectively) was very similar to the starting impedance (50 Omega). In a median of 1 (range, 0-6) time per RF ablation procedure a reduction of 30 W from the selected power supply was observed during the RF ablation procedure linked to a slight increase of impedance. Volume and short diameter of thermal lesion were 21.28 cm3+/-11.78 and 2.85 cm+/-0.87 for group A, 87.51 cm3+/-25.20 and 4.31 cm+/-0.65 for group B. Continuous thermal between both electrodes were described with a global sphericity ratio of 1.91. One major complication (thermal injury to the stomach) was encountered in a case of cross-sectional necrosis of the targeted liver and attributed to heat diffusion after the procedure. This method has been shown to determine: (1) the relative control of impedance during the procedure; (2) ovoid and relatively large thermal lesions with less dependence upon closest vessels. PMID:16541228
Parameter estimation of hydrologic models using data assimilation
NASA Astrophysics Data System (ADS)
Kaheil, Y. H.
2005-12-01
The uncertainties associated with the modeling of hydrologic systems sometimes demand that data should be incorporated in an on-line fashion in order to understand the behavior of the system. This paper represents a Bayesian strategy to estimate parameters for hydrologic models in an iterative mode. The paper presents a modified technique called localized Bayesian recursive estimation (LoBaRE) that efficiently identifies the optimum parameter region, avoiding convergence to a single best parameter set. The LoBaRE methodology is tested for parameter estimation for two different types of models: a support vector machine (SVM) model for predicting soil moisture, and the Sacramento Soil Moisture Accounting (SAC-SMA) model for estimating streamflow. The SAC-SMA model has 13 parameters that must be determined. The SVM model has three parameters. Bayesian inference is used to estimate the best parameter set in an iterative fashion. This is done by narrowing the sampling space by imposing uncertainty bounds on the posterior best parameter set and/or updating the "parent" bounds based on their fitness. The new approach results in fast convergence towards the optimal parameter set using minimum training/calibration data and evaluation of fewer parameter sets. The efficacy of the localized methodology is also compared with the previously used Bayesian recursive estimation (BaRE) algorithm.
Multivariate Regression Models for Estimating Journal Usefulness in Physics.
ERIC Educational Resources Information Center
Bennion, Bruce C.; Karschamroon, Sunee
1984-01-01
This study examines possibility of ranking journals in physics by means of bibliometric regression models that estimate usefulness as it is reported by 167 physicists in United States and Canada. Development of four models, patterns of deviation from models, and validity and application are discussed. Twenty-six references are cited. (EJS)
Parameter Estimates in Differential Equation Models for Population Growth
ERIC Educational Resources Information Center
Winkel, Brian J.
2011-01-01
We estimate the parameters present in several differential equation models of population growth, specifically logistic growth models and two-species competition models. We discuss student-evolved strategies and offer "Mathematica" code for a gradient search approach. We use historical (1930s) data from microbial studies of the Russian biologist,…
Local Solutions in the Estimation of Growth Mixture Models
ERIC Educational Resources Information Center
Hipp, John R.; Bauer, Daniel J.
2006-01-01
Finite mixture models are well known to have poorly behaved likelihood functions featuring singularities and multiple optima. Growth mixture models may suffer from fewer of these problems, potentially benefiting from the structure imposed on the estimated class means and covariances by the specified growth model. As demonstrated here, however,…
A multiresolution model for small-body gravity estimation
NASA Astrophysics Data System (ADS)
Jones, Brandon A.; Beylkin, Gregory; Born, George H.; Provence, Robert S.
2011-11-01
A new model, dubbed the MRQSphere, provides a multiresolution representation of the gravity field designed for its estimation. The multiresolution representation uses an approximation via Gaussians of the solution of the Laplace's equation in the exterior of a sphere. Also, instead of the spherical harmonics, variations in the angular variables are modeled by a set of functions constructed using quadratures for the sphere invariant under the icosahedral group. When combined, these tools specify the spatial resolution of the gravity field as a function of altitude and required accuracy. We define this model, and apply it to representing and estimating the gravity field of the asteroid 433 Eros. We verified that a MRQSphere model derived directly from the true spherical harmonics gravity model satisfies the user defined precision. We also use the MRQSphere model to estimate the gravity field of Eros for a simulated satellite mission, yielding a solution with accuracy only limited by measurement errors and their spatial distribution.
Srivastava, Shashikant; Pasipanodya, Jotam G.; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E.; Cirrincione, Kayle N.; Sherman, Carleton M.; Swaminathan, Soumya; Gumbo, Tawanda
2016-01-01
Treatment of disseminated tuberculosis in children ≤ 6 years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose–response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100 mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children ≤ 6 years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555
Srivastava, Shashikant; Pasipanodya, Jotam G; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E; Cirrincione, Kayle N; Sherman, Carleton M; Swaminathan, Soumya; Gumbo, Tawanda
2016-04-01
Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children≤6years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555
Multi-model drought estimation using regional climate model output
NASA Astrophysics Data System (ADS)
McCabe, M. F.; Sung, B.; Evans, J. P.; Sheffield, J.
2012-12-01
Drought is a recurring climatic phenomenon in Australia and many other regions of the world. Apart from the considerable social and health repercussions that widespread drought has at a community level, there are major implications to the landscape, economy and water resources sectors. One of the key outputs in drought characterisation is determining the degree, extent and severity of the actual drought. However, there exist a range of techniques to quantify drought (each with its own definition) that adds to the level of uncertainty in accurate estimation. To examine the range and variability in multi-model drought prediction, a study of drought characteristics is undertaken, focusing on one of Australia's most significant agricultural regions: the Murray Darling Basin (MDB). Common drought indices including the Reconnaissance Drought Index (RDI), Standard Runoff Index (SRI), Soil Moisture Percentiles (SMP) and Palmer Drought Severity Index (PDSI) were derived using output from a high resolution regional climate simulation of the MDB for the period from 1985 to 2008. Spatial and temporal analyses were conducted by comparing these indices across regional scales. A severity-area-duration analysis and drought clustering approach were also used to characterize the extent and severity of these events across south-eastern Australia. Overall it was found that the four drought indices responded similarly to precipitation anomalies and successfully captured the major droughts over the nearly 25 years of simulation. The recent Australian drought from 2002-2008 was the most severe as shown by various analyses. Indeed, the Murray Darling Basin experienced contiguous moderate to extreme drought conditions for long periods, covering almost 100% of both the Darling and Murray Basins. Analysis of results also showed that the duration of droughts varied greatly between indices, as drought assessments using soil moisture parameters tended to recover in response to precipitation at
Estimating turf pesticide volatilization from simple evapotranspiration models.
Walden, Rebecca R; Haith, Douglas A
2003-01-01
A previously developed model by Haith et al. (2002) related pesticide volatilization from turf to evapotranspiration (ET) by scaling factors determined from vapor pressures and heats of vaporization. Although the model provided volatilization estimates that compared well with field measurements, it relied on the Penman ET equation, requiring hourly temperature, wind speed, and solar radiation data, none of which are routinely available at field sites. The current study determined that the volatilization model works equally well with a simpler ET equation requiring only daily temperatures. Three daily temperature-based ET models were evaluated as vehicles for estimating pesticide volatilization from turf: Hamon, Hargreaves-Samani, and a modified Priestley-Taylor. When compared with field volatilization measurements for eight pesticides, volatilization estimates produced from the Hargreaves-Samani model most closely approximated both the field observations and the previous estimates based on the more data-intensive Penman model. Mean estimated volatilization exceeded mean observations by 15% and the coefficient of variation (R2) between estimates and observations was 0.65. The comparable values based on Penman ET were 17% and 0.63, respectively. PMID:12809316
Parametric Estimation in a Recurrent Competing Risks Model
Peña, Edsel A.
2014-01-01
A resource-efficient approach to making inferences about the distributional properties of the failure times in a competing risks setting is presented. Efficiency is gained by observing recurrences of the competing risks over a random monitoring period. The resulting model is called the recurrent competing risks model (RCRM) and is coupled with two repair strategies whenever the system fails. Maximum likelihood estimators of the parameters of the marginal distribution functions associated with each of the competing risks and also of the system lifetime distribution function are presented. Estimators are derived under perfect and partial repair strategies. Consistency and asymptotic properties of the estimators are obtained. The estimation methods are applied to a data set of failures for cars under warranty. Simulation studies are used to ascertain the small sample properties and the efficiency gains of the resulting estimators. PMID:25346751
Nonlinear modeling and estimation of slew induced structural deformations
NASA Technical Reports Server (NTRS)
Dwyer, T. A. W., III; Karray, F.
1988-01-01
A model of the nonlinear dynamics of a deformable maneuvering multibody system is described, whereby elastic deformation are modeled by restoring forces and dissipative forces at point mass appendages. This model is brought into bilinear form. Estimation of deformations occasioned by rapid slewing maneuvers is carried out by a filter based on a globally equivalent linear model of the bilinear dynamics, and is shown to be an improvement over the extended Kalman filter. To further alleviate the computational burden, the estimated deformation state is propagated between observations by a low dimensional operator spline interpolator of bilinear system Volterra series, which is easily implemented.
Development of CSAMT impedance modeling and its estimation
NASA Astrophysics Data System (ADS)
Sutarno, D.
2015-04-01
Accurate modeling and estimation of impedance functions is essential for the correct interpretation of Controlled Source Audio Magnetotelluric (CSAMT) measurements. Non plane wave effect of CSAMT source and noises are inevitably encountered when CSAMT observations are conducted and, consequently, impedance estimates are usually based on least-squares (LS) approximation, and the resulting estimates need to be corrected for the non plane wave field fraction. However, estimation procedure based on LS would not be statistically optimal, as outliers (abnormal data) are frequently superimposed on a normal ambient CSAMT noise field. In this situation, the estimation can be seriously misleading, while plane wave correction has also limited application, as the non plane wave field fraction is reasonably strong. This paper briefly discus the recent development of alternative methods for the CSAMT impedance modeling and its estimation, those are efficient in nature. The means for accomplishing the non plane wave problem is based on full solution numerical modeling of CSAMT impedance function that accommodates the non plane wave effect in the function. Whilst, one appealing approach to dealing with outliers is to make the estimation procedure robust. This is based on the M-estimation and the Hilbert transform operating on the causal CSAMT impedance functions. As demonstrated, the full solution based modeling for CSAMT impedance function is applied for all measurement zones, including near-, transition- as well as the far-field zones, and suitably, the plane wave correction is no longer needed for the impedance function. In the resulting impedance estimates, outlier contamination is removed and the self consistency between the real and imaginary parts of the impedance estimates is guaranteed. Using synthetic data, it is shown that the proposed methods can produce usable CSAMT impedance functions for all measurement zones, even under condition of severe noise contamination.
Campbell, D A; Chkrebtii, O
2013-12-01
Statistical inference for biochemical models often faces a variety of characteristic challenges. In this paper we examine state and parameter estimation for the JAK-STAT intracellular signalling mechanism, which exemplifies the implementation intricacies common in many biochemical inference problems. We introduce an extension to the Generalized Smoothing approach for estimating delay differential equation models, addressing selection of complexity parameters, choice of the basis system, and appropriate optimization strategies. Motivated by the JAK-STAT system, we further extend the generalized smoothing approach to consider a nonlinear observation process with additional unknown parameters, and highlight how the approach handles unobserved states and unevenly spaced observations. The methodology developed is generally applicable to problems of estimation for differential equation models with delays, unobserved states, nonlinear observation processes, and partially observed histories. PMID:23579098
NASA Astrophysics Data System (ADS)
Bambang Avip Priatna, M.; Lukman, Sumiaty, Encum
2016-02-01
This paper aims to determine the properties of Correspondence Analysis (CA) estimator to estimate latent variable models. The method used is the High-Dimensional AIC (HAIC) method with simulation of Bernoulli distribution data. Stages are: (1) determine the matrix CA; (2) create a model of the CA estimator to estimate the latent variables by using HAIC; (3) simulated the Bernoulli distribution data with repetition 1,000,748 times. The simulation results show the CA estimator models work well.
Error Estimation for Reduced Order Models of Dynamical systems
Homescu, C; Petzold, L R; Serban, R
2003-12-16
The use of reduced order models to describe a dynamical system is pervasive in science and engineering. Often these models are used without an estimate of their error or range of validity. In this paper we consider dynamical systems and reduced models built using proper orthogonal decomposition. We show how to compute estimates and bounds for these errors, by a combination of the small sample statistical condition estimation method and of error estimation using the adjoint method. More importantly, the proposed approach allows the assessment of so-called regions of validity for reduced models, i.e., ranges of perturbations in the original system over which the reduced model is still appropriate. This question is particularly important for applications in which reduced models are used not just to approximate the solution to the system that provided the data used in constructing the reduced model, but rather to approximate the solution of systems perturbed from the original one. Numerical examples validate our approach: the error norm estimates approximate well the forward error while the derived bounds are within an order of magnitude.
A hierarchical model for estimating change in American Woodcock populations
Sauer, J.R.; Link, W.A.; Kendall, W.L.; Kelley, J.R.; Niven, D.K.
2008-01-01
The Singing-Ground Survey (SGS) is a primary source of information on population change for American woodcock (Scolopax minor). We analyzed the SGS using a hierarchical log-linear model and compared the estimates of change and annual indices of abundance to a route regression analysis of SGS data. We also grouped SGS routes into Bird Conservation Regions (BCRs) and estimated population change and annual indices using BCRs within states and provinces as strata. Based on the hierarchical model?based estimates, we concluded that woodcock populations were declining in North America between 1968 and 2006 (trend = -0.9%/yr, 95% credible interval: -1.2, -0.5). Singing-Ground Survey results are generally similar between analytical approaches, but the hierarchical model has several important advantages over the route regression. Hierarchical models better accommodate changes in survey efficiency over time and space by treating strata, years, and observers as random effects in the context of a log-linear model, providing trend estimates that are derived directly from the annual indices. We also conducted a hierarchical model analysis of woodcock data from the Christmas Bird Count and the North American Breeding Bird Survey. All surveys showed general consistency in patterns of population change, but the SGS had the shortest credible intervals. We suggest that population management and conservation planning for woodcock involving interpretation of the SGS use estimates provided by the hierarchical model.
Jalil, Rufaihah Abdul; Huang, Ngan F; Jame, Sina; Lee, Jerry; Nguyen, Ha N; Byers, Blake; De, Abhijit; Okogbaa, Janet; Rollins, Mark; Reijo-Pera, Renee; Gambhir, Sanjiv S; Cooke, John P
2011-01-01
Objective Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease. Methods and Results Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and VEGF. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144 and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging (BLI) and green fluorescence protein (GFP) for fluorescent detection (pUb-Fluc-GFP). The hiPSC-ECs (5×105) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). BLI showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 vs 0.44±0.04; P=0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284 ±155 vs. 797±206 capillaries/mm2) (P<0.002). Conclusion This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs. PMID:21836062
Accuracy of Aerodynamic Model Parameters Estimated from Flight Test Data
NASA Technical Reports Server (NTRS)
Morelli, Eugene A.; Klein, Vladislav
1997-01-01
An important put of building mathematical models based on measured date is calculating the accuracy associated with statistical estimates of the model parameters. Indeed, without some idea of this accuracy, the parameter estimates themselves have limited value. An expression is developed for computing quantitatively correct parameter accuracy measures for maximum likelihood parameter estimates when the output residuals are colored. This result is important because experience in analyzing flight test data reveals that the output residuals from maximum likelihood estimation are almost always colored. The calculations involved can be appended to conventional maximum likelihood estimation algorithms. Monte Carlo simulation runs were used to show that parameter accuracy measures from the new technique accurately reflect the quality of the parameter estimates from maximum likelihood estimation without the need for correction factors or frequency domain analysis of the output residuals. The technique was applied to flight test data from repeated maneuvers flown on the F-18 High Alpha Research Vehicle. As in the simulated cases, parameter accuracy measures from the new technique were in agreement with the scatter in the parameter estimates from repeated maneuvers, whereas conventional parameter accuracy measures were optimistic.
2010-01-01
Background Quantitative estimates of myocardial perfusion generally require accurate measurement of the arterial input function (AIF). The saturation of signal intensity in the blood that occurs with most doses of contrast agent makes obtaining an accurate AIF challenging. This work seeks to evaluate the performance of a method that uses a radial k-space perfusion sequence and multiple saturation recovery times (SRT) to quantify myocardial perfusion with cardiovascular magnetic resonance (CMR). Methods Perfusion CMR was performed at 3 Tesla with a saturation recovery radial turboFLASH sequence with 72 rays. Fourteen subjects were given a low dose (0.004 mmol/kg) of dilute (1/5 concentration) contrast agent (Gd-BOPTA) and then a higher non-dilute dose of the same volume (0.02 mmol/kg). AIFs were calculated from the blood signal in three sub-images with differing effective saturation recovery times. The full and sub-images were reconstructed iteratively with a total variation constraint. The images from the full 72 ray data were processed to obtain six tissue enhancement curves in two slices of the left ventricle in each subject. A 2-compartment model was used to determine absolute flows Results The proposed multi-SRT method resulted in AIFs that were similar to those obtained with the dual-bolus method. Myocardial blood flow (MBF) estimates from the dual-bolus and the multi-SRT methods were related by MBFmulti-SRT = 0.85MBFdual-bolus + 0.18 (r = 0.91). Conclusions The multi-SRT method, which uses a radial k-space perfusion sequence, can be used to obtain an accurate AIF and thus quantify myocardial perfusion for doses of contrast agent that result in a relatively saturated AIF. PMID:20653961
Inverse estimation of parameters for an estuarine eutrophication model
Shen, J.; Kuo, A.Y.
