Deflection load characteristics of laser-welded orthodontic wires.

PubMed

Watanabe, Etsuko; Stigall, Garrett; Elshahawy, Waleed; Watanabe, Ikuya

2012-07-01

To compare the deflection load characteristics of homogeneous and heterogeneous joints made by laser welding using various types of orthodontic wires. Four kinds of straight orthodontic rectangular wires (0.017 inch × 0.025 inch) were used: stainless-steel (SS), cobalt-chromium-nickel (Co-Cr-Ni), beta-titanium alloy (β-Ti), and nickel-titanium (Ni-Ti). Homogeneous and heterogeneous end-to-end joints (12 mm long each) were made by Nd:YAG laser welding. Two types of welding methods were used: two-point welding and four-point welding. Nonwelded wires were also used as a control. Deflection load (N) was measured by conducting the three-point bending test. The data (n  =  5) were statistically analyzed using analysis of variance/Tukey test (P < .05). The deflection loads for control wires measured were as follows: SS: 21.7 ± 0.8 N; Co-Cr-Ni: 20.0 ± 0.3 N; β-Ti: 13.9 ± 1.3 N; and Ni-Ti: 6.6 ± 0.4 N. All of the homogeneously welded specimens showed lower deflection loads compared to corresponding control wires and exhibited higher deflection loads compared to heterogeneously welded combinations. For homogeneous combinations, Co-Cr-Ni/Co-Cr-Ni showed a significantly (P < .05) higher deflection load than those of the remaining homogeneously welded groups. In heterogeneous combinations, SS/Co-Cr-Ni and β-Ti/Ni-Ti showed higher deflection loads than those of the remaining heterogeneously welded combinations (significantly higher for SS/Co-Cr-Ni). Significance (P < .01) was shown for the interaction between the two factors (materials combination and welding method). However, no significant difference in deflection load was found between four-point and two-point welding in each homogeneous or heterogeneous combination. Heterogeneously laser-welded SS/Co-Cr-Ni and β-Ti/Ni-Ti wires provide a deflection load that is comparable to that of homogeneously welded orthodontic wires.

Analysis of the dynamics of multi-team Bertrand game with heterogeneous players

NASA Astrophysics Data System (ADS)

Ding, Zhanwen; Hang, Qinglan; Yang, Honglin

2011-06-01

In this article, we study the dynamics of a two-team Bertrand game with players having heterogeneous expectations. We study the equilibrium solutions and the conditions of their locally asymptotic stability. Numerical simulations are used to illustrate the complex behaviours of the proposed model of the Bertrand game. We demonstrate that some parameters of the model have great influence on the stability of Nash equilibrium and on the speed of convergence to Nash equilibrium. The chaotic behaviour of the model has been controlled by using feedback control method.

Variable synaptic strengths controls the firing rate distribution in feedforward neural networks.

PubMed

Ly, Cheng; Marsat, Gary

2018-02-01

Heterogeneity of firing rate statistics is known to have severe consequences on neural coding. Recent experimental recordings in weakly electric fish indicate that the distribution-width of superficial pyramidal cell firing rates (trial- and time-averaged) in the electrosensory lateral line lobe (ELL) depends on the stimulus, and also that network inputs can mediate changes in the firing rate distribution across the population. We previously developed theoretical methods to understand how two attributes (synaptic and intrinsic heterogeneity) interact and alter the firing rate distribution in a population of integrate-and-fire neurons with random recurrent coupling. Inspired by our experimental data, we extend these theoretical results to a delayed feedforward spiking network that qualitatively capture the changes of firing rate heterogeneity observed in in-vivo recordings. We demonstrate how heterogeneous neural attributes alter firing rate heterogeneity, accounting for the effect with various sensory stimuli. The model predicts how the strength of the effective network connectivity is related to intrinsic heterogeneity in such delayed feedforward networks: the strength of the feedforward input is positively correlated with excitability (threshold value for spiking) when firing rate heterogeneity is low and is negatively correlated with excitability with high firing rate heterogeneity. We also show how our theory can be used to predict effective neural architecture. We demonstrate that neural attributes do not interact in a simple manner but rather in a complex stimulus-dependent fashion to control neural heterogeneity and discuss how it can ultimately shape population codes.

A Comparison of Performance versus Presentation Based Methods of Instructing Pre-service Teachers in Media Competencies.

ERIC Educational Resources Information Center

Mattox, Daniel V., Jr.

Research compared conventional and experimental methods of instruction in a teacher education media course. The conventional method relied upon factual presentations to heterogeneous groups, while the experimental utilized homogeneous clusters of students and stressed individualized instruction. A pretest-posttest, experimental-control group…

Cohesive fracture of elastically heterogeneous materials: An integrative modeling and experimental study

NASA Astrophysics Data System (ADS)

Wang, Neng; Xia, Shuman

2017-01-01

A combined modeling and experimental effort is made in this work to examine the cohesive fracture mechanisms of heterogeneous elastic solids. A two-phase laminated composite, which mimics the key microstructural features of many tough engineering and biological materials, is selected as a model material system. Theoretical and finite element analyses with cohesive zone modeling are performed to study the effective fracture resistance of the heterogeneous material associated with unstable crack propagation and arrest. A crack-tip-position controlled algorithm is implemented in the finite element analysis to overcome the inherent instability issues resulting from crack pinning and depinning at local heterogeneities. Systematic parametric studies are carried out to investigate the effects of various material and geometrical parameters, including the modulus mismatch ratio, phase volume fraction, cohesive zone size, and cohesive law shape. Concurrently, a novel stereolithography-based three-dimensional (3D) printing system is developed and used for fabricating heterogeneous test specimens with well-controlled structural and material properties. Fracture testing of the specimens is performed using the tapered double-cantilever beam (TDCB) test method. With optimal material and geometrical parameters, heterogeneous TDCB specimens are shown to exhibit enhanced effective fracture energy and effective fracture toughness than their homogeneous counterparts, which is in good agreement with the modeling predictions. The integrative computational and experimental study presented here provides a fundamental mechanistic understanding of the fracture mechanisms in brittle heterogeneous materials and sheds light on the rational design of tough materials through patterned heterogeneities.

Robust scalable stabilisability conditions for large-scale heterogeneous multi-agent systems with uncertain nonlinear interactions: towards a distributed computing architecture

NASA Astrophysics Data System (ADS)

Manfredi, Sabato

2016-06-01

Large-scale dynamic systems are becoming highly pervasive in their occurrence with applications ranging from system biology, environment monitoring, sensor networks, and power systems. They are characterised by high dimensionality, complexity, and uncertainty in the node dynamic/interactions that require more and more computational demanding methods for their analysis and control design, as well as the network size and node system/interaction complexity increase. Therefore, it is a challenging problem to find scalable computational method for distributed control design of large-scale networks. In this paper, we investigate the robust distributed stabilisation problem of large-scale nonlinear multi-agent systems (briefly MASs) composed of non-identical (heterogeneous) linear dynamical systems coupled by uncertain nonlinear time-varying interconnections. By employing Lyapunov stability theory and linear matrix inequality (LMI) technique, new conditions are given for the distributed control design of large-scale MASs that can be easily solved by the toolbox of MATLAB. The stabilisability of each node dynamic is a sufficient assumption to design a global stabilising distributed control. The proposed approach improves some of the existing LMI-based results on MAS by both overcoming their computational limits and extending the applicative scenario to large-scale nonlinear heterogeneous MASs. Additionally, the proposed LMI conditions are further reduced in terms of computational requirement in the case of weakly heterogeneous MASs, which is a common scenario in real application where the network nodes and links are affected by parameter uncertainties. One of the main advantages of the proposed approach is to allow to move from a centralised towards a distributed computing architecture so that the expensive computation workload spent to solve LMIs may be shared among processors located at the networked nodes, thus increasing the scalability of the approach than the network size. Finally, a numerical example shows the applicability of the proposed method and its advantage in terms of computational complexity when compared with the existing approaches.

Optimal estimation and scheduling in aquifer management using the rapid feedback control method

NASA Astrophysics Data System (ADS)

Ghorbanidehno, Hojat; Kokkinaki, Amalia; Kitanidis, Peter K.; Darve, Eric

2017-12-01

Management of water resources systems often involves a large number of parameters, as in the case of large, spatially heterogeneous aquifers, and a large number of "noisy" observations, as in the case of pressure observation in wells. Optimizing the operation of such systems requires both searching among many possible solutions and utilizing new information as it becomes available. However, the computational cost of this task increases rapidly with the size of the problem to the extent that textbook optimization methods are practically impossible to apply. In this paper, we present a new computationally efficient technique as a practical alternative for optimally operating large-scale dynamical systems. The proposed method, which we term Rapid Feedback Controller (RFC), provides a practical approach for combined monitoring, parameter estimation, uncertainty quantification, and optimal control for linear and nonlinear systems with a quadratic cost function. For illustration, we consider the case of a weakly nonlinear uncertain dynamical system with a quadratic objective function, specifically a two-dimensional heterogeneous aquifer management problem. To validate our method, we compare our results with the linear quadratic Gaussian (LQG) method, which is the basic approach for feedback control. We show that the computational cost of the RFC scales only linearly with the number of unknowns, a great improvement compared to the basic LQG control with a computational cost that scales quadratically. We demonstrate that the RFC method can obtain the optimal control values at a greatly reduced computational cost compared to the conventional LQG algorithm with small and controllable losses in the accuracy of the state and parameter estimation.

Subplane collision probabilities method applied to control rod cusping in 2D/1D

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

Graham, Aaron M.; Collins, Benjamin S.; Stimpson, Shane G.

The MPACT code is being jointly developed by the University of Michigan and Oak Ridge National Laboratory. It uses the 2D/1D method to solve neutron transport problems for reactors. The 2D/1D method decomposes the problem into a stack of 2D planes, and uses a high fidelity transport method to resolve all heterogeneity in each plane. These planes are then coupled axially using a lower order solver. Using this scheme, 3D solutions to the transport equation can be obtained at a much lower cost.One assumption made by the 2D/1D method is that the materials are axially homogeneous for each 2D plane.more » Violation of this assumption requires homogenization, which can significantly reduce the accuracy of the calculation. This paper presents two new subgrid methods to address this issue. The first method is polynomial decusping, a simple correction used to address control rods partially inserted into a 2D plane. The second is the subplane collision probabilities method, which is a more accurate, more robust subgrid method that can be applied to other axial heterogeneities.Each method was applied to a variety of problems. Results were compared to fine mesh solutions which had no axial heterogeneity and to Monte Carlo reference solutions generated using KENO-VI. It was shown that the polynomial decusping method was effective in many cases, but it had some limitations, with 3D pin power errors as high as 25% compared to KENO-VI. In conclusion, the subplane collision probabilities method performed much better, lowering the maximum pin power error to less than 5% in every calculation.« less

Subplane collision probabilities method applied to control rod cusping in 2D/1D

DOE PAGES

Graham, Aaron M.; Collins, Benjamin S.; Stimpson, Shane G.; ...

2018-04-06

The MPACT code is being jointly developed by the University of Michigan and Oak Ridge National Laboratory. It uses the 2D/1D method to solve neutron transport problems for reactors. The 2D/1D method decomposes the problem into a stack of 2D planes, and uses a high fidelity transport method to resolve all heterogeneity in each plane. These planes are then coupled axially using a lower order solver. Using this scheme, 3D solutions to the transport equation can be obtained at a much lower cost.One assumption made by the 2D/1D method is that the materials are axially homogeneous for each 2D plane.more » Violation of this assumption requires homogenization, which can significantly reduce the accuracy of the calculation. This paper presents two new subgrid methods to address this issue. The first method is polynomial decusping, a simple correction used to address control rods partially inserted into a 2D plane. The second is the subplane collision probabilities method, which is a more accurate, more robust subgrid method that can be applied to other axial heterogeneities.Each method was applied to a variety of problems. Results were compared to fine mesh solutions which had no axial heterogeneity and to Monte Carlo reference solutions generated using KENO-VI. It was shown that the polynomial decusping method was effective in many cases, but it had some limitations, with 3D pin power errors as high as 25% compared to KENO-VI. In conclusion, the subplane collision probabilities method performed much better, lowering the maximum pin power error to less than 5% in every calculation.« less

Comparison of statistical tests for association between rare variants and binary traits.

PubMed

Bacanu, Silviu-Alin; Nelson, Matthew R; Whittaker, John C

2012-01-01

Genome-wide association studies have found thousands of common genetic variants associated with a wide variety of diseases and other complex traits. However, a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some of the missing variation is due to the effects of rare variants. Nonetheless, the statistical analysis of rare variants is challenging. A commonly used method is to contrast, within the same region (gene), the frequency of minor alleles at rare variants between cases and controls. However, this strategy is most useful under the assumption that the tested variants have similar effects. We previously proposed a method that can accommodate heterogeneous effects in the analysis of quantitative traits. Here we extend this method to include binary traits that can accommodate covariates. We use simulations for a variety of causal and covariate impact scenarios to compare the performance of the proposed method to standard logistic regression, C-alpha, SKAT, and EREC. We found that i) logistic regression methods perform well when the heterogeneity of the effects is not extreme and ii) SKAT and EREC have good performance under all tested scenarios but they can be computationally intensive. Consequently, it would be more computationally desirable to use a two-step strategy by (i) selecting promising genes by faster methods and ii) analyzing selected genes using SKAT/EREC. To select promising genes one can use (1) regression methods when effect heterogeneity is assumed to be low and the covariates explain a non-negligible part of trait variability, (2) C-alpha when heterogeneity is assumed to be large and covariates explain a small fraction of trait's variability and (3) the proposed trend and heterogeneity test when the heterogeneity is assumed to be non-trivial and the covariates explain a large fraction of trait variability.

Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

PubMed

Gough, Albert H; Chen, Ning; Shun, Tong Ying; Lezon, Timothy R; Boltz, Robert C; Reese, Celeste E; Wagner, Jacob; Vernetti, Lawrence A; Grandis, Jennifer R; Lee, Adrian V; Stern, Andrew M; Schurdak, Mark E; Taylor, D Lansing

2014-01-01

One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

Multifunctional 3D printing of heterogeneous hydrogel structures

NASA Astrophysics Data System (ADS)

Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

2016-09-01

Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing.

Multifunctional 3D printing of heterogeneous hydrogel structures

PubMed Central

Nadernezhad, Ali; Khani, Navid; Skvortsov, Gözde Akdeniz; Toprakhisar, Burak; Bakirci, Ezgi; Menceloglu, Yusuf; Unal, Serkan; Koc, Bahattin

2016-01-01

Multimaterial additive manufacturing or three-dimensional (3D) printing of hydrogel structures provides the opportunity to engineer geometrically dependent functionalities. However, current fabrication methods are mostly limited to one type of material or only provide one type of functionality. In this paper, we report a novel method of multimaterial deposition of hydrogel structures based on an aspiration-on-demand protocol, in which the constitutive multimaterial segments of extruded filaments were first assembled in liquid state by sequential aspiration of inks into a glass capillary, followed by in situ gel formation. We printed different patterned objects with varying chemical, electrical, mechanical, and biological properties by tuning process and material related parameters, to demonstrate the abilities of this method in producing heterogeneous and multi-functional hydrogel structures. Our results show the potential of proposed method in producing heterogeneous objects with spatially controlled functionalities while preserving structural integrity at the switching interface between different segments. We anticipate that this method would introduce new opportunities in multimaterial additive manufacturing of hydrogels for diverse applications such as biosensors, flexible electronics, tissue engineering and organ printing. PMID:27630079

Methods and codes for neutronic calculations of the MARIA research reactor.

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

Andrzejewski, K.; Kulikowska, T.; Bretscher, M. M.

2002-02-18

The core of the MARIA high flux multipurpose research reactor is highly heterogeneous. It consists of beryllium blocks arranged in 6 x 8 matrix, tubular fuel assemblies, control rods and irradiation channels. The reflector is also heterogeneous and consists of graphite blocks clad with aluminum. Its structure is perturbed by the experimental beam tubes. This paper presents methods and codes used to calculate the MARIA reactor neutronics characteristics and experience gained thus far at IAE and ANL. At ANL the methods of MARIA calculations were developed in connection with the RERTR program. At IAE the package of programs was developedmore » to help its operator in optimization of fuel utilization.« less

A regulation probability model-based meta-analysis of multiple transcriptomics data sets for cancer biomarker identification.

PubMed

Xie, Xin-Ping; Xie, Yu-Feng; Wang, Hong-Qiang

2017-08-23

Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal. This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis. Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.

Sources of heterogeneity in case-control studies on associations between statins, ACE-inhibitors, and proton pump inhibitors and risk of pneumonia.

PubMed

de Groot, Mark C H; Klungel, Olaf H; Leufkens, Hubert G M; van Dijk, Liset; Grobbee, Diederick E; van de Garde, Ewoudt M W

2014-10-01

The heterogeneity in case-control studies on the associations between community-acquired pneumonia (CAP) and ACE-inhibitors (ACEi), statins, and proton pump inhibitors (PPI) hampers translation to clinical practice. Our objective is to explore sources of this heterogeneity by applying a common protocol in different data settings. We conducted ten case-control studies using data from five different health care databases. Databases varied on type of patients (hospitalised vs. GP), level of case validity, and mode of exposure ascertainment (prescription or dispensing based). Identified CAP patients and controls were matched on age, gender, and calendar year. Conditional logistic regression was used to calculate odds ratios (OR) for the associations between the drugs of interest and CAP. Associations were adjusted by a common set of potential confounders. Data of 38,742 cases and 118,019 controls were studied. Comparable patterns of variation between case-control studies were observed for ACEi, statins and PPI use and pneumonia risk with adjusted ORs varying from 1.04 to 1.49, 0.82 to 1.50 and 1.16 to 2.71, respectively. Overall, higher ORs were found for hospitalised CAP patients matched to population controls versus GP CAP patients matched to population controls. Prevalence of drug exposure was higher in dispensing data versus prescription data. We show that case-control selection and methods of exposure ascertainment induce bias that cannot be adjusted for and to a considerable extent explain the heterogeneity in results obtained in case-control studies on statins, ACEi and PPIs and CAP. The common protocol approach helps to better understand sources of variation in observational studies.

Bacteria as living patchy colloids: Phenotypic heterogeneity in surface adhesion

PubMed Central

Hermes, Michiel; Schwarz-Linek, Jana; Poon, Wilson C. K.

2018-01-01

Understanding and controlling the surface adhesion of pathogenic bacteria is of urgent biomedical importance. However, many aspects of this process remain unclear (for example, microscopic details of the initial adhesion and possible variations between individual cells). Using a new high-throughput method, we identify and follow many single cells within a clonal population of Escherichia coli near a glass surface. We find strong phenotypic heterogeneities: A fraction of the cells remain in the free (planktonic) state, whereas others adhere with an adhesion strength that itself exhibits phenotypic heterogeneity. We explain our observations using a patchy colloid model; cells bind with localized, adhesive patches, and the strength of adhesion is determined by the number of patches: Nonadherers have no patches, weak adherers bind with a single patch only, and strong adherers bind via a single or multiple patches. We discuss possible implications of our results for controlling bacterial adhesion in biomedical and other applications. PMID:29719861

Predicting Upscaled Behavior of Aqueous Reactants in Heterogeneous Porous Media

NASA Astrophysics Data System (ADS)

Wright, E. E.; Hansen, S. K.; Bolster, D.; Richter, D. H.; Vesselinov, V. V.

2017-12-01

When modeling reactive transport, reaction rates are often overestimated due to the improper assumption of perfect mixing at the support scale of the transport model. In reality, fronts tend to form between participants in thermodynamically favorable reactions, leading to segregation of reactants into islands or fingers. When such a configuration arises, reactions are limited to the interface between the reactive solutes. Closure methods for estimating control-volume-effective reaction rates in terms of quantities defined at the control volume scale do not presently exist, but their development is crucial for effective field-scale modeling. We attack this problem through a combination of analytical and numerical means. Specifically, we numerically study reactive transport through an ensemble of realizations of two-dimensional heterogeneous porous media. We then employ regression analysis to calibrate an analytically-derived relationship between reaction rate and various dimensionless quantities representing conductivity-field heterogeneity and the respective strengths of diffusion, reaction and advection.

Fabrication of heterogeneous nanomaterial array by programmable heating and chemical supply within microfluidic platform towards multiplexed gas sensing application

PubMed Central

Yang, Daejong; Kang, Kyungnam; Kim, Donghwan; Li, Zhiyong; Park, Inkyu

2015-01-01

A facile top-down/bottom-up hybrid nanofabrication process based on programmable temperature control and parallel chemical supply within microfluidic platform has been developed for the all liquid-phase synthesis of heterogeneous nanomaterial arrays. The synthesized materials and locations can be controlled by local heating with integrated microheaters and guided liquid chemical flow within microfluidic platform. As proofs-of-concept, we have demonstrated the synthesis of two types of nanomaterial arrays: (i) parallel array of TiO2 nanotubes, CuO nanospikes and ZnO nanowires, and (ii) parallel array of ZnO nanowire/CuO nanospike hybrid nanostructures, CuO nanospikes and ZnO nanowires. The laminar flow with negligible ionic diffusion between different precursor solutions as well as localized heating was verified by numerical calculation and experimental result of nanomaterial array synthesis. The devices made of heterogeneous nanomaterial array were utilized as a multiplexed sensor for toxic gases such as NO2 and CO. This method would be very useful for the facile fabrication of functional nanodevices based on highly integrated arrays of heterogeneous nanomaterials. PMID:25634814

Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery

PubMed Central

Gough, Albert H.; Chen, Ning; Shun, Tong Ying; Lezon, Timothy R.; Boltz, Robert C.; Reese, Celeste E.; Wagner, Jacob; Vernetti, Lawrence A.; Grandis, Jennifer R.; Lee, Adrian V.; Stern, Andrew M.; Schurdak, Mark E.; Taylor, D. Lansing

2014-01-01

One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology. PMID:25036749

Heterogeneously Assembled Metamaterials and Metadevices via 3D Modular Transfer Printing

NASA Astrophysics Data System (ADS)

Lee, Seungwoo; Kang, Byungsoo; Keum, Hohyun; Ahmed, Numair; Rogers, John A.; Ferreira, Placid M.; Kim, Seok; Min, Bumki

2016-06-01

Metamaterials have made the exotic control of the flow of electromagnetic waves possible, which is difficult to achieve with natural materials. In recent years, the emergence of functional metadevices has shown immense potential for the practical realization of highly efficient photonic devices. However, complex and heterogeneous architectures that enable diverse functionalities of metamaterials and metadevices have been challenging to realize because of the limited manufacturing capabilities of conventional fabrication methods. Here, we show that three-dimensional (3D) modular transfer printing can be used to construct diverse metamaterials in complex 3D architectures on universal substrates, which is attractive for achieving on-demand photonic properties. Few repetitive processing steps and rapid constructions are additional advantages of 3D modular transfer printing. Thus, this method provides a fascinating route to generate flexible and stretchable 2D/3D metamaterials and metadevices with heterogeneous material components, complex device architectures, and diverse functionalities.

Heterogeneously Assembled Metamaterials and Metadevices via 3D Modular Transfer Printing.

PubMed

Lee, Seungwoo; Kang, Byungsoo; Keum, Hohyun; Ahmed, Numair; Rogers, John A; Ferreira, Placid M; Kim, Seok; Min, Bumki

2016-06-10

Metamaterials have made the exotic control of the flow of electromagnetic waves possible, which is difficult to achieve with natural materials. In recent years, the emergence of functional metadevices has shown immense potential for the practical realization of highly efficient photonic devices. However, complex and heterogeneous architectures that enable diverse functionalities of metamaterials and metadevices have been challenging to realize because of the limited manufacturing capabilities of conventional fabrication methods. Here, we show that three-dimensional (3D) modular transfer printing can be used to construct diverse metamaterials in complex 3D architectures on universal substrates, which is attractive for achieving on-demand photonic properties. Few repetitive processing steps and rapid constructions are additional advantages of 3D modular transfer printing. Thus, this method provides a fascinating route to generate flexible and stretchable 2D/3D metamaterials and metadevices with heterogeneous material components, complex device architectures, and diverse functionalities.

Heterogeneously Assembled Metamaterials and Metadevices via 3D Modular Transfer Printing

PubMed Central

Lee, Seungwoo; Kang, Byungsoo; Keum, Hohyun; Ahmed, Numair; Rogers, John A.; Ferreira, Placid M.; Kim, Seok; Min, Bumki

2016-01-01

Metamaterials have made the exotic control of the flow of electromagnetic waves possible, which is difficult to achieve with natural materials. In recent years, the emergence of functional metadevices has shown immense potential for the practical realization of highly efficient photonic devices. However, complex and heterogeneous architectures that enable diverse functionalities of metamaterials and metadevices have been challenging to realize because of the limited manufacturing capabilities of conventional fabrication methods. Here, we show that three-dimensional (3D) modular transfer printing can be used to construct diverse metamaterials in complex 3D architectures on universal substrates, which is attractive for achieving on-demand photonic properties. Few repetitive processing steps and rapid constructions are additional advantages of 3D modular transfer printing. Thus, this method provides a fascinating route to generate flexible and stretchable 2D/3D metamaterials and metadevices with heterogeneous material components, complex device architectures, and diverse functionalities. PMID:27283594

Control of coupled oscillator networks with application to microgrid technologies.

PubMed

Skardal, Per Sebastian; Arenas, Alex

2015-08-01

The control of complex systems and network-coupled dynamical systems is a topic of vital theoretical importance in mathematics and physics with a wide range of applications in engineering and various other sciences. Motivated by recent research into smart grid technologies, we study the control of synchronization and consider the important case of networks of coupled phase oscillators with nonlinear interactions-a paradigmatic example that has guided our understanding of self-organization for decades. We develop a method for control based on identifying and stabilizing problematic oscillators, resulting in a stable spectrum of eigenvalues, and in turn a linearly stable synchronized state. The amount of control, that is, number of oscillators, required to stabilize the network is primarily dictated by the coupling strength, dynamical heterogeneity, and mean degree of the network, and depends little on the structural heterogeneity of the network itself.

Control of coupled oscillator networks with application to microgrid technologies

PubMed Central

Skardal, Per Sebastian; Arenas, Alex

2015-01-01

The control of complex systems and network-coupled dynamical systems is a topic of vital theoretical importance in mathematics and physics with a wide range of applications in engineering and various other sciences. Motivated by recent research into smart grid technologies, we study the control of synchronization and consider the important case of networks of coupled phase oscillators with nonlinear interactions—a paradigmatic example that has guided our understanding of self-organization for decades. We develop a method for control based on identifying and stabilizing problematic oscillators, resulting in a stable spectrum of eigenvalues, and in turn a linearly stable synchronized state. The amount of control, that is, number of oscillators, required to stabilize the network is primarily dictated by the coupling strength, dynamical heterogeneity, and mean degree of the network, and depends little on the structural heterogeneity of the network itself. PMID:26601231

Control of coupled oscillator networks with application to microgrid technologies

NASA Astrophysics Data System (ADS)

Arenas, Alex

The control of complex systems and network-coupled dynamical systems is a topic of vital theoretical importance in mathematics and physics with a wide range of applications in engineering and various other sciences. Motivated by recent research into smart grid technologies, we study the control of synchronization and consider the important case of networks of coupled phase oscillators with nonlinear interactions-a paradigmatic example that has guided our understanding of self-organization for decades. We develop a method for control based on identifying and stabilizing problematic oscillators, resulting in a stable spectrum of eigenvalues, and in turn a linearly stable syn- chronized state. The amount of control, that is, number of oscillators, required to stabilize the network is primarily dictated by the coupling strength, dynamical heterogeneity, and mean degree of the network, and depends little on the structural heterogeneity of the network itself.