1996-11-01
An inverse model of an estuarine eutrophication model with eight state variables is developed. It provides a framework to estimate parameter values of the eutrophication model by assimilation of concentration data of these state variables. The inverse model using the variational technique in conjunction with a vertical two-dimensional eutrophication model is general enough to be applicable to aid model calibration. The formulation is illustrated by conducting a series of numerical experiments for the tidal Rappahannock River, a western shore tributary of the Chesapeake Bay. The numerical experiments of short-period model simulations with different hypothetical data sets and long-period model simulations with limited hypothetical data sets demonstrated that the inverse model can be satisfactorily used to estimate parameter values of the eutrophication model. The experiments also showed that the inverse model is useful to address some important questions, such as uniqueness of the parameter estimation and data requirements for model calibration. Because of the complexity of the eutrophication system, degrading of speed of convergence may occur. Two major factors which cause degradation of speed of convergence are cross effects among parameters and the multiple scales involved in the parameter system.
Wilkinson, Michelle J; Smith, Henry G; Pencavel, Timothy D; Mansfield, David C; Kyula-Currie, Joan; Khan, Aadil A; McEntee, Gráinne; Roulstone, Victoria; Hayes, Andrew J; Harrington, Kevin J
2016-09-15
The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ILP and, in this study, we report further improvements from combining ILP-delivered oncolytic virotherapy with radiation and surgical resection. In vitro, the combination of radiation with an oncolytic vaccinia virus (GLV-1h68) and melphalan demonstrated increased cytotoxicity in a panel of sarcoma cell lines. The effects were mediated through activation of the intrinsic apoptotic pathway. In vivo, combinations of radiation, oncolytic virotherapy and standard ILP resulted in delayed tumour growth and prolonged survival when compared with standard ILP alone. However, local disease control could only be secured when such treatment was combined with surgical resection, the timing of which was crucial in determining outcome. Combinations of oncolytic virotherapy with surgical resection and radiation have direct clinical relevance in extremity sarcoma and represent an exciting prospect for improving outcomes in this pathology. PMID:27116656
Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon
2014-11-01
Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672
Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon
2014-01-01
Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672
Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease
Cannon, Paul J.; Dell, Ralph B.; Dwyer, Edward M.
1972-01-01
Regional myocardial perfusion rates were estimated from the myocardial washout of 133Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of 133Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary
Comparing interval estimates for small sample ordinal CFA models.
Natesan, Prathiba
2015-01-01
Robust maximum likelihood (RML) and asymptotically generalized least squares (AGLS) methods have been recommended for fitting ordinal structural equation models. Studies show that some of these methods underestimate standard errors. However, these studies have not investigated the coverage and bias of interval estimates. An estimate with a reasonable standard error could still be severely biased. This can only be known by systematically investigating the interval estimates. The present study compares Bayesian, RML, and AGLS interval estimates of factor correlations in ordinal confirmatory factor analysis models (CFA) for small sample data. Six sample sizes, 3 factor correlations, and 2 factor score distributions (multivariate normal and multivariate mildly skewed) were studied. Two Bayesian prior specifications, informative and relatively less informative were studied. Undercoverage of confidence intervals and underestimation of standard errors was common in non-Bayesian methods. Underestimated standard errors may lead to inflated Type-I error rates. Non-Bayesian intervals were more positive biased than negatively biased, that is, most intervals that did not contain the true value were greater than the true value. Some non-Bayesian methods had non-converging and inadmissible solutions for small samples and non-normal data. Bayesian empirical standard error estimates for informative and relatively less informative priors were closer to the average standard errors of the estimates. The coverage of Bayesian credibility intervals was closer to what was expected with overcoverage in a few cases. Although some Bayesian credibility intervals were wider, they reflected the nature of statistical uncertainty that comes with the data (e.g., small sample). Bayesian point estimates were also more accurate than non-Bayesian estimates. The results illustrate the importance of analyzing coverage and bias of interval estimates, and how ignoring interval estimates can be misleading
Comparing interval estimates for small sample ordinal CFA models
Natesan, Prathiba
2015-01-01
Robust maximum likelihood (RML) and asymptotically generalized least squares (AGLS) methods have been recommended for fitting ordinal structural equation models. Studies show that some of these methods underestimate standard errors. However, these studies have not investigated the coverage and bias of interval estimates. An estimate with a reasonable standard error could still be severely biased. This can only be known by systematically investigating the interval estimates. The present study compares Bayesian, RML, and AGLS interval estimates of factor correlations in ordinal confirmatory factor analysis models (CFA) for small sample data. Six sample sizes, 3 factor correlations, and 2 factor score distributions (multivariate normal and multivariate mildly skewed) were studied. Two Bayesian prior specifications, informative and relatively less informative were studied. Undercoverage of confidence intervals and underestimation of standard errors was common in non-Bayesian methods. Underestimated standard errors may lead to inflated Type-I error rates. Non-Bayesian intervals were more positive biased than negatively biased, that is, most intervals that did not contain the true value were greater than the true value. Some non-Bayesian methods had non-converging and inadmissible solutions for small samples and non-normal data. Bayesian empirical standard error estimates for informative and relatively less informative priors were closer to the average standard errors of the estimates. The coverage of Bayesian credibility intervals was closer to what was expected with overcoverage in a few cases. Although some Bayesian credibility intervals were wider, they reflected the nature of statistical uncertainty that comes with the data (e.g., small sample). Bayesian point estimates were also more accurate than non-Bayesian estimates. The results illustrate the importance of analyzing coverage and bias of interval estimates, and how ignoring interval estimates can be misleading
Hydrological model uncertainty due to spatial evapotranspiration estimation methods
NASA Astrophysics Data System (ADS)
Yu, Xuan; Lamačová, Anna; Duffy, Christopher; Krám, Pavel; Hruška, Jakub
2016-05-01
Evapotranspiration (ET) continues to be a difficult process to estimate in seasonal and long-term water balances in catchment models. Approaches to estimate ET typically use vegetation parameters (e.g., leaf area index [LAI], interception capacity) obtained from field observation, remote sensing data, national or global land cover products, and/or simulated by ecosystem models. In this study we attempt to quantify the uncertainty that spatial evapotranspiration estimation introduces into hydrological simulations when the age of the forest is not precisely known. The Penn State Integrated Hydrologic Model (PIHM) was implemented for the Lysina headwater catchment, located 50°03‧N, 12°40‧E in the western part of the Czech Republic. The spatial forest patterns were digitized from forest age maps made available by the Czech Forest Administration. Two ET methods were implemented in the catchment model: the Biome-BGC forest growth sub-model (1-way coupled to PIHM) and with the fixed-seasonal LAI method. From these two approaches simulation scenarios were developed. We combined the estimated spatial forest age maps and two ET estimation methods to drive PIHM. A set of spatial hydrologic regime and streamflow regime indices were calculated from the modeling results for each method. Intercomparison of the hydrological responses to the spatial vegetation patterns suggested considerable variation in soil moisture and recharge and a small uncertainty in the groundwater table elevation and streamflow. The hydrologic modeling with ET estimated by Biome-BGC generated less uncertainty due to the plant physiology-based method. The implication of this research is that overall hydrologic variability induced by uncertain management practices was reduced by implementing vegetation models in the catchment models.
Estimation of Model Error Variances During Data Assimilation
NASA Technical Reports Server (NTRS)
Dee, Dick
2003-01-01
Data assimilation is all about understanding the error characteristics of the data and models that are used in the assimilation process. Reliable error estimates are needed to implement observational quality control, bias correction of observations and model fields, and intelligent data selection. Meaningful covariance specifications are obviously required for the analysis as well, since the impact of any single observation strongly depends on the assumed structure of the background errors. Operational atmospheric data assimilation systems still rely primarily on climatological background error covariances. To obtain error estimates that reflect both the character of the flow and the current state of the observing system, it is necessary to solve three problems: (1) how to account for the short-term evolution of errors in the initial conditions; (2) how to estimate the additional component of error caused by model defects; and (3) how to compute the error reduction in the analysis due to observational information. Various approaches are now available that provide approximate solutions to the first and third of these problems. However, the useful accuracy of these solutions very much depends on the size and character of the model errors and the ability to account for them. Model errors represent the real-world forcing of the error evolution in a data assimilation system. Clearly, meaningful model error estimates and/or statistics must be based on information external to the model itself. The most obvious information source is observational, and since the volume of available geophysical data is growing rapidly, there is some hope that a purely statistical approach to model error estimation can be viable. This requires that the observation errors themselves are well understood and quantifiable. We will discuss some of these challenges and present a new sequential scheme for estimating model error variances from observations in the context of an atmospheric data
The DOE National Transportation Program Cost-Estimating Model
Rawl, R.R.
2001-09-25
The United States Department of Energy (DOE) carries out a significant amount of transportation each year, including waste remediation activities at the sites for which it is responsible. In future years, the amount of material transported is expected to increase, and the costs of this transportation are expected to be large. To support the assessment of such costs, a cost-estimating model was developed in 1996, peer-reviewed against other available packaging and transportation cost data, and used to calculate the costs for a significant number of shipping campaigns of radioactive waste. This cost-estimating model, known as the Ten-year Plan Transportation Model (TEPTRAM), served as the cost-estimating model for radioactive material shipments in developing the DOE Office of Environmental Management's Ten Year Plan. The TEPTRAM model considered costs for recovery and processing of the wastes, packaging of the wastes for transport, carriage of the waste and a rough estimate of labor cost s associated with preparing and undertaking the shipments. At the user's direction, the model could also include the cost for DOE's interaction with its external stakeholders (e.g., state and local governments and tribal entities) and the cost associated with tracking and communication (e.g., use of the DOE TRANSCOM system). By considering all of these sources of costs, it provided a mechanism for assessing and comparing the costs of various waste processing and shipping campaign alternatives to help guide decision-making. Recognizing that a more user-friendly version of a cost-estimating model would be more useful to the DOE packaging and transportation community, the National Transportation Program sponsored an update of the TEPTRAM model. The new Transportation Cost Estimating Model (TRANSCOST) was developed to fulfill this need. TRANSCOST utilizes a series of input and output screens to facilitate information flow, and a number of new features were added on the basis of features
Estimating Tree Height-Diameter Models with the Bayesian Method
Duan, Aiguo; Zhang, Jianguo; Xiang, Congwei
2014-01-01
Six candidate height-diameter models were used to analyze the height-diameter relationships. The common methods for estimating the height-diameter models have taken the classical (frequentist) approach based on the frequency interpretation of probability, for example, the nonlinear least squares method (NLS) and the maximum likelihood method (ML). The Bayesian method has an exclusive advantage compared with classical method that the parameters to be estimated are regarded as random variables. In this study, the classical and Bayesian methods were used to estimate six height-diameter models, respectively. Both the classical method and Bayesian method showed that the Weibull model was the “best” model using data1. In addition, based on the Weibull model, data2 was used for comparing Bayesian method with informative priors with uninformative priors and classical method. The results showed that the improvement in prediction accuracy with Bayesian method led to narrower confidence bands of predicted value in comparison to that for the classical method, and the credible bands of parameters with informative priors were also narrower than uninformative priors and classical method. The estimated posterior distributions for parameters can be set as new priors in estimating the parameters using data2. PMID:24711733
MODIS-derived Potential Evapotranspiration Estimates for Operational Hydrologic Modeling
NASA Astrophysics Data System (ADS)
Kim, J.; Hogue, T.
2005-12-01
The current SACramento Soil Moisture Accounting Model (SAC-SMA), used by the National Weather Service, is the primarily model for hydrologic forecasting across the United States. Potential evapotranspiration (PET), one of the required inputs, remains rather simplistic. The model traditionally uses a regional pan evaporation estimate due to the difficulty in acquiring more sophisticated measurements. This study explores an alternative methodology using only remote sensing information to capture the monthly mean distribution of potential evapotranspiration (PET) for the SAC-SMA model. We apply a simple scheme proposed by Jiang and Islam (2005) to estimate the net radiation and estimate PET within the context of the Priestley-Taylor equation using data gathered from the MODIS Terra platform. PET estimates from the MODIS data are compared with those derived from Oklahoma Mesonet ground-based measurements and traditional pan evaporation estimates. Preliminary results will be presented for the Illinois River basin at Watts (OK) identified as part of the National Weather Service's Distributed Modeling Intercomparison Project (DMIP). The resultant streamflow simulations will illustrate the sensitivity of the SAC-SMA model to potential evaporation inputs from different sources and the possibility of the application of a stand-alone PET method for un-gauged basins.
Application of variance components estimation to calibrate geoid error models.
Guo, Dong-Mei; Xu, Hou-Ze
2015-01-01
The method of using Global Positioning System-leveling data to obtain orthometric heights has been well studied. A simple formulation for the weighted least squares problem has been presented in an earlier work. This formulation allows one directly employing the errors-in-variables models which completely descript the covariance matrices of the observables. However, an important question that what accuracy level can be achieved has not yet to be satisfactorily solved by this traditional formulation. One of the main reasons for this is the incorrectness of the stochastic models in the adjustment, which in turn allows improving the stochastic models of measurement noises. Therefore the issue of determining the stochastic modeling of observables in the combined adjustment with heterogeneous height types will be a main focus point in this paper. Firstly, the well-known method of variance component estimation is employed to calibrate the errors of heterogeneous height data in a combined least square adjustment of ellipsoidal, orthometric and gravimetric geoid. Specifically, the iterative algorithms of minimum norm quadratic unbiased estimation are used to estimate the variance components for each of heterogeneous observations. Secondly, two different statistical models are presented to illustrate the theory. The first method directly uses the errors-in-variables as a priori covariance matrices and the second method analyzes the biases of variance components and then proposes bias-corrected variance component estimators. Several numerical test results show the capability and effectiveness of the variance components estimation procedure in combined adjustment for calibrating geoid error model. PMID:26306296
Estimating tree height-diameter models with the Bayesian method.
Zhang, Xiongqing; Duan, Aiguo; Zhang, Jianguo; Xiang, Congwei
2014-01-01
Six candidate height-diameter models were used to analyze the height-diameter relationships. The common methods for estimating the height-diameter models have taken the classical (frequentist) approach based on the frequency interpretation of probability, for example, the nonlinear least squares method (NLS) and the maximum likelihood method (ML). The Bayesian method has an exclusive advantage compared with classical method that the parameters to be estimated are regarded as random variables. In this study, the classical and Bayesian methods were used to estimate six height-diameter models, respectively. Both the classical method and Bayesian method showed that the Weibull model was the "best" model using data1. In addition, based on the Weibull model, data2 was used for comparing Bayesian method with informative priors with uninformative priors and classical method. The results showed that the improvement in prediction accuracy with Bayesian method led to narrower confidence bands of predicted value in comparison to that for the classical method, and the credible bands of parameters with informative priors were also narrower than uninformative priors and classical method. The estimated posterior distributions for parameters can be set as new priors in estimating the parameters using data2. PMID:24711733
Thyrotropin-releasing hormone metabolism and extraction by the perfused guinea pig placenta
Nogimori, T.; Alex, S.; Baker, S.; Emerson, C.H.
1985-08-01
This report describes the extraction of synthetic TRH and its metabolic conversion in the perfused guinea pig placenta. These studies were performed to obtain an estimate of fractional fetal TRH losses through the placenta and to determine if some of these losses are due to TRH metabolism. Experiments were performed in which the perfusion buffer contained 0.01, 1, and 10 micrograms/ml or no synthetic TRH. In experiments in which TRH was perfused, the perfusion reservoir contents and placental effluent fractions were counted for TH, and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro) was measured when 10 micrograms/ml TRH were perfused. When synthetic TRH was perfused, steady state TRH concentrations were achieved in placental effluent fractions by 20-30 min. The single pass extraction of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/- 7.0% for TH22O. No significant difference was detected regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A portion of the TRH that perfused the placenta was converted to deamido-TRH at all concentrations of perfused TRH. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a single pass. When the perfusion buffer was devoid of synthetic TRH, a small but significant increase in the content of TRH immunoreactivity was noted in the placental effluent compared to that in the perfusion reservoir.
Error magnitude estimation in model-reference adaptive systems
NASA Technical Reports Server (NTRS)
Colburn, B. K.; Boland, J. S., III
1975-01-01
A second order approximation is derived from a linearized error characteristic equation for Lyapunov designed model-reference adaptive systems and is used to estimate the maximum error between the model and plant states, and the time to reach this peak following a plant perturbation. The results are applicable in the analysis of plants containing magnitude-dependent nonlinearities.
Estimating demographic parameters using hidden process dynamic models.
Gimenez, Olivier; Lebreton, Jean-Dominique; Gaillard, Jean-Michel; Choquet, Rémi; Pradel, Roger
2012-12-01
Structured population models are widely used in plant and animal demographic studies to assess population dynamics. In matrix population models, populations are described with discrete classes of individuals (age, life history stage or size). To calibrate these models, longitudinal data are collected at the individual level to estimate demographic parameters. However, several sources of uncertainty can complicate parameter estimation, such as imperfect detection of individuals inherent to monitoring in the wild and uncertainty in assigning a state to an individual. Here, we show how recent statistical models can help overcome these issues. We focus on hidden process models that run two time series in parallel, one capturing the dynamics of the true states and the other consisting of observations arising from these underlying possibly unknown states. In a first case study, we illustrate hidden Markov models with an example of how to accommodate state uncertainty using Frequentist theory and maximum likelihood estimation. In a second case study, we illustrate state-space models with an example of how to estimate lifetime reproductive success despite imperfect detection, using a Bayesian framework and Markov Chain Monte Carlo simulation. Hidden process models are a promising tool as they allow population biologists to cope with process variation while simultaneously accounting for observation error. PMID:22373775
Tube-Load Model Parameter Estimation for Monitoring Arterial Hemodynamics
Zhang, Guanqun; Hahn, Jin-Oh; Mukkamala, Ramakrishna
2011-01-01
A useful model of the arterial system is the uniform, lossless tube with parametric load. This tube-load model is able to account for wave propagation and reflection (unlike lumped-parameter models such as the Windkessel) while being defined by only a few parameters (unlike comprehensive distributed-parameter models). As a result, the parameters may be readily estimated by accurate fitting of the model to available arterial pressure and flow waveforms so as to permit improved monitoring of arterial hemodynamics. In this paper, we review tube-load model parameter estimation techniques that have appeared in the literature for monitoring wave reflection, large artery compliance, pulse transit time, and central aortic pressure. We begin by motivating the use of the tube-load model for parameter estimation. We then describe the tube-load model, its assumptions and validity, and approaches for estimating its parameters. We next summarize the various techniques and their experimental results while highlighting their advantages over conventional techniques. We conclude the review by suggesting future research directions and describing potential applications. PMID:22053157
ESTIMATING NATURAL EMISSIONS FOR EPA'S REGIONAL OXIDANT MODEL
This paper documents the methodology used to estimate natural sources of nitrogen oxide (NOx) and nonmethane hydrocarbon (NMHC) emissions in the Regional Oxidant Model (ROM). The ROM is a three-dimensional photochemical grid model designed to simulate hourly concentrations of ozo...
Yield estimation of sugarcane based on agrometeorological-spectral models
NASA Technical Reports Server (NTRS)
Rudorff, Bernardo Friedrich Theodor; Batista, Getulio Teixeira
1990-01-01
This work has the objective to assess the performance of a yield estimation model for sugarcane (Succharum officinarum). The model uses orbital gathered spectral data along with yield estimated from an agrometeorological model. The test site includes the sugarcane plantations of the Barra Grande Plant located in Lencois Paulista municipality in Sao Paulo State. Production data of four crop years were analyzed. Yield data observed in the first crop year (1983/84) were regressed against spectral and agrometeorological data of that same year. This provided the model to predict the yield for the following crop year i.e., 1984/85. The model to predict the yield of subsequent years (up to 1987/88) were developed similarly, incorporating all previous years data. The yield estimations obtained from these models explained 69, 54, and 50 percent of the yield variation in the 1984/85, 1985/86, and 1986/87 crop years, respectively. The accuracy of yield estimations based on spectral data only (vegetation index model) and on agrometeorological data only (agrometeorological model) were also investigated.
Estimability of Parameters in the Generalized Graded Unfolding Model.
ERIC Educational Resources Information Center
Roberts, James S.; Donoghue, John R.; Laughlin, James E.
The generalized graded unfolding model (GGUM) (J. Roberts, J. Donoghue, and J. Laughlin, 1998) is an item response theory model designed to analyze binary or graded responses that are based on a proximity relation. The purpose of this study was to assess conditions under which item parameter estimation accuracy increases or decreases, with special…
Estimating Independent Locally Shifted Random Utility Models for Ranking Data
ERIC Educational Resources Information Center
Lam, Kar Yin; Koning, Alex J.; Franses, Philip Hans
2011-01-01
We consider the estimation of probabilistic ranking models in the context of conjoint experiments. By using approximate rather than exact ranking probabilities, we avoided the computation of high-dimensional integrals. We extended the approximation technique proposed by Henery (1981) in the context of the Thurstone-Mosteller-Daniels model to any…
Estimation of an Occupational Choice Model when Occupations Are Misclassified
ERIC Educational Resources Information Center
Sullivan, Paul
2009-01-01
This paper develops an empirical occupational choice model that corrects for misclassification in occupational choices and measurement error in occupation-specific work experience. The model is used to estimate the extent of measurement error in occupation data and quantify the bias that results from ignoring measurement error in occupation codes…
Maximum likelihood estimation for distributed parameter models of flexible spacecraft
NASA Technical Reports Server (NTRS)
Taylor, L. W., Jr.; Williams, J. L.
1989-01-01
A distributed-parameter model of the NASA Solar Array Flight Experiment spacecraft structure is constructed on the basis of measurement data and analyzed to generate a priori estimates of modal frequencies and mode shapes. A Newton-Raphson maximum-likelihood algorithm is applied to determine the unknown parameters, using a truncated model for the estimation and the full model for the computation of the higher modes. Numerical results are presented in a series of graphs and briefly discussed, and the significant improvement in computation speed obtained by parallel implementation of the method on a supercomputer is noted.
Estimating the minimum control count of random network models
Ruths, Derek; Ruths, Justin
2016-01-01
The study of controllability of complex networks has introduced the minimum number of controls required for full controllability as a new network measure of interest. This network measure, like many others, is non-trivial to compute. As a result, establishing the significance of minimum control counts (MCCs) in real networks using random network null models is expensive. Here we derive analytic estimates for the expected MCCs of networks drawn from three commonly-used random network models. Our estimates show good agreement with exact control counts. Furthermore, the analytic expressions we derive offer insights into the structures within each random network model that induce the need for controls. PMID:26817434
Online robust model estimation during in vivo needle insertions.
Barbé, Laurent; Bayle, Bernard; de Mathelin, Michel
2006-01-01
Soft tissue modeling is of key importance in medical robotics and simulation. In the case of percutaneous operations, a fine model of layers transitions and target tissues is required. However, the nature and the variety of these tissues is such that this problem is extremely complex. In this article, we propose a method to estimate the interaction between in vivo tissues and a surgical needle. The online robust estimation of a varying parameters model is achieved during an insertion in standard operating conditions. PMID:16404010
Model-based approach for elevator performance estimation
NASA Astrophysics Data System (ADS)
Esteban, E.; Salgado, O.; Iturrospe, A.; Isasa, I.
2016-02-01
In this paper, a dynamic model for an elevator installation is presented in the state space domain. The model comprises both the mechanical and the electrical subsystems, including the electrical machine and a closed-loop field oriented control. The proposed model is employed for monitoring the condition of the elevator installation. The adopted model-based approach for monitoring employs the Kalman filter as an observer. A Kalman observer estimates the elevator car acceleration, which determines the elevator ride quality, based solely on the machine control signature and the encoder signal. Finally, five elevator key performance indicators are calculated based on the estimated car acceleration. The proposed procedure is experimentally evaluated, by comparing the key performance indicators calculated based on the estimated car acceleration and the values obtained from actual acceleration measurements in a test bench. Finally, the proposed procedure is compared with the sliding mode observer.
Parameter Estimation in a Delay Differential Model of ENSO
NASA Astrophysics Data System (ADS)
Roux, J.; Gerchinovitz, S.; Ghil, M.
2009-04-01
In this talk, we present very generic statistical methods to perform parameter estimation in a Delay Differential Equation. Our reference DDE is the toy model of El Nino/Southern Oscillation introduced by Ghil, Zaliapin and Thompson (2008). We first recall some properties of this model in comparison with other models, together with basic results in Functional Differential Equation theory. We then briefly describe two statistical estimation procedures (the very classic Ordinary Least Squares estimator computed via simulated annealing, and a new two stage method based on nonparametric regression using the Nadaraya-Watson kernel). We finally comment on the numerical tests we performed on simulated noised data. These results encourage further application of this kind of methods to more complex (and more realistic) models of ENSO, to other problems in the Geosciences or to other fields.
Spatial Distribution of Hydrologic Ecosystem Service Estimates: Comparing Two Models
NASA Astrophysics Data System (ADS)
Dennedy-Frank, P. J.; Ghile, Y.; Gorelick, S.; Logsdon, R. A.; Chaubey, I.; Ziv, G.
2014-12-01
We compare estimates of the spatial distribution of water quantity provided (annual water yield) from two ecohydrologic models: the widely-used Soil and Water Assessment Tool (SWAT) and the much simpler water models from the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) toolbox. These two models differ significantly in terms of complexity, timescale of operation, effort, and data required for calibration, and so are often used in different management contexts. We compare two study sites in the US: the Wildcat Creek Watershed (2083 km2) in Indiana, a largely agricultural watershed in a cold aseasonal climate, and the Upper Upatoi Creek Watershed (876 km2) in Georgia, a mostly forested watershed in a temperate aseasonal climate. We evaluate (1) quantitative estimates of water yield to explore how well each model represents this process, and (2) ranked estimates of water yield to indicate how useful the models are for management purposes where other social and financial factors may play significant roles. The SWAT and InVEST models provide very similar estimates of the water yield of individual subbasins in the Wildcat Creek Watershed (Pearson r = 0.92, slope = 0.89), and a similar ranking of the relative water yield of those subbasins (Spearman r = 0.86). However, the two models provide relatively different estimates of the water yield of individual subbasins in the Upper Upatoi Watershed (Pearson r = 0.25, slope = 0.14), and very different ranking of the relative water yield of those subbasins (Spearman r = -0.10). The Upper Upatoi watershed has a significant baseflow contribution due to its sandy, well-drained soils. InVEST's simple seasonality terms, which assume no change in storage over the time of the model run, may not accurately estimate water yield processes when baseflow provides such a strong contribution. Our results suggest that InVEST users take care in situations where storage changes are significant.
Nonparametric identification and maximum likelihood estimation for hidden Markov models
Alexandrovich, G.; Holzmann, H.; Leister, A.
2016-01-01
Nonparametric identification and maximum likelihood estimation for finite-state hidden Markov models are investigated. We obtain identification of the parameters as well as the order of the Markov chain if the transition probability matrices have full-rank and are ergodic, and if the state-dependent distributions are all distinct, but not necessarily linearly independent. Based on this identification result, we develop a nonparametric maximum likelihood estimation theory. First, we show that the asymptotic contrast, the Kullback–Leibler divergence of the hidden Markov model, also identifies the true parameter vector nonparametrically. Second, for classes of state-dependent densities which are arbitrary mixtures of a parametric family, we establish the consistency of the nonparametric maximum likelihood estimator. Here, identification of the mixing distributions need not be assumed. Numerical properties of the estimates and of nonparametric goodness of fit tests are investigated in a simulation study.
Development on electromagnetic impedance function modeling and its estimation
Sutarno, D.
2015-09-30
Today the Electromagnetic methods such as magnetotellurics (MT) and controlled sources audio MT (CSAMT) is used in a broad variety of applications. Its usefulness in poor seismic areas and its negligible environmental impact are integral parts of effective exploration at minimum cost. As exploration was forced into more difficult areas, the importance of MT and CSAMT, in conjunction with other techniques, has tended to grow continuously. However, there are obviously important and difficult problems remaining to be solved concerning our ability to collect process and interpret MT as well as CSAMT in complex 3D structural environments. This talk aim at reviewing and discussing the recent development on MT as well as CSAMT impedance functions modeling, and also some improvements on estimation procedures for the corresponding impedance functions. In MT impedance modeling, research efforts focus on developing numerical method for computing the impedance functions of three dimensionally (3-D) earth resistivity models. On that reason, 3-D finite elements numerical modeling for the impedances is developed based on edge element method. Whereas, in the CSAMT case, the efforts were focused to accomplish the non-plane wave problem in the corresponding impedance functions. Concerning estimation of MT and CSAMT impedance functions, researches were focused on improving quality of the estimates. On that objective, non-linear regression approach based on the robust M-estimators and the Hilbert transform operating on the causal transfer functions, were used to dealing with outliers (abnormal data) which are frequently superimposed on a normal ambient MT as well as CSAMT noise fields. As validated, the proposed MT impedance modeling method gives acceptable results for standard three dimensional resistivity models. Whilst, the full solution based modeling that accommodate the non-plane wave effect for CSAMT impedances is applied for all measurement zones, including near-, transition
Development on electromagnetic impedance function modeling and its estimation
NASA Astrophysics Data System (ADS)
Sutarno, D.
2015-09-01
Today the Electromagnetic methods such as magnetotellurics (MT) and controlled sources audio MT (CSAMT) is used in a broad variety of applications. Its usefulness in poor seismic areas and its negligible environmental impact are integral parts of effective exploration at minimum cost. As exploration was forced into more difficult areas, the importance of MT and CSAMT, in conjunction with other techniques, has tended to grow continuously. However, there are obviously important and difficult problems remaining to be solved concerning our ability to collect process and interpret MT as well as CSAMT in complex 3D structural environments. This talk aim at reviewing and discussing the recent development on MT as well as CSAMT impedance functions modeling, and also some improvements on estimation procedures for the corresponding impedance functions. In MT impedance modeling, research efforts focus on developing numerical method for computing the impedance functions of three dimensionally (3-D) earth resistivity models. On that reason, 3-D finite elements numerical modeling for the impedances is developed based on edge element method. Whereas, in the CSAMT case, the efforts were focused to accomplish the non-plane wave problem in the corresponding impedance functions. Concerning estimation of MT and CSAMT impedance functions, researches were focused on improving quality of the estimates. On that objective, non-linear regression approach based on the robust M-estimators and the Hilbert transform operating on the causal transfer functions, were used to dealing with outliers (abnormal data) which are frequently superimposed on a normal ambient MT as well as CSAMT noise fields. As validated, the proposed MT impedance modeling method gives acceptable results for standard three dimensional resistivity models. Whilst, the full solution based modeling that accommodate the non-plane wave effect for CSAMT impedances is applied for all measurement zones, including near-, transition
Estimation of Unsteady Aerodynamic Models from Dynamic Wind Tunnel Data
NASA Technical Reports Server (NTRS)
Murphy, Patrick; Klein, Vladislav
2011-01-01
Demanding aerodynamic modelling requirements for military and civilian aircraft have motivated researchers to improve computational and experimental techniques and to pursue closer collaboration in these areas. Model identification and validation techniques are key components for this research. This paper presents mathematical model structures and identification techniques that have been used successfully to model more general aerodynamic behaviours in single-degree-of-freedom dynamic testing. Model parameters, characterizing aerodynamic properties, are estimated using linear and nonlinear regression methods in both time and frequency domains. Steps in identification including model structure determination, parameter estimation, and model validation, are addressed in this paper with examples using data from one-degree-of-freedom dynamic wind tunnel and water tunnel experiments. These techniques offer a methodology for expanding the utility of computational methods in application to flight dynamics, stability, and control problems. Since flight test is not always an option for early model validation, time history comparisons are commonly made between computational and experimental results and model adequacy is inferred by corroborating results. An extension is offered to this conventional approach where more general model parameter estimates and their standard errors are compared.
Combined Estimation of Hydrogeologic Conceptual Model and Parameter Uncertainty
Meyer, Philip D.; Ye, Ming; Neuman, Shlomo P.; Cantrell, Kirk J.