Imparting magnetic dipole heterogeneity to internalized iron oxide nanoparticles for microorganism swarm control

NASA Astrophysics Data System (ADS)

Kim, Paul Seung Soo; Becker, Aaron; Ou, Yan; Julius, Anak Agung; Kim, Min Jun

2015-03-01

Tetrahymena pyriformis is a single cell eukaryote that can be modified to respond to magnetic fields, a response called magnetotaxis. Naturally, this microorganism cannot respond to magnetic fields, but after modification using iron oxide nanoparticles, cells are magnetized and exhibit a constant magnetic dipole strength. In experiments, a rotating field is applied to cells using a two-dimensional approximate Helmholtz coil system. Using rotating magnetic fields, we characterize discrete cells' swarm swimming which is affected by several factors. The behavior of the cells under these fields is explained in detail. After the field is removed, relatively straight swimming is observed. We also generate increased heterogeneity within a population of cells to improve controllability of a swarm, which is explored in a cell model. By exploiting this straight swimming behavior, we propose a method to control discrete cells utilizing a single global magnetic input. Successful implementation of this swarm control method would enable teams of microrobots to perform a variety of in vitro microscale tasks impossible for single microrobots, such as pushing objects or simultaneous micromanipulation of discrete entities.

Control of collective network chaos.

PubMed

Wagemakers, Alexandre; Barreto, Ernest; Sanjuán, Miguel A F; So, Paul

2014-06-01

Under certain conditions, the collective behavior of a large globally-coupled heterogeneous network of coupled oscillators, as quantified by the macroscopic mean field or order parameter, can exhibit low-dimensional chaotic behavior. Recent advances describe how a small set of "reduced" ordinary differential equations can be derived that captures this mean field behavior. Here, we show that chaos control algorithms designed using the reduced equations can be successfully applied to imperfect realizations of the full network. To systematically study the effectiveness of this technique, we measure the quality of control as we relax conditions that are required for the strict accuracy of the reduced equations, and hence, the controller. Although the effects are network-dependent, we show that the method is effective for surprisingly small networks, for modest departures from global coupling, and even with mild inaccuracy in the estimate of network heterogeneity.

Organizing Heterogeneous Samples Using Community Detection of GIMME-Derived Resting State Functional Networks

PubMed Central

Gates, Kathleen M.; Molenaar, Peter C. M.; Iyer, Swathi P.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Clinical investigations of many neuropsychiatric disorders rely on the assumption that diagnostic categories and typical control samples each have within-group homogeneity. However, research using human neuroimaging has revealed that much heterogeneity exists across individuals in both clinical and control samples. This reality necessitates that researchers identify and organize the potentially varied patterns of brain physiology. We introduce an analytical approach for arriving at subgroups of individuals based entirely on their brain physiology. The method begins with Group Iterative Multiple Model Estimation (GIMME) to assess individual directed functional connectivity maps. GIMME is one of the only methods to date that can recover both the direction and presence of directed functional connectivity maps in heterogeneous data, making it an ideal place to start since it addresses the problem of heterogeneity. Individuals are then grouped based on similarities in their connectivity patterns using a modularity approach for community detection. Monte Carlo simulations demonstrate that using GIMME in combination with the modularity algorithm works exceptionally well - on average over 97% of simulated individuals are placed in the accurate subgroup with no prior information on functional architecture or group identity. Having demonstrated reliability, we examine resting-state data of fronto-parietal regions drawn from a sample (N = 80) of typically developing and attention-deficit/hyperactivity disorder (ADHD) -diagnosed children. Here, we find 5 subgroups. Two subgroups were predominantly comprised of ADHD, suggesting that more than one biological marker exists that can be used to identify children with ADHD based from their brain physiology. Empirical evidence presented here supports notions that heterogeneity exists in brain physiology within ADHD and control samples. This type of information gained from the approach presented here can assist in better characterizing patients in terms of outcomes, optimal treatment strategies, potential gene-environment interactions, and the use of biological phenomenon to assist with mental health. PMID:24642753

An open, object-based modeling approach for simulating subsurface heterogeneity

NASA Astrophysics Data System (ADS)

Bennett, J.; Ross, M.; Haslauer, C. P.; Cirpka, O. A.

2017-12-01

Characterization of subsurface heterogeneity with respect to hydraulic and geochemical properties is critical in hydrogeology as their spatial distribution controls groundwater flow and solute transport. Many approaches of characterizing subsurface heterogeneity do not account for well-established geological concepts about the deposition of the aquifer materials; those that do (i.e. process-based methods) often require forcing parameters that are difficult to derive from site observations. We have developed a new method for simulating subsurface heterogeneity that honors concepts of sequence stratigraphy, resolves fine-scale heterogeneity and anisotropy of distributed parameters, and resembles observed sedimentary deposits. The method implements a multi-scale hierarchical facies modeling framework based on architectural element analysis, with larger features composed of smaller sub-units. The Hydrogeological Virtual Reality simulator (HYVR) simulates distributed parameter models using an object-based approach. Input parameters are derived from observations of stratigraphic morphology in sequence type-sections. Simulation outputs can be used for generic simulations of groundwater flow and solute transport, and for the generation of three-dimensional training images needed in applications of multiple-point geostatistics. The HYVR algorithm is flexible and easy to customize. The algorithm was written in the open-source programming language Python, and is intended to form a code base for hydrogeological researchers, as well as a platform that can be further developed to suit investigators' individual needs. This presentation will encompass the conceptual background and computational methods of the HYVR algorithm, the derivation of input parameters from site characterization, and the results of groundwater flow and solute transport simulations in different depositional settings.

Heterogeneous asymmetric recombinase polymerase amplification (haRPA) for rapid hygiene control of large-volume water samples.

PubMed

Elsäßer, Dennis; Ho, Johannes; Niessner, Reinhard; Tiehm, Andreas; Seidel, Michael

2018-04-01

Hygiene of drinking water is periodically controlled by cultivation and enumeration of indicator bacteria. Rapid and comprehensive measurements of emerging pathogens are of increasing interest to improve drinking water safety. In this study, the feasibility to detect bacteriophage PhiX174 as a potential indicator for virus contamination in large volumes of water is demonstrated. Three consecutive concentration methods (continuous ultrafiltration, monolithic adsorption filtration, and centrifugal ultrafiltration) were combined to concentrate phages stepwise from 1250 L drinking water into 1 mL. Heterogeneous asymmetric recombinase polymerase amplification (haRPA) is applied as rapid detection method. Field measurements were conducted to test the developed system for hygiene online monitoring under realistic conditions. We could show that this system allows the detection of artificial contaminations of bacteriophage PhiX174 in drinking water pipelines. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimating Causal Effects from Family Planning Health Communication Campaigns Using Panel Data: The “Your Health, Your Wealth” Campaign in Egypt

PubMed Central

Hutchinson, Paul L.; Meekers, Dominique

2012-01-01

Background Health communication campaigns – involving mass media and interpersonal communication - have long been utilized by national family planning programs to create awareness about contraceptive methods, to shift social norms related to fertility control, and to promote specific behaviors, such as the use of condoms, injectable methods or permanent sterilization. However, demonstrating the effectiveness of these campaigns is often complicated because the infeasibility of experimental designs generally yields statistically non-equivalent samples of campaign-exposed and unexposed individuals. Methods Using data from a panel survey of reproductive age women in Egypt, we estimate the effects of the multimedia health communication campaign “Your Health, Your Wealth” (“Sahatek Sarwetek”) on precursors to contraceptive use (e.g., spousal communication, birth spacing attitudes) and on modern contraceptive use. Difference-in-differences and fixed effects estimators that exploit the panel nature of the data are employed to control for both observed and unobserved heterogeneity in the sample of women who self-report recall of the messages, thereby potentially improving upon methods that make no such controls or that rely solely on cross-sectional data. Findings All of the estimators find positive effects of the “Your Health, Your Wealth” campaign on reproductive health outcomes, though the magnitudes of those effects diverge, often considerably. Difference-in-differences estimators find that exposure to the campaign increases the likelihood of spousal discussions by 14.4 percentage points (pp.) (SE = .039, p<0.001) but has no effect on contraceptive use. In contrast, the fixed effects, instrumental variables estimator, controlling for unobserved heterogeneity, finds a large, statistically significant effect on modern contraceptive use (27.4 pp., SE = 0.135, p = 0.043). Conclusions The difficulties of evaluating family planning communication programs may be surmountable using panel data and analytic methods that address both observed and unobserved heterogeneity in exposure. Not controlling for such effects may lead to substantial underestimates of the effectiveness of such campaigns. PMID:23049961

Experimental methods for the simulation of supercritical CO2 injection at laboratory scale aimed to investigate capillary trapping

NASA Astrophysics Data System (ADS)

Trevisan, L.; Illangasekare, T. H.; Rodriguez, D.; Sakaki, T.; Cihan, A.; Birkholzer, J. T.; Zhou, Q.

2011-12-01

Geological storage of carbon dioxide in deep geologic formations is being considered as a technical option to reduce greenhouse gas loading to the atmosphere. The processes associated with the movement and stable trapping are complex in deep naturally heterogeneous formations. Three primary mechanisms contribute to trapping; capillary entrapment due to immobilization of the supercritical fluid CO2 within soil pores, liquid CO2 dissolving in the formation water and mineralization. Natural heterogeneity in the formation is expected to affect all three mechanisms. A research project is in progress with the primary goal to improve our understanding of capillary and dissolution trapping during injection and post-injection process, focusing on formation heterogeneity. It is expected that this improved knowledge will help to develop site characterization methods targeting on obtaining the most critical parameters that capture the heterogeneity to design strategies and schemes to maximize trapping. This research combines experiments at the laboratory scale with multiphase modeling to upscale relevant trapping processes to the field scale. This paper presents the results from a set of experiments that were conducted in an intermediate scale test tanks. Intermediate scale testing provides an attractive alternative to investigate these processes under controlled conditions in the laboratory. Conducting these types of experiments is highly challenging as methods have to be developed to extrapolate the data from experiments that are conducted under ambient laboratory conditions to high temperatures and pressures settings in deep geologic formations. We explored the use of a combination of surrogate fluids that have similar density, viscosity contrasts and analogous solubility and interfacial tension as supercritical CO2-brine in deep formations. The extrapolation approach involves the use of dimensionless numbers such as Capillary number (Ca) and the Bond number (Bo). A set of experiments that captures some of the complexities of the geologic heterogeneity and injection scenarios are planned in a 4.8 m long tank. To test the experimental methods and instrumentation, a set of preliminary experiments were conducted in a smaller tank with dimensions 90 cm x 60 cm. The tank was packed to represent both homogeneous and heterogeneous conditions. Using the surrogate fluids, different injection scenarios were tested. Images of the migration plume showed the critical role that heterogeneity plays in stable entrapment. Destructive sampling done at the end of the experiments provided data on the final saturation distributions. Preliminary analysis suggests the entrapment configuration is controlled by the large-scale heterogeneities as well as the pore-scale entrapment mechanisms. The data was used in modeling analysis that is presented in a companion abstract.

Birth order and sibship size: evaluation of the role of selection bias in a case-control study of non-Hodgkin's lymphoma.

PubMed

Mensah, F K; Willett, E V; Simpson, J; Smith, A G; Roman, E

2007-09-15

Substantial heterogeneity has been observed among case-control studies investigating associations between non-Hodgkin's lymphoma and familial characteristics, such as birth order and sibship size. The potential role of selection bias in explaining such heterogeneity is considered within this study. Selection bias according to familial characteristics and socioeconomic status is investigated within a United Kingdom-based case-control study of non-Hodgkin's lymphoma diagnosed during 1998-2001. Reported distributions of birth order and maternal age are each compared with expected reference distributions derived using national birth statistics from the United Kingdom. A method is detailed in which yearly data are used to derive expected distributions, taking account of variability in birth statistics over time. Census data are used to reweight both the case and control study populations such that they are comparable with the general population with regard to socioeconomic status. The authors found little support for an association between non-Hodgkin's lymphoma and birth order or family size and little evidence for an influence of selection bias. However, the findings suggest that between-study heterogeneity could be explained by selection biases that influence the demographic characteristics of participants.

Combined virtual and real robotic test-bed for single operator control of multiple robots

NASA Astrophysics Data System (ADS)

Lee, Sam Y.-S.; Hunt, Shawn; Cao, Alex; Pandya, Abhilash

2010-04-01

Teams of heterogeneous robots with different dynamics or capabilities could perform a variety of tasks such as multipoint surveillance, cooperative transport and explorations in hazardous environments. In this study, we work with heterogeneous robots of semi-autonomous ground and aerial robots for contaminant localization. We developed a human interface system which linked every real robot to its virtual counterpart. A novel virtual interface has been integrated with Augmented Reality that can monitor the position and sensory information from video feed of ground and aerial robots in the 3D virtual environment, and improve user situational awareness. An operator can efficiently control the real multi-robots using the Drag-to-Move method on the virtual multi-robots. This enables an operator to control groups of heterogeneous robots in a collaborative way for allowing more contaminant sources to be pursued simultaneously. The advanced feature of the virtual interface system is guarded teleoperation. This can be used to prevent operators from accidently driving multiple robots into walls and other objects. Moreover, the feature of the image guidance and tracking is able to reduce operator workload.

PHENOTYPIC AND GENETIC HETEROGENEITY AMONG SUBJECTS WITH MILD AIRFLOW OBSTRUCTION IN COPDGENE

PubMed Central

Lee, Jin Hwa; Cho, Michael H.; McDonald, Merry-Lynn N.; Hersh, Craig P.; Castaldi, Peter J.; Crapo, James D.; Wan, Emily S.; Dy, Jennifer G.; Chang, Yale; Regan, Elizabeth A.; Hardin, Megan; DeMeo, Dawn L.; Silverman, Edwin K.

2014-01-01

Background Chronic obstructive pulmonary disease (COPD) is characterized by marked phenotypic heterogeneity. Most previous studies have focused on COPD subjects with FEV1 < 80% predicted. We investigated the clinical and genetic heterogeneity in subjects with mild airflow limitation in spirometry grade 1 defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD 1). Methods Data from current and former smokers participating in the COPDGene Study (NCT00608764) were analyzed. K-means clustering was performed to explore subtypes within 794 GOLD 1 subjects. For all subjects with GOLD 1 and with each cluster, a genome-wide association study and candidate gene testing were performed using smokers with normal lung function as a control group. Combinations of COPD genome-wide significant single nucleotide polymorphisms (SNPs) were tested for association with FEV1 (% predicted) in GOLD 1 and in a combined group of GOLD1 and smoking control subjects. Results K-means clustering of GOLD 1 subjects identified putative “near-normal”, “airway-predominant”, “emphysema-predominant” and “lowest FEV1 % predicted” subtypes. In non-Hispanic whites, the only SNP nominally associated with GOLD 1 status relative to smoking controls was rs7671167 (FAM13A) in logistic regression models with adjustment for age, sex, pack-years of smoking, and genetic ancestry. The emphysema-predominant GOLD 1 cluster was nominally associated with rs7671167 (FAM13A) and rs161976 (BICD1). The lowest FEV1 % predicted cluster was nominally associated with rs1980057 (HHIP) and rs1051730 (CHRNA3). Combinations of COPD genome-wide significant SNPs were associated with FEV1 (% predicted) in a combined group of GOLD 1 and smoking control subjects. Conclusions Our results indicate that GOLD 1 subjects show substantial clinical heterogeneity, which is at least partially related to genetic heterogeneity. PMID:25154699

Assembly of hydrogel units for 3D microenvironment in a poly(dimethylsiloxane) channel

NASA Astrophysics Data System (ADS)

Cho, Chang Hyun; Kwon, Seyong; Park, Je-Kyun

2017-12-01

Construction of three-dimensional (3D) microenvironment become an important issue in recent biological studies due to their biological relevance compared to conventional two-dimensional (2D) microenvironment. Various fabrication techniques have been employed to construct a 3D microenvironment, however, it is difficult to fully satisfy the biological and mechanical properties required for the 3D cell culture system, such as heterogeneous tissue structures generated from the functional differences or diseases. We propose here an assembly method for facile construction of 3D microenvironment in a poly(dimethylsiloxane) (PDMS) channel using hydrogel units. The high-aspect-ratio of hydrogel units was achieved by fabricating these units using a 2D mold. With this approach, 3D heterogeneous hydrogel units were produced and assembled in a PDMS channel by structural hookup. In vivo-like 3D heterogeneous microenvironment in a precisely controllable fluidic system was also demonstrated using a controlled assembly of different types of hydrogel units, which was difficult to obtain from previous methods. By regulating the flow condition, the mechanical stability of the assembled hydrogel units was verified by the flow-induced deformation of hydrogel units. In addition, in vivo-like cell culture environment was demonstrated using an assembly of cell-coated hydrogel units in the fluidic channel. Based on these features, our method expects to provide a beneficial tool for the 3D cell culture module and biomimetic engineering.

Systematic Review on Acupuncture for Treatment of Dysphagia after Stroke

PubMed Central

Ye, Qiuping; Xie, Yu; Shi, Junheng; Ou, Aihua; Xu, Nenggui

2017-01-01

Objective To assess the therapeutic efficacy of acupuncture for dysphagia after stroke. Methods Seven electronic databases were searched from their inception until 31 September 2016. All randomized controlled trials (RCTs) incorporating acupuncture or acupuncture combined with other interventions for treatment of dysphagia after stroke were enrolled. Then they were extracted and assessed by two independent evaluators. Direct comparisons were conducted in RevMan 5.3.0 software. Results 6010 patients of 71 papers were included. The pooled analysis of efficacy rate of 58 studies indicated that acupuncture group was superior to the control group with moderate heterogeneity (RR = 1.17, 95% CI: 1.13 1.21, Z = 9.08, and P < 0.00001); meta-analysis of the studies using blind method showed that the efficacy rate of acupuncture group was 3.01 times that of control group with no heterogeneity (RR = 3.01, 95% CI: 1.95 4.65, Z = 4.97, and P < 0.00001). Only 13 studies mentioned the safety evaluation. Conclusion The result showed that the acupuncture group was better than control group in terms of efficacy rate of dysphagia after stroke. And the combining result of those researches using blind method was more strong in proof. Strict evaluation standard and high-quality RCT design are necessary for further exploration. PMID:28852414

Effectiveness of Multidimensional Family Therapy with Higher Severity Substance-Abusing Adolescents: Report from Two Randomized Controlled Trials

ERIC Educational Resources Information Center

Henderson, Craig E.; Dakof, Gayle A.; Greenbaum, Paul E.; Liddle, Howard A.

2010-01-01

Objective: We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 randomized controlled trials testing multidimensional family therapy (MDFT), an established evidence-based therapy for adolescent drug abuse and delinquency. Method: The first study compared 2 evidence-based adolescent substance…

Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies.

PubMed

Liu, Jia; Duffy, Ben A; Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung

2017-02-15

A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods' performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.

Living systematic reviews: 3. Statistical methods for updating meta-analyses.

PubMed

Simmonds, Mark; Salanti, Georgia; McKenzie, Joanne; Elliott, Julian

2017-11-01

A living systematic review (LSR) should keep the review current as new research evidence emerges. Any meta-analyses included in the review will also need updating as new material is identified. If the aim of the review is solely to present the best current evidence standard meta-analysis may be sufficient, provided reviewers are aware that results may change at later updates. If the review is used in a decision-making context, more caution may be needed. When using standard meta-analysis methods, the chance of incorrectly concluding that any updated meta-analysis is statistically significant when there is no effect (the type I error) increases rapidly as more updates are performed. Inaccurate estimation of any heterogeneity across studies may also lead to inappropriate conclusions. This paper considers four methods to avoid some of these statistical problems when updating meta-analyses: two methods, that is, law of the iterated logarithm and the Shuster method control primarily for inflation of type I error and two other methods, that is, trial sequential analysis and sequential meta-analysis control for type I and II errors (failing to detect a genuine effect) and take account of heterogeneity. This paper compares the methods and considers how they could be applied to LSRs. Copyright © 2017 Elsevier Inc. All rights reserved.

Computational Assessment of Blood Flow Heterogeneity in Peritoneal Dialysis Patients' Cardiac Ventricles

PubMed Central

Kharche, Sanjay R.; So, Aaron; Salerno, Fabio; Lee, Ting-Yim; Ellis, Chris; Goldman, Daniel; McIntyre, Christopher W.

2018-01-01

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status. PMID:29867555

Heterogeneity, pore pressure, and injectate chemistry: Control measures for geologic carbon storage

DOE PAGES

Dewers, Thomas; Eichhubl, Peter; Ganis, Ben; ...

2017-11-28

Desirable outcomes for geologic carbon storage include maximizing storage efficiency, preserving injectivity, and avoiding unwanted consequences such as caprock or wellbore leakage or induced seismicity during and post injection. Here, to achieve these outcomes, three control measures are evident including pore pressure, injectate chemistry, and knowledge and prudent use of geologic heterogeneity. Field, experimental, and modeling examples are presented that demonstrate controllable GCS via these three measures. Observed changes in reservoir response accompanying CO 2 injection at the Cranfield (Mississippi, USA) site, along with lab testing, show potential for use of injectate chemistry as a means to alter fracture permeabilitymore » (with concomitant improvements for sweep and storage efficiency). Further control of reservoir sweep attends brine extraction from reservoirs, with benefit for pressure control, mitigation of reservoir and wellbore damage, and water use. State-of-the-art validated models predict the extent of damage and deformation associated with pore pressure hazards in reservoirs, timing and location of networks of fractures, and development of localized leakage pathways. Experimentally validated geomechanics models show where wellbore failure is likely to occur during injection, and efficiency of repair methods. Use of heterogeneity as a control measure includes where best to inject, and where to avoid attempts at storage. Lastly, an example is use of waste zones or leaky seals to both reduce pore pressure hazards and enhance residual CO 2 trapping.« less

Heterogeneity, pore pressure, and injectate chemistry: Control measures for geologic carbon storage

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

Dewers, Thomas; Eichhubl, Peter; Ganis, Ben

Desirable outcomes for geologic carbon storage include maximizing storage efficiency, preserving injectivity, and avoiding unwanted consequences such as caprock or wellbore leakage or induced seismicity during and post injection. Here, to achieve these outcomes, three control measures are evident including pore pressure, injectate chemistry, and knowledge and prudent use of geologic heterogeneity. Field, experimental, and modeling examples are presented that demonstrate controllable GCS via these three measures. Observed changes in reservoir response accompanying CO 2 injection at the Cranfield (Mississippi, USA) site, along with lab testing, show potential for use of injectate chemistry as a means to alter fracture permeabilitymore » (with concomitant improvements for sweep and storage efficiency). Further control of reservoir sweep attends brine extraction from reservoirs, with benefit for pressure control, mitigation of reservoir and wellbore damage, and water use. State-of-the-art validated models predict the extent of damage and deformation associated with pore pressure hazards in reservoirs, timing and location of networks of fractures, and development of localized leakage pathways. Experimentally validated geomechanics models show where wellbore failure is likely to occur during injection, and efficiency of repair methods. Use of heterogeneity as a control measure includes where best to inject, and where to avoid attempts at storage. Lastly, an example is use of waste zones or leaky seals to both reduce pore pressure hazards and enhance residual CO 2 trapping.« less

Observer-based output consensus of a class of heterogeneous multi-agent systems with unmatched disturbances

NASA Astrophysics Data System (ADS)

Zhang, Jiancheng; Zhu, Fanglai

2018-03-01

In this paper, the output consensus of a class of linear heterogeneous multi-agent systems with unmatched disturbances is considered. Firstly, based on the relative output information among neighboring agents, we propose an asymptotic sliding-mode based consensus control scheme, under which, the output consensus error can converge to zero by removing the disturbances from output channels. Secondly, in order to reach the consensus goal, we design a novel high-order unknown input observer for each agent. It can estimate not only each agent's states and disturbances, but also the disturbances' high-order derivatives, which are required in the control scheme aforementioned above. The observer-based consensus control laws and the convergence analysis of the consensus error dynamics are given. Finally, a simulation example is provided to verify the validity of our methods.

Characterization of heterogeneities from core X-ray scans and borehole wall images in a reefal carbonate reservoir: influence on the porosity structure.

NASA Astrophysics Data System (ADS)

Hebert, V.; Garing, C.; Pezard, P. A.; Gouze, P.; Maria-Sube, Y.; Camoin, G.; Lapointe, P.

2009-04-01

Petrophysical properties of rocks can be largely influenced by heterogeneities. This is particularly true in reefal carbonates, with heterogeneities due to the primary structure of the reef, the degradation of that structure into a fossil form, and fluid circulations with associated dissolutions and recrystallization. We report here a study conducted on Miocene reefal carbonates drilled in the context of salt water intrusion in coastal reservoirs. Salt water intrusion along coastlines is highly influenced by geological and petrophysical structures. In particular, heterogeneities and anisotropy in porous media (karsts, vugs…) control fluid flow and dispersion. A new experimental site has been developed in the South East of Mallorca Island (Spain) in the context of the ALIANCE EC project (2002-2005). This project aimed at developing a strategy for the quantitative analysis and description of fluid flow and salt transport in coastal carbonate aquifers. The site drilled the Miocene carbonate reef platform at Ses Sitjoles, 6 km inland, near the city of Campos. Sea water is found there at 60 to 80 m depth. The geological structure present multi-scale heterogeneities, often bound to either lateral variations of geological facies, or dissolution patterns. The Campos site provides a unique laboratory to study the heterogeneities of carbonate rocks with a saltwater intrusion and develop new borehole investigation methods in this context. The present study focuses on borehole geophysical measurements and images, and core scans. New image analysis methods have been developed to better characterize the presence of heterogeneities in terms of grain-size distribution, formation factor changes and porosity. Cores scans from RX tomography can lead to the extraction of petrophysical parameters from 3D images. For this, the AVIZO software was used here to represent the micro-porosity and vuggy porosity structure. Beyond core analyses, the optical and acoustic borehole wall images provide a direct look at meso-scale porosity beyond cm-scale heterogeneities, such as karstic channels and megapores. The reefal complex is dominated by moldic secondary porosity, which in the upper part of the boreholes. These heterogeneities are characterized by large and elongated molds mainly detected by the acoustic images. In slope, corresponding to the lower part of the structure, moldic porosity is characterized by small and round shaped molds. Vuggy porosity varies mainly from 5 to 40% along 100 m deep boreholes. But, in the slope part, the porosity is about 0% although it can reach 90% in karstic area. In all, the distribution of pore types is strongly controlled by that of lithofacies and water paleo-levels, leading to extensive cementation processes with the resulting occlusion of pore spaces. The combined analysis of porosity with complementary methods in terms of spacial resolution leads to the quantitative determination and description of microstructural heterogeneities in carbonate porous media. It is a key to model the reservoir mesoscale structure and fluid flows within it.