2004-03-01
The objective of the research described in this report is the development and application of a methodology for comprehensively assessing the hydrogeologic uncertainties involved in dose assessment, including uncertainties associated with conceptual models, parameters, and scenarios. This report describes and applies a statistical method to quantitatively estimate the combined uncertainty in model predictions arising from conceptual model and parameter uncertainties. The method relies on model averaging to combine the predictions of a set of alternative models. Implementation is driven by the available data. When there is minimal site-specific data the method can be carried out with prior parameter estimates based on generic data and subjective prior model probabilities. For sites with observations of system behavior (and optionally data characterizing model parameters), the method uses model calibration to update the prior parameter estimates and model probabilities based on the correspondence between model predictions and site observations. The set of model alternatives can contain both simplified and complex models, with the requirement that all models be based on the same set of data. The method was applied to the geostatistical modeling of air permeability at a fractured rock site. Seven alternative variogram models of log air permeability were considered to represent data from single-hole pneumatic injection tests in six boreholes at the site. Unbiased maximum likelihood estimates of variogram and drift parameters were obtained for each model. Standard information criteria provided an ambiguous ranking of the models, which would not justify selecting one of them and discarding all others as is commonly done in practice. Instead, some of the models were eliminated based on their negligibly small updated probabilities and the rest were used to project the measured log permeabilities by kriging onto a rock volume containing the six boreholes. These four
Models and estimation methods for clinical HIV-1 data
NASA Astrophysics Data System (ADS)
Verotta, Davide
2005-12-01
Clinical HIV-1 data include many individual factors, such as compliance to treatment, pharmacokinetics, variability in respect to viral dynamics, race, sex, income, etc., which might directly influence or be associated with clinical outcome. These factors need to be taken into account to achieve a better understanding of clinical outcome and mathematical models can provide a unifying framework to do so. The first objective of this paper is to demonstrate the development of comprehensive HIV-1 dynamics models that describe viral dynamics and also incorporate different factors influencing such dynamics. The second objective of this paper is to describe alternative estimation methods that can be applied to the analysis of data with such models. In particular, we consider: (i) simple but effective two-stage estimation methods, in which data from each patient are analyzed separately and summary statistics derived from the results, (ii) more complex nonlinear mixed effect models, used to pool all the patient data in a single analysis. Bayesian estimation methods are also considered, in particular: (iii) maximum posterior approximations, MAP, and (iv) Markov chain Monte Carlo, MCMC. Bayesian methods incorporate prior knowledge into the models, thus avoiding some of the model simplifications introduced when the data are analyzed using two-stage methods, or a nonlinear mixed effect framework. We demonstrate the development of the models and the different estimation methods using real AIDS clinical trial data involving patients receiving multiple drugs regimens.
Michiels, J J
1998-01-01
A prospective management decision analysis for the exclusion and diagnosis of pulmonary embolism (PE) based on pre-test clinical probability (PCP) estimation for PE, a rapid ELISA D-dimer test, perfusion lungscan (P-scan), CUS, spiral CT, and pulmonary angiography is proposed. The modified PCP model for PE of Wells et al. allows reasonably accurate classification of patients with no, low, moderate, and high probability for PE. The combined rational use of the evidence-based noninvasive imaging techniques P-scan, CUS, and spiral CT with the rapid ELISA D-dimer test and PCP will reduce the need for invasive pulmonary angiography to perhaps 10 to 15% of patients, who initially presented with suspected PE. A Rational Diagnosis of Pulmonary Embolism (RADIA PE) model is proposed for testing in a large multicenter study of patients with suspected PE. PMID:9763360
Estimation of Time-Varying Pilot Model Parameters
NASA Technical Reports Server (NTRS)
Zaal, Peter M. T.; Sweet, Barbara T.
2011-01-01
Human control behavior is rarely completely stationary over time due to fatigue or loss of attention. In addition, there are many control tasks for which human operators need to adapt their control strategy to vehicle dynamics that vary in time. In previous studies on the identification of time-varying pilot control behavior wavelets were used to estimate the time-varying frequency response functions. However, the estimation of time-varying pilot model parameters was not considered. Estimating these parameters can be a valuable tool for the quantification of different aspects of human time-varying manual control. This paper presents two methods for the estimation of time-varying pilot model parameters, a two-step method using wavelets and a windowed maximum likelihood estimation method. The methods are evaluated using simulations of a closed-loop control task with time-varying pilot equalization and vehicle dynamics. Simulations are performed with and without remnant. Both methods give accurate results when no pilot remnant is present. The wavelet transform is very sensitive to measurement noise, resulting in inaccurate parameter estimates when considerable pilot remnant is present. Maximum likelihood estimation is less sensitive to pilot remnant, but cannot detect fast changes in pilot control behavior.
Model Year 2011 Fuel Economy Guide: EPA Fuel Economy Estimates
2010-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Model Year 2013 Fuel Economy Guide: EPA Fuel Economy Estimates
2012-12-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Model Year 2012 Fuel Economy Guide: EPA Fuel Economy Estimates
2011-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Random effects and shrinkage estimation in capture-recapture models
Royle, J. Andrew; Link, W.A.
2002-01-01
We discuss the analysis of random effects in capture-recapture models, and outline Bayesian and frequentists approaches to their analysis. Under a normal model, random effects estimators derived from Bayesian or frequentist considerations have a common form as shrinkage estimators. We discuss some of the difficulties of analysing random effects using traditional methods, and argue that a Bayesian formulation provides a rigorous framework for dealing with these difficulties. In capture-recapture models, random effects may provide a parsimonious compromise between constant and completely time-dependent models for the parameters (e.g. survival probability). We consider application of random effects to band-recovery models, although the principles apply to more general situations, such as Cormack-Jolly-Seber models. We illustrate these ideas using a commonly analysed band recovery data set.
An Integrated Modelling Approach to Estimate Urban Traffic Emissions
NASA Astrophysics Data System (ADS)
Misra, Aarshabh
Vehicular emissions contribute significantly to poor air quality in urban areas. An integrated modelling approach is adopted to estimate microscale urban traffic emissions. The modelling framework consists of a traffic microsimulation model, a microscopic emissions model, and two dispersion models. This framework is applied to a traffic network in downtown Toronto to evaluate summer time morning peak traffic emissions during weekdays for carbon monoxide and nitrogen oxide. The model predicted results are validated against sensor observations with a reasonably good fit. Availability of local estimates of ambient concentration is useful for accurate comparisons of total predicted concentrations with observed concentrations. Both predicted and observed concentrations are significantly smaller than the National Ambient Air Quality Objectives established by Environment Canada. Sensitivity analysis is performed on a set of input parameters and horizontal wind speed is found to be the most influential factor in pollutant dispersion.
[Hyperspectral remote sensing estimation models for snow grain size].
Wang, Jian-Geng; Feng, Xue-Zhi; Xiao, Peng-Feng; Liang, Ji; Zhang, Xue-Liang; Li, Hai-Xing; Li, Yun
2013-01-01
Snow grain size is a key parameter not only to affect the energy budget of the global or local region but also characterizing the status of snow vapor transport and temperature gradient. It is significant to monitor and estimate the snow grain size in large area for global or local climate change and water resource management. Recently, remote sensing technology has become a useful tool for snow grain size monitoring and estimating. In the present paper, the estimate models were built based on simulating the snow surface spectral reflectance curve in visible-infrared region and the sensitive bands and snow indices for snow grain size were selected. These models help estimate snow grain size by hyperspectral remote sensing. Through validating with ground true data, the results show that these models have higher explorative accuracy using 1 030, 1 260 nm and normalized difference snow index (460 and 1 030 nm). In addition, the correlation slopes of estimated and observed valves are 1.37, 0.61 and 0.62, respectively. R2 are 0.82, 0.86 and 0.93 and RMSE are 55.65, 50.83 and 35.91 microm, respectively. The result can provide a scientific basis for snow grain size monitoring and estimating. PMID:23586251
Estimation of exposure to toxic releases using spatial interaction modeling
2011-01-01
Background The United States Environmental Protection Agency's Toxic Release Inventory (TRI) data are frequently used to estimate a community's exposure to pollution. However, this estimation process often uses underdeveloped geographic theory. Spatial interaction modeling provides a more realistic approach to this estimation process. This paper uses four sets of data: lung cancer age-adjusted mortality rates from the years 1990 through 2006 inclusive from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, TRI releases of carcinogens from 1987 to 1996, covariates associated with lung cancer, and the EPA's Risk-Screening Environmental Indicators (RSEI) model. Results The impact of the volume of carcinogenic TRI releases on each county's lung cancer mortality rates was calculated using six spatial interaction functions (containment, buffer, power decay, exponential decay, quadratic decay, and RSEI estimates) and evaluated with four multivariate regression methods (linear, generalized linear, spatial lag, and spatial error). Akaike Information Criterion values and P values of spatial interaction terms were computed. The impacts calculated from the interaction models were also mapped. Buffer and quadratic interaction functions had the lowest AIC values (22298 and 22525 respectively), although the gains from including the spatial interaction terms were diminished with spatial error and spatial lag regression. Conclusions The use of different methods for estimating the spatial risk posed by pollution from TRI sites can give different results about the impact of those sites on health outcomes. The most reliable estimates did not always come from the most complex methods. PMID:21418644
Parameter Estimation and Model Selection in Computational Biology
Lillacci, Gabriele; Khammash, Mustafa
2010-01-01
A central challenge in computational modeling of biological systems is the determination of the model parameters. Typically, only a fraction of the parameters (such as kinetic rate constants) are experimentally measured, while the rest are often fitted. The fitting process is usually based on experimental time course measurements of observables, which are used to assign parameter values that minimize some measure of the error between these measurements and the corresponding model prediction. The measurements, which can come from immunoblotting assays, fluorescent markers, etc., tend to be very noisy and taken at a limited number of time points. In this work we present a new approach to the problem of parameter selection of biological models. We show how one can use a dynamic recursive estimator, known as extended Kalman filter, to arrive at estimates of the model parameters. The proposed method follows. First, we use a variation of the Kalman filter that is particularly well suited to biological applications to obtain a first guess for the unknown parameters. Secondly, we employ an a posteriori identifiability test to check the reliability of the estimates. Finally, we solve an optimization problem to refine the first guess in case it should not be accurate enough. The final estimates are guaranteed to be statistically consistent with the measurements. Furthermore, we show how the same tools can be used to discriminate among alternate models of the same biological process. We demonstrate these ideas by applying our methods to two examples, namely a model of the heat shock response in E. coli, and a model of a synthetic gene regulation system. The methods presented are quite general and may be applied to a wide class of biological systems where noisy measurements are used for parameter estimation or model selection. PMID:20221262
Automated sonographic evaluation of testicular perfusion
NASA Astrophysics Data System (ADS)
Thierman, Jonathan S.; Clement, Gregory T.; Kalish, Leslie A.; O'Kane, Patrick L.; Frauscher, Ferdinand; Paltiel, Harriet J.
2006-07-01
Contrast-enhanced ultrasound (US) imaging is potentially applicable to the investigation of vascular disorders of the testis. We investigated the ability of two automated computer algorithms to analyse contrast-enhanced pulse inversion US data in a rabbit model of unilateral testicular ischaemia and to correctly determine relative testicular perfusion: nonlinear curve fitting of the US backscatter intensity as a function of time; and spectral analysis of the intensity time trace. We compared (i) five metrics based on the algorithmic data to testicular perfusion ratios obtained with radiolabelled microspheres, a reference standard; (ii) qualitative assessment of the US images by two independent readers blinded to the side of the experimental and control testes to the radiolabelled microsphere perfusion ratios; and (iii) results of the algorithmically-derived metrics to the qualitative assessments of the two readers. For the curve fit method, the algorithmically-derived metrics agreed with the reference standard in 54% to 68% of all cases. For the spectral method, the results agreed in 70% of all cases. The two readers agreed with the reference standard in 40% and 35% of all cases, respectively. These results suggest that automated methods of analysis may provide useful information in the assessment of testicular perfusion.
Stochastic algorithms for Markov models estimation with intermittent missing data.
Deltour, I; Richardson, S; Le Hesran, J Y
1999-06-01
Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed. PMID:11318215
Synchronous Generator Model Parameter Estimation Based on Noisy Dynamic Waveforms
NASA Astrophysics Data System (ADS)
Berhausen, Sebastian; Paszek, Stefan
2016-01-01
In recent years, there have occurred system failures in many power systems all over the world. They have resulted in a lack of power supply to a large number of recipients. To minimize the risk of occurrence of power failures, it is necessary to perform multivariate investigations, including simulations, of power system operating conditions. To conduct reliable simulations, the current base of parameters of the models of generating units, containing the models of synchronous generators, is necessary. In the paper, there is presented a method for parameter estimation of a synchronous generator nonlinear model based on the analysis of selected transient waveforms caused by introducing a disturbance (in the form of a pseudorandom signal) in the generator voltage regulation channel. The parameter estimation was performed by minimizing the objective function defined as a mean square error for deviations between the measurement waveforms and the waveforms calculated based on the generator mathematical model. A hybrid algorithm was used for the minimization of the objective function. In the paper, there is described a filter system used for filtering the noisy measurement waveforms. The calculation results of the model of a 44 kW synchronous generator installed on a laboratory stand of the Institute of Electrical Engineering and Computer Science of the Silesian University of Technology are also given. The presented estimation method can be successfully applied to parameter estimation of different models of high-power synchronous generators operating in a power system.
A new geometric-based model to accurately estimate arm and leg inertial estimates.
Wicke, Jason; Dumas, Geneviève A
2014-06-01
Segment estimates of mass, center of mass and moment of inertia are required input parameters to analyze the forces and moments acting across the joints. The objectives of this study were to propose a new geometric model for limb segments, to evaluate it against criterion values obtained from DXA, and to compare its performance to five other popular models. Twenty five female and 24 male college students participated in the study. For the criterion measures, the participants underwent a whole body DXA scan, and estimates for segment mass, center of mass location, and moment of inertia (frontal plane) were directly computed from the DXA mass units. For the new model, the volume was determined from two standing frontal and sagittal photographs. Each segment was modeled as a stack of slices, the sections of which were ellipses if they are not adjoining another segment and sectioned ellipses if they were adjoining another segment (e.g. upper arm and trunk). Length of axes of the ellipses was obtained from the photographs. In addition, a sex-specific, non-uniform density function was developed for each segment. A series of anthropometric measurements were also taken by directly following the definitions provided of the different body segment models tested, and the same parameters determined for each model. Comparison of models showed that estimates from the new model were consistently closer to the DXA criterion than those from the other models, with an error of less than 5% for mass and moment of inertia and less than about 6% for center of mass location. PMID:24735506
Coupling Hydrologic and Hydrodynamic Models to Estimate PMF
NASA Astrophysics Data System (ADS)
Felder, G.; Weingartner, R.
2015-12-01
Most sophisticated probable maximum flood (PMF) estimations derive the PMF from the probable maximum precipitation (PMP) by applying deterministic hydrologic models calibrated with observed data. This method is based on the assumption that the hydrological system is stationary, meaning that the system behaviour during the calibration period or the calibration event is presumed to be the same as it is during the PMF. However, as soon as a catchment-specific threshold is reached, the system is no longer stationary. At or beyond this threshold, retention areas, new flow paths, and changing runoff processes can strongly affect downstream peak discharge. These effects can be accounted for by coupling hydrologic and hydrodynamic models, a technique that is particularly promising when the expected peak discharge may considerably exceed the observed maximum discharge. In such cases, the coupling of hydrologic and hydraulic models has the potential to significantly increase the physical plausibility of PMF estimations. This procedure ensures both that the estimated extreme peak discharge does not exceed the physical limit based on riverbed capacity and that the dampening effect of inundation processes on peak discharge is considered. Our study discusses the prospect of considering retention effects on PMF estimations by coupling hydrologic and hydrodynamic models. This method is tested by forcing PREVAH, a semi-distributed deterministic hydrological model, with randomly generated, physically plausible extreme precipitation patterns. The resulting hydrographs are then used to externally force the hydraulic model BASEMENT-ETH (riverbed in 1D, potential inundation areas in 2D). Finally, the PMF estimation results obtained using the coupled modelling approach are compared to the results obtained using ordinary hydrologic modelling.
Functional and stochastic models estimation for GNSS coordinates time series
NASA Astrophysics Data System (ADS)
Galera Monico, J. F.; Silva, H. A.; Marques, H. A.
2014-12-01
GNSS has been largely used in Geodesy and correlated areas for positioning. The position and velocity of terrestrial stations have been estimated using GNSS data based on daily solutions. So, currently it is possible to analyse the GNSS coordinates time series aiming to improve the functional and stochastic models what can help to understand geodynamic phenomena. Several sources of errors are mathematically modelled or estimated in the GNSS data processing to obtain precise coordinates what in general is carried out by using scientific software. However, due to impossibility to model all errors some kind of noises can remain contaminating the coordinate time series, especially those related with seasonal effects. The noise affecting GNSS coordinate time series can be composed by white and coloured noises what can be characterized from Variance Component Estimation technique through Least Square Method. The methodology to characterize noise in GNSS coordinates time series will be presented in this paper so that the estimated variance can be used to reconstruct stochastic and functional models of the times series providing a more realistic and reliable modeling of time series. Experiments were carried out by using GNSS time series for few Brazilian stations considering almost ten years of daily solutions. The noises components were characterized as white, flicker and random walk noise and applied to estimate the times series functional model considering semiannual and annual effects. The results show that the adoption of an adequate stochastic model considering the noises variances of time series can produce more realistic and reliable functional model for GNSS coordinate time series. Such results may be applied in the context of the realization of the Brazilian Geodetic System.
Combining Empirical and Stochastic Models for Extreme Floods Estimation
NASA Astrophysics Data System (ADS)
Zemzami, M.; Benaabidate, L.
2013-12-01
Hydrological models can be defined as physical, mathematical or empirical. The latter class uses mathematical equations independent of the physical processes involved in the hydrological system. The linear regression and Gradex (Gradient of Extreme values) are classic examples of empirical models. However, conventional empirical models are still used as a tool for hydrological analysis by probabilistic approaches. In many regions in the world, watersheds are not gauged. This is true even in developed countries where the gauging network has continued to decline as a result of the lack of human and financial resources. Indeed, the obvious lack of data in these watersheds makes it impossible to apply some basic empirical models for daily forecast. So we had to find a combination of rainfall-runoff models in which it would be possible to create our own data and use them to estimate the flow. The estimated design floods would be a good choice to illustrate the difficulties facing the hydrologist for the construction of a standard empirical model in basins where hydrological information is rare. The construction of the climate-hydrological model, which is based on frequency analysis, was established to estimate the design flood in the Anseghmir catchments, Morocco. The choice of using this complex model returns to its ability to be applied in watersheds where hydrological information is not sufficient. It was found that this method is a powerful tool for estimating the design flood of the watershed and also other hydrological elements (runoff, volumes of water...).The hydrographic characteristics and climatic parameters were used to estimate the runoff, water volumes and design flood for different return periods.
Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps
Fichter, Andreas M.; Ritschl, Lucas M.; Borgmann, Anna; Humbs, Martin; Luppa, Peter B.; Wolff, Klaus-Dietrich; Mücke, Thomas
2016-01-01
Background Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. Methods After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. Results ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. Conclusions Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies. PMID:26808996
Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.
2014-01-01
Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401
Estimation of Accumulation Parameters for Urban Runoff Quality Modeling
NASA Astrophysics Data System (ADS)
Alley, William M.; Smith, Peter E.
1981-12-01
Many recently developed watershed models utilize accumulation and washoff equations to simulate the quality of runofffrom urban impervious areas. These models often have been calibrated by trial and error and with little understanding of model sensitivity to the various parameters. Methodologies for estimating best fit values of the washoff parameters commonly used in these models have been presented previously. In this paper, parameter identification techniques for estimating the accumulation parameters from measured runoff quality data are presented along with a sensitivity analysis of the parameters. Results from application of the techniques and the sensitivity analysis suggest a need for data quantifying the magnitude and identifying the shape of constituent accumulation curves. An exponential accumulation curve is shown to be more general than the linear accumulation curves used in most urban runoff quality models. When determining accumulation rates, attention needs to be given to the effects of residual amounts of constituents remaining after the previous period of storm runoff or street sweeping.
A Bayesian approach to parameter estimation in HIV dynamical models.
Putter, H; Heisterkamp, S H; Lange, J M A; de Wolf, F
2002-08-15
In the context of a mathematical model describing HIV infection, we discuss a Bayesian modelling approach to a non-linear random effects estimation problem. The model and the data exhibit a number of features that make the use of an ordinary non-linear mixed effects model intractable: (i) the data are from two compartments fitted simultaneously against the implicit numerical solution of a system of ordinary differential equations; (ii) data from one compartment are subject to censoring; (iii) random effects for one variable are assumed to be from a beta distribution. We show how the Bayesian framework can be exploited by incorporating prior knowledge on some of the parameters, and by combining the posterior distributions of the parameters to obtain estimates of quantities of interest that follow from the postulated model. PMID:12210633
Man power/cost estimation model: Automated planetary projects
NASA Technical Reports Server (NTRS)
Kitchen, L. D.
1975-01-01
A manpower/cost estimation model is developed which is based on a detailed level of financial analysis of over 30 million raw data points which are then compacted by more than three orders of magnitude to the level at which the model is applicable. The major parameter of expenditure is manpower (specifically direct labor hours) for all spacecraft subsystem and technical support categories. The resultant model is able to provide a mean absolute error of less than fifteen percent for the eight programs comprising the model data base. The model includes cost saving inheritance factors, broken down in four levels, for estimating follow-on type programs where hardware and design inheritance are evident or expected.
Cumulus cloud model estimates of trace gas transports
NASA Technical Reports Server (NTRS)
Garstang, Michael; Scala, John; Simpson, Joanne; Tao, Wei-Kuo; Thompson, A.; Pickering, K. E.; Harris, R.
1989-01-01
Draft structures in convective clouds are examined with reference to the results of the NASA Amazon Boundary Layer Experiments (ABLE IIa and IIb) and calculations based on a multidimensional time dependent dynamic and microphysical numerical cloud model. It is shown that some aspects of the draft structures can be calculated from measurements of the cloud environment. Estimated residence times in the lower regions of the cloud based on surface observations (divergence and vertical velocities) are within the same order of magnitude (about 20 min) as model trajectory estimates.
Regionalized rainfall-runoff model to estimate low flow indices
NASA Astrophysics Data System (ADS)
Garcia, Florine; Folton, Nathalie; Oudin, Ludovic
2016-04-01
Estimating low flow indices is of paramount importance to manage water resources and risk assessments. These indices are derived from river discharges which are measured at gauged stations. However, the lack of observations at ungauged sites bring the necessity of developing methods to estimate these low flow indices from observed discharges in neighboring catchments and from catchment characteristics. Different estimation methods exist. Regression or geostatistical methods performed on the low flow indices are the most common types of methods. Another less common method consists in regionalizing rainfall-runoff model parameters, from catchment characteristics or by spatial proximity, to estimate low flow indices from simulated hydrographs. Irstea developed GR2M-LoiEau, a conceptual monthly rainfall-runoff model, combined with a regionalized model of snow storage and melt. GR2M-LoiEau relies on only two parameters, which are regionalized and mapped throughout France. This model allows to cartography monthly reference low flow indices. The inputs data come from SAFRAN, the distributed mesoscale atmospheric analysis system, which provides daily solid and liquid precipitation and temperature data from everywhere in the French territory. To exploit fully these data and to estimate daily low flow indices, a new version of GR-LoiEau has been developed at a daily time step. The aim of this work is to develop and regionalize a GR-LoiEau model that can provide any daily, monthly or annual estimations of low flow indices, yet keeping only a few parameters, which is a major advantage to regionalize them. This work includes two parts. On the one hand, a daily conceptual rainfall-runoff model is developed with only three parameters in order to simulate daily and monthly low flow indices, mean annual runoff and seasonality. On the other hand, different regionalization methods, based on spatial proximity and similarity, are tested to estimate the model parameters and to simulate
Estimating and Modeling S-Band Lunar Radar Backscatter
NASA Technical Reports Server (NTRS)
Thompson, Tommy; Ustinov, Eugene
2006-01-01
This viewgraph presentation reviews the estimates and modeling for S-band Lunar radar backscatter. By way of basic review it shows the average lunar radar behavior, the average lunar radar cross-section at 3.8-cm, 23-cm and 68-cm wavelengths. It also reviews the equations for estimating 13 cm scattering from 3.8 and 23 cm data. Charts show the inferred 13-cm average scattering derived from interpolation of the 1960's observations and the modeled 13-cm average scattering. It also reviews the scattering differences: between linear polarizations from slopes from roughness.
Observational constraints on biogenic VOC emission model estimates (Invited)
NASA Astrophysics Data System (ADS)
Guenther, A. B.
2013-12-01
Chemistry and transport models require accurate estimates of biogenic volatile organic compound (BVOC) emissions in order to simulate the atmospheric constituents controlling air quality and climate, such as ozone and particles, and so the uncertainties associated with BVOC estimates may be limiting the development of effective air quality and climate management strategies. BVOC emission models include driving variables and algorithms that span scales from the leaf level to entire landscapes. While considerable effort has been made to improve BVOC emission models in the past decades, there have been relatively few attempts to quantify the uncertainties associated with these estimates or to rigorously assess emission modeling approaches. This presentation will summarize the availability of observations that can be used to constrain BVOC emission models including flux measurements (leaf enclosure, above canopy tower, and aircraft platforms) and ambient concentrations of BVOC and their products. Results from studies targeting specific BVOC emission processes (e.g., the response of isoprene emission to drought and the response of monoterpene emissions to bark beetle attack) will be shown and the application of these observations for BVOC model evaluation will be discussed. In addition, the results from multi-scale BVOC emission studies (leaf enclosure, whole canopy flux tower, regional aircraft eddy covariance) will be presented and a approach for incorporating these observations into a community model testbed will be described and used to evaluate regional BVOC emission models.
Errors-in-variables modeling in optical flow estimation.
Ng, L; Solo, V
2001-01-01
Gradient-based optical flow estimation methods typically do not take into account errors in the spatial derivative estimates. The presence of these errors causes an errors-in-variables (EIV) problem. Moreover, the use of finite difference methods to calculate these derivatives ensures that the errors are strongly correlated between pixels. Total least squares (TLS) has often been used to address this EIV problem. However, its application in this context is flawed as TLS implicitly assumes that the errors between neighborhood pixels are independent. In this paper, a new optical flow estimation method (EIVM) is formulated to properly treat the EIV problem in optical flow. EIVM is based on Sprent's (1966) procedure which allows the incorporation of a general EIV model in the estimation process. In EIVM, the neighborhood size acts as a smoothing parameter. Due to the weights in the EIVM objective function, the effect of changing the neighborhood size is more complex than in other local model methods such as Lucas and Kanade (1981). These weights, which are functions of the flow estimate, can alter the effective size and orientation of the neighborhood. In this paper, we also present a data-driven method for choosing the neighborhood size based on Stein's unbiased risk estimators (SURE). PMID:18255496
Parameter Estimation and Parameterization Uncertainty Using Bayesian Model Averaging
NASA Astrophysics Data System (ADS)
Tsai, F. T.; Li, X.
2007-12-01
This study proposes Bayesian model averaging (BMA) to address parameter estimation uncertainty arisen from non-uniqueness in parameterization methods. BMA provides a means of incorporating multiple parameterization methods for prediction through the law of total probability, with which an ensemble average of hydraulic conductivity distribution is obtained. Estimation uncertainty is described by the BMA variances, which contain variances within and between parameterization methods. BMA shows the facts that considering more parameterization methods tends to increase estimation uncertainty and estimation uncertainty is always underestimated using a single parameterization method. Two major problems in applying BMA to hydraulic conductivity estimation using a groundwater inverse method will be discussed in the study. The first problem is the use of posterior probabilities in BMA, which tends to single out one best method and discard other good methods. This problem arises from Occam's window that only accepts models in a very narrow range. We propose a variance window to replace Occam's window to cope with this problem. The second problem is the use of Kashyap information criterion (KIC), which makes BMA tend to prefer high uncertain parameterization methods due to considering the Fisher information matrix. We found that Bayesian information criterion (BIC) is a good approximation to KIC and is able to avoid controversial results. We applied BMA to hydraulic conductivity estimation in the 1,500-foot sand aquifer in East Baton Rouge Parish, Louisiana.
Virtual Patient Simulator for the Perfusion Resource Management Drill
Ninomiya, Shinji; Tokaji, Megumi; Tokumine, Asako; Kurosaki, Tatsuya
2009-01-01
Abstract: Perfusionists require a detailed understanding of a patient’s physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extra-corporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simula tor systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed. PMID:20092074
Virtual patient simulator for the perfusion resource management drill.
Ninomiya, Shinji; Tokaji, Megumi; Tokumine, Asako; Kurosaki, Tatsuya
2009-12-01
Perfusionists require a detailed understanding of a patient's physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extracorporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simulator systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed. PMID:20092074
Lung Ventilation/Perfusion Scan
... from the NHLBI on Twitter. What Is a Lung Ventilation/Perfusion Scan? A lung ventilation/perfusion scan, or VQ scan, is a ... that measures air and blood flow in your lungs. A VQ scan most often is used to ...
Similarity-based semi-local estimation of EMOS models
NASA Astrophysics Data System (ADS)
Lerch, Sebastian; Baran, Sandor
2016-04-01
Weather forecasts are typically given in the form of forecast ensembles obtained from multiple runs of numerical weather prediction models with varying initial conditions and physics parameterizations. Such ensemble predictions tend to be biased and underdispersive and thus require statistical postprocessing. In the ensemble model output statistics (EMOS) approach, a probabilistic forecast is given by a single parametric distribution with parameters depending on the ensemble members. This article proposes two semi-local methods for estimating the EMOS coefficients where the training data for a specific observation station are augmented with corresponding forecast cases from stations with similar characteristics. Similarities between stations are determined using either distance functions or clustering based on various features of the climatology, forecast errors, ensemble predictions and locations of the observation stations. In a case study on wind speed over Europe with forecasts from the Grand Limited Area Model Ensemble Prediction System, the proposed similarity-based semi-local models show significant improvement in predictive performance compared to standard regional and local estimation methods. They further allow for estimating complex models without numerical stability issues and are computationally more efficient than local parameter estimation.
Parameter Estimation for Single Diode Models of Photovoltaic Modules
Hansen, Clifford
2015-03-01
Many popular models for photovoltaic system performance employ a single diode model to compute the I - V curve for a module or string of modules at given irradiance and temperature conditions. A single diode model requires a number of parameters to be estimated from measured I - V curves. Many available parameter estimation methods use only short circuit, o pen circuit and maximum power points for a single I - V curve at standard test conditions together with temperature coefficients determined separately for individual cells. In contrast, module testing frequently records I - V curves over a wide range of irradi ance and temperature conditions which, when available , should also be used to parameterize the performance model. We present a parameter estimation method that makes use of a fu ll range of available I - V curves. We verify the accuracy of the method by recov ering known parameter values from simulated I - V curves . We validate the method by estimating model parameters for a module using outdoor test data and predicting the outdoor performance of the module.
Global parameter estimation for thermodynamic models of transcriptional regulation.
Suleimenov, Yerzhan; Ay, Ahmet; Samee, Md Abul Hassan; Dresch, Jacqueline M; Sinha, Saurabh; Arnosti, David N
2013-07-15
Deciphering the mechanisms involved in gene regulation holds the key to understanding the control of central biological processes, including human disease, population variation, and the evolution of morphological innovations. New experimental techniques including whole genome sequencing and transcriptome analysis have enabled comprehensive modeling approaches to study gene regulation. In many cases, it is useful to be able to assign biological significance to the inferred model parameters, but such interpretation should take into account features that affect these parameters, including model construction and sensitivity, the type of fitness calculation, and the effectiveness of parameter estimation. This last point is often neglected, as estimation methods are often selected for historical reasons or for computational ease. Here, we compare the performance of two parameter estimation techniques broadly representative of local and global approaches, namely, a quasi-Newton/Nelder-Mead simplex (QN/NMS) method and a covariance matrix adaptation-evolutionary strategy (CMA-ES) method. The estimation methods were applied to a set of thermodynamic models of gene transcription applied to regulatory elements active in the Drosophila embryo. Measuring overall fit, the global CMA-ES method performed significantly better than the local QN/NMS method on high quality data sets, but this difference was negligible on lower quality data sets with increased noise or on data sets simplified by stringent thresholding. Our results suggest that the choice of parameter estimation technique for evaluation of gene expression models depends both on quality of data, the nature of the models [again, remains to be established] and the aims of the modeling effort. PMID:23726942
Stochastic EM algorithm for nonlinear state estimation with model uncertainties
NASA Astrophysics Data System (ADS)
Zia, Amin; Kirubarajan, Thiagalingam; Reilly, James P.; Shirani, Shahram
2004-01-01
In most solutions to state estimation problems like, for example, target tracking, it is generally assumed that the state evolution and measurement models are known a priori. The model parameters include process and measurement matrices or functions as well as the corresponding noise statistics. However, there are situations where the model parameters are not known a priori or are known only partially (i.e., with some uncertainty). Moreover, there are situations where the measurement is biased. In these scenarios, standard estimation algorithms like the Kalman filter and the extended Kalman Filter (EKF), which assume perfect knowledge of the model parameters, are not accurate. In this paper, the problem with uncertain model parameters is considered as a special case of maximum likelihood estimation with incomplete-data, for which a standard solution called the expectation-maximization (EM) algorithm exists. In this paper a new extension to the EM algorithm is proposed to solve the more general problem of joint state estimation and model parameter identification for nonlinear systems with possibly non-Gaussian noise. In the expectation (E) step, it is shown that the best variational distribution over the state variables is the conditional posterior distribution of states given all the available measurements and inputs. Therefore, a particular type of particle filter is used to estimate and update the posterior distribution. In the maximization (M) step the nonlinear measurement process parameters are approximated using a nonlinear regression method for adjusting the parameters of a mixture of Gaussians (MofG). The proposed algorithm is used to solve a nonlinear bearing-only tracking problem similar to the one reported recently with uncertain measurement process. It is shown that the algorithm is capable of accurately tracking the state vector while identifying the unknown measurement dynamics. Simulation results show the advantages of the new technique over standard
Stochastic EM algorithm for nonlinear state estimation with model uncertainties
NASA Astrophysics Data System (ADS)
Zia, Amin; Kirubarajan, Thiagalingam; Reilly, James P.; Shirani, Shahram
2003-12-01
In most solutions to state estimation problems like, for example, target tracking, it is generally assumed that the state evolution and measurement models are known a priori. The model parameters include process and measurement matrices or functions as well as the corresponding noise statistics. However, there are situations where the model parameters are not known a priori or are known only partially (i.e., with some uncertainty). Moreover, there are situations where the measurement is biased. In these scenarios, standard estimation algorithms like the Kalman filter and the extended Kalman Filter (EKF), which assume perfect knowledge of the model parameters, are not accurate. In this paper, the problem with uncertain model parameters is considered as a special case of maximum likelihood estimation with incomplete-data, for which a standard solution called the expectation-maximization (EM) algorithm exists. In this paper a new extension to the EM algorithm is proposed to solve the more general problem of joint state estimation and model parameter identification for nonlinear systems with possibly non-Gaussian noise. In the expectation (E) step, it is shown that the best variational distribution over the state variables is the conditional posterior distribution of states given all the available measurements and inputs. Therefore, a particular type of particle filter is used to estimate and update the posterior distribution. In the maximization (M) step the nonlinear measurement process parameters are approximated using a nonlinear regression method for adjusting the parameters of a mixture of Gaussians (MofG). The proposed algorithm is used to solve a nonlinear bearing-only tracking problem similar to the one reported recently with uncertain measurement process. It is shown that the algorithm is capable of accurately tracking the state vector while identifying the unknown measurement dynamics. Simulation results show the advantages of the new technique over standard
Model Error Estimation for the CPTEC Eta Model
NASA Technical Reports Server (NTRS)
Tippett, Michael K.; daSilva, Arlindo
1999-01-01
Statistical data assimilation systems require the specification of forecast and observation error statistics. Forecast error is due to model imperfections and differences between the initial condition and the actual state of the atmosphere. Practical four-dimensional variational (4D-Var) methods try to fit the forecast state to the observations and assume that the model error is negligible. Here with a number of simplifying assumption, a framework is developed for isolating the model error given the forecast error at two lead-times. Two definitions are proposed for the Talagrand ratio tau, the fraction of the forecast error due to model error rather than initial condition error. Data from the CPTEC Eta Model running operationally over South America are used to calculate forecast error statistics and lower bounds for tau.