A comparison of solute-transport solution techniques based on inverse modelling results

USGS Publications Warehouse

Mehl, S.; Hill, M.C.

2000-01-01

Five common numerical techniques (finite difference, predictor-corrector, total-variation-diminishing, method-of-characteristics, and modified-method-of-characteristics) were tested using simulations of a controlled conservative tracer-test experiment through a heterogeneous, two-dimensional sand tank. The experimental facility was constructed using randomly distributed homogeneous blocks of five sand types. This experimental model provides an outstanding opportunity to compare the solution techniques because of the heterogeneous hydraulic conductivity distribution of known structure, and the availability of detailed measurements with which to compare simulated concentrations. The present work uses this opportunity to investigate how three common types of results-simulated breakthrough curves, sensitivity analysis, and calibrated parameter values-change in this heterogeneous situation, given the different methods of simulating solute transport. The results show that simulated peak concentrations, even at very fine grid spacings, varied because of different amounts of numerical dispersion. Sensitivity analysis results were robust in that they were independent of the solution technique. They revealed extreme correlation between hydraulic conductivity and porosity, and that the breakthrough curve data did not provide enough information about the dispersivities to estimate individual values for the five sands. However, estimated hydraulic conductivity values are significantly influenced by both the large possible variations in model dispersion and the amount of numerical dispersion present in the solution technique.Five common numerical techniques (finite difference, predictor-corrector, total-variation-diminishing, method-of-characteristics, and modified-method-of-characteristics) were tested using simulations of a controlled conservative tracer-test experiment through a heterogeneous, two-dimensional sand tank. The experimental facility was constructed using randomly distributed homogeneous blocks of five sand types. This experimental model provides an outstanding opportunity to compare the solution techniques because of the heterogeneous hydraulic conductivity distribution of known structure, and the availability of detailed measurements with which to compare simulated concentrations. The present work uses this opportunity to investigate how three common types of results - simulated breakthrough curves, sensitivity analysis, and calibrated parameter values - change in this heterogeneous situation, given the different methods of simulating solute transport. The results show that simulated peak concentrations, even at very fine grid spacings, varied because of different amounts of numerical dispersion. Sensitivity analysis results were robust in that they were independent of the solution technique. They revealed extreme correlation between hydraulic conductivity and porosity, and that the breakthrough curve data did not provide enough information about the dispersivities to estimate individual values for the five sands. However, estimated hydraulic conductivity values are significantly influenced by both the large possible variations in model dispersion and the amount of numerical dispersion present in the solution technique.

Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies.

PubMed

Rahmani, Elior; Zaitlen, Noah; Baran, Yael; Eng, Celeste; Hu, Donglei; Galanter, Joshua; Oh, Sam; Burchard, Esteban G; Eskin, Eleazar; Zou, James; Halperin, Eran

2016-05-01

In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) and designed for the correction of cell type heterogeneity in EWAS. ReFACTor does not require knowledge of cell counts, and it provides improved estimates of cell type composition, resulting in improved power and control for false positives in EWAS. Corresponding software is available at http://www.cs.tau.ac.il/~heran/cozygene/software/refactor.html.

Chaotic dynamics in nonlinear duopoly Stackelberg game with heterogeneous players

NASA Astrophysics Data System (ADS)

Xiao, Yue; Peng, Yu; Lu, Qian; Wu, Xue

2018-02-01

In this paper, a nonlinear duopoly Stackelberg game of competition on output is concerned. In consideration of the effects of difference between plan products and actual products, the two heterogeneous players always adopt suitable strategies which can improve their benefits most. In general, status of each firm is unequal. As the firms take strategies sequentially and produce simultaneously, complex behaviors are brought about. Numerical simulation presents period doubling bifurcation, maximal Lyapunov exponent and chaos. Moreover, an appropriate method of chaos controlling is applied and fractal dimension is analyzed as well.

Detecting defective electrical components in heterogeneous infra-red images by spatial control charts

NASA Astrophysics Data System (ADS)

Jamshidieini, Bahman; Fazaee, Reza

2016-05-01

Distribution network components connect machines and other loads to electrical sources. If resistance or current of any component is more than specified range, its temperature may exceed the operational limit which can cause major problems. Therefore, these defects should be found and eliminated according to their severity. Although infra-red cameras have been used for inspection of electrical components, maintenance prioritization of distribution cubicles is mostly based on personal perception and lack of training data prevents engineers from developing image processing methods. New research on the spatial control chart encouraged us to use statistical approaches instead of the pattern recognition for the image processing. In the present study, a new scanning pattern which can tolerate heavy autocorrelation among adjacent pixels within infra-red image was developed and for the first time combination of kernel smoothing, spatial control charts and local robust regression were used for finding defects within heterogeneous infra-red images of old distribution cubicles. This method does not need training data and this advantage is crucially important when the training data is not available.

Modeling Heterogeneity in Momentary Interpersonal and Affective Dynamic Processes in Borderline Personality Disorder

PubMed Central

Wright, Aidan G. C.; Hallquist, Michael N.; Stepp, Stephanie D.; Scott, Lori N.; Beeney, Joseph E.; Lazarus, Sophie A.; Pilkonis, Paul A.

2016-01-01

Borderline personality disorder (BPD) is a diagnosis defined by impairments in several dynamic processes (e.g., interpersonal relating, affect regulation, behavioral control). Theories of BPD emphasize that these impairments appear in specific contexts, and emerging results confirm this view. At the same time, BPD is a complex construct that encompasses individuals with heterogeneous pathology. These features—dynamic processes, situational specificity, and individual heterogeneity—pose significant assessment challenges. In the current study, we demonstrate assessment and analytic methods that capture both between-person differences and within-person changes over time. Twenty-five participants diagnosed with BPD completed event-contingent, ambulatory assessment protocols over 21 days. We used p-technique factor analyses to identify person-specific psychological structures consistent with clinical theories of personality. Five exemplar cases are selected and presented in detail to showcase the potential utility of these methods. The presented cases' factor structures reflect not only heterogeneity but also suggest points of convergence. The factors also demonstrated significant associations with important clinical targets (self-harm, interpersonal violence). PMID:27317561

[Application of Stata software to test heterogeneity in meta-analysis method].

PubMed

Wang, Dan; Mou, Zhen-yun; Zhai, Jun-xia; Zong, Hong-xia; Zhao, Xiao-dong

2008-07-01

To introduce the application of Stata software to heterogeneity test in meta-analysis. A data set was set up according to the example in the study, and the corresponding commands of the methods in Stata 9 software were applied to test the example. The methods used were Q-test and I2 statistic attached to the fixed effect model forest plot, H statistic and Galbraith plot. The existence of the heterogeneity among studies could be detected by Q-test and H statistic and the degree of the heterogeneity could be detected by I2 statistic. The outliers which were the sources of the heterogeneity could be spotted from the Galbraith plot. Heterogeneity test in meta-analysis can be completed by the four methods in Stata software simply and quickly. H and I2 statistics are more robust, and the outliers of the heterogeneity can be clearly seen in the Galbraith plot among the four methods.

Modeling the heterogeneous traffic correlations in urban road systems using traffic-enhanced community detection approach

NASA Astrophysics Data System (ADS)

Lu, Feng; Liu, Kang; Duan, Yingying; Cheng, Shifen; Du, Fei

2018-07-01

A better characterization of the traffic influence among urban roads is crucial for traffic control and traffic forecasting. The existence of spatial heterogeneity imposes great influence on modeling the extent and degree of road traffic correlation, which is usually neglected by the traditional distance based method. In this paper, we propose a traffic-enhanced community detection approach to spatially reveal the traffic correlation in city road networks. First, the road network is modeled as a traffic-enhanced dual graph with the closeness between two road segments determined not only by their topological connection, but also by the traffic correlation between them. Then a flow-based community detection algorithm called Infomap is utilized to identify the road segment clusters. Evaluated by Moran's I, Calinski-Harabaz Index and the traffic interpolation application, we find that compared to the distance based method and the community based method, our proposed traffic-enhanced community based method behaves better in capturing the extent of traffic relevance as both the topological structure of the road network and the traffic correlations among urban roads are considered. It can be used in more traffic-related applications, such as traffic forecasting, traffic control and guidance.

Comparing methods for estimation of heterogeneous treatment effects using observational data from health care databases.

PubMed

Wendling, T; Jung, K; Callahan, A; Schuler, A; Shah, N H; Gallego, B

2018-06-03

There is growing interest in using routinely collected data from health care databases to study the safety and effectiveness of therapies in "real-world" conditions, as it can provide complementary evidence to that of randomized controlled trials. Causal inference from health care databases is challenging because the data are typically noisy, high dimensional, and most importantly, observational. It requires methods that can estimate heterogeneous treatment effects while controlling for confounding in high dimensions. Bayesian additive regression trees, causal forests, causal boosting, and causal multivariate adaptive regression splines are off-the-shelf methods that have shown good performance for estimation of heterogeneous treatment effects in observational studies of continuous outcomes. However, it is not clear how these methods would perform in health care database studies where outcomes are often binary and rare and data structures are complex. In this study, we evaluate these methods in simulation studies that recapitulate key characteristics of comparative effectiveness studies. We focus on the conditional average effect of a binary treatment on a binary outcome using the conditional risk difference as an estimand. To emulate health care database studies, we propose a simulation design where real covariate and treatment assignment data are used and only outcomes are simulated based on nonparametric models of the real outcomes. We apply this design to 4 published observational studies that used records from 2 major health care databases in the United States. Our results suggest that Bayesian additive regression trees and causal boosting consistently provide low bias in conditional risk difference estimates in the context of health care database studies. Copyright © 2018 John Wiley & Sons, Ltd.

An empirical likelihood ratio test robust to individual heterogeneity for differential expression analysis of RNA-seq.

PubMed

Xu, Maoqi; Chen, Liang

2018-01-01

The individual sample heterogeneity is one of the biggest obstacles in biomarker identification for complex diseases such as cancers. Current statistical models to identify differentially expressed genes between disease and control groups often overlook the substantial human sample heterogeneity. Meanwhile, traditional nonparametric tests lose detailed data information and sacrifice the analysis power, although they are distribution free and robust to heterogeneity. Here, we propose an empirical likelihood ratio test with a mean-variance relationship constraint (ELTSeq) for the differential expression analysis of RNA sequencing (RNA-seq). As a distribution-free nonparametric model, ELTSeq handles individual heterogeneity by estimating an empirical probability for each observation without making any assumption about read-count distribution. It also incorporates a constraint for the read-count overdispersion, which is widely observed in RNA-seq data. ELTSeq demonstrates a significant improvement over existing methods such as edgeR, DESeq, t-tests, Wilcoxon tests and the classic empirical likelihood-ratio test when handling heterogeneous groups. It will significantly advance the transcriptomics studies of cancers and other complex disease. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mach wave properties in the presence of source and medium heterogeneity

NASA Astrophysics Data System (ADS)

Vyas, J. C.; Mai, P. M.; Galis, M.; Dunham, Eric M.; Imperatori, W.

2018-06-01

We investigate Mach wave coherence for kinematic supershear ruptures with spatially heterogeneous source parameters, embedded in 3D scattering media. We assess Mach wave coherence considering: 1) source heterogeneities in terms of variations in slip, rise time and rupture speed; 2) small-scale heterogeneities in Earth structure, parameterized from combinations of three correlation lengths and two standard deviations (assuming von Karman power spectral density with fixed Hurst exponent); and 3) joint effects of source and medium heterogeneities. Ground-motion simulations are conducted using a generalized finite-difference method, choosing a parameterization such that the highest resolved frequency is ˜5 Hz. We discover that Mach wave coherence is slightly diminished at near fault distances (< 10 km) due to spatially variable slip and rise time; beyond this distance the Mach wave coherence is more strongly reduced by wavefield scattering due to small-scale heterogeneities in Earth structure. Based on our numerical simulations and theoretical considerations we demonstrate that the standard deviation of medium heterogeneities controls the wavefield scattering, rather than the correlation length. In addition, we find that peak ground accelerations in the case of combined source and medium heterogeneities are consistent with empirical ground motion prediction equations for all distances, suggesting that in nature ground shaking amplitudes for supershear ruptures may not be elevated due to complexities in the rupture process and seismic wave-scattering.

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions -We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

Using Naturalistic Methods to Examine Real-World Driving Behavior in Individuals With TBI Upon Return to Driving: A Pilot Study.

PubMed

Hua, Phuong; Charlton, Judith L; Ponsford, Jennie L; Gooden, James R; Ross, Pamela E; Bédard, Michel; Marshall, Shawn; Gagnon, Sylvain; Stolwyk, Renerus J

2018-05-31

To characterize the real-world driving habits of individuals with traumatic brain injury (TBI) using naturalistic methods and to demonstrate the feasibility of such methods in exploring return to driving after TBI. After passing an on-road driving assessment, 8 participants with TBI and 23 matched controls had an in-vehicle device installed to record information regarding their driving patterns (distance, duration, and start/end times) for 90 days. The overall number of trips, distance and duration or percentage of trips during peak hour, above 15 km from home or on freeways/highways did not differ between groups. However, the TBI group drove significantly less at night, and more during the daytime, than controls. Exploratory analyses using geographic information system (GIS) also demonstrated significant within-group heterogeneity for the TBI group in terms of location of travel. The TBI and control groups were largely comparable in terms of driving exposure, except for when they drove, which may indicate small group differences in driving self-regulatory practices. However, the GIS evidence suggests driving patterns within the TBI group were heterogeneous. These findings provide evidence for the feasibility of employing noninvasive in-car recording devices to explore real-world driving behavior post-TBI.

Multilayer Optimization of Heterogeneous Networks Using Grammatical Genetic Programming.

PubMed

Fenton, Michael; Lynch, David; Kucera, Stepan; Claussen, Holger; O'Neill, Michael

2017-09-01

Heterogeneous cellular networks are composed of macro cells (MCs) and small cells (SCs) in which all cells occupy the same bandwidth. Provision has been made under the third generation partnership project-long term evolution framework for enhanced intercell interference coordination (eICIC) between cell tiers. Expanding on previous works, this paper instruments grammatical genetic programming to evolve control heuristics for heterogeneous networks. Three aspects of the eICIC framework are addressed including setting SC powers and selection biases, MC duty cycles, and scheduling of user equipments (UEs) at SCs. The evolved heuristics yield minimum downlink rates three times higher than a baseline method, and twice that of a state-of-the-art benchmark. Furthermore, a greater number of UEs receive transmissions under the proposed scheme than in either the baseline or benchmark cases.

New heterogeneous test statistics for the unbalanced fixed-effect nested design.

PubMed

Guo, Jiin-Huarng; Billard, L; Luh, Wei-Ming

2011-05-01

When the underlying variances are unknown or/and unequal, using the conventional F test is problematic in the two-factor hierarchical data structure. Prompted by the approximate test statistics (Welch and Alexander-Govern methods), the authors develop four new heterogeneous test statistics to test factor A and factor B nested within A for the unbalanced fixed-effect two-stage nested design under variance heterogeneity. The actual significance levels and statistical power of the test statistics were compared in a simulation study. The results show that the proposed procedures maintain better Type I error rate control and have greater statistical power than those obtained by the conventional F test in various conditions. Therefore, the proposed test statistics are recommended in terms of robustness and easy implementation. ©2010 The British Psychological Society.

Changing cluster composition in cluster randomised controlled trials: design and analysis considerations

PubMed Central

2014-01-01

Background There are many methodological challenges in the conduct and analysis of cluster randomised controlled trials, but one that has received little attention is that of post-randomisation changes to cluster composition. To illustrate this, we focus on the issue of cluster merging, considering the impact on the design, analysis and interpretation of trial outcomes. Methods We explored the effects of merging clusters on study power using standard methods of power calculation. We assessed the potential impacts on study findings of both homogeneous cluster merges (involving clusters randomised to the same arm of a trial) and heterogeneous merges (involving clusters randomised to different arms of a trial) by simulation. To determine the impact on bias and precision of treatment effect estimates, we applied standard methods of analysis to different populations under analysis. Results Cluster merging produced a systematic reduction in study power. This effect depended on the number of merges and was most pronounced when variability in cluster size was at its greatest. Simulations demonstrate that the impact on analysis was minimal when cluster merges were homogeneous, with impact on study power being balanced by a change in observed intracluster correlation coefficient (ICC). We found a decrease in study power when cluster merges were heterogeneous, and the estimate of treatment effect was attenuated. Conclusions Examples of cluster merges found in previously published reports of cluster randomised trials were typically homogeneous rather than heterogeneous. Simulations demonstrated that trial findings in such cases would be unbiased. However, simulations also showed that any heterogeneous cluster merges would introduce bias that would be hard to quantify, as well as having negative impacts on the precision of estimates obtained. Further methodological development is warranted to better determine how to analyse such trials appropriately. Interim recommendations include avoidance of cluster merges where possible, discontinuation of clusters following heterogeneous merges, allowance for potential loss of clusters and additional variability in cluster size in the original sample size calculation, and use of appropriate ICC estimates that reflect cluster size. PMID:24884591

Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies

PubMed Central

Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung

2017-01-01

A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods’ performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. PMID:27993672

A new ghost-node method for linking different models and initial investigations of heterogeneity and nonmatching grids

USGS Publications Warehouse

Dickinson, J.E.; James, S.C.; Mehl, S.; Hill, M.C.; Leake, S.A.; Zyvoloski, G.A.; Faunt, C.C.; Eddebbarh, A.-A.

2007-01-01

A flexible, robust method for linking parent (regional-scale) and child (local-scale) grids of locally refined models that use different numerical methods is developed based on a new, iterative ghost-node method. Tests are presented for two-dimensional and three-dimensional pumped systems that are homogeneous or that have simple heterogeneity. The parent and child grids are simulated using the block-centered finite-difference MODFLOW and control-volume finite-element FEHM models, respectively. The models are solved iteratively through head-dependent (child model) and specified-flow (parent model) boundary conditions. Boundary conditions for models with nonmatching grids or zones of different hydraulic conductivity are derived and tested against heads and flows from analytical or globally-refined models. Results indicate that for homogeneous two- and three-dimensional models with matched grids (integer number of child cells per parent cell), the new method is nearly as accurate as the coupling of two MODFLOW models using the shared-node method and, surprisingly, errors are slightly lower for nonmatching grids (noninteger number of child cells per parent cell). For heterogeneous three-dimensional systems, this paper compares two methods for each of the two sets of boundary conditions: external heads at head-dependent boundary conditions for the child model are calculated using bilinear interpolation or a Darcy-weighted interpolation; specified-flow boundary conditions for the parent model are calculated using model-grid or hydrogeologic-unit hydraulic conductivities. Results suggest that significantly more accurate heads and flows are produced when both Darcy-weighted interpolation and hydrogeologic-unit hydraulic conductivities are used, while the other methods produce larger errors at the boundary between the regional and local models. The tests suggest that, if posed correctly, the ghost-node method performs well. Additional testing is needed for highly heterogeneous systems. ?? 2007 Elsevier Ltd. All rights reserved.

HYDRA: Revealing heterogeneity of imaging and genetic patterns through a multiple max-margin discriminative analysis framework.

PubMed

Varol, Erdem; Sotiras, Aristeidis; Davatzikos, Christos

2017-01-15

Multivariate pattern analysis techniques have been increasingly used over the past decade to derive highly sensitive and specific biomarkers of diseases on an individual basis. The driving assumption behind the vast majority of the existing methodologies is that a single imaging pattern can distinguish between healthy and diseased populations, or between two subgroups of patients (e.g., progressors vs. non-progressors). This assumption effectively ignores the ample evidence for the heterogeneous nature of brain diseases. Neurodegenerative, neuropsychiatric and neurodevelopmental disorders are largely characterized by high clinical heterogeneity, which likely stems in part from underlying neuroanatomical heterogeneity of various pathologies. Detecting and characterizing heterogeneity may deepen our understanding of disease mechanisms and lead to patient-specific treatments. However, few approaches tackle disease subtype discovery in a principled machine learning framework. To address this challenge, we present a novel non-linear learning algorithm for simultaneous binary classification and subtype identification, termed HYDRA (Heterogeneity through Discriminative Analysis). Neuroanatomical subtypes are effectively captured by multiple linear hyperplanes, which form a convex polytope that separates two groups (e.g., healthy controls from pathologic samples); each face of this polytope effectively defines a disease subtype. We validated HYDRA on simulated and clinical data. In the latter case, we applied the proposed method independently to the imaging and genetic datasets of the Alzheimer's Disease Neuroimaging Initiative (ADNI 1) study. The imaging dataset consisted of T1-weighted volumetric magnetic resonance images of 123 AD patients and 177 controls. The genetic dataset consisted of single nucleotide polymorphism information of 103 AD patients and 139 controls. We identified 3 reproducible subtypes of atrophy in AD relative to controls: (1) diffuse and extensive atrophy, (2) precuneus and extensive temporal lobe atrophy, as well some prefrontal atrophy, (3) atrophy pattern very much confined to the hippocampus and the medial temporal lobe. The genetics dataset yielded two subtypes of AD characterized mainly by the presence/absence of the apolipoprotein E (APOE) ε4 genotype, but also involving differential presence of risk alleles of CD2AP, SPON1 and LOC39095 SNPs that were associated with differences in the respective patterns of brain atrophy, especially in the precuneus. The results demonstrate the potential of the proposed approach to map disease heterogeneity in neuroimaging and genetic studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Assembly of tissue engineered blood vessels with spatially-controlled heterogeneities.

PubMed

Strobel, Hannah A; Hookway, Tracy; Piola, Marco; Fiore, Gianfranco Beniamino; Soncini, Monica; Alsberg, Eben; Rolle, Marsha

2018-05-04

Tissue-engineered human blood vessels may enable in vitro disease modeling and drug screening to accelerate advances in vascular medicine. Existing methods for tissue engineered blood vessel (TEBV) fabrication create homogenous tubes not conducive to modeling the focal pathologies characteristic of vascular disease. We developed a system for generating self-assembled human smooth muscle cell ring-units, which were fused together into TEBVs. The goal of this study was to assess the feasibility of modular assembly and fusion of ring building units to fabricate spatially-controlled, heterogeneous tissue tubes. We first aimed to enhance fusion and reduce total culture time, and determined that reducing ring pre-culture duration improved tube fusion. Next, we incorporated electrospun polymer ring units onto tube ends as reinforced extensions, which allowed us to cannulate tubes after only 7 days of fusion, and culture tubes with luminal flow in a custom bioreactor. To create focal heterogeneities, we incorporated gelatin microspheres into select ring units during self-assembly, and fused these rings between ring units without microspheres. Cells within rings maintained their spatial position within tissue tubes after fusion. This work describes a platform approach for creating modular TEBVs with spatially-defined structural heterogeneities, which may ultimately be applied to mimic focal diseases such as intimal hyperplasia or aneurysm.

Distributed adaptive neural network control for a class of heterogeneous nonlinear multi-agent systems subject to actuation failures

NASA Astrophysics Data System (ADS)

Cui, Bing; Zhao, Chunhui; Ma, Tiedong; Feng, Chi

2017-02-01

In this paper, the cooperative adaptive consensus tracking problem for heterogeneous nonlinear multi-agent systems on directed graph is addressed. Each follower is modelled as a general nonlinear system with the unknown and nonidentical nonlinear dynamics, disturbances and actuator failures. Cooperative fault tolerant neural network tracking controllers with online adaptive learning features are proposed to guarantee that all agents synchronise to the trajectory of one leader with bounded adjustable synchronisation errors. With the help of linear quadratic regulator-based optimal design, a graph-dependent Lyapunov proof provides error bounds that depend on the graph topology, one virtual matrix and some design parameters. Of particular interest is that if the control gain is selected appropriately, the proposed control scheme can be implemented in a unified framework no matter whether there are faults or not. Furthermore, the fault detection and isolation are not needed to implement. Finally, a simulation is given to verify the effectiveness of the proposed method.

Visual evoked potentials of mildly mentally retarded and control children.

PubMed

Gasser, T; Pietz, J; Schellberg, D; Köhler, W

1988-10-01

Visual evoked potentials (VEPs) were recorded from 25 10- to 13-year-old mildly mentally retarded children and compared with those from 31 control children of the same age-range. Correlations of VEPs with age were weak, but a relationship between VEPs and IQ was demonstrated for the control group. The retarded group had significantly longer latencies and higher amplitude peaks than the control group, with the differences occurring primarily over non-specific cortex and for secondary components. Analysis also showed that the retarded group were neurophysiologically heterogeneous. Since the same children had been analyzed earlier by quantitative EEG methods, comparisons are made with respect to these two methods of investigating brain function.

Host species heterogeneity in the epidemiology of Nesopora caninum

PubMed Central

Pomeroy, Laura W.; Moritz, Mark; Saville, William; Wolfe, Barbara; Garabed, Rebecca

2017-01-01

Pathogen transmission across species drives disease emergence; however, mechanisms by which multi-host pathogens cross species boundaries are not well identified. This knowledge gap prevents integrated and targeted control in an epidemiologically continuous ecosystem. Our goal is to describe the impact of host species heterogeneity on the epidemiology of Neospora caninum circulating between livestock and wildlife in southeastern Ohio. We collected biological samples from Père David’s deer (Elaphurus davidianus) located at an outdoor wildlife conservation center; from cattle raised at farms adjacent to the center; and from wild white-tailed deer that roamed across farm and center boundaries. We designed nested infectious disease models of competing hypotheses about transmission and used collected data to fit the models, thereby estimating important immunological and transmission quantities which describe the species-specific contribution to the persistence of this pathogen in the community. We applied these data and models to suggest appropriate species-specific disease control methods. Results show that immunity in cattle and Pére David’s deer wanes over time, while in white-tailed deer immunity appears to be lifelong. Transmission quantities for cattle were estimated at values below the threshold for an outbreak (Rt < 1), meaning that chains of transmission are not maintained within this population and infections must occur due to reintroduction from an outside source. Pére David’s deer and white-tailed deer both could maintain continuous chains of transmission within their group (Rt > 1). Therefore, we propose that control of contact with outside sources will be useful for disease control in cattle; boosting immunity with vaccines might be an avenue to prevent infection in cattle and Père David’s deer. White-tailed deer are a potential maintenance host for infection and require further study to determine optimal control methods. Community-level investigations like this allow us to better evaluate heterogeneities in transmission processes that ultimately guide targeted control. PMID:28850580

Heat and solute tracers: how do they compare in heterogeneous aquifers?