Estimating blood pressure using Windkessel model on Photoplethysmogram.
Choudhury, Anirban Dutta; Banerjee, Rohan; Sinha, Aniruddha; Kundu, Shaswati
2014-01-01
Simple and non-invasive methods to estimate vital signs are very important for preventive healthcare. In this paper, we present a methodology to estimate Blood Pressure (BP) using Photoplethysmography (PPG). Instead of directly relating systolic and diastolic BP values with PPG features, our proposed methodology initially maps PPG features with some person specific intermediate latent parameters and later derives BP values from them. The 2-Element Windkessel model has been considered in the current context to estimate total peripheral resistance and arterial compliance of a person using PPG features, followed by linear regression for simulating arterial blood pressure. Experimental results, performed on a standard hospital dataset yielded absolute errors of 0.78±13.1 mmHg and 0.59 ± 10.23 mmHg for systolic and diastolic BP values respectively. Results also indicate that the methodology is more robust than the standard methodologies that directly estimate BP values from PPG signal. PMID:25571008
Estimation of mediation effects for zero-inflated regression models.
Wang, Wei; Albert, Jeffrey M
2012-11-20
The goal of mediation analysis is to identify and explicate the mechanism that underlies a relationship between a risk factor and an outcome via an intermediate variable (mediator). In this paper, we consider the estimation of mediation effects in zero-inflated (ZI) models intended to accommodate 'extra' zeros in count data. Focusing on the ZI negative binomial models, we provide a mediation formula approach to estimate the (overall) mediation effect in the standard two-stage mediation framework under a key sequential ignorability assumption. We also consider a novel decomposition of the overall mediation effect for the ZI context using a three-stage mediation model. Estimation of the components of the overall mediation effect requires an assumption involving the joint distribution of two counterfactuals. Simulation study results demonstrate low bias of mediation effect estimators and close-to-nominal coverage probability of confidence intervals. We also modify the mediation formula method by replacing 'exact' integration with a Monte Carlo integration method. The method is applied to a cohort study of dental caries in very low birth weight adolescents. For overall mediation effect estimation, sensitivity analysis was conducted to quantify the degree to which key assumption must be violated to reverse the original conclusion. PMID:22714572
Estimation of Mediation Effects for Zero-inflated Regression Models
Wang, Wei; Albert, Jeffrey M.
2012-01-01
The goal of mediation analysis is to identify and explicate the mechanism that underlies a relationship between a risk factor and an outcome via an intermediate variable (mediator). In this paper, we consider the estimation of mediation effects in zero-inflated (ZI) models intended to accommodate `extra' zeros in count data. Focusing on the ZI negative binomial (ZINB) models, we provide a mediation formula approach to estimate the (overall) mediation effect in the standard two-stage mediation framework under a key sequential ignorability assumption. We also consider a novel decomposition of the overall mediation effect for the ZI context using a three-stage mediation model. Estimation of the components of the overall mediation effect requires an assumption involving the joint distribution of two counterfactuals. Simulation study results demonstrate low bias of mediation effect estimators and close-to-nominal coverage probability (CP) of confidence intervals. We also modify the mediation formula method by replacing `exact' integration with a Monte Carlo integration method. The method is applied to a cohort study of dental caries in very low birth weight adolescents. For overall mediation effect estimation, sensitivity analysis was conducted to quantify the degree to which key assumption must be violated to reverse the original conclusion. PMID:22714572
Low dose CT perfusion using k-means clustering
NASA Astrophysics Data System (ADS)
Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc
2016-03-01
We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.
Models for estimating daily rainfall erosivity in China
NASA Astrophysics Data System (ADS)
Xie, Yun; Yin, Shui-qing; Liu, Bao-yuan; Nearing, Mark A.; Zhao, Ying
2016-04-01
The rainfall erosivity factor (R) represents the multiplication of rainfall energy and maximum 30 min intensity by event (EI30) and year. This rainfall erosivity index is widely used for empirical soil loss prediction. Its calculation, however, requires high temporal resolution rainfall data that are not readily available in many parts of the world. The purpose of this study was to parameterize models suitable for estimating erosivity from daily rainfall data, which are more widely available. One-minute resolution rainfall data recorded in sixteen stations over the eastern water erosion impacted regions of China were analyzed. The R-factor ranged from 781.9 to 8258.5 MJ mm ha-1 h-1 y-1. A total of 5942 erosive events from one-minute resolution rainfall data of ten stations were used to parameterize three models, and 4949 erosive events from the other six stations were used for validation. A threshold of daily rainfall between days classified as erosive and non-erosive was suggested to be 9.7 mm based on these data. Two of the models (I and II) used power law functions that required only daily rainfall totals. Model I used different model coefficients in the cool season (Oct.-Apr.) and warm season (May-Sept.), and Model II was fitted with a sinusoidal curve of seasonal variation. Both Model I and Model II estimated the erosivity index for average annual, yearly, and half-month temporal scales reasonably well, with the symmetric mean absolute percentage error MAPEsym ranging from 10.8% to 32.1%. Model II predicted slightly better than Model I. However, the prediction efficiency for the daily erosivity index was limited, with the symmetric mean absolute percentage error being 68.0% (Model I) and 65.7% (Model II) and Nash-Sutcliffe model efficiency being 0.55 (Model I) and 0.57 (Model II). Model III, which used the combination of daily rainfall amount and daily maximum 60-min rainfall, improved predictions significantly, and produced a Nash-Sutcliffe model efficiency
Research of a new model for abundance estimation
NASA Astrophysics Data System (ADS)
Xie, Hong-ye; Song, Mei-ping; Lin, Bin; An, Ju-bai
2013-08-01
Hyperspectral remote sensing has been widely used in more and more fields nowadays, such as the oil spill analysis and chlorophyll estimation in green plants. To decompose the mixed pixels people always turns to the traditional method of Least Squares Method now. But its main drawback is that it involves a large amount of matrix operations, especially regarding to the huge dimension of hyperspectral images. So it will take much time. Motivated by this, in this paper we have developed a new model of endmember abundance estimate which is referred to as Spectral Characteristic Based Abundance Estimation Model (SCBAEM). The model is based on the fitted curve in which spectral characteristic were considered. To establish the model, Spectral Angle Mapper (SAM) and Spectral Information Divergence (SID) were utilized between endmember and mixed pixels. The main contributions of the paper are summarized as follows: Firstly, we build the model by calculating normalized SAM (NSAM) and normalized SID (NSID). Secondly, to test and verify the accuracy of the model, oil slick experiment is carried out. Finally, we further conduct its application in the real hyperspectral oil spill images which is from Peng-lai 19-3C platform. The results of simulation experiments and real hyperspectral image demonstrate that the proposed model could achieve the efficiency of LSM. At the same time, the time cost can be reduced greatly. So it can satisfy the real-time need.
Conical-Domain Model for Estimating GPS Ionospheric Delays
NASA Technical Reports Server (NTRS)
Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony
2009-01-01
The conical-domain model is a computational model, now undergoing development, for estimating ionospheric delays of Global Positioning System (GPS) signals. Relative to the standard ionospheric delay model described below, the conical-domain model offers improved accuracy. In the absence of selective availability, the ionosphere is the largest source of error for single-frequency users of GPS. Because ionospheric signal delays contribute to errors in GPS position and time measurements, satellite-based augmentation systems (SBASs) have been designed to estimate these delays and broadcast corrections. Several national and international SBASs are currently in various stages of development to enhance the integrity and accuracy of GPS measurements for airline navigation. In the Wide Area Augmentation System (WAAS) of the United States, slant ionospheric delay errors and confidence bounds are derived from estimates of vertical ionospheric delay modeled on a grid at regularly spaced intervals of latitude and longitude. The estimate of vertical delay at each ionospheric grid point (IGP) is calculated from a planar fit of neighboring slant delay measurements, projected to vertical using a standard, thin-shell model of the ionosphere. Interpolation on the WAAS grid enables estimation of the vertical delay at the ionospheric pierce point (IPP) corresponding to any arbitrary measurement of a user. (The IPP of a given user s measurement is the point where the GPS signal ray path intersects a reference ionospheric height.) The product of the interpolated value and the user s thin-shell obliquity factor provides an estimate of the user s ionospheric slant delay. Two types of error that restrict the accuracy of the thin-shell model are absent in the conical domain model: (1) error due to the implicit assumption that the electron density is independent of the azimuthal angle at the IPP and (2) error arising from the slant-to-vertical conversion. At low latitudes or at mid
Comparison of models for piping transmission loss estimations
NASA Astrophysics Data System (ADS)
Catron, Fred W.; Mann, J. Adin
2005-09-01
A frequency dependent model for the transmission loss of piping is important for accurate estimates of the external radiation from pipes and the vibration level of the pipe walls. A statistical energy analysis model is used to predict the transmission loss of piping. Key terms in the model are the modal density and the radiation efficiency of the piping wall. Several available models for each are compared in reference to measured data. In low frequency octave bands, the modal density is low. The model of the transmission loss in these octave bands is augmented with a mass law model in the low frequency regime where the number of modes is small. The different models and a comparison of the models will be presented.
Adaptive Error Estimation in Linearized Ocean General Circulation Models
NASA Technical Reports Server (NTRS)
Chechelnitsky, Michael Y.
1999-01-01
Data assimilation methods are routinely used in oceanography. The statistics of the model and measurement errors need to be specified a priori. This study addresses the problem of estimating model and measurement error statistics from observations. We start by testing innovation based methods of adaptive error estimation with low-dimensional models in the North Pacific (5-60 deg N, 132-252 deg E) to TOPEX/POSEIDON (TIP) sea level anomaly data, acoustic tomography data from the ATOC project, and the MIT General Circulation Model (GCM). A reduced state linear model that describes large scale internal (baroclinic) error dynamics is used. The methods are shown to be sensitive to the initial guess for the error statistics and the type of observations. A new off-line approach is developed, the covariance matching approach (CMA), where covariance matrices of model-data residuals are "matched" to their theoretical expectations using familiar least squares methods. This method uses observations directly instead of the innovations sequence and is shown to be related to the MT method and the method of Fu et al. (1993). Twin experiments using the same linearized MIT GCM suggest that altimetric data are ill-suited to the estimation of internal GCM errors, but that such estimates can in theory be obtained using acoustic data. The CMA is then applied to T/P sea level anomaly data and a linearization of a global GFDL GCM which uses two vertical modes. We show that the CMA method can be used with a global model and a global data set, and that the estimates of the error statistics are robust. We show that the fraction of the GCM-T/P residual variance explained by the model error is larger than that derived in Fukumori et al.(1999) with the method of Fu et al.(1993). Most of the model error is explained by the barotropic mode. However, we find that impact of the change in the error statistics on the data assimilation estimates is very small. This is explained by the large
Som, P.; Oster, Z.H.; Knapp, F.F. Jr.
1987-01-01
We have studied two animal models of non-coronary heart disease. The salt-sensitive Dahl strain hypertensive rats and their genetically matched normotensive controls and the cardiomyopathic BIO 53.58 (CM) strain Syrian hamsters with age and sex-matched RB strain controls. The CM strain hamster seems to be a very good model of human congestive cardiomyopathy and the Dahl strain hypertensive rats have also been found to be good models for studying the effects of hypertension on the myocardium. In our studies we compared the utilization of various metabolic substrates, viz., fatty acids, glucose analogs, and the early distribution of /sup 201/Tl, as an indicator of myocardial flow. The routine studies involving dissection of animals for assaying the radioactivity following the injection of radiopharmaceuticals is not suitable for assessing regional changes in metabolism and flow. The use of quantitative autoradiographic microimaging (ARG) enables the visualization of discrete regional as well as global changes from normal and to quantitate them. This paper describes the methodology and results of these investigations. 14 refs., 5 figs.
Mazzuca, Enrico; Aliverti, Andrea; Miserocchi, Giuseppe
2016-07-01
A computational model of a morphologically-based alveolar capillary unit (ACU) in the rabbit is developed to relate lung fluid balance to mechanical forces between capillary surface and interstitium during development of interstitial edema. We hypothesize that positive values of interstitial liquid pressure Pliq impact on capillary transmural pressure and on blood flow. ACU blood flow, capillary recruitment and filtration are computed by modulating vascular and interstitial pressures. Model results are compared with experimental data of Pliq increasing from ~-10 (control) up to ~4cmH2O in two conditions, hypoxia and collagenase injection. For hypoxia exposure, fitting data requires a linear increase in hydraulic conductivity Lp and capillary pressure PC, that fulfils the need of increase in oxygen delivery. For severe fragmentation of capillary endothelial barrier (collagenase injection), fitting requires a rapid increase in both hydraulic and protein permeability, causing ACU de-recruitment, followed by an increase in PC as a late response to restore blood flow. In conclusion, the model allows to describe the lung adaptive response to edemagenic perturbations; the increase in Pliq, related to the low interstitial compliance, provides an efficient control of extravascular water, by limiting microvascular filtration. PMID:27059893
Evaluation and refinement of leak-rate estimation models
Paul, D.D.; Ahmad, J.; Scott, P.M.; Flanigan, L.F.; Wilkowski, G.M. )
1991-04-01
Leak-rate estimation models are important elements in developing a leak-before-break methodology in piping integrity and safety analyses. Existing thermal-hydraulic and crack-opening-area models used in current leak-rate estimations have been incorporated into a single computer code for leak-rate estimation. The code is called SQUIRT, which stands for Seepage Quantification of Upsets In Reactor Tubes. The SQUIRT program has been validated by comparing its thermal-hydraulic predictions with the limited experimental data that have been published on two-phase flow through slits and cracks, and by comparing its crack-opening-area predictions with data from the Degraded Piping Program. In addition, leak-rate experiments were conducted to obtain validation data for a circumferential fatigue crack in a carbon steel pipe girth weld. 56 refs., 30 figs., 4 tabs.
HIGH DIMENSIONAL COVARIANCE MATRIX ESTIMATION IN APPROXIMATE FACTOR MODELS
Fan, Jianqing; Liao, Yuan; Mincheva, Martina
2012-01-01
The variance covariance matrix plays a central role in the inferential theories of high dimensional factor models in finance and economics. Popular regularization methods of directly exploiting sparsity are not directly applicable to many financial problems. Classical methods of estimating the covariance matrices are based on the strict factor models, assuming independent idiosyncratic components. This assumption, however, is restrictive in practical applications. By assuming sparse error covariance matrix, we allow the presence of the cross-sectional correlation even after taking out common factors, and it enables us to combine the merits of both methods. We estimate the sparse covariance using the adaptive thresholding technique as in Cai and Liu (2011), taking into account the fact that direct observations of the idiosyncratic components are unavailable. The impact of high dimensionality on the covariance matrix estimation based on the factor structure is then studied. PMID:22661790
MAXIMUM LIKELIHOOD ESTIMATION FOR PERIODIC AUTOREGRESSIVE MOVING AVERAGE MODELS.
Vecchia, A.V.
1985-01-01
A useful class of models for seasonal time series that cannot be filtered or standardized to achieve second-order stationarity is that of periodic autoregressive moving average (PARMA) models, which are extensions of ARMA models that allow periodic (seasonal) parameters. An approximation to the exact likelihood for Gaussian PARMA processes is developed, and a straightforward algorithm for its maximization is presented. The algorithm is tested on several periodic ARMA(1, 1) models through simulation studies and is compared to moment estimation via the seasonal Yule-Walker equations. Applicability of the technique is demonstrated through an analysis of a seasonal stream-flow series from the Rio Caroni River in Venezuela.
Zou, Li-Hua; Liu, Jin-Ping; Zhang, Hao; Wu, Shu-Bin; Ji, Bing-Yang
2016-01-01
Background: Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods: To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without (DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups. Results: Metabolic profiling of brain was distinctive significantly between the two groups (Q2Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D. Conclusions: The present study applied metabolomics analysis to identify the cerebral
Estimating Nonlinear Structural Models: EMM and the Kenny-Judd Model
ERIC Educational Resources Information Center
Lyhagen, Johan
2007-01-01
The estimation of nonlinear structural models is not trivial. One reason for this is that a closed form solution of the likelihood may not be feasible or does not exist. We propose to estimate nonlinear structural models using the efficient method of moments, as generating data according to the models is often very easy. A simulation study of the…
Estimating soil water retention using soil component additivity model
NASA Astrophysics Data System (ADS)
Zeiliger, A.; Ermolaeva, O.; Semenov, V.
2009-04-01
Soil water retention is a major soil hydraulic property that governs soil functioning in ecosystems and greatly affects soil management. Data on soil water retention are used in research and applications in hydrology, agronomy, meteorology, ecology, environmental protection, and many other soil-related fields. Soil organic matter content and composition affect both soil structure and adsorption properties; therefore water retention may be affected by changes in soil organic matter that occur because of both climate change and modifications of management practices. Thus, effects of organic matter on soil water retention should be understood and quantified. Measurement of soil water retention is relatively time-consuming, and become impractical when soil hydrologic estimates are needed for large areas. One approach to soil water retention estimation from readily available data is based on the hypothesis that soil water retention may be estimated as an additive function obtained by summing up water retention of pore subspaces associated with soil textural and/or structural components and organic matter. The additivity model and was tested with 550 soil samples from the international database UNSODA and 2667 soil samples from the European database HYPRES containing all textural soil classes after USDA soil texture classification. The root mean square errors (RMSEs) of the volumetric water content estimates for UNSODA vary from 0.021 m3m-3 for coarse sandy loam to 0.075 m3m-3 for sandy clay. Obtained RMSEs are at the lower end of the RMSE range for regression-based water retention estimates found in literature. Including retention estimates of organic matter significantly improved RMSEs. The attained accuracy warrants testing the 'additivity' model with additional soil data and improving this model to accommodate various types of soil structure. Keywords: soil water retention, soil components, additive model, soil texture, organic matter.
Hybrid Simulation Modeling to Estimate U.S. Energy Elasticities
NASA Astrophysics Data System (ADS)
Baylin-Stern, Adam C.
This paper demonstrates how an U.S. application of CIMS, a technologically explicit and behaviourally realistic energy-economy simulation model which includes macro-economic feedbacks, can be used to derive estimates of elasticity of substitution (ESUB) and autonomous energy efficiency index (AEEI) parameters. The ability of economies to reduce greenhouse gas emissions depends on the potential for households and industry to decrease overall energy usage, and move from higher to lower emissions fuels. Energy economists commonly refer to ESUB estimates to understand the degree of responsiveness of various sectors of an economy, and use estimates to inform computable general equilibrium models used to study climate policies. Using CIMS, I have generated a set of future, 'pseudo-data' based on a series of simulations in which I vary energy and capital input prices over a wide range. I then used this data set to estimate the parameters for transcendental logarithmic production functions using regression techniques. From the production function parameter estimates, I calculated an array of elasticity of substitution values between input pairs. Additionally, this paper demonstrates how CIMS can be used to calculate price-independent changes in energy-efficiency in the form of the AEEI, by comparing energy consumption between technologically frozen and 'business as usual' simulations. The paper concludes with some ideas for model and methodological improvement, and how these might figure into future work in the estimation of ESUBs from CIMS. Keywords: Elasticity of substitution; hybrid energy-economy model; translog; autonomous energy efficiency index; rebound effect; fuel switching.
DEVELOPING SEASONAL AMMONIA EMISSION ESTIMATES WITH AN INVERSE MODELING TECHNIQUE
Significant uncertainty exists in magnitude and variability of ammonia (NH3) emissions, which are needed for air quality modeling of aerosols and deposition of nitrogen compounds. Approximately 85% of NH3 emissions are estimated to come from agricultural non-point sources. We sus...
Maximum Likelihood Estimation of Nonlinear Structural Equation Models.
ERIC Educational Resources Information Center
Lee, Sik-Yum; Zhu, Hong-Tu
2002-01-01
Developed an EM type algorithm for maximum likelihood estimation of a general nonlinear structural equation model in which the E-step is completed by a Metropolis-Hastings algorithm. Illustrated the methodology with results from a simulation study and two real examples using data from previous studies. (SLD)
Rabotti, C; Mischi, M; van Laar, J O E H; Oei, S G; Bergmans, J W M
2009-01-01
During delivery, quantitative information on the uterine activity can be provided by internal uterine pressure (IUP) recordings using an invasive intrauterine pressure catheter (IUPC). The electrohysterogram, which measures the electrical signal that drives the mechanical contraction of the uterine muscle and the consequent IUP increase, is recorded by electrodes placed on the abdomen. Recent work demonstrated the possibility of reliably estimating the IUP noninvasively by electrohysterographic (EHG) signal analysis. To further improve the accuracy of IUP estimates, we investigated the use of three nonlinear functions for modeling the relationship between the electrical activation measured by the EHG signal and the mechanical response of the uterine muscle. The feature employed for obtaining a first estimate of the IUP is the unnormalized first statistical moment of the EHG spectrum. The relationship between the extracted feature and the IUP is modeled by a second-order polynomial, a logarithmic, and an exponential function. For validation, the IUPC and the EHG signals were recorded on nine women in labor. A second-order polynomial model already provided estimates that are highly correlated with the IUPC signal (r = 0.73). However, the logarithmic model resulted to be the most accurate, especially in terms of root mean squared error (RMSE = 5.13 mmHg). PMID:19963667
Parameter estimation for distributed parameter models of complex, flexible structures
NASA Technical Reports Server (NTRS)
Taylor, Lawrence W., Jr.
1991-01-01
Distributed parameter modeling of structural dynamics has been limited to simple spacecraft configurations because of the difficulty of handling several distributed parameter systems linked at their boundaries. Although there is other computer software able to generate such models or complex, flexible spacecraft, unfortunately, neither is suitable for parameter estimation. Because of this limitation the computer software PDEMOD is being developed for the express purposes of modeling, control system analysis, parameter estimation and structure optimization. PDEMOD is capable of modeling complex, flexible spacecraft which consist of a three-dimensional network of flexible beams and rigid bodies. Each beam has bending (Bernoulli-Euler or Timoshenko) in two directions, torsion, and elongation degrees of freedom. The rigid bodies can be attached to the beam ends at any angle or body location. PDEMOD is also capable of performing parameter estimation based on matching experimental modal frequencies and static deflection test data. The underlying formulation and the results of using this approach for test data of the Mini-MAST truss will be discussed. The resulting accuracy of the parameter estimates when using such limited data can impact significantly the instrumentation requirements for on-orbit tests.
A model for estimating the life of electrical submersible pumps
Patterson, M.M.
1993-11-01
This paper presents a mathematical model to estimate the life expectancy of an electrical submersible pump (ESP). The premise uses a statistical method known as the Poisson pure death process, which calculates the probability of system failure on the basis of sparse data. The technique needs only one parameter and was tested on ESP failure data from a west Texas field.
Robust Estimation of Latent Ability in Item Response Models
ERIC Educational Resources Information Center
Schuster, Christof; Yuan, Ke-Hai
2011-01-01
Because of response disturbances such as guessing, cheating, or carelessness, item response models often can only approximate the "true" individual response probabilities. As a consequence, maximum-likelihood estimates of ability will be biased. Typically, the nature and extent to which response disturbances are present is unknown, and, therefore,…
NASA Astrophysics Data System (ADS)
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.
2015-03-01
Cardiac CT acquisitions for perfusion assessment can be performed in a dynamic or static mode. In this simulation study, we evaluate the relative classification and quantification performance of these modes for assessing myocardial blood flow (MBF). In the dynamic method, a series of low dose cardiac CT acquisitions yields data on contrast bolus dynamics over time; these data are fit with a model to give a quantitative MBF estimate. In the static method, a single CT acquisition is obtained, and the relative CT numbers in the myocardium are used to infer perfusion states. The static method does not directly yield a quantitative estimate of MBF, but these estimates can be roughly approximated by introducing assumed linear relationships between CT number and MBF, consistent with the ways such images are typically visually interpreted. Data obtained by either method may be used for a variety of clinical tasks, including 1) stratifying patients into differing categories of ischemia and 2) using the quantitative MBF estimate directly to evaluate ischemic disease severity. Through simulations, we evaluate the performance on each of these tasks. The dynamic method has very low bias in MBF estimates, making it particularly suitable for quantitative estimation. At matched radiation dose levels, ROC analysis demonstrated that the static method, with its high bias but generally lower variance, has superior performance in stratifying patients, especially for larger patients.
A mathematical model for efficient estimation of aircraft motions
NASA Technical Reports Server (NTRS)
Bach, R. E., Jr.
1983-01-01
In the usual formulation of the aircraft state-estimation problem, motions along a flight trajectory are represented by a plant consisting of nonlinear state and measurement models. Problem solution using this formulation requires that both state- and measurement-dependent Jacobian matrices be evaluated along any trajectory. In this paper it is shown that a set of state variables can be chosen to realize a linear state model of very simple form, such that all nonlinearities appear in the measurement model. The potential advantage of the new formulation is computational: the Jacobian matrix corresponding to a linear state model is constant, a feature that should outweigh the fact that the measurement model is more complicated than in the conventinal formulation. To compare the modeling methods, aircraft motions from typical flight-test and accident data were estimated, using each formulation with the same off-line (smoothing) algorithm. The results of these experiments, reported in the paper, demonstrate clearly the computational superiority of the linear state-variable formulation. The procedure advocated here may be extended to other nonlinear estimation problems, including on-line (filtering) applications.
High speed parameter estimation for a homogenized energy model
NASA Astrophysics Data System (ADS)
Ernstberger, Jon M.
Industrial, commercial, military, biomedical, and civilian uses of smart materials are increasingly investigated for high performance applications. These compounds couple applied field or thermal energy to mechanical forces that are generated within the material. The devices utilizing these compounds are often much smaller than their traditional counterparts and provide greater design capabilities and energy efficiency. The relations that couple field and mechanical energies are often hysteretic and nonlinear. To accurately control devices employing these compounds, models must quantify these effects. Further, since these compounds exhibit environment-dependent behavior, the models must be robust for accurate actuator quantification. In this dissertation, we investigate the construction of models that characterize these internal mechanisms and that manifest themselves in material deformation in a hysteretic fashion. Results of previously-presented model formulations are given. New techniques for generating model components are presented which reduce the computational load for parameter estimations. The use of various deterministic and stochastic search algorithms for parameter estimation are discussed with strengths and weaknesses of each examined. New end-user graphical tools for properly initiating the parameter estimation are also presented. Finally, results from model fits to data from ferroelectric---e.g., Lead Zirconate Titanate (PZT)---and ferromagnetic---e.g., Terfenol-D---materials are presented.
Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin
2016-01-01
Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro. PMID:27092500
CT Perfusion of the Liver: Principles and Applications in Oncology
Kim, Se Hyung; Kamaya, Aya
2014-01-01
With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging—such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods—remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented. © RSNA, 2014 Online supplemental material is available for this article. PMID:25058132
An integrated modelling approach to estimate urban traffic emissions
NASA Astrophysics Data System (ADS)
Misra, Aarshabh; Roorda, Matthew J.; MacLean, Heather L.
2013-07-01
An integrated modelling approach is adopted to estimate microscale urban traffic emissions. The modelling framework consists of a traffic microsimulation model developed in PARAMICS, a microscopic emissions model (Comprehensive Modal Emissions Model), and two dispersion models, AERMOD and the Quick Urban and Industrial Complex (QUIC). This framework is applied to a traffic network in downtown Toronto, Canada to evaluate summer time morning peak traffic emissions of carbon monoxide (CO) and nitrogen oxides (NOx) during five weekdays at a traffic intersection. The model predicted results are validated against sensor observations with 100% of the AERMOD modelled CO concentrations and 97.5% of the QUIC modelled NOx concentrations within a factor of two of the corresponding observed concentrations. Availability of local estimates of ambient concentration is useful for accurate comparisons of predicted concentrations with observed concentrations. Predicted and sensor measured concentrations are significantly lower than the hourly threshold Maximum Acceptable Levels for CO (31 ppm, ˜90 times lower) and NO2 (0.4 mg/m3, ˜12 times lower), within the National Ambient Air Quality Objectives established by Environment Canada.
Estimating Predictive Variance for Statistical Gas Distribution Modelling
Lilienthal, Achim J.; Asadi, Sahar; Reggente, Matteo
2009-05-23
Recent publications in statistical gas distribution modelling have proposed algorithms that model mean and variance of a distribution. This paper argues that estimating the predictive concentration variance entails not only a gradual improvement but is rather a significant step to advance the field. This is, first, since the models much better fit the particular structure of gas distributions, which exhibit strong fluctuations with considerable spatial variations as a result of the intermittent character of gas dispersal. Second, because estimating the predictive variance allows to evaluate the model quality in terms of the data likelihood. This offers a solution to the problem of ground truth evaluation, which has always been a critical issue for gas distribution modelling. It also enables solid comparisons of different modelling approaches, and provides the means to learn meta parameters of the model, to determine when the model should be updated or re-initialised, or to suggest new measurement locations based on the current model. We also point out directions of related ongoing or potential future research work.
van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur
2016-01-01
Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042
van den Brom, Charissa E.; Boly, Chantal A.; Bulte, Carolien S. E.; van den Akker, Rob F. P.; Kwekkeboom, Rick F. J.; Loer, Stephan A.; Boer, Christa; Bouwman, R. Arthur
2016-01-01
Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042
Cost estimation model for advanced planetary programs, fourth edition
NASA Technical Reports Server (NTRS)
Spadoni, D. J.
1983-01-01
The development of the planetary program cost model is discussed. The Model was updated to incorporate cost data from the most recent US planetary flight projects and extensively revised to more accurately capture the information in the historical cost data base. This data base is comprised of the historical cost data for 13 unmanned lunar and planetary flight programs. The revision was made with a two fold objective: to increase the flexibility of the model in its ability to deal with the broad scope of scenarios under consideration for future missions, and to maintain and possibly improve upon the confidence in the model's capabilities with an expected accuracy of 20%. The Model development included a labor/cost proxy analysis, selection of the functional forms of the estimating relationships, and test statistics. An analysis of the Model is discussed and two sample applications of the cost model are presented.
Parameterized modeling and estimation of spatially varying optical blur
NASA Astrophysics Data System (ADS)
Simpkins, Jonathan D.; Stevenson, Robert L.
2015-02-01
Optical blur can display significant spatial variation across the image plane, even for constant camera settings and object depth. Existing solutions to represent this spatially varying blur requires a dense sampling of blur kernels across the image, where each kernel is defined independent of the neighboring kernels. This approach requires a large amount of data collection, and the estimation of the kernels is not as robust as if it were possible to incorporate knowledge of the relationship between adjacent kernels. A novel parameterized model is presented which relates the blur kernels at different locations across the image plane. The model is motivated by well-established optical models, including the Seidel aberration model. It is demonstrated that the proposed model can unify a set of hundreds of blur kernel observations across the image plane under a single 10-parameter model, and the accuracy of the model is demonstrated with simulations and measurement data collected by two separate research groups.
Model-based estimation of muscle forces exerted during movements.