PubMed

Irvine, Dylan J; Simmons, Craig T; Werner, Adrian D; Graf, Thomas

2015-04-01

A comparison of groundwater velocity in heterogeneous aquifers estimated from hydraulic methods, heat and solute tracers was made using numerical simulations. Aquifer heterogeneity was described by geostatistical properties of the Borden, Cape Cod, North Bay, and MADE aquifers. Both heat and solute tracers displayed little systematic under- or over-estimation in velocity relative to a hydraulic control. The worst cases were under-estimates of 6.63% for solute and 2.13% for the heat tracer. Both under- and over-estimation of velocity from the heat tracer relative to the solute tracer occurred. Differences between the estimates from the tracer methods increased as the mean velocity decreased, owing to differences in rates of molecular diffusion and thermal conduction. The variance in estimated velocity using all methods increased as the variance in log-hydraulic conductivity (K) and correlation length scales increased. The variance in velocity for each scenario was remarkably small when compared to σ2 ln(K) for all methods tested. The largest variability identified was for the solute tracer where 95% of velocity estimates ranged by a factor of 19 in simulations where 95% of the K values varied by almost four orders of magnitude. For the same K-fields, this range was a factor of 11 for the heat tracer. The variance in estimated velocity was always lowest when using heat as a tracer. The study results suggest that a solute tracer will provide more understanding about the variance in velocity caused by aquifer heterogeneity and a heat tracer provides a better approximation of the mean velocity. © 2013, National Ground Water Association.

A jaw calibration method to provide a homogeneous dose distribution in the matching region when using a monoisocentric beam split technique.

PubMed

Cenizo, E; García-Pareja, S; Galán, P; Bodineau, C; Caudepón, F; Casado, F J

2011-05-01

Asymmetric collimators are currently available in most of linear accelerators. They involve a lot of clinical improvements, such as the monoisocentric beam split technique that is more and more used in many external radiotherapy treatments. The tolerance established for each independent jaw positioning is 1 mm. Within this tolerance, a gap or overlap of the collimators up to 2 mm can occur in the half beams matching region, causing dose heterogeneities up to 40%. In order to solve this dosimetric problem, we propose an accurate jaw calibration method based on the Monte Carlo modeling of linac photon beams. Simulating different jaw misalignments, the dose distribution occurring in the matching region for each particular configuration is precisely known, so we can relate the misalignment of the jaws with the maximum heterogeneity produced. From experimental measurements using film dosimetry, and taking into account Monte Carlo results, we obtain the actual misalignment of each jaw. By direct inspection of the readings of the potentiometers that control the position of the jaws, high precision correction can be performed, adjusting the obtained misalignments. In the linac studied, the dose heterogeneity in the junction performed with X jaws (those farther from the source), and 6 MV photon beam was initially over 12%, although each jaw was within the tolerance in position. After jaw calibration, the heterogeneity was reduced to below 3%. With this method, we are able to reduce the positioning accuracy to 0.2 mm. Consequently, the dose distribution in the junction of abutted fields is highly smoothed, achieving the maximum dose heterogeneity to be less than 3%.

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

PubMed Central

2010-01-01

Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID:20540727

The finite state projection approach to analyze dynamics of heterogeneous populations

NASA Astrophysics Data System (ADS)

Johnson, Rob; Munsky, Brian

2017-06-01

Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity. The finite state projection (FSP) approach has often been used to analyze the statistics of independent cells. Here, we extend the FSP analysis to explore the coupling of cell dynamics and biomolecule dynamics within a population. This extension allows a general framework with which to model the state occupations of a heterogeneous, isogenic population of dividing and expiring cells. The method is demonstrated with a simple model of cell-cycle progression, which we use to explore possible dynamics of drug resistance phenotypes in dividing cells. We use this method to show how stochastic single-cell behaviors affect population level efficacy of drug treatments, and we illustrate how slight modifications to treatment regimens may have dramatic effects on drug efficacy.

Size and composition-controlled fabrication of VO2 nanocrystals by terminated cluster growth

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

Anders, Andre; Slack, Jonathan

2013-05-14

A physical vapor deposition-based route for the fabrication of VO2 nanoparticles is demonstrated, consisting of reactive sputtering and vapor condensation at elevated pressures. The oxidation of vanadium atoms is an efficient heterogeneous nucleation method, leading to high nanoparticle throughtput. Fine control of the nanoparticle size and composition is obtained. Post growth annealing leads to crystalline VO2 nanoparticles with optimum thermocromic and plasmonic properties.

Delay-based virtual congestion control in multi-tenant datacenters

NASA Astrophysics Data System (ADS)

Liu, Yuxin; Zhu, Danhong; Zhang, Dong

2018-03-01

With the evolution of cloud computing and virtualization, the congestion control of virtual datacenters has become the basic issue for multi-tenant datacenters transmission. Regarding to the friendly conflict of heterogeneous congestion control among multi-tenant, this paper proposes a delay-based virtual congestion control, which translates the multi-tenant heterogeneous congestion control into delay-based feedback uniformly by setting the hypervisor translation layer, modifying three-way handshake of explicit feedback and packet loss feedback and throttling receive window. The simulation results show that the delay-based virtual congestion control can effectively solve the unfairness of heterogeneous feedback congestion control algorithms.

Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood.

PubMed

Price, Rebecca B; Lane, Stephanie; Gates, Kathleen; Kraynak, Thomas E; Horner, Michelle S; Thase, Michael E; Siegle, Greg J

2017-02-15

There is well-known heterogeneity in affective mechanisms in depression that may extend to positive affect. We used data-driven parsing of neural connectivity to reveal subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention. Ninety-two individuals (68 depressed patients, 24 never-depressed control subjects) completed a sustained positive mood induction during functional magnetic resonance imaging. Directed functional connectivity paths within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation (GIMME), a method shown to accurately recover the direction and presence of connectivity paths in individual participants. During model selection, individuals were clustered using community detection on neural connectivity estimates. Subgroups were externally tested across multiple levels of analysis. Two connectivity-based subgroups emerged: subgroup A, characterized by weaker connectivity overall, and subgroup B, exhibiting hyperconnectivity (relative to subgroup A), particularly among ventral affective regions. Subgroup predicted diagnostic status (subgroup B contained 81% of patients; 50% of control subjects; χ 2 = 8.6, p = .003) and default mode network connectivity during a separate resting-state task. Among patients, subgroup B members had higher self-reported symptoms, lower sustained positive mood during the induction, and higher negative bias on a reaction-time task. Symptom-based depression subgroups did not predict these external variables. Neural connectivity-based categorization travels with diagnostic category and is clinically predictive, but not clinically deterministic. Both patients and control subjects showed heterogeneous, and overlapping, profiles. The larger and more severely affected patient subgroup was characterized by ventrally driven hyperconnectivity during positive processing. Data-driven parsing suggests heterogeneous substrates of depression and possible resilience in control subjects in spite of biological overlap. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Prevalence of arterial hypertension among Brazilian adolescents: systematic review and meta-analysis

PubMed Central

2013-01-01

Background Cardiovascular diseases are the leading cause of death in the world and are responsible for a high number of disability-adjusted life years. Elevated blood pressure is an independent, linear and continuous risk factor for cardiovascular disease and has also been reported in the young population. Brazil is a country of continental dimensions, and is very heterogeneous with respect to socioeconomic and cultural aspects. Brazilian studies on the subject of hypertension in adolescence are not nationally representative, and this provides a rationale for the conduction of a meta-analysis to assess the magnitude of the problem in the country. Methods Hypertension studies in adolescents published from 1990 to September 2010 were searched in six electronic databases. Forest plots of the prevalence of hypertension were built for the overall population and by gender. Heterogeneity was assessed using I2 statistics. Meta-regression models were adjusted in order to identify possible sources of heterogeneity. Results Of 3,631 articles initially identified, 17 were considered eligible for systematic review. The pooled prevalence of hypertension, estimated through random effects models, was 8.12% (95% CI 6.24 - 10.52) for the total population. Overall, prevalence was higher in males, 8.75% (95% CI 5.81 - 12.96) than females, 6.31%, (95% CI 4.41 - 8.96). Several variables were investigated in the heterogeneity analysis: region of the study, sample size, age and method of blood pressure measurement. The only variables that partially and inconsistently explained the observed heterogeneity (I2 = 95.3%) were the region of the country where the study was conducted and sample. Conclusions There was a large variation in hypertension prevalence and in the methods used for its evaluation throughout studies with Brazilian adolescents, indicating the need for standardized procedures and validated methods for hypertension measurement. Despite the large observed heterogeneity, and the small number of studies in some regions of Brazil, the pooled prevalence found in both males and females shows that systemic arterial hypertension should be monitored in the population aged 10–20 years and that specific measures are required to prevent and control the disease, as well as its risk factors. Studies that compare regional heterogeneities may contribute to the knowledge of factors associated with increased blood pressure among adolescents. PMID:24025095

Quantification of heterogeneity observed in medical images.

PubMed

Brooks, Frank J; Grigsby, Perry W

2013-03-02

There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities. In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection. We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts. These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity.

Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation.

PubMed

Chisholm, Rebecca H; Lorenzi, Tommaso; Clairambault, Jean

2016-11-01

Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level. We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies. Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies. Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.

Random sphere packing model of heterogeneous propellants

NASA Astrophysics Data System (ADS)

Kochevets, Sergei Victorovich

It is well recognized that combustion of heterogeneous propellants is strongly dependent on the propellant morphology. Recent developments in computing systems make it possible to start three-dimensional modeling of heterogeneous propellant combustion. A key component of such large scale computations is a realistic model of industrial propellants which retains the true morphology---a goal never achieved before. The research presented develops the Random Sphere Packing Model of heterogeneous propellants and generates numerical samples of actual industrial propellants. This is done by developing a sphere packing algorithm which randomly packs a large number of spheres with a polydisperse size distribution within a rectangular domain. First, the packing code is developed, optimized for performance, and parallelized using the OpenMP shared memory architecture. Second, the morphology and packing fraction of two simple cases of unimodal and bimodal packs are investigated computationally and analytically. It is shown that both the Loose Random Packing and Dense Random Packing limits are not well defined and the growth rate of the spheres is identified as the key parameter controlling the efficiency of the packing. For a properly chosen growth rate, computational results are found to be in excellent agreement with experimental data. Third, two strategies are developed to define numerical samples of polydisperse heterogeneous propellants: the Deterministic Strategy and the Random Selection Strategy. Using these strategies, numerical samples of industrial propellants are generated. The packing fraction is investigated and it is shown that the experimental values of the packing fraction can be achieved computationally. It is strongly believed that this Random Sphere Packing Model of propellants is a major step forward in the realistic computational modeling of heterogeneous propellant of combustion. In addition, a method of analysis of the morphology of heterogeneous propellants is developed which uses the concept of multi-point correlation functions. A set of intrinsic length scales of local density fluctuations in random heterogeneous propellants is identified by performing a Monte-Carlo study of the correlation functions. This method of analysis shows great promise for understanding the origins of the combustion instability of heterogeneous propellants, and is believed to become a valuable tool for the development of safe and reliable rocket engines.

Statistical Modeling of Single Target Cell Encapsulation

PubMed Central

Moon, SangJun; Ceyhan, Elvan; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems. PMID:21814548

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

Evaluation of the new control methods for oral poliomyelitis vaccine.

PubMed

Grachev, V P; Karganova, G G; Rumyantsev, A A; Ivanova, O E; Eremeeva, T P; Drozdov, S G

2001-01-01

In the draft recommendations for production and control of OPV the WHO proposed new control methods: (i) mutant analysis with PCR and restriction enzyme cleavage (MAPREC) assay that allows evaluation of poliovirus population heterogeneity at the molecular level; (ii) neurovirulence (NV) test using transgenic mice susceptible to polioviruses and (iii) control of the seed lots for the presence of the simian virus 40 (SV40) DNA sequence. This paper is focused on our experience in the practical implementation of the new methods at the Institute of Poliomyelitis and Viral Encephalitides (IPVE). Using methods based on PCR we have demonstrated that working seed viruses used by IPVE for OPV production are free from SV40 DNA sequences. Our experience on the conduction of the OPV type 3 control using TgPVR21 mice NV test (seven vaccine lots) and the MAPREC assay (more than 150 samples of single harvests and monovalent bulks) showed that these methods may be used instead of the monkey NV test, because they could not pass the vaccine failed monkey NV test. The necessity for single harvests control is discussed.

Not simply more of the same: distinguishing between patient heterogeneity and parameter uncertainty.

PubMed

Vemer, Pepijn; Goossens, Lucas M A; Rutten-van Mölken, Maureen P M H

2014-11-01

In cost-effectiveness (CE) Markov models, heterogeneity in the patient population is not automatically taken into account. We aimed to compare methods of dealing with heterogeneity on estimates of CE, using a case study in chronic obstructive pulmonary disease (COPD). We first present a probabilistic sensitivity analysis (PSA) in which we sampled only from distributions representing parameter uncertainty. This ignores any heterogeneity. Next, we explored heterogeneity by presenting results for subgroups, using a method that samples parameter uncertainty simultaneously with heterogeneity in a single-loop PSA. Finally, we distinguished parameter uncertainty from heterogeneity in a double-loop PSA by performing a nested simulation within each PSA iteration. Point estimates and uncertainty differed substantially between methods. The incremental CE ratio (ICER) ranged from € 4900 to € 13,800. The single-loop PSA led to a substantially different shape of the CE plane and an overestimation of the uncertainty compared with the other 3 methods. The CE plane for the double-loop PSA showed substantially less uncertainty and a stronger negative correlation between the difference in costs and the difference in effects compared with the other methods. This came at the cost of higher calculation times. Not accounting for heterogeneity, subgroup analysis and the double-loop PSA can be viable options, depending on the decision makers' information needs. The single-loop PSA should not be used in CE research. It disregards the fundamental differences between heterogeneity and sampling uncertainty and overestimates uncertainty as a result. © The Author(s) 2014.

Imaging genetics paradigms in depression research: Systematic review and meta-analysis.

PubMed

Pereira, Lícia P; Köhler, Cristiano A; Stubbs, Brendon; Miskowiak, Kamilla W; Morris, Gerwyn; de Freitas, Bárbara P; Thompson, Trevor; Fernandes, Brisa S; Brunoni, André R; Maes, Michael; Pizzagalli, Diego A; Carvalho, André F

2018-05-17

Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30th, 2017. Sixty-five studies met eligibility criteria (N = 4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included studies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met 'Met' (386 participants with MDD and 376 controls) or the 5-HTTLPR short 'S' (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short 'S' alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met 'Met' risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short 'S' allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met 'Met' allele had larger gray matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that included participants with MDD. Nevertheless, we explored and identified specific sources of heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field. Copyright © 2018 Elsevier Inc. All rights reserved.

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry

PubMed Central

Taylor, Kimberly E.; Wong, Quenna; Levine, David M.; McHugh, Caitlin; Laurie, Cathy; Doheny, Kimberly; Lam, Mi Y.; Baer, Alan N.; Challacombe, Stephen; Lanfranchi, Hector; Schiødt, Morten; Srinivasan, M.; Umehara, Hisanori; Vivino, Frederick B.; Zhao, Yan; Shiboski, Stephen; Daniels, Troy E.; Greenspan, John S.; Shiboski, Caroline H.; Criswell, Lindsey A.

2017-01-01

Objective Sjögren's Syndrome (SS) is a systemic autoimmune disease affecting primarily the lacrimal and salivary glands. The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international multisite observational study whose participants have been genotyped on the Omni 2.5M platform and undergone deep phenotyping using common protocol-directed methods, providing a unique opportunity to examine the genetic etiology of SS across ancestry and disease subsets. Methods We perform GWAS analyses utilizing dbGaP controls on all subjects (1405 cases, 1622 SICCA controls, 3125 external controls), European (similarly 585, 966, 2580), and Asian (similarly 460, 224, 901) with ancestry adjustments via principal component analyses. We also investigate whether subphenotype distributions differ by ethnicity and if this contributes to heterogeneity of genetic associations. Results We see significant associations in established regions of the MHC, IRF5, and STAT4 (p=3e-42, p=3e-14, p=9e-10, respectively), and several suggestive novel regions (2 or more associations with p<1e-5). Two regions have been previously implicated in autoimmune disease: KLRG1 (p=6e-7, Asian) and SH2D2A (p=2e-6, all). We observe striking differences between the European and Asian associations, with high heterogeneity especially in the MHC; representative SNPs from established and suggestive regions have highly significant differences in population allele frequencies. We show that SSA/SSB autoantibody production and labial salivary gland Focus Score criteria are associated with higher non-European ancestry (p=4e-15, 4e-5, respectively), but that subphenotype differences do not explain most of the ancestry differences in genetic associations. Conclusion Genetic associations with SS differ markedly by ancestry, however this is not explained by differences in subphenotypes. PMID:28076899

Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

NASA Astrophysics Data System (ADS)

Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-Hung

2016-04-01

Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface.

Control of the surface quality parameters of machine components during static pulsed treatment

NASA Astrophysics Data System (ADS)

Komkov, V. A.; Rabinskii, L. N.; Kokoreva, O. G.; Kuprikov, N. M.

2016-12-01

A technique is developed to determine the homogeneity of the structure in a surface layer subjected to strain hardening. Static pulsed treatment is found to be one of the most effective surface plastic deformation methods that can be used to control the uniformity of hardening a surface layer. This treatment makes it possible to create a hardened surface layer to a depth of 10 mm with a homogeneous or heterogeneous structure.

Multi-Scale Experiments to Evaluate Mobility Control Methods for Enhancing the Sweep Efficiency of Injected Subsurface Remediation Amendments

DTIC Science & Technology

2010-08-01

petroleum industry. Moreover, heterogeneity control strategies can be applied to improve the efficiency of a variety of in situ remediation technologies...conditions that differ significantly from those found in environmental systems . Therefore many of the design criteria used by the petroleum industry for...were helpful in constructing numerical models in up-scaled systems (2-D tanks). The UTCHEM model was able to successfully simulate 2-D experimental

Estimating finite-population reproductive numbers in heterogeneous populations.

PubMed

Keegan, Lindsay T; Dushoff, Jonathan

2016-05-21

The basic reproductive number, R0, is one of the most important epidemiological quantities. R0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate "finite-population reproductive numbers" with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R0 is small relative to the size of the population and decreases the finite-population reproductive number when R0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R0. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data.

PubMed

Paulson, Joseph N; Chen, Cho-Yi; Lopes-Ramos, Camila M; Kuijjer, Marieke L; Platig, John; Sonawane, Abhijeet R; Fagny, Maud; Glass, Kimberly; Quackenbush, John

2017-10-03

Although ultrahigh-throughput RNA-Sequencing has become the dominant technology for genome-wide transcriptional profiling, the vast majority of RNA-Seq studies typically profile only tens of samples, and most analytical pipelines are optimized for these smaller studies. However, projects are generating ever-larger data sets comprising RNA-Seq data from hundreds or thousands of samples, often collected at multiple centers and from diverse tissues. These complex data sets present significant analytical challenges due to batch and tissue effects, but provide the opportunity to revisit the assumptions and methods that we use to preprocess, normalize, and filter RNA-Seq data - critical first steps for any subsequent analysis. We find that analysis of large RNA-Seq data sets requires both careful quality control and the need to account for sparsity due to the heterogeneity intrinsic in multi-group studies. We developed Yet Another RNA Normalization software pipeline (YARN), that includes quality control and preprocessing, gene filtering, and normalization steps designed to facilitate downstream analysis of large, heterogeneous RNA-Seq data sets and we demonstrate its use with data from the Genotype-Tissue Expression (GTEx) project. An R package instantiating YARN is available at http://bioconductor.org/packages/yarn .

Distributed Interplanetary Delay/Disruption Tolerant Network (DTN) Monitor and Control System

NASA Technical Reports Server (NTRS)

Wang, Shin-Ywan

2012-01-01

The main purpose of Distributed interplanetary Delay Tolerant Network Monitor and Control System as a DTN system network management implementation in JPL is defined to provide methods and tools that can monitor the DTN operation status, detect and resolve DTN operation failures in some automated style while either space network or some heterogeneous network is infused with DTN capability. In this paper, "DTN Monitor and Control system in Deep Space Network (DSN)" exemplifies a case how DTN Monitor and Control system can be adapted into a space network as it is DTN enabled.

A Coral Reef Algorithm Based on Learning Automata for the Coverage Control Problem of Heterogeneous Directional Sensor Networks

PubMed Central

Li, Ming; Miao, Chunyan; Leung, Cyril

2015-01-01

Coverage control is one of the most fundamental issues in directional sensor networks. In this paper, the coverage optimization problem in a directional sensor network is formulated as a multi-objective optimization problem. It takes into account the coverage rate of the network, the number of working sensor nodes and the connectivity of the network. The coverage problem considered in this paper is characterized by the geographical irregularity of the sensed events and heterogeneity of the sensor nodes in terms of sensing radius, field of angle and communication radius. To solve this multi-objective problem, we introduce a learning automata-based coral reef algorithm for adaptive parameter selection and use a novel Tchebycheff decomposition method to decompose the multi-objective problem into a single-objective problem. Simulation results show the consistent superiority of the proposed algorithm over alternative approaches. PMID:26690162

Using Natural Language to Enable Mission Managers to Control Multiple Heterogeneous UAVs

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.; Puig-Navarro, Javier; Mehdi, S. Bilal; Mcquarry, A. Kyle

2016-01-01

The availability of highly capable, yet relatively cheap, unmanned aerial vehicles (UAVs) is opening up new areas of use for hobbyists and for commercial activities. This research is developing methods beyond classical control-stick pilot inputs, to allow operators to manage complex missions without in-depth vehicle expertise. These missions may entail several heterogeneous UAVs flying coordinated patterns or flying multiple trajectories deconflicted in time or space to predefined locations. This paper describes the functionality and preliminary usability measures of an interface that allows an operator to define a mission using speech inputs. With a defined and simple vocabulary, operators can input the vast majority of mission parameters using simple, intuitive voice commands. Although the operator interface is simple, it is based upon autonomous algorithms that allow the mission to proceed with minimal input from the operator. This paper also describes these underlying algorithms that allow an operator to manage several UAVs.

A Coral Reef Algorithm Based on Learning Automata for the Coverage Control Problem of Heterogeneous Directional Sensor Networks.

PubMed

Li, Ming; Miao, Chunyan; Leung, Cyril

2015-12-04

Coverage control is one of the most fundamental issues in directional sensor networks. In this paper, the coverage optimization problem in a directional sensor network is formulated as a multi-objective optimization problem. It takes into account the coverage rate of the network, the number of working sensor nodes and the connectivity of the network. The coverage problem considered in this paper is characterized by the geographical irregularity of the sensed events and heterogeneity of the sensor nodes in terms of sensing radius, field of angle and communication radius. To solve this multi-objective problem, we introduce a learning automata-based coral reef algorithm for adaptive parameter selection and use a novel Tchebycheff decomposition method to decompose the multi-objective problem into a single-objective problem. Simulation results show the consistent superiority of the proposed algorithm over alternative approaches.

Identification of Chinese medicinal fungus Cordyceps sinensis by depth-profiling mid-infrared photoacoustic spectroscopy

NASA Astrophysics Data System (ADS)

Du, Changwen; Zhou, Jianmin; Liu, Jianfeng

2017-02-01

With increased demand for Cordyceps sinensis it needs rapid methods to meet the challenge of identification raised in quality control. In this study Cordyceps sinensis from four typical natural habitats in China was characterized by depth-profiling Fourier transform infrared photoacoustic spectroscopy. Results demonstrated that Cordyceps sinensis samples resulted in typical photoacoustic spectral appearance, but heterogeneity was sensed in the whole sample; due to the heterogeneity Cordyceps sinensis was represented by spectra of four groups including head, body, tail and leaf under a moving mirror velocity of 0.30 cm s- 1. The spectra of the four groups were used as input of a probabilistic neural network (PNN) to identify the source of Cordyceps sinensis, and all the samples were correctly identified by the PNN model. Therefore, depth-profiling Fourier transform infrared photoacoustic spectroscopy provides novel and unique technique to identify Cordyceps sinensis, which shows great potential in quality control of Cordyceps sinensis.

Electrical Matching at Metal/Molecule Contacts for Efficient Heterogeneous Charge Transfer.

PubMed

Sato, Shino; Iwase, Shigeru; Namba, Kotaro; Ono, Tomoya; Hara, Kenji; Fukuoka, Atsushi; Uosaki, Kohei; Ikeda, Katsuyoshi

2018-02-27

In a metal/molecule hybrid system, unavoidable electrical mismatch exists between metal continuum states and frontier molecular orbitals. This causes energy loss in the electron conduction across the metal/molecule interface. For efficient use of energy in a metal/molecule hybrid system, it is necessary to control interfacial electronic structures. Here we demonstrate that electrical matching between a gold substrate and π-conjugated molecular wires can be obtained by using monatomic foreign metal interlayers, which can change the degree of d-π* back-donation at metal/anchor contacts. This interfacial control leads to energy level alignment between the Fermi level of the metal electrode and conduction molecular orbitals, resulting in resonant electron conduction in the metal/molecule hybrid system. When this method is applied to molecule-modified electrocatalysts, the heterogeneous electrochemical reaction rate is considerably improved with significant suppression of energy loss at the internal electron conduction.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

PubMed

Kindred, John H; Ketelhut, Nathaniel B; Rudroff, Thorsten

2015-02-01

Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (P<0.03). Glucose uptake heterogeneity between the groups was not different for any muscle group or individual muscle of the legs (P>0.16, P≥0.05). Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties. Published by Elsevier Ltd.

Integration of heterogeneous features for remote sensing scene classification

NASA Astrophysics Data System (ADS)

Wang, Xin; Xiong, Xingnan; Ning, Chen; Shi, Aiye; Lv, Guofang

2018-01-01

Scene classification is one of the most important issues in remote sensing (RS) image processing. We find that features from different channels (shape, spectral, texture, etc.), levels (low-level and middle-level), or perspectives (local and global) could provide various properties for RS images, and then propose a heterogeneous feature framework to extract and integrate heterogeneous features with different types for RS scene classification. The proposed method is composed of three modules (1) heterogeneous features extraction, where three heterogeneous feature types, called DS-SURF-LLC, mean-Std-LLC, and MS-CLBP, are calculated, (2) heterogeneous features fusion, where the multiple kernel learning (MKL) is utilized to integrate the heterogeneous features, and (3) an MKL support vector machine classifier for RS scene classification. The proposed method is extensively evaluated on three challenging benchmark datasets (a 6-class dataset, a 12-class dataset, and a 21-class dataset), and the experimental results show that the proposed method leads to good classification performance. It produces good informative features to describe the RS image scenes. Moreover, the integration of heterogeneous features outperforms some state-of-the-art features on RS scene classification tasks.