Erdemir, Ahmet; McLean, Scott; Herzog, Walter; van den Bogert, Antonie J
2007-02-01
Estimation of individual muscle forces during human movement can provide insight into neural control and tissue loading and can thus contribute to improved diagnosis and management of both neurological and orthopaedic conditions. Direct measurement of muscle forces is generally not feasible in a clinical setting, and non-invasive methods based on musculoskeletal modeling should therefore be considered. The current state of the art in clinical movement analysis is that resultant joint torques can be reliably estimated from motion data and external forces (inverse dynamic analysis). Static optimization methods to transform joint torques into estimates of individual muscle forces using musculoskeletal models, have been known for several decades. To date however, none of these methods have been successfully translated into clinical practice. The main obstacles are the lack of studies reporting successful validation of muscle force estimates, and the lack of user-friendly and efficient computer software. Recent advances in forward dynamics methods have opened up new opportunities. Forward dynamic optimization can be performed such that solutions are less dependent on measured kinematics and ground reaction forces, and are consistent with additional knowledge, such as the force-length-velocity-activation relationships of the muscles, and with observed electromyography signals during movement. We conclude that clinical applications of current research should be encouraged, supported by further development of computational tools and research into new algorithms for muscle force estimation and their validation. PMID:17070969
Tyre pressure monitoring using a dynamical model-based estimator
NASA Astrophysics Data System (ADS)
Reina, Giulio; Gentile, Angelo; Messina, Arcangelo
2015-04-01
In the last few years, various control systems have been investigated in the automotive field with the aim of increasing the level of safety and stability, avoid roll-over, and customise handling characteristics. One critical issue connected with their integration is the lack of state and parameter information. As an example, vehicle handling depends to a large extent on tyre inflation pressure. When inflation pressure drops, handling and comfort performance generally deteriorate. In addition, it results in an increase in fuel consumption and in a decrease in lifetime. Therefore, it is important to keep tyres within the normal inflation pressure range. This paper introduces a model-based approach to estimate online tyre inflation pressure. First, basic vertical dynamic modelling of the vehicle is discussed. Then, a parameter estimation framework for dynamic analysis is presented. Several important vehicle parameters including tyre inflation pressure can be estimated using the estimated states. This method aims to work during normal driving using information from standard sensors only. On the one hand, the driver is informed about the inflation pressure and he is warned for sudden changes. On the other hand, accurate estimation of the vehicle states is available as possible input to onboard control systems.
Can modeling improve estimation of desert tortoise population densities?
Nussear, K.E.; Tracy, C.R.
2007-01-01
The federally listed desert tortoise (Gopherus agassizii) is currently monitored using distance sampling to estimate population densities. Distance sampling, as with many other techniques for estimating population density, assumes that it is possible to quantify the proportion of animals available to be counted in any census. Because desert tortoises spend much of their life in burrows, and the proportion of tortoises in burrows at any time can be extremely variable, this assumption is difficult to meet. This proportion of animals available to be counted is used as a correction factor (g0) in distance sampling and has been estimated from daily censuses of small populations of tortoises (6-12 individuals). These censuses are costly and produce imprecise estimates of g0 due to small sample sizes. We used data on tortoise activity from a large (N = 150) experimental population to model activity as a function of the biophysical attributes of the environment, but these models did not improve the precision of estimates from the focal populations. Thus, to evaluate how much of the variance in tortoise activity is apparently not predictable, we assessed whether activity on any particular day can predict activity on subsequent days with essentially identical environmental conditions. Tortoise activity was only weakly correlated on consecutive days, indicating that behavior was not repeatable or consistent among days with similar physical environments. ?? 2007 by the Ecological Society of America.
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data.
Demissie, Yonas; Valocchi, Albert; Cai, Ximing; Brozovic, Nicholas; Senay, Gabriel; Gebremichael, Mekonnen
2015-01-01
The success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression-based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least-squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least-squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least-squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes. PMID:25040235
Gridded rainfall estimation for distributed modeling in western mountainous areas
NASA Astrophysics Data System (ADS)
Moreda, F.; Cong, S.; Schaake, J.; Smith, M.
2006-05-01
Estimation of precipitation in mountainous areas continues to be problematic. It is well known that radar-based methods are limited due to beam blockage. In these areas, in order to run a distributed model that accounts for spatially variable precipitation, we have generated hourly gridded rainfall estimates from gauge observations. These estimates will be used as basic data sets to support the second phase of the NWS-sponsored Distributed Hydrologic Model Intercomparison Project (DMIP 2). One of the major foci of DMIP 2 is to better understand the modeling and data issues in western mountainous areas in order to provide better water resources products and services to the Nation. We derive precipitation estimates using three data sources for the period of 1987-2002: 1) hourly cooperative observer (coop) gauges, 2) daily total coop gauges and 3) SNOw pack TELemetry (SNOTEL) daily gauges. The daily values are disaggregated using the hourly gauge values and then interpolated to approximately 4km grids using an inverse-distance method. Following this, the estimates are adjusted to match monthly mean values from the Parameter-elevation Regressions on Independent Slopes Model (PRISM). Several analyses are performed to evaluate the gridded estimates for DMIP 2 experiments. These gridded inputs are used to generate mean areal precipitation (MAPX) time series for comparison to the traditional mean areal precipitation (MAP) time series derived by the NWS' California-Nevada River Forecast Center for model calibration. We use two of the DMIP 2 basins in California and Nevada: the North Fork of the American River (catchment area 885 sq. km) and the East Fork of the Carson River (catchment area 922 sq. km) as test areas. The basins are sub-divided into elevation zones. The North Fork American basin is divided into two zones above and below an elevation threshold. Likewise, the Carson River basin is subdivided in to four zones. For each zone, the analyses include: a) overall
Bayesian Model Averaging of Artificial Intelligence Models for Hydraulic Conductivity Estimation
NASA Astrophysics Data System (ADS)
Nadiri, A.; Chitsazan, N.; Tsai, F. T.; Asghari Moghaddam, A.
2012-12-01
This research presents a Bayesian artificial intelligence model averaging (BAIMA) method that incorporates multiple artificial intelligence (AI) models to estimate hydraulic conductivity and evaluate estimation uncertainties. Uncertainty in the AI model outputs stems from error in model input as well as non-uniqueness in selecting different AI methods. Using one single AI model tends to bias the estimation and underestimate uncertainty. BAIMA employs Bayesian model averaging (BMA) technique to address the issue of using one single AI model for estimation. BAIMA estimates hydraulic conductivity by averaging the outputs of AI models according to their model weights. In this study, the model weights were determined using the Bayesian information criterion (BIC) that follows the parsimony principle. BAIMA calculates the within-model variances to account for uncertainty propagation from input data to AI model output. Between-model variances are evaluated to account for uncertainty due to model non-uniqueness. We employed Takagi-Sugeno fuzzy logic (TS-FL), artificial neural network (ANN) and neurofuzzy (NF) to estimate hydraulic conductivity for the Tasuj plain aquifer, Iran. BAIMA combined three AI models and produced better fitting than individual models. While NF was expected to be the best AI model owing to its utilization of both TS-FL and ANN models, the NF model is nearly discarded by the parsimony principle. The TS-FL model and the ANN model showed equal importance although their hydraulic conductivity estimates were quite different. This resulted in significant between-model variances that are normally ignored by using one AI model.
Negative binomial models for abundance estimation of multiple closed populations
Boyce, Mark S.; MacKenzie, Darry I.; Manly, Bryan F.J.; Haroldson, Mark A.; Moody, David W.
2001-01-01
Counts of uniquely identified individuals in a population offer opportunities to estimate abundance. However, for various reasons such counts may be burdened by heterogeneity in the probability of being detected. Theoretical arguments and empirical evidence demonstrate that the negative binomial distribution (NBD) is a useful characterization for counts from biological populations with heterogeneity. We propose a method that focuses on estimating multiple populations by simultaneously using a suite of models derived from the NBD. We used this approach to estimate the number of female grizzly bears (Ursus arctos) with cubs-of-the-year in the Yellowstone ecosystem, for each year, 1986-1998. Akaike's Information Criteria (AIC) indicated that a negative binomial model with a constant level of heterogeneity across all years was best for characterizing the sighting frequencies of female grizzly bears. A lack-of-fit test indicated the model adequately described the collected data. Bootstrap techniques were used to estimate standard errors and 95% confidence intervals. We provide a Monte Carlo technique, which confirms that the Yellowstone ecosystem grizzly bear population increased during the period 1986-1998.
Parameter estimation of multiple item response profile model.
Cho, Sun-Joo; Partchev, Ivailo; De Boeck, Paul
2012-11-01
Multiple item response profile (MIRP) models are models with crossed fixed and random effects. At least one between-person factor is crossed with at least one within-person factor, and the persons nested within the levels of the between-person factor are crossed with the items within levels of the within-person factor. Maximum likelihood estimation (MLE) of models for binary data with crossed random effects is challenging. This is because the marginal likelihood does not have a closed form, so that MLE requires numerical or Monte Carlo integration. In addition, the multidimensional structure of MIRPs makes the estimation complex. In this paper, three different estimation methods to meet these challenges are described: the Laplace approximation to the integrand; hierarchical Bayesian analysis, a simulation-based method; and an alternating imputation posterior with adaptive quadrature as the approximation to the integral. In addition, this paper discusses the advantages and disadvantages of these three estimation methods for MIRPs. The three algorithms are compared in a real data application and a simulation study was also done to compare their behaviour. PMID:22070786
Inversion of canopy reflectance models for estimation of vegetation parameters
NASA Technical Reports Server (NTRS)
Goel, Narendra S.
1987-01-01
One of the keys to successful remote sensing of vegetation is to be able to estimate important agronomic parameters like leaf area index (LAI) and biomass (BM) from the bidirectional canopy reflectance (CR) data obtained by a space-shuttle or satellite borne sensor. One approach for such an estimation is through inversion of CR models which relate these parameters to CR. The feasibility of this approach was shown. The overall objective of the research carried out was to address heretofore uninvestigated but important fundamental issues, develop the inversion technique further, and delineate its strengths and limitations.
Estimation of nonlinear pilot model parameters including time delay.
NASA Technical Reports Server (NTRS)
Schiess, J. R.; Roland, V. R.; Wells, W. R.
1972-01-01
Investigation of the feasibility of using a Kalman filter estimator for the identification of unknown parameters in nonlinear dynamic systems with a time delay. The problem considered is the application of estimation theory to determine the parameters of a family of pilot models containing delayed states. In particular, the pilot-plant dynamics are described by differential-difference equations of the retarded type. The pilot delay, included as one of the unknown parameters to be determined, is kept in pure form as opposed to the Pade approximations generally used for these systems. Problem areas associated with processing real pilot response data are included in the discussion.
[Cancer incidence estimates for Germany via log-linear models].
Haberland, J; Bertz, J; Görsch, B; Schön, D
2001-01-01
In Germany presently no nationwide cancer registration exists. To estimate national cancer incidence, Poisson regression models were fitted to incidence/mortality ratios using age and sex specific data of the cancer registry of Saarland, Germany and were then applied to national mortality. The models estimate the absolute number of incident cases at a given point in time and moreover allow the assessment of time trends. Applied to nationwide mortality the models imply a total of 347,000 new cancer cases in Germany for 1998 with 179,000 females and 168,000 males. During the nineties the age-standardised rate (European standard) has slightly decreased for males and slightly increased for females. PMID:11561205
Linking Gap Model with MODIS Biophysical Products for Biomass Estimation
NASA Astrophysics Data System (ADS)
Wang, D.; Sun, G.; Cai, Y.; Guo, Z.; Fu, A.; Ni, W.; Liu, D.
With the development of earth observation technology and data processing technology biophysical data from remote sensing means such as MODIS LAI and NPP are accessible now However it is still difficult for direct measurement of biomass from remote sensors One possibility for overcoming this problem is using ecological models to link the vegetation parameters currently available from remote sensing to biomass In this paper a combined work is done for estimating forest biomass A calibrated gap model ZELIG was run to simulate the forest development in a temperate forested area in NE China The output relationship between age and biomass was linked to registered MODIS LAI NPP and land cover type images of the same area From the above work forest age or biomass was estimated from existing remote sensed data Obviously there is a lot of work to be done such as optimal combination of biophysical parameters to improve the linkage between MODIS product and ecological modeling
Parameter Estimation for a Model of Space-Time Rainfall
NASA Astrophysics Data System (ADS)
Smith, James A.; Karr, Alan F.
1985-08-01
In this paper, parameter estimation procedures, based on data from a network of rainfall gages, are developed for a class of space-time rainfall models. The models, which are designed to represent the spatial distribution of daily rainfall, have three components, one that governs the temporal occurrence of storms, a second that distributes rain cells spatially for a given storm, and a third that determines the rainfall pattern within a rain cell. Maximum likelihood and method of moments procedures are developed. We illustrate that limitations on model structure are imposed by restricting data sources to rain gage networks. The estimation procedures are applied to a 240-mi2 (621 km2) catchment in the Potomac River basin.
New model and estimation of the danger of ball lightning
NASA Astrophysics Data System (ADS)
Shmatov, M. L.
2003-12-01
A new model of ball lightning is proposed. The main model assumption is that ball lightning has a core consisting of clouds of electrons and totally ionized ions which oscillate with respect to each other. According to the model, ball lightning emits high energy photons that are sometimes dangerous for human beings, and in a number of situations it can kill humans by electric pulses; the ball lightning energy can be of the order of 106 J and even greater. The electric charges that need to be injected into the atmosphere to create ball lightning and the currents, providing the injection of such charges, are estimated. These estimates predict that ball lightning can be created in the experiments with ordinary lightning or powerful electrical installations.
Machuca, Tiago N; Cypel, Marcelo
2014-08-01
Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972
Machuca, Tiago N.
2014-01-01
Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972
Estimation of Trace Gas Fluxes by Inverse Modelling
NASA Astrophysics Data System (ADS)
Prinn, R. G.; Chen, Y.; Huang, J.; Golombek, A.
2003-12-01
A wide range of scientific questions regarding chemically and/or radiatively important trace gases necessitate determinations of their sources and sinks at local to global scales. A powerful method for such determinations involves solution of an inverse problem in which the observed concentrations are effectively Lagrangian line integrals and the unknown sources or sinks are contained in the integrands. The inverse problem consists of calculating optimal estimates of the unknowns in the Bayesian sense using an atmospheric transport model and trace gas measurements gathered over space and time. Great care is necessary to include the effects of both measurement and transport model errors in calculating the uncertainty in the optimal estimates. We review the results of recent studies which use three-dimensional Eulerian (specifically MATCH) or Lagrangian transport models and Kalman filter and other optimization methods to compute emissions of methane, nitrous oxide, and selected halocarbons. These studies use high frequency trace gas observations from global networks (AGAGE, CMDL) to calibrate a priori emission maps for particular processes and geographic regions. The methods allow estimation of time varying emissions. For the hydrogen-containing gases these emission estimates require accurate specification of the concentrations of the hydroxyl radical which constitute their major sink. Hydroxyl radical levels can be optimally estimated in a separate problem using measurements of methyl chloroform whose global emissions are already very well known. The results show that the inverse approach is a powerful complement to traditional surface flux aggregation methods. At the same time, the inverse approach has its own limitations associated especially with transport model errors and/or inadequate atmospheric measurements.
Evaluation of Black Carbon Estimations in Global Aerosol Models
Koch, D.; Schulz, M.; Kinne, Stefan; McNaughton, C. S.; Spackman, J. R.; Balkanski, Y.; Bauer, S.; Berntsen, T.; Bond, Tami C.; Boucher, Olivier; Chin, M.; Clarke, A. D.; De Luca, N.; Dentener, F.; Diehl, T.; Dubovik, O.; Easter, Richard C.; Fahey, D. W.; Feichter, J.; Fillmore, D.; Freitag, S.; Ghan, Steven J.; Ginoux, P.; Gong, S.; Horowitz, L.; Iversen, T.; Kirkevag, A.; Klimont, Z.; Kondo, Yutaka; Krol, M.; Liu, Xiaohong; Miller, R.; Montanaro, V.; Moteki, N.; Myhre, G.; Penner, J.; Perlwitz, Ja; Pitari, G.; Reddy, S.; Sahu, L.; Sakamoto, H.; Schuster, G.; Schwarz, J. P.; Seland, O.; Stier, P.; Takegawa, Nobuyuki; Takemura, T.; Textor, C.; van Aardenne, John; Zhao, Y.
2009-11-27
We evaluate black carbon (BC) model predictions from the AeroCom model intercomparison project by considering the diversity among year 2000 model simulations and comparing model predictions with available measurements. These model-measurement intercomparisons include BC surface and aircraft concentrations, aerosol absorption optical depth (AAOD) from AERONET and OMI retrievals and BC column estimations based on AERONET. In regions other than Asia, most models are biased high compared to surface concentration measurements. However compared with (column) AAOD or BC burden retreivals, the models are generally biased low. The average ratio of model to retrieved AAOD is less than 0.7 in South American and 0.6 in African biomass burning regions; both of these regions lack surface concentration measurements. In Asia the average model to observed ratio is 0.6 for AAOD and 0.5 for BC surface concentrations. Compared with aircraft measurements over the Americas at latitudes between 0 and 50N, the average model is a factor of 10 larger than observed, and most models exceed the measured BC standard deviation in the mid to upper troposphere. At higher latitudes the average model to aircraft BC is 0.6 and underestimate the observed BC loading in the lower and middle troposphere associated with springtime Arctic haze. Low model bias for AAOD but overestimation of surface and upper atmospheric BC concentrations at lower latitudes suggests that most models are underestimating BC absorption and should improve estimates for refractive index, particle size, and optical effects of BC coating. Retrieval uncertainties and/or differences wit