Reducing selection bias in case-control studies from rare disease registries.

PubMed

Cole, J Alexander; Taylor, John S; Hangartner, Thomas N; Weinreb, Neal J; Mistry, Pramod K; Khan, Aneal

2011-09-12

In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example. A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching. The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

An attribute-based approach to contingent valuation of forest protection programs

Treesearch

Christopher C. Moore; Thomas P. Holmes; Kathleen P. Bell

2011-01-01

The hemlock woolly adelgid is an invasive insect that is damaging hemlock forests in the eastern United States. Several control methods are available but forest managers are constrained by cost, availability, and environmental concerns. As a result forest managers must decide how to allocate limited conservation resources over heterogeneous landscapes. We develop an...

Firing rate dynamics in recurrent spiking neural networks with intrinsic and network heterogeneity.

PubMed

Ly, Cheng

2015-12-01

Heterogeneity of neural attributes has recently gained a lot of attention and is increasing recognized as a crucial feature in neural processing. Despite its importance, this physiological feature has traditionally been neglected in theoretical studies of cortical neural networks. Thus, there is still a lot unknown about the consequences of cellular and circuit heterogeneity in spiking neural networks. In particular, combining network or synaptic heterogeneity and intrinsic heterogeneity has yet to be considered systematically despite the fact that both are known to exist and likely have significant roles in neural network dynamics. In a canonical recurrent spiking neural network model, we study how these two forms of heterogeneity lead to different distributions of excitatory firing rates. To analytically characterize how these types of heterogeneities affect the network, we employ a dimension reduction method that relies on a combination of Monte Carlo simulations and probability density function equations. We find that the relationship between intrinsic and network heterogeneity has a strong effect on the overall level of heterogeneity of the firing rates. Specifically, this relationship can lead to amplification or attenuation of firing rate heterogeneity, and these effects depend on whether the recurrent network is firing asynchronously or rhythmically firing. These observations are captured with the aforementioned reduction method, and furthermore simpler analytic descriptions based on this dimension reduction method are developed. The final analytic descriptions provide compact and descriptive formulas for how the relationship between intrinsic and network heterogeneity determines the firing rate heterogeneity dynamics in various settings.

Imaging Tumor Response and Tumoral Heterogeneity in Non-Small Cell Lung Cancer Treated With Antiangiogenic Therapy: Comparison of the Prognostic Ability of RECIST 1.1, an Alternate Method (Crabb), and Image Heterogeneity Analysis.

PubMed

Yip, Connie; Tacelli, Nunzia; Remy-Jardin, Martine; Scherpereel, Arnaud; Cortot, Alexis; Lafitte, Jean-Jacques; Wallyn, Frederic; Remy, Jacques; Bassett, Paul; Siddique, Musib; Cook, Gary J R; Landau, David B; Goh, Vicky

2015-09-01

We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

Soil Microbiome Is More Heterogeneous in Organic Than in Conventional Farming System

PubMed Central

Lupatini, Manoeli; Korthals, Gerard W.; de Hollander, Mattias; Janssens, Thierry K. S.; Kuramae, Eiko E.

2017-01-01

Organic farming system and sustainable management of soil pathogens aim at reducing the use of agricultural chemicals in order to improve ecosystem health. Despite the essential role of microbial communities in agro-ecosystems, we still have limited understanding of the complex response of microbial diversity and composition to organic and conventional farming systems and to alternative methods for controlling plant pathogens. In this study we assessed the microbial community structure, diversity and richness using 16S rRNA gene next generation sequences and report that conventional and organic farming systems had major influence on soil microbial diversity and community composition while the effects of the soil health treatments (sustainable alternatives for chemical control) in both farming systems were of smaller magnitude. Organically managed system increased taxonomic and phylogenetic richness, diversity and heterogeneity of the soil microbiota when compared with conventional farming system. The composition of microbial communities, but not the diversity nor heterogeneity, were altered by soil health treatments. Soil health treatments exhibited an overrepresentation of specific microbial taxa which are known to be involved in soil suppressiveness to pathogens (plant-parasitic nematodes and soil-borne fungi). Our results provide a comprehensive survey on the response of microbial communities to different agricultural systems and to soil treatments for controlling plant pathogens and give novel insights to improve the sustainability of agro-ecosystems by means of beneficial microorganisms. PMID:28101080

Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews

PubMed Central

Turner, Rebecca M; Davey, Jonathan; Clarke, Mike J; Thompson, Simon G; Higgins, Julian PT

2012-01-01

Background Many meta-analyses contain only a small number of studies, which makes it difficult to estimate the extent of between-study heterogeneity. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, and offers advantages over conventional random-effects meta-analysis. To assist in this, we provide empirical evidence on the likely extent of heterogeneity in particular areas of health care. Methods Our analyses included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews. We classified each meta-analysis according to the type of outcome, type of intervention comparison and medical specialty. By modelling the study data from all meta-analyses simultaneously, using the log odds ratio scale, we investigated the impact of meta-analysis characteristics on the underlying between-study heterogeneity variance. Predictive distributions were obtained for the heterogeneity expected in future meta-analyses. Results Between-study heterogeneity variances for meta-analyses in which the outcome was all-cause mortality were found to be on average 17% (95% CI 10–26) of variances for other outcomes. In meta-analyses comparing two active pharmacological interventions, heterogeneity was on average 75% (95% CI 58–95) of variances for non-pharmacological interventions. Meta-analysis size was found to have only a small effect on heterogeneity. Predictive distributions are presented for nine different settings, defined by type of outcome and type of intervention comparison. For example, for a planned meta-analysis comparing a pharmacological intervention against placebo or control with a subjectively measured outcome, the predictive distribution for heterogeneity is a log-normal (−2.13, 1.582) distribution, which has a median value of 0.12. In an example of meta-analysis of six studies, incorporating external evidence led to a smaller heterogeneity estimate and a narrower confidence interval for the combined intervention effect. Conclusions Meta-analysis characteristics were strongly associated with the degree of between-study heterogeneity, and predictive distributions for heterogeneity differed substantially across settings. The informative priors provided will be very beneficial in future meta-analyses including few studies. PMID:22461129

Adaptive Control of Synchronization in Delay-Coupled Heterogeneous Networks of FitzHugh-Nagumo Nodes

NASA Astrophysics Data System (ADS)

Plotnikov, S. A.; Lehnert, J.; Fradkov, A. L.; Schöll, E.

We study synchronization in delay-coupled neural networks of heterogeneous nodes. It is well known that heterogeneities in the nodes hinder synchronization when becoming too large. We show that an adaptive tuning of the overall coupling strength can be used to counteract the effect of the heterogeneity. Our adaptive controller is demonstrated on ring networks of FitzHugh-Nagumo systems which are paradigmatic for excitable dynamics but can also — depending on the system parameters — exhibit self-sustained periodic firing. We show that the adaptively tuned time-delayed coupling enables synchronization even if parameter heterogeneities are so large that excitable nodes coexist with oscillatory ones.

Fine scale spatial variability of microbial pesticide degradation in soil: scales, controlling factors, and implications

PubMed Central

Dechesne, Arnaud; Badawi, Nora; Aamand, Jens; Smets, Barth F.

2014-01-01

Pesticide biodegradation is a soil microbial function of critical importance for modern agriculture and its environmental impact. While it was once assumed that this activity was homogeneously distributed at the field scale, mounting evidence indicates that this is rarely the case. Here, we critically examine the literature on spatial variability of pesticide biodegradation in agricultural soil. We discuss the motivations, methods, and main findings of the primary literature. We found significant diversity in the approaches used to describe and quantify spatial heterogeneity, which complicates inter-studies comparisons. However, it is clear that the presence and activity of pesticide degraders is often highly spatially variable with coefficients of variation often exceeding 50% and frequently displays non-random spatial patterns. A few controlling factors have tentatively been identified across pesticide classes: they include some soil characteristics (pH) and some agricultural management practices (pesticide application, tillage), while other potential controlling factors have more conflicting effects depending on the site or the pesticide. Evidence demonstrating the importance of spatial heterogeneity on the fate of pesticides in soil has been difficult to obtain but modeling and experimental systems that do not include soil's full complexity reveal that this heterogeneity must be considered to improve prediction of pesticide biodegradation rates or of leaching risks. Overall, studying the spatial heterogeneity of pesticide biodegradation is a relatively new field at the interface of agronomy, microbial ecology, and geosciences and a wealth of novel data is being collected from these different disciplinary perspectives. We make suggestions on possible avenues to take full advantage of these investigations for a better understanding and prediction of the fate of pesticides in soil. PMID:25538691

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

PubMed

Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

2017-06-22

BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials

PubMed Central

Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

2017-01-01

Background It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). Material/Methods An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. Results A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], −0.38; confidence interval [CI], −0.62 to −0.14, P=0.002; I2=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, −0.38; CI −0.59 to −0.18, P=0.0003; I2=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, −0.99; CI −1.52 to −0.47, P=0.0002; I2=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. Conclusions This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions. PMID:28638006

HETEROGENEITY IN TREATMENT EFFECT AND COMPARATIVE EFFECTIVENESS RESEARCH.

PubMed

Luo, Zhehui

2011-10-01

The ultimate goal of comparative effectiveness research (CER) is to develop and disseminate evidence-based information about which interventions are most effective for which patients under what circumstances. To achieve this goal it is crucial that researchers in methodology development find appropriate methods for detecting the presence and sources of heterogeneity in treatment effect (HTE). Comparing with the typically reported average treatment effect (ATE) in randomized controlled trials and non-experimental (i.e., observational) studies, identifying and reporting HTE better reflect the nature and purposes of CER. Methodologies of CER include meta-analysis, systematic review, design of experiments that encompasses HTE, and statistical correction of various types of estimation bias, which is the focus of this review.

Optimizing acupuncture treatment for dry eye syndrome: a systematic review.

PubMed

Kim, Bong Hyun; Kim, Min Hee; Kang, Se Hyun; Nam, Hae Jeong

2018-05-03

In a former meta-analysis review, acupuncture was considered a potentially effective treatment for dry eye syndrome (DES), but there were heterogeneities among the outcomes. We updated the meta-analysis and conducted subgroup analysis to reduce the heterogeneity and suggest the most effective acupuncture method based on clinical trials. We searched for randomized controlled trials (RCTs) in 10 databases (MEDLINE, EMBASE, CENTAL, AMED, SCOPUS, CNKI, Wangfang database, Oriental Medicine Advanced Searching Integrated System (OASIS), Koreamed, J-stage) and searched by hand to compare the effects of acupuncture and artificial tears (AT). We also conducted subgroup analysis by (1) method of intervention (acupuncture only or acupuncture plus AT), (2) intervention frequency (less than 3 times a week or more than 3 times a week), (3) period of treatment (less than 4 weeks or more than 4 weeks), and (4) acupoints (BL1, BL2, ST1, ST2, TE23, Ex-HN5). The Bucher method was used for subgroup comparisons. Nineteen studies with 1126 patients were included. Significant improvements on the Schirmer test (weighted mean difference[WMD], 2.14; 95% confidence interval[CI], 0.93 to 3.34; p = 0.0005) and break up time (BUT) (WMD, 0.98; 95% CI, 0.79 to 1.18; p < 0.00001) were reported. In the subgroup analysis, acupuncture plus AT treatment had a weaker effect in BUT but a stronger effect on the Schirmer test and a better overall effect than acupuncture alone. For treatment duration, treatment longer than 1 month was more effective than shorter treatment. With regard to treatment frequency, treatment less than three times a week was more effective than more frequent treatment. In the acupoint analysis, acupuncture treatment including the BL2 and ST1 acupoints was less effective than treatment that did not include them. None of those factors reduced the heterogeneity. Acupuncture was more effective than AT in treating DES but showed high heterogeneity. Intervention differences did not influence the heterogeneity.

Finite and spectral cell method for wave propagation in heterogeneous materials

NASA Astrophysics Data System (ADS)

Joulaian, Meysam; Duczek, Sascha; Gabbert, Ulrich; Düster, Alexander

2014-09-01

In the current paper we present a fast, reliable technique for simulating wave propagation in complex structures made of heterogeneous materials. The proposed approach, the spectral cell method, is a combination of the finite cell method and the spectral element method that significantly lowers preprocessing and computational expenditure. The spectral cell method takes advantage of explicit time-integration schemes coupled with a diagonal mass matrix to reduce the time spent on solving the equation system. By employing a fictitious domain approach, this method also helps to eliminate some of the difficulties associated with mesh generation. Besides introducing a proper, specific mass lumping technique, we also study the performance of the low-order and high-order versions of this approach based on several numerical examples. Our results show that the high-order version of the spectral cell method together requires less memory storage and less CPU time than other possible versions, when combined simultaneously with explicit time-integration algorithms. Moreover, as the implementation of the proposed method in available finite element programs is straightforward, these properties turn the method into a viable tool for practical applications such as structural health monitoring [1-3], quantitative ultrasound applications [4], or the active control of vibrations and noise [5, 6].

Distributed Control of Inverter-Based Lossy Microgrids for Power Sharing and Frequency Regulation Under Voltage Constraints

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

Chang, Chin-Yao; Zhang, Wei

This paper presents a new distributed control framework to coordinate inverter-interfaced distributed energy resources (DERs) in island microgrids. We show that under bounded load uncertainties, the proposed control method can steer the microgrid to a desired steady state with synchronized inverter frequency across the network and proportional sharing of both active and reactive powers among the inverters. We also show that such convergence can be achieved while respecting constraints on voltage magnitude and branch angle differences. The controller is robust under various contingency scenarios, including loss of communication links and failures of DERs. The proposed controller is applicable to lossymore » mesh microgrids with heterogeneous R/X distribution lines and reasonable parameter variations. Simulations based on various microgrid operation scenarios are also provided to show the effectiveness of the proposed control method.« less

Identifying candidate drivers of drug response in heterogeneous cancer by mining high throughput genomics data.

PubMed

Nabavi, Sheida

2016-08-15

With advances in technologies, huge amounts of multiple types of high-throughput genomics data are available. These data have tremendous potential to identify new and clinically valuable biomarkers to guide the diagnosis, assessment of prognosis, and treatment of complex diseases, such as cancer. Integrating, analyzing, and interpreting big and noisy genomics data to obtain biologically meaningful results, however, remains highly challenging. Mining genomics datasets by utilizing advanced computational methods can help to address these issues. To facilitate the identification of a short list of biologically meaningful genes as candidate drivers of anti-cancer drug resistance from an enormous amount of heterogeneous data, we employed statistical machine-learning techniques and integrated genomics datasets. We developed a computational method that integrates gene expression, somatic mutation, and copy number aberration data of sensitive and resistant tumors. In this method, an integrative method based on module network analysis is applied to identify potential driver genes. This is followed by cross-validation and a comparison of the results of sensitive and resistance groups to obtain the final list of candidate biomarkers. We applied this method to the ovarian cancer data from the cancer genome atlas. The final result contains biologically relevant genes, such as COL11A1, which has been reported as a cis-platinum resistant biomarker for epithelial ovarian carcinoma in several recent studies. The described method yields a short list of aberrant genes that also control the expression of their co-regulated genes. The results suggest that the unbiased data driven computational method can identify biologically relevant candidate biomarkers. It can be utilized in a wide range of applications that compare two conditions with highly heterogeneous datasets.

Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

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

Mayr, Nina A., E-mail: Nina.Mayr@osumc.edu; Huang Zhibin; Wang, Jian Z.

2012-07-01

Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB{sub 2}-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the totalmore » volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). Results: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm{sup 3}, respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 Multiplication-Sign 10{sup -8}, 2.0 Multiplication-Sign 10{sup -8}) and disease-specific survival (p = 1.9 Multiplication-Sign 10{sup -4}, 2.1 Multiplication-Sign 10{sup -6}, 2.5 Multiplication-Sign 10{sup -7}, respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2-5 weeks into treatment.« less

Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.

PubMed

Peeks, Fabian; Steunenberg, Thomas A H; de Boer, Foekje; Rubio-Gozalbo, M Estela; Williams, Monique; Burghard, Rob; Rajas, Fabienne; Oosterveer, Maaike H; Weinstein, David A; Derks, Terry G J

2017-09-01

To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase). Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed. Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis). Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

Stochastic simulation in systems biology

PubMed Central

Székely, Tamás; Burrage, Kevin

2014-01-01

Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest. PMID:25505503

An Empirical Comparison of Heterogeneity Variance Estimators in 12,894 Meta-Analyses

ERIC Educational Resources Information Center

Langan, Dean; Higgins, Julian P. T.; Simmonds, Mark

2015-01-01

Heterogeneity in meta-analysis is most commonly estimated using a moment-based approach described by DerSimonian and Laird. However, this method has been shown to produce biased estimates. Alternative methods to estimate heterogeneity include the restricted maximum likelihood approach and those proposed by Paule and Mandel, Sidik and Jonkman, and…

A Genetic Algorithm Method for Direct estimation of paleostress states from heterogeneous fault-slip observations

NASA Astrophysics Data System (ADS)

Srivastava, D. C.

2016-12-01

A Genetic Algorithm Method for Direct estimation of paleostress states from heterogeneous fault-slip observationsDeepak C. Srivastava, Prithvi Thakur and Pravin K. GuptaDepartment of Earth Sciences, Indian Institute of Technology Roorkee, Roorkee 247667, India. Abstract Paleostress estimation from a group of heterogeneous fault-slip observations entails first the classification of the observations into homogeneous fault sets and then a separate inversion of each homogeneous set. This study combines these two issues into a nonlinear inverse problem and proposes a heuristic search method that inverts the heterogeneous fault-slip observations. The method estimates different paleostress states in a group of heterogeneous fault-slip observations and classifies it into homogeneous sets as a byproduct. It uses the genetic algorithm operators, elitism, selection, encoding, crossover and mutation. These processes translate into a guided search that finds successively fitter solutions and operate iteratively until the termination criteria is met and the globally fittest stress tensors are obtained. We explain the basic steps of the algorithm on a working example and demonstrate validity of the method on several synthetic and a natural group of heterogeneous fault-slip observations. The method is independent of any user-defined bias or any entrapment of solution in a local optimum. It succeeds even in the difficult situations where other classification methods are found to fail.

Exploring the reproducibility of functional connectivity alterations in Parkinson’s disease

PubMed Central

Onu, Mihaela; Wu, Tao; Roceanu, Adina; Bajenaru, Ovidiu

2017-01-01

Since anatomic MRI is presently not able to directly discern neuronal loss in Parkinson’s Disease (PD), studying the associated functional connectivity (FC) changes seems a promising approach toward developing non-invasive and non-radioactive neuroimaging markers for this disease. While several groups have reported such FC changes in PD, there are also significant discrepancies between studies. Investigating the reproducibility of PD-related FC changes on independent datasets is therefore of crucial importance. We acquired resting-state fMRI scans for 43 subjects (27 patients and 16 normal controls, with 2 replicate scans per subject) and compared the observed FC changes with those obtained in two independent datasets, one made available by the PPMI consortium (91 patients, 18 controls) and a second one by the group of Tao Wu (20 patients, 20 controls). Unfortunately, PD-related functional connectivity changes turned out to be non-reproducible across datasets. This could be due to disease heterogeneity, but also to technical differences. To distinguish between the two, we devised a method to directly check for disease heterogeneity using random splits of a single dataset. Since we still observe non-reproducibility in a large fraction of random splits of the same dataset, we conclude that functional heterogeneity may be a dominating factor behind the lack of reproducibility of FC alterations in different rs-fMRI studies of PD. While global PD-related functional connectivity changes were non-reproducible across datasets, we identified a few individual brain region pairs with marginally consistent FC changes across all three datasets. However, training classifiers on each one of the three datasets to discriminate PD scans from controls produced only low accuracies on the remaining two test datasets. Moreover, classifiers trained and tested on random splits of the same dataset (which are technically homogeneous) also had low test accuracies, directly substantiating disease heterogeneity. PMID:29182621

Revisiting the Basic Reproductive Number for Malaria and Its Implications for Malaria Control

PubMed Central

Smith, David L; McKenzie, F. Ellis; Snow, Robert W; Hay, Simon I

2007-01-01

The prospects for the success of malaria control depend, in part, on the basic reproductive number for malaria, R 0. Here, we estimate R 0 in a novel way for 121 African populations, and thereby increase the number of R 0 estimates for malaria by an order of magnitude. The estimates range from around one to more than 3,000. We also consider malaria transmission and control in finite human populations, of size H. We show that classic formulas approximate the expected number of mosquitoes that could trace infection back to one mosquito after one parasite generation, Z 0(H), but they overestimate the expected number of infected humans per infected human, R 0(H). Heterogeneous biting increases R 0 and, as we show, Z 0(H), but we also show that it sometimes reduces R 0(H); those who are bitten most both infect many vectors and absorb infectious bites. The large range of R 0 estimates strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum. In populations where R 0 is highest, malaria control will require multiple, integrated methods that target those who are bitten most. Therefore, strategic planning for malaria control should consider R 0, the spatial scale of transmission, human population density, and heterogeneous biting. PMID:17311470

Effects of surface roughness and electrokinetic heterogeneity on electroosmotic flow in microchannel

NASA Astrophysics Data System (ADS)

Masilamani, Kannan; Ganguly, Suvankar; Feichtinger, Christian; Bartuschat, Dominik; Rüde, Ulrich

2015-06-01

In this paper, a hybrid lattice-Boltzmann and finite-difference (LB-FD) model is applied to simulate the effects of three-dimensional surface roughness and electrokinetic heterogeneity on electroosmotic flow (EOF) in a microchannel. The lattice-Boltzmann (LB) method has been employed to obtain the flow field and a finite-difference (FD) method is used to solve the Poisson-Boltzmann (PB) equation for the electrostatic potential distribution. Numerical simulation of flow through a square cross-section microchannel with designed roughness is conducted and the results are critically analysed. The effects of surface heterogeneity on the electroosmotic transport are investigated for different roughness height, width, roughness interval spacing, and roughness surface potential. Numerical simulations reveal that the presence of surface roughness changes the nature of electroosmotic transport through the microchannel. It is found that the electroosmotic velocity decreases with the increase in roughness height and the velocity profile becomes asymmetric. For the same height of the roughness elements, the EOF velocity rises with the increase in roughness width. For the heterogeneously charged rough channel, the velocity profile shows a distinct deviation from the conventional plug-like flow pattern. The simulation results also indicate locally induced flow vortices which can be utilized to enhance the flow and mixing within the microchannel. The present study has important implications towards electrokinetic flow control in the microchannel, and can provide an efficient way to design a microfluidic system of practical interest.

Unlocking Proteomic Heterogeneity in Complex Diseases through Visual Analytics

PubMed Central

Bhavnani, Suresh K.; Dang, Bryant; Bellala, Gowtham; Divekar, Rohit; Visweswaran, Shyam; Brasier, Allan; Kurosky, Alex

2015-01-01

Despite years of preclinical development, biological interventions designed to treat complex diseases like asthma often fail in phase III clinical trials. These failures suggest that current methods to analyze biomedical data might be missing critical aspects of biological complexity such as the assumption that cases and controls come from homogeneous distributions. Here we discuss why and how methods from the rapidly evolving field of visual analytics can help translational teams (consisting of biologists, clinicians, and bioinformaticians) to address the challenge of modeling and inferring heterogeneity in the proteomic and phenotypic profiles of patients with complex diseases. Because a primary goal of visual analytics is to amplify the cognitive capacities of humans for detecting patterns in complex data, we begin with an overview of the cognitive foundations for the field of visual analytics. Next, we organize the primary ways in which a specific form of visual analytics called networks have been used to model and infer biological mechanisms, which help to identify the properties of networks that are particularly useful for the discovery and analysis of proteomic heterogeneity in complex diseases. We describe one such approach called subject-protein networks, and demonstrate its application on two proteomic datasets. This demonstration provides insights to help translational teams overcome theoretical, practical, and pedagogical hurdles for the widespread use of subject-protein networks for analyzing molecular heterogeneities, with the translational goal of designing biomarker-based clinical trials, and accelerating the development of personalized approaches to medicine. PMID:25684269

Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder

PubMed Central

Kessler, R.C.; van Loo, H.M.; Wardenaar, K.J.; Bossarte, R.M.; Brenner, L.A.; Ebert, D.D; de Jonge, P.; Nierenberg, A.A.; Rosellini, A.J.; Sampson, N.A.; Schoevers, R.A.; Wilcox, M.A.; Zaslavsky, A.M.

2016-01-01

Aims Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful. Methods We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalized) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments. Results Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention versus control) or differential treatment outcomes (i.e., intervention A versus intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalized treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials. Conclusions Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment studies, applying and refining these models in subsequent pragmatic trials, carrying out pooled secondary analyses to extract the maximum amount of information from these coordinated studies, and using this information to focus future discovery efforts in the segment of the patient population in which continued uncertainty about treatment response exists. PMID:26810628

Parameter Sensitivity Study of the Unreacted-Core Shrinking Model: A Computer Activity for Chemical Reaction Engineering Courses

ERIC Educational Resources Information Center

Tudela, Ignacio; Bonete, Pedro; Fullana, Andres; Conesa, Juan Antonio

2011-01-01

The unreacted-core shrinking (UCS) model is employed to characterize fluid-particle reactions that are important in industry and research. An approach to understand the UCS model by numerical methods is presented, which helps the visualization of the influence of the variables that control the overall heterogeneous process. Use of this approach in…

Subsurface high resolution definition of subsurface heterogeneity for understanding the biodynamics of natural field systems: Advancing the ability for scaling to field conditions. 1998 annual progress report

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

Majer, E.L.; Brockman, F.J.

1998-06-01

'This research is an integrated physical (geophysical and hydrologic) and microbial study using innovative geophysical imaging and microbial characterization methods to identify key scales of physical heterogeneities that affect the biodynamics of natural subsurface environments. Data from controlled laboratory and in-situ experiments at the INEEL Test Area North (TAN) site are being used to determine the dominant physical characteristics (lithologic, structural, and hydrologic) that can be imaged in-situ and correlated with microbial properties. The overall goal of this research is to contribute to the understanding of the interrelationships between transport properties and spatially varying physical, chemical, and microbiological heterogeneity. Themore » outcome will be an improved understanding of the relationship between physical and microbial heterogeneity, thus facilitating the design of bioremediation strategies in similar environments. This report summarizes work as of May 1998, the second year of the project. This work is an extension of basic research on natural heterogeneity first initiated within the DOE/OHER Subsurface Science Program (SSP) and is intended to be one of the building blocks of an integrated and collaborative approach with an INEEL/PNNL effort aimed at understanding the effect of physical heterogeneity on transport properties and biodynamics in natural systems. The work is closely integrated with other EMSP projects at INEEL (Rick Colwell et al.) and PNNL (Fred Brockman and Jim Fredrickson).'« less

Cross-Country Heterogeneity in Students' Reporting Behavior: The Use of the Anchoring Vignette Method

ERIC Educational Resources Information Center

Vonkova, Hana; Zamarro, Gema; Hitt, Collin

2018-01-01

Self-reports are an indispensable source of information in education research but they are often affected by heterogeneity in reporting behavior. Failing to correct for this heterogeneity can lead to invalid comparisons across groups. The researchers use the parametric anchoring vignette method to correct for cross-country incomparability of…

A Decision-Making Method with Grey Multi-Source Heterogeneous Data and Its Application in Green Supplier Selection

PubMed Central

Dang, Yaoguo; Mao, Wenxin

2018-01-01

In view of the multi-attribute decision-making problem that the attribute values are grey multi-source heterogeneous data, a decision-making method based on kernel and greyness degree is proposed. The definitions of kernel and greyness degree of an extended grey number in a grey multi-source heterogeneous data sequence are given. On this basis, we construct the kernel vector and greyness degree vector of the sequence to whiten the multi-source heterogeneous information, then a grey relational bi-directional projection ranking method is presented. Considering the multi-attribute multi-level decision structure and the causalities between attributes in decision-making problem, the HG-DEMATEL method is proposed to determine the hierarchical attribute weights. A green supplier selection example is provided to demonstrate the rationality and validity of the proposed method. PMID:29510521

A Decision-Making Method with Grey Multi-Source Heterogeneous Data and Its Application in Green Supplier Selection.

PubMed

Sun, Huifang; Dang, Yaoguo; Mao, Wenxin

2018-03-03

In view of the multi-attribute decision-making problem that the attribute values are grey multi-source heterogeneous data, a decision-making method based on kernel and greyness degree is proposed. The definitions of kernel and greyness degree of an extended grey number in a grey multi-source heterogeneous data sequence are given. On this basis, we construct the kernel vector and greyness degree vector of the sequence to whiten the multi-source heterogeneous information, then a grey relational bi-directional projection ranking method is presented. Considering the multi-attribute multi-level decision structure and the causalities between attributes in decision-making problem, the HG-DEMATEL method is proposed to determine the hierarchical attribute weights. A green supplier selection example is provided to demonstrate the rationality and validity of the proposed method.

Accounting for Scale Heterogeneity in Healthcare-Related Discrete Choice Experiments when Comparing Stated Preferences: A Systematic Review.

PubMed

Wright, Stuart J; Vass, Caroline M; Sim, Gene; Burton, Michael; Fiebig, Denzil G; Payne, Katherine

2018-02-28

Scale heterogeneity, or differences in the error variance of choices, may account for a significant amount of the observed variation in the results of discrete choice experiments (DCEs) when comparing preferences between different groups of respondents. The aim of this study was to identify if, and how, scale heterogeneity has been addressed in healthcare DCEs that compare the preferences of different groups. A systematic review identified all healthcare DCEs published between 1990 and February 2016. The full-text of each DCE was then screened to identify studies that compared preferences using data generated from multiple groups. Data were extracted and tabulated on year of publication, samples compared, tests for scale heterogeneity, and analytical methods to account for scale heterogeneity. Narrative analysis was used to describe if, and how, scale heterogeneity was accounted for when preferences were compared. A total of 626 healthcare DCEs were identified. Of these 199 (32%) aimed to compare the preferences of different groups specified at the design stage, while 79 (13%) compared the preferences of groups identified at the analysis stage. Of the 278 included papers, 49 (18%) discussed potential scale issues, 18 (7%) used a formal method of analysis to account for scale between groups, and 2 (1%) accounted for scale differences between preference groups at the analysis stage. Scale heterogeneity was present in 65% (n = 13) of studies that tested for it. Analytical methods to test for scale heterogeneity included coefficient plots (n = 5, 2%), heteroscedastic conditional logit models (n = 6, 2%), Swait and Louviere tests (n = 4, 1%), generalised multinomial logit models (n = 5, 2%), and scale-adjusted latent class analysis (n = 2, 1%). Scale heterogeneity is a prevalent issue in healthcare DCEs. Despite this, few published DCEs have discussed such issues, and fewer still have used formal methods to identify and account for the impact of scale heterogeneity. The use of formal methods to test for scale heterogeneity should be used, otherwise the results of DCEs potentially risk producing biased and potentially misleading conclusions regarding preferences for aspects of healthcare.

Adaptive adjustment of the randomization ratio using historical control data

PubMed Central

Hobbs, Brian P.; Carlin, Bradley P.; Sargent, Daniel J.

2013-01-01

Background Prospective trial design often occurs in the presence of “acceptable” [1] historical control data. Typically this data is only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. Purpose We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al. [2], succeeded a similar trial reported by Saltz et al. [3], and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. Methods The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS) characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors [4] are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial’s frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Results Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure leads to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Limitations Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. Conclusions The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on pre-existing information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare. PMID:23690095

Provably Secure Heterogeneous Access Control Scheme for Wireless Body Area Network.

PubMed

Omala, Anyembe Andrew; Mbandu, Angolo Shem; Mutiria, Kamenyi Domenic; Jin, Chunhua; Li, Fagen

2018-04-28

Wireless body area network (WBAN) provides a medium through which physiological information could be harvested and transmitted to application provider (AP) in real time. Integrating WBAN in a heterogeneous Internet of Things (IoT) ecosystem would enable an AP to monitor patients from anywhere and at anytime. However, the IoT roadmap of interconnected 'Things' is still faced with many challenges. One of the challenges in healthcare is security and privacy of streamed medical data from heterogeneously networked devices. In this paper, we first propose a heterogeneous signcryption scheme where a sender is in a certificateless cryptographic (CLC) environment while a receiver is in identity-based cryptographic (IBC) environment. We then use this scheme to design a heterogeneous access control protocol. Formal security proof for indistinguishability against adaptive chosen ciphertext attack and unforgeability against adaptive chosen message attack in random oracle model is presented. In comparison with some of the existing access control schemes, our scheme has lower computation and communication cost.

Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

PubMed Central

Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-hung

2016-01-01

Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface. PMID:27034255

Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome

PubMed Central

O’Connor, James P.B.; Rose, Chris J.; Waterton, John C.; Carano, Richard A.D.; Parker, Geoff J.M.; Jackson, Alan

2014-01-01

Tumors exhibit genomic and phenotypic heterogeneity which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks. These methods can establish whether one tumor is more or less heterogeneous than another and can identify sub-regions with differing biology. In this article we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, rather than be developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. PMID:25421725

Analytical studies on the instabilities of heterogeneous intelligent traffic flow

NASA Astrophysics Data System (ADS)

Ngoduy, D.

2013-10-01

It has been widely reported in literature that a small perturbation in traffic flow such as a sudden deceleration of a vehicle could lead to the formation of traffic jams without a clear bottleneck. These traffic jams are usually related to instabilities in traffic flow. The applications of intelligent traffic systems are a potential solution to reduce the amplitude or to eliminate the formation of such traffic instabilities. A lot of research has been conducted to theoretically study the effect of intelligent vehicles, for example adaptive cruise control vehicles, using either computer simulation or analytical method. However, most current analytical research has only applied to single class traffic flow. To this end, the main topic of this paper is to perform a linear stability analysis to find the stability threshold of heterogeneous traffic flow using microscopic models, particularly the effect of intelligent vehicles on heterogeneous (or multi-class) traffic flow instabilities. The analytical results will show how intelligent vehicle percentages affect the stability of multi-class traffic flow.

Meta-Analysis of Rare Binary Adverse Event Data

PubMed Central

Bhaumik, Dulal K.; Amatya, Anup; Normand, Sharon-Lise; Greenhouse, Joel; Kaizar, Eloise; Neelon, Brian; Gibbons, Robert D.

2013-01-01

We examine the use of fixed-effects and random-effects moment-based meta-analytic methods for analysis of binary adverse event data. Special attention is paid to the case of rare adverse events which are commonly encountered in routine practice. We study estimation of model parameters and between-study heterogeneity. In addition, we examine traditional approaches to hypothesis testing of the average treatment effect and detection of the heterogeneity of treatment effect across studies. We derive three new methods, simple (unweighted) average treatment effect estimator, a new heterogeneity estimator, and a parametric bootstrapping test for heterogeneity. We then study the statistical properties of both the traditional and new methods via simulation. We find that in general, moment-based estimators of combined treatment effects and heterogeneity are biased and the degree of bias is proportional to the rarity of the event under study. The new methods eliminate much, but not all of this bias. The various estimators and hypothesis testing methods are then compared and contrasted using an example dataset on treatment of stable coronary artery disease. PMID:23734068

TSOS and TSOS-FK hybrid methods for modelling the propagation of seismic waves

NASA Astrophysics Data System (ADS)

Ma, Jian; Yang, Dinghui; Tong, Ping; Ma, Xiao

2018-05-01

We develop a new time-space optimized symplectic (TSOS) method for numerically solving elastic wave equations in heterogeneous isotropic media. We use the phase-preserving symplectic partitioned Runge-Kutta method to evaluate the time derivatives and optimized explicit finite-difference (FD) schemes to discretize the space derivatives. We introduce the averaged medium scheme into the TSOS method to further increase its capability of dealing with heterogeneous media and match the boundary-modified scheme for implementing free-surface boundary conditions and the auxiliary differential equation complex frequency-shifted perfectly matched layer (ADE CFS-PML) non-reflecting boundaries with the TSOS method. A comparison of the TSOS method with analytical solutions and standard FD schemes indicates that the waveform generated by the TSOS method is more similar to the analytic solution and has a smaller error than other FD methods, which illustrates the efficiency and accuracy of the TSOS method. Subsequently, we focus on the calculation of synthetic seismograms for teleseismic P- or S-waves entering and propagating in the local heterogeneous region of interest. To improve the computational efficiency, we successfully combine the TSOS method with the frequency-wavenumber (FK) method and apply the ADE CFS-PML to absorb the scattered waves caused by the regional heterogeneity. The TSOS-FK hybrid method is benchmarked against semi-analytical solutions provided by the FK method for a 1-D layered model. Several numerical experiments, including a vertical cross-section of the Chinese capital area crustal model, illustrate that the TSOS-FK hybrid method works well for modelling waves propagating in complex heterogeneous media and remains stable for long-time computation. These numerical examples also show that the TSOS-FK method can tackle the converted and scattered waves of the teleseismic plane waves caused by local heterogeneity. Thus, the TSOS and TSOS-FK methods proposed in this study present an essential tool for the joint inversion of local, regional, and teleseismic waveform data.

A New Equivalence Theory Method for Treating Doubly Heterogeneous Fuel - I. Theory

DOE PAGES

Williams, Mark L.; Lee, Deokjung; Choi, Sooyoung

2015-03-04

A new methodology has been developed to treat resonance self-shielding in doubly heterogeneous very high temperature gas-cooled reactor systems in which the fuel compact region of a reactor lattice consists of small fuel grains dispersed in a graphite matrix. This new method first homogenizes the fuel grain and matrix materials using an analytically derived disadvantage factor from a two-region problem with equivalence theory and intermediate resonance method. This disadvantage factor accounts for spatial self-shielding effects inside each grain within the framework of an infinite array of grains. Then the homogenized fuel compact is self-shielded using a Bondarenko method to accountmore » for interactions between the fuel compact regions in the fuel lattice. In the final form of the equations for actual implementations, the double-heterogeneity effects are accounted for by simply using a modified definition of a background cross section, which includes geometry parameters and cross sections for both the grain and fuel compact regions. With the new method, the doubly heterogeneous resonance self-shielding effect can be treated easily even with legacy codes programmed only for a singly heterogeneous system by simple modifications in the background cross section for resonance integral interpolations. This paper presents a detailed derivation of the new method and a sensitivity study of double-heterogeneity parameters introduced during the derivation. The implementation of the method and verification results for various test cases are presented in the companion paper.« less

Characterizing heterogeneous cellular responses to perturbations.

PubMed

Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

2008-12-09

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis

PubMed Central

Manheimer, Eric; van der Windt, Daniëlle; Cheng, Ke; Stafford, Kristen; Liu, Jianping; Tierney, Jayne; Lao, Lixing; Berman, Brian M.; Langenberg, Patricia; Bouter, Lex M.

2013-01-01

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96–1.31; I2 = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83–1.26; I2 = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97–1.52; I2 = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R2 = 93%; I2 residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28–1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80–1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias. PMID:23814102

Investigating the 3-D Subduction Initiation Processes at Transform Faults and Passive Margins

NASA Astrophysics Data System (ADS)

Peng, H.; Leng, W.

2017-12-01

Studying the processes of subduction initiation is a key for understanding the Wilson cycle and improving the theory of plate tectonics. Previous studies investigated subduction initiation with geological synthesis and geodynamic modeling methods, discovering that subduction intends to initiate at the transform faults close to oceanic arcs, and that its evolutionary processes and surface volcanic expressions are controlled by plate strength. However, these studies are mainly conducted with 2-D models, which cannot deal with lateral heterogeneities of crustal thickness and strength along the plate interfaces. Here we extend the 2-D model to a 3-D parallel subduction model with high computational efficiency. With the new model, we study the dynamic controlling factors, morphology evolutionary processes and surface expressions for subduction initiation with lateral heterogeneities of material properties along transform faults and passive margins. We find that lateral lithospheric heterogeneities control the starting point of the subduction initiation along the newly formed trenches and the propagation speed for the trench formation. New subduction tends to firstly initiate at the property changing point along the transform faults or passive margins. Such finds may be applied to explain the formation process of the Izu-Bonin-Mariana (IBM) subduction zone in the western Pacific and the Scotia subduction zone at the south end of the South America. Our results enhance our understanding for the formation of new trenches and help to provide geodynamic modeling explanations for the observed remnant slabs in the upper mantle and the surface volcanic expressions.

Formation Learning Control of Multiple Autonomous Underwater Vehicles With Heterogeneous Nonlinear Uncertain Dynamics.

PubMed

Yuan, Chengzhi; Licht, Stephen; He, Haibo

2017-09-26

In this paper, a new concept of formation learning control is introduced to the field of formation control of multiple autonomous underwater vehicles (AUVs), which specifies a joint objective of distributed formation tracking control and learning/identification of nonlinear uncertain AUV dynamics. A novel two-layer distributed formation learning control scheme is proposed, which consists of an upper-layer distributed adaptive observer and a lower-layer decentralized deterministic learning controller. This new formation learning control scheme advances existing techniques in three important ways: 1) the multi-AUV system under consideration has heterogeneous nonlinear uncertain dynamics; 2) the formation learning control protocol can be designed and implemented by each local AUV agent in a fully distributed fashion without using any global information; and 3) in addition to the formation control performance, the distributed control protocol is also capable of accurately identifying the AUVs' heterogeneous nonlinear uncertain dynamics and utilizing experiences to improve formation control performance. Extensive simulations have been conducted to demonstrate the effectiveness of the proposed results.

Wave Scattering in Heterogeneous Media using the Finite Element Method

DTIC Science & Technology

2016-10-21

AFRL-AFOSR-JP-TR-2016-0086 Wave Scattering in Heterogeneous Media using the Finite Element Method Chiruvai Vendhan INDIAN INSTITUTE OF TECHNOLOGY...Scattering in Heterogeneous Media using the Finite Element Method 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386-12-1-4026 5c.  PROGRAM ELEMENT NUMBER 61102F 6...14.  ABSTRACT The primary aim of this study is to develop a finite element model for elastic scattering by axisymmetric bodies submerged in a

Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.

PubMed

Alhijjaj, Muqdad; Reading, Mike; Belton, Peter; Qi, Sheng

2015-11-03

Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.

Optimization of Residual Stresses in MMC's through Process Parameter Control and the use of Heterogeneous Compensating/Compliant Interfacial Layers. OPTCOMP2 User's Guide

NASA Technical Reports Server (NTRS)

Pindera, Marek-Jerzy; Salzar, Robert S.

1996-01-01

A user's guide for the computer program OPTCOMP2 is presented in this report. This program provides a capability to optimize the fabrication or service-induced residual stresses in unidirectional metal matrix composites subjected to combined thermomechanical axisymmetric loading by altering the processing history, as well as through the microstructural design of interfacial fiber coatings. The user specifies the initial architecture of the composite and the load history, with the constituent materials being elastic, plastic, viscoplastic, or as defined by the 'user-defined' constitutive model, in addition to the objective function and constraints, through a user-friendly data input interface. The optimization procedure is based on an efficient solution methodology for the inelastic response of a fiber/interface layer(s)/matrix concentric cylinder model where the interface layers can be either homogeneous or heterogeneous. The response of heterogeneous layers is modeled using Aboudi's three-dimensional method of cells micromechanics model. The commercial optimization package DOT is used for the nonlinear optimization problem. The solution methodology for the arbitrarily layered cylinder is based on the local-global stiffness matrix formulation and Mendelson's iterative technique of successive elastic solutions developed for elastoplastic boundary-value problems. The optimization algorithm employed in DOT is based on the method of feasible directions.

Sequential change detection and monitoring of temporal trends in random-effects meta-analysis.

PubMed

Dogo, Samson Henry; Clark, Allan; Kulinskaya, Elena

2017-06-01

Temporal changes in magnitude of effect sizes reported in many areas of research are a threat to the credibility of the results and conclusions of meta-analysis. Numerous sequential methods for meta-analysis have been proposed to detect changes and monitor trends in effect sizes so that meta-analysis can be updated when necessary and interpreted based on the time it was conducted. The difficulties of sequential meta-analysis under the random-effects model are caused by dependencies in increments introduced by the estimation of the heterogeneity parameter τ 2 . In this paper, we propose the use of a retrospective cumulative sum (CUSUM)-type test with bootstrap critical values. This method allows retrospective analysis of the past trajectory of cumulative effects in random-effects meta-analysis and its visualization on a chart similar to CUSUM chart. Simulation results show that the new method demonstrates good control of Type I error regardless of the number or size of the studies and the amount of heterogeneity. Application of the new method is illustrated on two examples of medical meta-analyses. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

Elucidation of Heterogeneous Processes Controlling Boost Phase Signatures

DTIC Science & Technology

1990-09-12

three year research program to develop efficient theoretical methods to study collisional processes involved in radiative signature modeling . The...Marlboro, MD 20772 I. Statement of Problem For strategic defense, it is important to be able to effectively model radiative signaturesl arising from...Thus our computational work was on problems or models for which exact results for making comparisons were available. Our key validations were

Towards an Approach of Semantic Access Control for Cloud Computing

NASA Astrophysics Data System (ADS)

Hu, Luokai; Ying, Shi; Jia, Xiangyang; Zhao, Kai

With the development of cloud computing, the mutual understandability among distributed Access Control Policies (ACPs) has become an important issue in the security field of cloud computing. Semantic Web technology provides the solution to semantic interoperability of heterogeneous applications. In this paper, we analysis existing access control methods and present a new Semantic Access Control Policy Language (SACPL) for describing ACPs in cloud computing environment. Access Control Oriented Ontology System (ACOOS) is designed as the semantic basis of SACPL. Ontology-based SACPL language can effectively solve the interoperability issue of distributed ACPs. This study enriches the research that the semantic web technology is applied in the field of security, and provides a new way of thinking of access control in cloud computing.

An event-triggered control approach for the leader-tracking problem with heterogeneous agents

NASA Astrophysics Data System (ADS)

Garcia, Eloy; Cao, Yongcan; Casbeer, David W.

2018-05-01

This paper presents an event-triggered control and communication framework for the cooperative leader-tracking problem with communication constraints. Continuous communication among agents is not assumed in this work and decentralised event-based strategies are proposed for agents with heterogeneous linear dynamics. Also, the leader dynamics are unknown and only intermittent measurements of its states are obtained by a subset of the followers. The event-based method not only represents a way to restrict communication among agents, but it also provides a decentralised scheme for scheduling information broadcasts. Notably, each agent is able to determine its own broadcasting instants independently of any other agent in the network. In an extension, the case where transmission of information is affected by time-varying communication delays is addressed. Finally, positive lower-bounds on the inter-event time intervals are obtained in order to show that Zeno behaviour does not exist and, therefore, continuous exchange of information is never needed in this framework.

Inter-allotropic transformations in the heterogeneous carbon nanotube networks.

PubMed

Jung, Hyun Young; Jung, Sung Mi; Kim, Dong Won; Jung, Yung Joon

2017-01-19

The allotropic transformations of carbon provide an immense technological interest for tailoring the desired molecular structures in the scalable nanoelectronic devices. Herein, we explore the effects of morphology and geometric alignment of the nanotubes for the re-engineering of carbon bonds in the heterogeneous carbon nanotube (CNT) networks. By applying alternating voltage pulses and electrical forces, the single-walled CNTs in networks were predominantly transformed into other predetermined sp 2 carbon structures (multi-walled CNTs and multi-layered graphitic nanoribbons), showing a larger intensity in a coalescence-induced mode of Raman spectra with the increasing channel width. Moreover, the transformed networks have a newly discovered sp 2 -sp 3 hybrid nanostructures in accordance with the alignment. The sp 3 carbon structures at the small channel are controlled, such that they contain up to about 29.4% networks. This study provides a controllable method for specific types of inter-allotropic transformations/hybridizations, which opens up the further possibility for the engineering of nanocarbon allotropes in the robust large-scale network-based devices.

Identification of Chinese medicinal fungus Cordyceps sinensis by depth-profiling mid-infrared photoacoustic spectroscopy.

PubMed

Du, Changwen; Zhou, Jianmin; Liu, Jianfeng

2017-02-15

With increased demand for Cordyceps sinensis it needs rapid methods to meet the challenge of identification raised in quality control. In this study Cordyceps sinensis from four typical natural habitats in China was characterized by depth-profiling Fourier transform infrared photoacoustic spectroscopy. Results demonstrated that Cordyceps sinensis samples resulted in typical photoacoustic spectral appearance, but heterogeneity was sensed in the whole sample; due to the heterogeneity Cordyceps sinensis was represented by spectra of four groups including head, body, tail and leaf under a moving mirror velocity of 0.30cms -1 . The spectra of the four groups were used as input of a probabilistic neural network (PNN) to identify the source of Cordyceps sinensis, and all the samples were correctly identified by the PNN model. Therefore, depth-profiling Fourier transform infrared photoacoustic spectroscopy provides novel and unique technique to identify Cordyceps sinensis, which shows great potential in quality control of Cordyceps sinensis. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive capacity of geographical clusters: Complexity science and network theory approach

NASA Astrophysics Data System (ADS)

Albino, Vito; Carbonara, Nunzia; Giannoccaro, Ilaria

This paper deals with the adaptive capacity of geographical clusters (GCs), that is a relevant topic in the literature. To address this topic, GC is considered as a complex adaptive system (CAS). Three theoretical propositions concerning the GC adaptive capacity are formulated by using complexity theory. First, we identify three main properties of CAS s that affect the adaptive capacity, namely the interconnectivity, the heterogeneity, and the level of control, and define how the value of these properties influence the adaptive capacity. Then, we associate these properties with specific GC characteristics so obtaining the key conditions of GCs that give them the adaptive capacity so assuring their competitive advantage. To test these theoretical propositions, a case study on two real GCs is carried out. The considered GCs are modeled as networks where firms are nodes and inter-firms relationships are links. Heterogeneity, interconnectivity, and level of control are considered as network properties and thus measured by using the methods of the network theory.

Supported Dendrimer-Encapsulated Metal Clusters: Toward Heterogenizing Homogeneous Catalysts

DOE PAGES

Ye, Rong; Zhukhovitskiy, Aleksandr V.; Deraedt, Christophe V.; ...

2017-07-13

Recyclable catalysts, especially those that display selective reactivity, are vital for the development of sustainable chemical processes. Among available catalyst platforms, heterogeneous catalysts are particularly well-disposed toward separation from the reaction mixture via filtration methods, which renders them readily recyclable. Furthermore, heterogeneous catalysts offer numerous handles—some without homogeneous analogues—for performance and selectivity optimization. These handles include nanoparticle size, pore profile of porous supports, surface ligands and interface with oxide supports, and flow rate through a solid catalyst bed. Despite these available handles, however, conventional heterogeneous catalysts are themselves often structurally heterogeneous compared to homogeneous catalysts, which complicates efforts to optimizemore » and expand the scope of their reactivity and selectivity. Ongoing efforts in our laboratories are aimed to address the above challenge by heterogenizing homogeneous catalysts, which can be defined as the modification of homogeneous catalysts to render them in a separable (solid) phase from the starting materials and products. Specifically, we grow the small nanoclusters in dendrimers, a class of uniform polymers with the connectivity of fractal trees and generally radial symmetry. Thanks to their dense multivalency, shape persistence, and structural uniformity, dendrimers have proven to be versatile scaffolds for the synthesis and stabilization of small nanoclusters. Then these dendrimer-encapsulated metal clusters (DEMCs) are adsorbed onto mesoporous silica. Through this method, we have achieved selective transformations that had been challenging to accomplish in a heterogeneous setting, e.g., π-bond activation and aldol reactions. Extensive investigation into the catalytic systems under reaction conditions allowed us to correlate the structural features (e.g., oxidation states) of the catalysts and their activity. Moreover, we have demonstrated that supported DEMCs are also excellent catalysts for typical heterogeneous reactions, including hydrogenation and alkane isomerization. Critically, these investigations also confirmed that the supported DEMCs are heterogeneous and stable against leaching. Catalysts optimization is achieved through the modulation of various parameters. The clusters are oxidized (e.g., with PhICl 2) or reduced (e.g., with H 2) in situ. Changing the dendrimer properties (e.g., generation, terminal functional groups) is analogous to ligand modification in homogeneous catalysts, which affect both catalytic activity and selectivity. Similarly, pore size of the support is another factor in determining product distribution. In a flow reactor, the flow rate is adjusted to control the residence time of the starting material and intermediates, and thus the final product selectivity. Our approach to heterogeneous catalysis affords various advantages: (1) the catalyst system can tap into the reactivity typical to homogeneous catalysts, which conventional heterogeneous catalysts could not achieve; (2) unlike most homogeneous catalysts with comparable performance, the heterogenized homogeneous catalysts can be recycled; (3) improved activity or selectivity compared to conventional homogeneous catalysts is possible because of uniquely heterogeneous parameters for optimization. Here in this Account, we will briefly introduce metal clusters and describe the synthesis and characterizations of supported DEMCs. We will present the catalysis studies of supported DEMCs in both the batch and flow modes. Lastly, we will summarize the current state of heterogenizing homogeneous catalysis and provide future directions for this area of research.« less

Beam angle selection incorporation of anatomical heterogeneities for pencil beam scanning charged-particle therapy

NASA Astrophysics Data System (ADS)

Toramatsu, Chie; Inaniwa, Taku

2016-12-01

In charged particle therapy with pencil beam scanning (PBS), localization of the dose in the Bragg peak makes dose distributions sensitive to lateral tissue heterogeneities. The sensitivity of a PBS plan to lateral tissue heterogeneities can be reduced by selecting appropriate beam angles. The purpose of this study is to develop a fast and accurate method of beam angle selection for PBS. The lateral tissue heterogeneity surrounding the path of the pencil beams at a given angle was quantified with the heterogeneity number representing the variation of the Bragg peak depth across the cross section of the beams using the stopping power ratio of body tissues with respect to water. To shorten the computation time, one-dimensional dose optimization was conducted along the central axis of the pencil beams as they were directed by the scanning magnets. The heterogeneity numbers were derived for all possible beam angles for treatment. The angles leading to the minimum mean heterogeneity number were selected as the optimal beam angle. Three clinical cases of head and neck cancer were used to evaluate the developed method. Dose distributions and their robustness to setup and range errors were evaluated for all tested angles, and their relation to the heterogeneity numbers was investigated. The mean heterogeneity number varied from 1.2 mm-10.6 mm in the evaluated cases. By selecting a field with a low mean heterogeneity number, target dose coverage and robustness against setup and range errors were improved. The developed method is simple, fast, accurate and applicable for beam angle selection in charged particle therapy with PBS.

Restoration of the fire-grazing interaction in Artemisia filifolia shrubland

USGS Publications Warehouse

Winter, S.L.; Fuhlendorf, S.D.; Goad, C.L.; Davis, C.A.; Hickman, K.R.; Leslie, David M.

2012-01-01

Patterns of landscape heterogeneity are crucial to the maintenance of biodiversity in shrublands and grasslands, yet management practices in these ecosystems typically seek to homogenize landscapes. Furthermore, there is limited understanding of how the interaction of ecological processes, such as fire and grazing, affects patterns of heterogeneity at different spatial scales. We conducted research in Artemisia filifolia (Asteraceae) shrublands located in the southern Great Plains of North America to determine the effect of restoring the fire-grazing interaction on vegetation structure. Data were collected for 3years in replicated pastures grazed by cattle Bos taurus where the fire-grazing interaction had been restored (fire and grazing=treatment pastures) and in pastures that were grazed but remained unburned (grazing only, no fire=control pastures). The effect of the fire-grazing interaction on heterogeneity (variance) of vegetation structure was assessed at scales from 12??5m 2 to 609ha. Most measurements of vegetation structure within treatment pastures differed from control pastures for 1-3years after being burned but were thereafter similar to the values found in unburned control pastures. Treatment pastures were characterized by a lower amount of total heterogeneity and a lower amount of heterogeneity through time. Heterogeneity of vegetation structure tended to decrease as the scale of measurement increased in both treatment and control pastures. There was deviation from this trend, however, in the treatment pastures that exhibited much higher heterogeneity at the patch scale (mean patch size=202ha) of measurement, the scale at which patch fires were conducted. Synthesis and applications.Vegetation structure in A. filifolia shrublands of our study was readily altered by the fire-grazing interaction but also demonstrated substantial resilience to these effects. The fire-grazing interaction also changed the total amount of heterogeneity characterizing this system, the scale at which heterogeneity in this system was expressed and the amount of heterogeneity expressed through time. Land managers seeking to impose a shifting mosaic of heterogeneity on this vegetation type can do so by restoring the fire-grazing interaction with potential conservation benefits similar to what has been achieved in other ecosystems where historic cycles of disturbance and rest have been restored. ?? 2011 The Authors. Journal of Applied Ecology ?? 2011 British Ecological Society.

Predictive distributions for between-study heterogeneity and simple methods for their application in Bayesian meta-analysis

PubMed Central

Turner, Rebecca M; Jackson, Dan; Wei, Yinghui; Thompson, Simon G; Higgins, Julian P T

2015-01-01

Numerous meta-analyses in healthcare research combine results from only a small number of studies, for which the variance representing between-study heterogeneity is estimated imprecisely. A Bayesian approach to estimation allows external evidence on the expected magnitude of heterogeneity to be incorporated. The aim of this paper is to provide tools that improve the accessibility of Bayesian meta-analysis. We present two methods for implementing Bayesian meta-analysis, using numerical integration and importance sampling techniques. Based on 14 886 binary outcome meta-analyses in the Cochrane Database of Systematic Reviews, we derive a novel set of predictive distributions for the degree of heterogeneity expected in 80 settings depending on the outcomes assessed and comparisons made. These can be used as prior distributions for heterogeneity in future meta-analyses. The two methods are implemented in R, for which code is provided. Both methods produce equivalent results to standard but more complex Markov chain Monte Carlo approaches. The priors are derived as log-normal distributions for the between-study variance, applicable to meta-analyses of binary outcomes on the log odds-ratio scale. The methods are applied to two example meta-analyses, incorporating the relevant predictive distributions as prior distributions for between-study heterogeneity. We have provided resources to facilitate Bayesian meta-analysis, in a form accessible to applied researchers, which allow relevant prior information on the degree of heterogeneity to be incorporated. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:25475839

A comparison of solute-transport solution techniques and their effect on sensitivity analysis and inverse modeling results

USGS Publications Warehouse

Mehl, S.; Hill, M.C.

2001-01-01

Five common numerical techniques for solving the advection-dispersion equation (finite difference, predictor corrector, total variation diminishing, method of characteristics, and modified method of characteristics) were tested using simulations of a controlled conservative tracer-test experiment through a heterogeneous, two-dimensional sand tank. The experimental facility was constructed using discrete, randomly distributed, homogeneous blocks of five sand types. This experimental model provides an opportunity to compare the solution techniques: the heterogeneous hydraulic-conductivity distribution of known structure can be accurately represented by a numerical model, and detailed measurements can be compared with simulated concentrations and total flow through the tank. The present work uses this opportunity to investigate how three common types of results - simulated breakthrough curves, sensitivity analysis, and calibrated parameter values - change in this heterogeneous situation given the different methods of simulating solute transport. The breakthrough curves show that simulated peak concentrations, even at very fine grid spacings, varied between the techniques because of different amounts of numerical dispersion. Sensitivity-analysis results revealed: (1) a high correlation between hydraulic conductivity and porosity given the concentration and flow observations used, so that both could not be estimated; and (2) that the breakthrough curve data did not provide enough information to estimate individual values of dispersivity for the five sands. This study demonstrates that the choice of assigned dispersivity and the amount of numerical dispersion present in the solution technique influence estimated hydraulic conductivity values to a surprising degree.

Differential Variance Analysis: a direct method to quantify and visualize dynamic heterogeneities

NASA Astrophysics Data System (ADS)

Pastore, Raffaele; Pesce, Giuseppe; Caggioni, Marco

2017-03-01

Many amorphous materials show spatially heterogenous dynamics, as different regions of the same system relax at different rates. Such a signature, known as Dynamic Heterogeneity, has been crucial to understand the nature of the jamming transition in simple model systems and is currently considered very promising to characterize more complex fluids of industrial and biological relevance. Unfortunately, measurements of dynamic heterogeneities typically require sophisticated experimental set-ups and are performed by few specialized groups. It is now possible to quantitatively characterize the relaxation process and the emergence of dynamic heterogeneities using a straightforward method, here validated on video microscopy data of hard-sphere colloidal glasses. We call this method Differential Variance Analysis (DVA), since it focuses on the variance of the differential frames, obtained subtracting images at different time-lags. Moreover, direct visualization of dynamic heterogeneities naturally appears in the differential frames, when the time-lag is set to the one corresponding to the maximum dynamic susceptibility. This approach opens the way to effectively characterize and tailor a wide variety of soft materials, from complex formulated products to biological tissues.

Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.

PubMed

O'Connor, James P B; Rose, Chris J; Waterton, John C; Carano, Richard A D; Parker, Geoff J M; Jackson, Alan

2015-01-15

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. ©2014 American Association for Cancer Research.

Testing for qualitative heterogeneity: An application to composite endpoints in survival analysis.

PubMed

Oulhaj, Abderrahim; El Ghouch, Anouar; Holman, Rury R

2017-01-01

Composite endpoints are frequently used in clinical outcome trials to provide more endpoints, thereby increasing statistical power. A key requirement for a composite endpoint to be meaningful is the absence of the so-called qualitative heterogeneity to ensure a valid overall interpretation of any treatment effect identified. Qualitative heterogeneity occurs when individual components of a composite endpoint exhibit differences in the direction of a treatment effect. In this paper, we develop a general statistical method to test for qualitative heterogeneity, that is to test whether a given set of parameters share the same sign. This method is based on the intersection-union principle and, provided that the sample size is large, is valid whatever the model used for parameters estimation. We propose two versions of our testing procedure, one based on a random sampling from a Gaussian distribution and another version based on bootstrapping. Our work covers both the case of completely observed data and the case where some observations are censored which is an important issue in many clinical trials. We evaluated the size and power of our proposed tests by carrying out some extensive Monte Carlo simulations in the case of multivariate time to event data. The simulations were designed under a variety of conditions on dimensionality, censoring rate, sample size and correlation structure. Our testing procedure showed very good performances in terms of statistical power and type I error. The proposed test was applied to a data set from a single-center, randomized, double-blind controlled trial in the area of Alzheimer's disease.

Analysis of the Coupled Influence of Hydraulic Conductivity and Porosity Heterogeneity on Probabilistic Risk Analysis

NASA Astrophysics Data System (ADS)

Libera, A.; Henri, C.; de Barros, F.

2017-12-01

Heterogeneities in natural porous formations, mainly manifested through the hydraulic conductivity (K) and, to a lesser degree, the porosity (Φ), largely control subsurface flow and solute transport. The influence of the heterogeneous structure of K on flow and solute transport processes has been widely studied, whereas less attention is dedicated to the joint heterogeneity of conductivity and porosity fields. Our study employs computational tools to investigate the joint effect of the spatial variabilities of K and Φ on the transport behavior of a solute plume. We explore multiple scenarios, characterized by different levels of heterogeneity of the geological system, and compare the computational results from the joint K and Φ heterogeneous system with the results originating from the generally adopted constant porosity case. In our work, we assume that the heterogeneous porosity is positively correlated to hydraulic conductivity. We perform numerical Monte Carlo simulations of conservative and reactive contaminant transport in a 3D aquifer. Contaminant mass and plume arrival times at multiple control planes and/or pumping wells operating under different extraction rates are analyzed. We employ different probabilistic metrics to quantify the risk at the monitoring locations, e.g., increased lifetime cancer risk and exceedance of Maximum Contaminant Levels (MCLs), under multiple transport scenarios (i.e., different levels of heterogeneity, conservative or reactive solutes and different contaminant species). Results show that early and late arrival times of the solute mass at the selected sensitive locations (i.e. control planes/pumping wells) as well as risk metrics are strongly influenced by the spatial variability of the Φ field.

Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung Cancer (A549) Cell Line.

PubMed

Halim, Noor Hanis Abu; Zakaria, Norashikin; Satar, Nazilah Abdul; Yahaya, Badrul Hisham

2016-01-01

Cancer is a major health problem worldwide. The failure of current treatments to completely eradicate cancer cells often leads to cancer recurrence and dissemination. Studies have suggested that tumor growth and spread are driven by a minority of cancer cells that exhibit characteristics similar to those of normal stem cells, thus these cells are called cancer stem cells (CSCs). CSCs are believed to play an important role in initiating and promoting cancer. CSCs are resistant to currently available cancer therapies, and understanding the mechanisms that control the growth of CSCs might have great implications for cancer therapy. Cancer cells are consist of heterogeneous population of cells, thus methods of identification, isolation, and characterisation of CSCs are fundamental to obtain a pure CSC populations. Therefore, this chapter describes in detail a method for isolating and characterizing a pure population of CSCs from heterogeneous population of cancer cells and CSCs based on specific cell surface markers.

Optimizing structure of complex technical system by heterogeneous vector criterion in interval form

NASA Astrophysics Data System (ADS)

Lysenko, A. V.; Kochegarov, I. I.; Yurkov, N. K.; Grishko, A. K.

2018-05-01

The article examines the methods of development and multi-criteria choice of the preferred structural variant of the complex technical system at the early stages of its life cycle in the absence of sufficient knowledge of parameters and variables for optimizing this structure. The suggested methods takes into consideration the various fuzzy input data connected with the heterogeneous quality criteria of the designed system and the parameters set by their variation range. The suggested approach is based on the complex use of methods of interval analysis, fuzzy sets theory, and the decision-making theory. As a result, the method for normalizing heterogeneous quality criteria has been developed on the basis of establishing preference relations in the interval form. The method of building preferential relations in the interval form on the basis of the vector of heterogeneous quality criteria suggest the use of membership functions instead of the coefficients considering the criteria value. The former show the degree of proximity of the realization of the designed system to the efficient or Pareto optimal variants. The study analyzes the example of choosing the optimal variant for the complex system using heterogeneous quality criteria.

Biologically Relevant Heterogeneity: Metrics and Practical Insights.

PubMed

Gough, Albert; Stern, Andrew M; Maier, John; Lezon, Timothy; Shun, Tong-Ying; Chennubhotla, Chakra; Schurdak, Mark E; Haney, Steven A; Taylor, D Lansing

2017-03-01

Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications, including basic biomedical research, drug discovery, diagnostics, and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high-throughput workflow. This review and perspective emphasizes the experimental methods that capture multiplexed cell-level data, as well as the need for standard metrics of the spatial, temporal, and population components of heterogeneity. A recommendation is made for the adoption of a set of three heterogeneity indices that can be implemented in any high-throughput workflow to optimize the decision-making process. In addition, a pairwise mutual information method is suggested as an approach to characterizing the spatial features of heterogeneity, especially in tissue-based imaging. Furthermore, metrics for temporal heterogeneity are in the early stages of development. Example studies indicate that the analysis of functional phenotypic heterogeneity can be exploited to guide decisions in the interpretation of biomedical experiments, drug discovery, diagnostics, and the design of optimal therapeutic strategies for individual patients.

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

PubMed

Bisanzio, Donal; Mutuku, Francis; LaBeaud, Angelle D; Mungai, Peter L; Muinde, Jackson; Busaidy, Hajara; Mukoko, Dunstan; King, Charles H; Kitron, Uriel

2015-12-01

Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system. Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM). Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012. The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

Charge Transfer and Catalysis at the Metal Support Interface

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

Baker, Lawrence Robert

Kinetic, electronic, and spectroscopic characterization of model Pt–support systems are used to demonstrate the relationship between charge transfer and catalytic activity and selectivity. The results show that charge flow controls the activity and selectivity of supported metal catalysts. This dissertation builds on extensive existing knowledge of metal–support interactions in heterogeneous catalysis. The results show the prominent role of charge transfer at catalytic interfaces to determine catalytic activity and selectivity. Further, this research demonstrates the possibility of selectively driving catalytic chemistry by controlling charge flow and presents solid-state devices and doped supports as novel methods for obtaining electronic control over catalyticmore » reaction kinetics.« less

Robust pinning control of heterogeneous complex networks with jointly connected topologies and time-varying parametric uncertainty

NASA Astrophysics Data System (ADS)

Manfredi, Sabato

2018-05-01

The pinning/leader control problems provide the design of the leader or pinning controller in order to guide a complex network to a desired trajectory or target (synchronisation or consensus). Let a time-invariant complex network, pinning/leader control problems include the design of the leader or pinning controller gain and number of nodes to pin in order to guide a network to a desired trajectory (synchronization or consensus). Usually, lower is the number of pinned nodes larger is the pinning gain required to assess network synchronisation. On the other side, realistic application scenario of complex networks is characterised by switching topologies, time-varying node coupling strength and link weight that make hard to solve the pinning/leader control problem. Additionally, the system dynamics at nodes can be heterogeneous. In this paper, we derive robust stabilisation conditions of time-varying heterogeneous complex networks with jointly connected topologies when coupling strength and link weight interactions are affected by time-varying uncertainties. By employing Lyapunov stability theory and linear matrix inequality (LMI) technique, we formulate low computationally demanding stabilisability conditions to design a pinning/leader control gain for robust network synchronisation. The effectiveness of the proposed approach is shown by several design examples applied to a paradigmatic well-known complex network composed of heterogeneous Chua's circuits.

Effect of Chinese patent medicine Si-Mo-Tang oral liquid for functional dyspepsia: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Hu, Yunxia; Bai, Yu; Hua, Zhiyun; Yang, Jie; Yang, Huahui; Chen, Wenjun; Xu, Junwei; Zhao, Zhiqiang

2017-01-01

Background Si-Mo-Tang oral liquid (SMT) has been widely used to treat functional dyspepsia (FD), but the effectiveness is still controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to assess the efficacy and adverse effects of SMT for FD. Methods Investigators searched for articles with publication dates to June 21, 2016, from 9 English and Chinese electronic databases. Comparisons were SMT alone or SMT in combination with western medicine as experimental intervention, and western medicine or placebo as the control. We used the Cochrane collaboration tool for assessing risk of bias to evaluate methodologies. Data were synthesized with RevMan 5.3 software. (PROSPERO Registration #CRD42016042003) Results Twenty-seven RCTs were included in the review, involving 2,713 participants: 1,383 subjects were in the experimental group and 1,330 in the control group. SMT showed a significant improvement in clinical efficacy (RR 1.14; 95% CI 1.09, 1.20; P<0.00001), but the heterogeneity was also significant (P = 0.0002, I2 = 56%). Because of the different interventions in the 2 groups, we performed subgroup and sensitivity analyses to investigate potential sources of heterogeneity. The heterogeneity was smaller after subgroup analysis and the exclusion of a study by Zhu from 2009. The corresponding pooled RR has no obvious change (RR 1.17; 95% CI 1.13, 1.21; P<0.00001). Subgroup analysis by age and drugs administered in control interventions between SMT and western medicine also showed improvement in the efficacy rate. But a data synthesis that excluded high risk of bias in the blinding of participants and personnel showed no significant difference (RR 1.14; 95% CI 0.97, 1.35; P = 0.12). Three studies measured gastric emptying. Two of these studies reported no significant difference between the experimental and control groups, while 1 study showed that SMT reduced the time of gastric emptying. The relapse rate and adverse effects had no difference between 2 groups. Conclusions This meta-analysis suggests that SMT is an effective and safe therapy option for patients with FD. However, because of the high clinical heterogeneity, poor quality, high risk of bias and small sample size of some included studies, further standardized large-scale and strictly designed studies are needed. PMID:28199409

Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: A systematic review and meta-analysis

PubMed Central

Bagshaw, Sean M; Ghali, William A

2004-01-01

Background Contrast-induced nephropathy is an important cause of acute renal failure. We assess the efficacy of acetylcysteine for prevention of contrast-induced nephropathy among patients undergoing intravascular angiography. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing prophylactic acetylcysteine plus hydration versus hydration alone in patients undergoing intravascular angiography. Studies were identified by searching MEDLINE, EMBASE, and CENTRAL databases. Our main outcome measures were the risk of contrast-induced nephropathy and the difference in serum creatinine between acetylcysteine and control groups at 48 h. Results Fourteen studies involving 1261 patients were identified and included for analysis, and findings were heterogeneous across studies. Acetylcysteine was associated with a significantly reduced incidence of contrast-induced nephropathy in five studies, and no difference in the other nine (with a trend toward a higher incidence in six of the latter studies). The pooled odds ratio for contrast-induced nephropathy with acetylcysteine relative to control was 0.54 (95% CI, 0.32–0.91, p = 0.02) and the pooled estimate of difference in 48-h serum creatinine for acetylcysteine relative to control was -7.2 μmol/L (95% CI -19.7 to 5.3, p = 0.26). These pooled values need to be interpreted cautiously because of the heterogeneity across studies, and due to evidence of publication bias. Meta-regression suggested that the heterogeneity might be partially explained by whether the angiography was performed electively or as emergency. Conclusion These findings indicate that published studies of acetylcysteine for prevention of contrast-induced nephropathy yield inconsistent results. The efficacy of acetylcysteine will remain uncertain unless a large well-designed multi-center trial is performed. PMID:15500690

Direction-sensitive smart monitoring of structures using heterogeneous smartphone sensor data and coordinate system transformation

NASA Astrophysics Data System (ADS)

Ozer, Ekin; Feng, Maria Q.

2017-04-01

Mobile, heterogeneous, and smart sensor networks produce pervasive structural health monitoring (SHM) information. With various embedded sensors, smartphones have emerged to innovate SHM by empowering citizens to serve as sensors. By default, smartphones meet the fundamental smart sensor criteria, thanks to the built-in processor, memory, wireless communication units and mobile operating system. SHM using smartphones, however, faces technical challenges due to citizen-induced uncertainties, undesired sensor-structure integration, and lack of control over the sensing platform. Previously, the authors presented successful applications of smartphone accelerometers for structural vibration measurement and proposed a monitoring framework under citizen-induced spatiotemporal uncertainties. This study aims at extending the capabilities of smartphone-based SHM with a special focus on the lack of control over the sensor (i.e., the phone) positioning by citizens resulting in unknown sensor orientations. Using smartphone gyroscope, accelerometer, and magnetometer; instantaneous sensor orientation can be obtained with respect to gravitational and magnetic north directions. Using these sensor data, mobile operating system frameworks return processed features such as attitude and heading that can be used to correct misaligned sensor signals. For this purpose, a coordinate transformation procedure is proposed and illustrated on a two-story laboratory structural model and real-scale bridges with various sensor positioning examples. The proposed method corrects the sensor signals by tracking their orientations and improves measurement accuracy. Moreover, knowing structure’s coordinate system a priori, even the data from arbitrarily positioned sensors can automatically be transformed to the structural coordinates. In addition, this paper also touches some secondary mobile and heterogeneous data issues including imperfect sampling and geolocation services. The coordinate system transformation methods proposed in this study can be implemented in other non-smartphone-based SHM systems as long as similar instrumentation is available.

The association between prostatitis and prostate cancer. Systematic review and meta-analysis.

PubMed

Perletti, Gianpaolo; Monti, Elena; Magri, Vittorio; Cai, Tommaso; Cleves, Anne; Trinchieri, Alberto; Montanari, Emanuele

2017-12-31

The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III) and a histologically confirmed diagnosis of prostate cancer. Crude odds ratios and 95% confidence intervals (CI) were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P < 0.00001). The total set of data showed considerable heterogeneity (I2 = 91%). Both the Egger's test and the Begg's test for funnel plot asymmetry did not reach statistical significance. The 'trim and fill' method applied to the funnel plot imputed 3 missing studies and the resulting adjusted estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

Final Technical Report - Investigation into the Relationship between Heterogeneity and Heavy-Tailed Solute Transport

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

Weissmann, Gary S

2013-12-06

The objective of this project was to characterize the influence that naturally complex geologic media has on anomalous dispersion and to determine if the nature of dispersion can be estimated from the underlying heterogeneous media. The UNM portion of this project was to provide detailed representations of aquifer heterogeneity through producing highly-resolved models of outcrop analogs to aquifer materials. This project combined outcrop-scale heterogeneity characterization (conducted at the University of New Mexico), laboratory experiments (conducted at Sandia National Laboratory), and numerical simulations (conducted at Sandia National Laboratory and Colorado School of Mines). The study was designed to test whether establishedmore » dispersion theory accurately predicts the behavior of solute transport through heterogeneous media and to investigate the relationship between heterogeneity and the parameters that populate these models. The dispersion theory tested by this work was based upon the fractional advection-dispersion equation (fADE) model. Unlike most dispersion studies that develop a solute transport model by fitting the solute transport breakthrough curve, this project explored the nature of the heterogeneous media to better understand the connection between the model parameters and the aquifer heterogeneity. We also evaluated methods for simulating the heterogeneity to see whether these approaches (e.g., geostatistical) could reasonably replicate realistic heterogeneity. The UNM portion of this study focused on capturing realistic geologic heterogeneity of aquifer analogs using advanced outcrop mapping methods.« less

A fast boosting-based screening method for large-scale association study in complex traits with genetic heterogeneity.

PubMed

Wang, Lu-Yong; Fasulo, D

2006-01-01

Genome-wide association study for complex diseases will generate massive amount of single nucleotide polymorphisms (SNPs) data. Univariate statistical test (i.e. Fisher exact test) was used to single out non-associated SNPs. However, the disease-susceptible SNPs may have little marginal effects in population and are unlikely to retain after the univariate tests. Also, model-based methods are impractical for large-scale dataset. Moreover, genetic heterogeneity makes the traditional methods harder to identify the genetic causes of diseases. A more recent random forest method provides a more robust method for screening the SNPs in thousands scale. However, for more large-scale data, i.e., Affymetrix Human Mapping 100K GeneChip data, a faster screening method is required to screening SNPs in whole-genome large scale association analysis with genetic heterogeneity. We propose a boosting-based method for rapid screening in large-scale analysis of complex traits in the presence of genetic heterogeneity. It provides a relatively fast and fairly good tool for screening and limiting the candidate SNPs for further more complex computational modeling task.

Meta-Analysis of Fluid Intelligence Tests of Children from the Chinese Mainland with Learning Difficulties

PubMed Central

Tong, Fang; Fu, Tong

2013-01-01

Objective To evaluate the differences in fluid intelligence tests between normal children and children with learning difficulties in China. Method PubMed, MD Consult, and other Chinese Journal Database were searched from their establishment to November 2012. After finding comparative studies of Raven measurements of normal children and children with learning difficulties, full Intelligent Quotation (FIQ) values and the original values of the sub-measurement were extracted. The corresponding effect model was selected based on the results of heterogeneity and parallel sub-group analysis was performed. Results Twelve documents were included in the meta-analysis, and the studies were all performed in mainland of China. Among these, two studies were performed at child health clinics, the other ten sites were schools and control children were schoolmates or classmates. FIQ was evaluated using a random effects model. WMD was −13.18 (95% CI: −16.50–−9.85). Children with learning difficulties showed significantly lower FIQ scores than controls (P<0.00001); Type of learning difficulty and gender differences were evaluated using a fixed-effects model (I2 = 0%). The sites and purposes of the studies evaluated here were taken into account, but the reasons of heterogeneity could not be eliminated; The sum IQ of all the subgroups showed considerable heterogeneity (I2 = 76.5%). The sub-measurement score of document A showed moderate heterogeneity among all documents, and AB, B, and E showed considerable heterogeneity, which was used in a random effect model. Individuals with learning difficulties showed heterogeneity as well. There was a moderate delay in the first three items (−0.5 to −0.9), and a much more pronounced delay in the latter three items (−1.4 to −1.6). Conclusion In the Chinese mainland, the level of fluid intelligence of children with learning difficulties was lower than that of normal children. Delayed development in sub-items of C, D, and E was more obvious. PMID:24236016

Elastic Rock Heterogeneity Controls Brittle Rock Failure during Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Langenbruch, C.; Shapiro, S. A.

2014-12-01

For interpretation and inversion of microseismic data it is important to understand, which properties of the reservoir rock control the occurrence probability of brittle rock failure and associated seismicity during hydraulic stimulation. This is especially important, when inverting for key properties like permeability and fracture conductivity. Although it became accepted that seismic events are triggered by fluid flow and the resulting perturbation of the stress field in the reservoir rock, the magnitude of stress perturbations, capable of triggering failure in rocks, can be highly variable. The controlling physical mechanism of this variability is still under discussion. We compare the occurrence of microseismic events at the Cotton Valley gas field to elastic rock heterogeneity, obtained from measurements along the treatment wells. The heterogeneity is characterized by scale invariant fluctuations of elastic properties. We observe that the elastic heterogeneity of the rock formation controls the occurrence of brittle failure. In particular, we find that the density of events is increasing with the Brittleness Index (BI) of the rock, which is defined as a combination of Young's modulus and Poisson's ratio. We evaluate the physical meaning of the BI. By applying geomechanical investigations we characterize the influence of fluctuating elastic properties in rocks on the probability of brittle rock failure. Our analysis is based on the computation of stress fluctuations caused by elastic heterogeneity of rocks. We find that elastic rock heterogeneity causes stress fluctuations of significant magnitude. Moreover, the stress changes necessary to open and reactivate fractures in rocks are strongly related to fluctuations of elastic moduli. Our analysis gives a physical explanation to the observed relation between elastic heterogeneity of the rock formation and the occurrence of brittle failure during hydraulic reservoir stimulations. A crucial factor for understanding seismicity in unconventional reservoirs is the role of anisotropy of rocks. We evaluate an elastic VTI rock model corresponding to a shale gas reservoir in the Horn River Basin to understand the relation between stress, event occurrence and elastic heterogeneity in anisotropic rocks.

Case–control and prospective studies of dietary α-linolenic acid intake and prostate cancer risk: a meta-analysis

PubMed Central

Carleton, Amanda J; Sievenpiper, John L; de Souza, Russell; McKeown-Eyssen, Gail; Jenkins, David J A

2013-01-01

Objective α-Linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case–control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk. Design A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case–control studies. Included studies We included all prospective cohort, case–control, nested case-cohort and nested case–control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates. Primary outcome measure Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95% CIs. Heterogeneity was assessed by χ2 and quantified by I2. Results Data from five prospective and seven case–control studies were pooled. The overall RR estimate showed ALA intake to be positively but non-significantly associated with prostate cancer risk (1.08 (0.90 to 1.29), p=0.40; I2=85%), but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant (0.91 (0.83 to 0.99), p=0.02) without evidence of heterogeneity (I2=8%, p=0.35) on removal of one study during sensitivity analyses. Conclusions This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer. PMID:23674441

Wave propagation simulation in the upper core of sodium-cooled fast reactors using a spectral-element method for heterogeneous media

NASA Astrophysics Data System (ADS)

Nagaso, Masaru; Komatitsch, Dimitri; Moysan, Joseph; Lhuillier, Christian

2018-01-01

ASTRID project, French sodium cooled nuclear reactor of 4th generation, is under development at the moment by Alternative Energies and Atomic Energy Commission (CEA). In this project, development of monitoring techniques for a nuclear reactor during operation are identified as a measure issue for enlarging the plant safety. Use of ultrasonic measurement techniques (e.g. thermometry, visualization of internal objects) are regarded as powerful inspection tools of sodium cooled fast reactors (SFR) including ASTRID due to opacity of liquid sodium. In side of a sodium cooling circuit, heterogeneity of medium occurs because of complex flow state especially in its operation and then the effects of this heterogeneity on an acoustic propagation is not negligible. Thus, it is necessary to carry out verification experiments for developments of component technologies, while such kind of experiments using liquid sodium may be relatively large-scale experiments. This is why numerical simulation methods are essential for preceding real experiments or filling up the limited number of experimental results. Though various numerical methods have been applied for a wave propagation in liquid sodium, we still do not have a method for verifying on three-dimensional heterogeneity. Moreover, in side of a reactor core being a complex acousto-elastic coupled region, it has also been difficult to simulate such problems with conventional methods. The objective of this study is to solve these 2 points by applying three-dimensional spectral element method. In this paper, our initial results on three-dimensional simulation study on heterogeneous medium (the first point) are shown. For heterogeneity of liquid sodium to be considered, four-dimensional temperature field (three spatial and one temporal dimension) calculated by computational fluid dynamics (CFD) with Large-Eddy Simulation was applied instead of using conventional method (i.e. Gaussian Random field). This three-dimensional numerical experiment yields that we could verify the effects of heterogeneity of propagation medium on waves in Liquid sodium.

Modeling Strain Rate Effect of Heterogeneous Materials Using SPH Method

NASA Astrophysics Data System (ADS)

Ma, G. W.; Wang, X. J.; Li, Q. M.

2010-11-01

The strain rate effect on the dynamic compressive failure of heterogeneous material based on the smoothed particle hydrodynamics (SPH) method is studied. The SPH method employs a rate-insensitive elasto-plastic damage model incorporated with a Weibull distribution law to reflect the mechanical behavior of heterogeneous rock-like materials. A series of simulations are performed for heterogeneous specimens by applying axial velocity conditions, which induce different strain-rate loadings to the specimen. A detailed failure process of the specimens in terms of microscopic crack-activities and the macro-mechanical response are discussed. Failure mechanisms between the low and high strain rate cases are compared. The result shows that the strain-rate effects on the rock strength are mainly caused by the changing internal pressure due to the inertial effects as well as the material heterogeneity. It also demonstrates that the inertial effect becomes significant only when the induced strain rate exceeds a threshold, below which, the dynamic strength enhancement can be explained due to the heterogeneities in the material. It also shows that the dynamic strength is affected more significantly for a relatively more heterogeneous specimen, which coincides with the experimental results showing that the poor quality specimen had a relatively larger increase in the dynamic strength.

Learning from Data with Heterogeneous Noise using SGD

PubMed Central

Song, Shuang; Chaudhuri, Kamalika; Sarwate, Anand D.

2015-01-01

We consider learning from data of variable quality that may be obtained from different heterogeneous sources. Addressing learning from heterogenous data in its full generality is a challenging problem. In this paper, we adopt instead a model in which data is observed through heterogeneous noise, where the noise level reflects the quality of the data source. We study how to use stochastic gradient algorithms to learn in this model. Our study is motivated by two concrete examples where this problem arises naturally: learning with local differential privacy based on data from multiple sources with different privacy requirements, and learning from data with labels of variable quality. The main contribution of this paper is to identify how heterogeneous noise impacts performance. We show that given two datasets with heterogeneous noise, the order in which to use them in standard SGD depends on the learning rate. We propose a method for changing the learning rate as a function of the heterogeneity, and prove new regret bounds for our method in two cases of interest. Experiments on real data show that our method performs better than using a single learning rate and using only the less noisy of the two datasets when the noise level is low to moderate. PMID:26705435

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

Ye, Rong; Zhukhovitskiy, Aleksandr V.; Deraedt, Christophe V.

Recyclable catalysts, especially those that display selective reactivity, are vital for the development of sustainable chemical processes. Among available catalyst platforms, heterogeneous catalysts are particularly well-disposed toward separation from the reaction mixture via filtration methods, which renders them readily recyclable. Furthermore, heterogeneous catalysts offer numerous handles—some without homogeneous analogues—for performance and selectivity optimization. These handles include nanoparticle size, pore profile of porous supports, surface ligands and interface with oxide supports, and flow rate through a solid catalyst bed. Despite these available handles, however, conventional heterogeneous catalysts are themselves often structurally heterogeneous compared to homogeneous catalysts, which complicates efforts to optimizemore » and expand the scope of their reactivity and selectivity. Ongoing efforts in our laboratories are aimed to address the above challenge by heterogenizing homogeneous catalysts, which can be defined as the modification of homogeneous catalysts to render them in a separable (solid) phase from the starting materials and products. Specifically, we grow the small nanoclusters in dendrimers, a class of uniform polymers with the connectivity of fractal trees and generally radial symmetry. Thanks to their dense multivalency, shape persistence, and structural uniformity, dendrimers have proven to be versatile scaffolds for the synthesis and stabilization of small nanoclusters. Then these dendrimer-encapsulated metal clusters (DEMCs) are adsorbed onto mesoporous silica. Through this method, we have achieved selective transformations that had been challenging to accomplish in a heterogeneous setting, e.g., π-bond activation and aldol reactions. Extensive investigation into the catalytic systems under reaction conditions allowed us to correlate the structural features (e.g., oxidation states) of the catalysts and their activity. Moreover, we have demonstrated that supported DEMCs are also excellent catalysts for typical heterogeneous reactions, including hydrogenation and alkane isomerization. Critically, these investigations also confirmed that the supported DEMCs are heterogeneous and stable against leaching. Catalysts optimization is achieved through the modulation of various parameters. The clusters are oxidized (e.g., with PhICl 2) or reduced (e.g., with H 2) in situ. Changing the dendrimer properties (e.g., generation, terminal functional groups) is analogous to ligand modification in homogeneous catalysts, which affect both catalytic activity and selectivity. Similarly, pore size of the support is another factor in determining product distribution. In a flow reactor, the flow rate is adjusted to control the residence time of the starting material and intermediates, and thus the final product selectivity. Our approach to heterogeneous catalysis affords various advantages: (1) the catalyst system can tap into the reactivity typical to homogeneous catalysts, which conventional heterogeneous catalysts could not achieve; (2) unlike most homogeneous catalysts with comparable performance, the heterogenized homogeneous catalysts can be recycled; (3) improved activity or selectivity compared to conventional homogeneous catalysts is possible because of uniquely heterogeneous parameters for optimization. Here in this Account, we will briefly introduce metal clusters and describe the synthesis and characterizations of supported DEMCs. We will present the catalysis studies of supported DEMCs in both the batch and flow modes. Lastly, we will summarize the current state of heterogenizing homogeneous catalysis and provide future directions for this area of research.« less

Image analysis of skin color heterogeneity focusing on skin chromophores and the age-related changes in facial skin.

PubMed

Kikuchi, Kumiko; Masuda, Yuji; Yamashita, Toyonobu; Kawai, Eriko; Hirao, Tetsuji

2015-05-01

Heterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age-related changes. A facial imaging system equipped with an illumination unit and a high-resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment-specific image-processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized. The proposed pigment-specific image-processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age-related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin. We have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Defense Small Business Innovation Research Program (SBIR), Volume 4, Defense Agencies Abstracts of Phase 1 Awards 1991

DTIC Science & Technology

1991-01-01

EXPERIENCE IN DEVELOPING INTEGRATED OPTICAL DEVICES, NONLINEAR MAGNETIC-OPTIC MATERIALS, HIGH FREQUENCY MODULATORS, COMPUTER-AIDED MODELING AND SOPHISTICATED... HIGH -LEVEL PRESENTATION AND DISTRIBUTED CONTROL MODELS FOR INTEGRATING HETEROGENEOUS MECHANICAL ENGINEERING APPLICATIONS AND TOOLS. THE DESIGN IS FOCUSED...STATISTICALLY ACCURATE WORST CASE DEVICE MODELS FOR CIRCUIT SIMULATION. PRESENT METHODS OF WORST CASE DEVICE DESIGN ARE AD HOC AND DO NOT ALLOW THE

Lifelong Transfer Learning for Heterogeneous Teams of Agents in Sequential Decision Processes

DTIC Science & Technology

2016-06-01

making (SDM) tasks in dynamic environments with simulated and physical robots . 15. SUBJECT TERMS Sequential decision making, lifelong learning, transfer...sequential decision-making (SDM) tasks in dynamic environments with both simple benchmark tasks and more complex aerial and ground robot tasks. Our work...and ground robots in the presence of disturbances: We applied our methods to the problem of learning controllers for robots with novel disturbances in

Bird functional diversity decreases with time since disturbance: Does patchy prescribed fire enhance ecosystem function?.

PubMed

Sitters, Holly; Di Stefano, Julian; Christie, Fiona; Swan, Matthew; York, Alan

2016-01-01

Animal species diversity is often associated with time since disturbance, but the effects of disturbances such as fire on functional diversity are unknown. Functional diversity measures the range, abundance, and distribution of trait values in a community, and links changes in species composition with the consequences for ecosystem function. Improved understanding of the relationship between time since fire (TSF) and functional diversity is critical given that the frequency of both prescribed fire and wildfire is expected to increase. To address this knowledge gap, we examined responses of avian functional diversity to TSF and two direct measures of environmental heterogeneity, plant diversity, and structural heterogeneity. We surveyed birds across a 70-year chronosequence spanning four vegetation types in southeast Australia. Six bird functional traits were used to derive four functional diversity indices (richness, evenness, divergence, and dispersion) and the effects of TSF, plant diversity and structural heterogeneity on species richness and the functional diversity indices were examined using mixed models. We used a regression tree method to identify traits associated with species more common in young vegetation. Functional richness and dispersion were negatively associated with TSF in all vegetation types, suggesting that recent prescribed fire generates heterogeneous vegetation and provides greater opportunities for resource partitioning. Species richness was not significantly associated with TSF, and is probably an unreliable surrogate for functional diversity in fire-prone systems. A positive, relationship between functional evenness and structural heterogeneity was comnon to all vegetation types, suggesting that fine-scale (tens of meters) structural variation can enhance ecosystem function. Species more common in young vegetation were primarily linked by their specialist diets, indicating that ecosystem services such as seed dispersal and insect control are enhanced in more recently burnt vegetation. We suggest that patchy prescribed fire sustains functional diversity, and that controlled use of patchy fire to break up large expanses of mature vegetation will enhance ecosystem function.

Meta-analysis of heterogeneous data sources for genome-scale identification of risk genes in complex phenotypes.

PubMed

Pers, Tune H; Hansen, Niclas Tue; Lage, Kasper; Koefoed, Pernille; Dworzynski, Piotr; Miller, Martin Lee; Flint, Tracey J; Mellerup, Erling; Dam, Henrik; Andreassen, Ole A; Djurovic, Srdjan; Melle, Ingrid; Børglum, Anders D; Werge, Thomas; Purcell, Shaun; Ferreira, Manuel A; Kouskoumvekaki, Irene; Workman, Christopher T; Hansen, Torben; Mors, Ole; Brunak, Søren

2011-07-01

Meta-analyses of large-scale association studies typically proceed solely within one data type and do not exploit the potential complementarities in other sources of molecular evidence. Here, we present an approach to combine heterogeneous data from genome-wide association (GWA) studies, protein-protein interaction screens, disease similarity, linkage studies, and gene expression experiments into a multi-layered evidence network which is used to prioritize the entire protein-coding part of the genome identifying a shortlist of candidate genes. We report specifically results on bipolar disorder, a genetically complex disease where GWA studies have only been moderately successful. We validate one such candidate experimentally, YWHAH, by genotyping five variations in 640 patients and 1,377 controls. We found a significant allelic association for the rs1049583 polymorphism in YWHAH (adjusted P = 5.6e-3) with an odds ratio of 1.28 [1.12-1.48], which replicates a previous case-control study. In addition, we demonstrate our approach's general applicability by use of type 2 diabetes data sets. The method presented augments moderately powered GWA data, and represents a validated, flexible, and publicly available framework for identifying risk genes in highly polygenic diseases. The method is made available as a web service at www.cbs.dtu.dk/services/metaranker. © 2011 Wiley-Liss, Inc.

INFLUENCE OF GENETIC FACTORS ON THE MAGNITUDE AND THE HETEROGENEITY OF THE IMMUNE RESPONSE IN THE RABBIT

PubMed Central

Eichmann, Klaus; Braun, Dietmar G.; Krause, Richard M.

1971-01-01

Selective breeding of rabbits immunized with Group C and Group A streptococcal vaccines was employed to reveal genetic influences on the magnitude and on the restriction in heterogeneity of the immune response to the group-specific carbohydrates. After two generations of selective breeding, complete segregation was achieved between a high-response population (>18 mg precipitins/ml serum, average 33 mg/ml) and a low-response population (<13 mg precipitins/ml serum, average 7.5 mg/ml) to Group C carbohydrate. This suggests that a limited number of genes controls the magnitude of the immune response to this antigen. Selective breeding of rabbits which were representative of heterogeneous, restricted, and monoclonal responses revealed that the degree of antibody heterogeneity in the parental rabbits is reflected in the offspring. More than 95% of the offspring derived from rabbits which had a heterogeneous immune response developed heterogeneous antibodies. 33% of the offspring derived from rabbits which had restricted and monoclonal immune responses developed monoclonal antibodies. This suggests that the degree of heterogeneity of the antibody response to the streptococcal carbohydrates is under genetic control. The degree of heterogeneity and the magnitude of the immune response appear to be independent variables. PMID:5558071

Fast hydrological model calibration based on the heterogeneous parallel computing accelerated shuffled complex evolution method

NASA Astrophysics Data System (ADS)

Kan, Guangyuan; He, Xiaoyan; Ding, Liuqian; Li, Jiren; Hong, Yang; Zuo, Depeng; Ren, Minglei; Lei, Tianjie; Liang, Ke

2018-01-01

Hydrological model calibration has been a hot issue for decades. The shuffled complex evolution method developed at the University of Arizona (SCE-UA) has been proved to be an effective and robust optimization approach. However, its computational efficiency deteriorates significantly when the amount of hydrometeorological data increases. In recent years, the rise of heterogeneous parallel computing has brought hope for the acceleration of hydrological model calibration. This study proposed a parallel SCE-UA method and applied it to the calibration of a watershed rainfall-runoff model, the Xinanjiang model. The parallel method was implemented on heterogeneous computing systems using OpenMP and CUDA. Performance testing and sensitivity analysis were carried out to verify its correctness and efficiency. Comparison results indicated that heterogeneous parallel computing-accelerated SCE-UA converged much more quickly than the original serial version and possessed satisfactory accuracy and stability for the task of fast hydrological model calibration.

Complex Nonlinear Dynamic System of Oligopolies Price Game with Heterogeneous Players Under Noise

NASA Astrophysics Data System (ADS)

Liu, Feng; Li, Yaguang

A nonlinear four oligopolies price game with heterogeneous players, that are boundedly rational and adaptive, is built using two different special demand costs. Based on the theory of complex discrete dynamical system, the stability and the existing equilibrium point are investigated. The complex dynamic behavior is presented via bifurcation diagrams, the Lyapunov exponents to show equilibrium state, bifurcation and chaos with the variation in parameters. As disturbance is ubiquitous in economic systems, this paper focuses on the analysis of delay feedback control method under noise circumstances. Stable dynamics is confirmed to depend mainly on the low price adjustment speed, and if all four players have limited opportunities to stabilize the market, the new adaptive player facing profits of scale are found to be higher than the incumbents of bounded rational.

Effective Information Extraction Framework for Heterogeneous Clinical Reports Using Online Machine Learning and Controlled Vocabularies

PubMed Central

Zheng, Shuai; Ghasemzadeh, Nima; Hayek, Salim S; Quyyumi, Arshed A

2017-01-01

Background Extracting structured data from narrated medical reports is challenged by the complexity of heterogeneous structures and vocabularies and often requires significant manual effort. Traditional machine-based approaches lack the capability to take user feedbacks for improving the extraction algorithm in real time. Objective Our goal was to provide a generic information extraction framework that can support diverse clinical reports and enables a dynamic interaction between a human and a machine that produces highly accurate results. Methods A clinical information extraction system IDEAL-X has been built on top of online machine learning. It processes one document at a time, and user interactions are recorded as feedbacks to update the learning model in real time. The updated model is used to predict values for extraction in subsequent documents. Once prediction accuracy reaches a user-acceptable threshold, the remaining documents may be batch processed. A customizable controlled vocabulary may be used to support extraction. Results Three datasets were used for experiments based on report styles: 100 cardiac catheterization procedure reports, 100 coronary angiographic reports, and 100 integrated reports—each combines history and physical report, discharge summary, outpatient clinic notes, outpatient clinic letter, and inpatient discharge medication report. Data extraction was performed by 3 methods: online machine learning, controlled vocabularies, and a combination of these. The system delivers results with F1 scores greater than 95%. Conclusions IDEAL-X adopts a unique online machine learning–based approach combined with controlled vocabularies to support data extraction for clinical reports. The system can quickly learn and improve, thus it is highly adaptable. PMID:28487265

Real-Time Monitoring of Heterogeneous Catalysis with Mass Spectrometry

ERIC Educational Resources Information Center

Young, Mark A.

2009-01-01

Heterogeneous, gas-solid processes constitute an important class of catalytic reactions that play a key role in a variety of applications, such as industrial processing and environmental controls. Heterogeneous catalytic chemistry can be demonstrated in a simple heated flow reactor containing a fragment of the catalytic converter from a vehicular…

Estimating age-specific reproductive numbers-A comparison of methods.

PubMed

Moser, Carlee B; White, Laura F

2016-01-01

Large outbreaks, such as those caused by influenza, put a strain on resources necessary for their control. In particular, children have been shown to play a key role in influenza transmission during recent outbreaks, and targeted interventions, such as school closures, could positively impact the course of emerging epidemics. As an outbreak is unfolding, it is important to be able to estimate reproductive numbers that incorporate this heterogeneity and to use surveillance data that is routinely collected to more effectively target interventions and obtain an accurate understanding of transmission dynamics. There are a growing number of methods that estimate age-group specific reproductive numbers with limited data that build on methods assuming a homogenously mixing population. In this article, we introduce a new approach that is flexible and improves on many aspects of existing methods. We apply this method to influenza data from two outbreaks, the 2009 H1N1 outbreaks in South Africa and Japan, to estimate age-group specific reproductive numbers and compare it to three other methods that also use existing data from social mixing surveys to quantify contact rates among different age groups. In this exercise, all estimates of the reproductive numbers for children exceeded the critical threshold of one and in most cases exceeded those of adults. We introduce a flexible new method to estimate reproductive numbers that describe heterogeneity in the population.

Quantifying Heterogeneous Malaria Exposure and Clinical Protection in a Cohort of Ugandan Children

PubMed Central

Rodriguez-Barraquer, Isabel; Arinaitwe, Emmanuel; Jagannathan, Prasanna; Boyle, Michelle J.; Tappero, Jordan; Muhindo, Mary; Kamya, Moses R.; Dorsey, Grant; Drakeley, Chris; Ssewanyana, Isaac; Smith, David L.; Greenhouse, Bryan

2016-01-01

Background. Plasmodium falciparum malaria remains a leading cause of childhood morbidity and mortality. There are important gaps in our understanding of the factors driving the development of antimalaria immunity as a function of age and exposure. Methods. We used data from a cohort of 93 children participating in a clinical trial in Tororo, Uganda, an area of very high exposure to P. falciparum. We jointly quantified individual heterogeneity in the risk of infection and the development of immunity against infection and clinical disease. Results. Results showed significant heterogeneity in the hazard of infection and independent effects of age and cumulative number of infections on the risk of infection and disease. The risk of developing clinical malaria upon infection decreased on average by 6% (95% confidence interval [CI], 0%–12%) for each additional year of age and by 2% (95% CI, 1%–3%) for each additional prior infection. Children randomly assigned to receive dihydroartemisinin-piperaquine for treatment appeared to develop immunity more slowly than those receiving artemether-lumefantrine. Conclusions. Heterogeneity in P. falciparum exposure and immunity can be independently evaluated using detailed longitudinal studies. Improved understanding of the factors driving immunity will provide key information to anticipate the impact of malaria-control interventions and to understand the mechanisms of clinical immunity. PMID:27481862

Image-guided spatial localization of heterogeneous compartments for magnetic resonance

PubMed Central

An, Li; Shen, Jun

2015-01-01

Purpose: Image-guided localization SPectral Localization Achieved by Sensitivity Heterogeneity (SPLASH) allows rapid measurement of signals from irregularly shaped anatomical compartments without using phase encoding gradients. Here, the authors propose a novel method to address the issue of heterogeneous signal distribution within the localized compartments. Methods: Each compartment was subdivided into multiple subcompartments and their spectra were solved by Tikhonov regularization to enforce smoothness within each compartment. The spectrum of a given compartment was generated by combining the spectra of the components of that compartment. The proposed method was first tested using Monte Carlo simulations and then applied to reconstructing in vivo spectra from irregularly shaped ischemic stroke and normal tissue compartments. Results: Monte Carlo simulations demonstrate that the proposed regularized SPLASH method significantly reduces localization and metabolite quantification errors. In vivo results show that the intracompartment regularization results in ∼40% reduction of error in metabolite quantification. Conclusions: The proposed method significantly reduces localization errors and metabolite quantification errors caused by intracompartment heterogeneous signal distribution. PMID:26328977

On the design of innovative heterogeneous tests using a shape optimization approach

NASA Astrophysics Data System (ADS)

Aquino, J.; Campos, A. Andrade; Souto, N.; Thuillier, S.

2018-05-01

The development of full-field measurement methods enabled a new trend of mechanical tests. By providing the inhomogeneous strain field from the tests, these techniques are being widely used in sheet metal identification strategies, through heterogeneous mechanical tests. In this work, a heterogeneous mechanical test with an innovative tool/specimen shape, capable of producing rich heterogeneous strain paths providing extensive information on material behavior, is aimed. The specimen is found using a shape optimization process where a dedicated indicator that evaluates the richness of strain information is used. The methodology and results here presented are extended to non-specimen geometry dependence and to the non-dependence of the geometry parametrization through the use of the Ritz method for boundary value problems. Different curve models, such as Splines, B-Splines and NURBS, are used and C1 continuity throughout the specimen is guaranteed. Moreover, various optimization methods are used, deterministic and stochastic, in order to find the method or a combination of methods able to effectively minimize the cost function.

Heterogeneous iris image hallucination using sparse representation on a learned heterogeneous patch dictionary

NASA Astrophysics Data System (ADS)

Li, Yung-Hui; Zheng, Bo-Ren; Ji, Dai-Yan; Tien, Chung-Hao; Liu, Po-Tsun

2014-09-01

Cross sensor iris matching may seriously degrade the recognition performance because of the sensor mis-match problem of iris images between the enrollment and test stage. In this paper, we propose two novel patch-based heterogeneous dictionary learning method to attack this problem. The first method applies the latest sparse representation theory while the second method tries to learn the correspondence relationship through PCA in heterogeneous patch space. Both methods learn the basic atoms in iris textures across different image sensors and build connections between them. After such connections are built, at test stage, it is possible to hallucinate (synthesize) iris images across different sensors. By matching training images with hallucinated images, the recognition rate can be successfully enhanced. The experimental results showed the satisfied results both visually and in terms of recognition rate. Experimenting with an iris database consisting of 3015 images, we show that the EER is decreased 39.4% relatively by the proposed method.

Assay validation for the assessment of adipogenesis of multipotential stromal cells—a direct comparison of four different methods

PubMed Central

Aldridge, Andrew; Kouroupis, Dimitrios; Churchman, Sarah; English, Anne; Ingham, Eileen; Jones, Elena

2013-01-01

Background aims Mesenchymal stromal cells (MSCs) are regenerative and immuno-privileged cells that are used for both tissue regeneration and treatment of severe inflammation-related disease. For quality control of manufactured MSC batches in regard to mature fat cell contamination, a quantitative method for measuring adipogenesis is needed. Methods Four previously proposed methods were validated with the use of bone marrow (BM) MSCs during a 21-day in vitro assay. Oil red staining was scored semiquantitatively; peroxisome proliferator activated receptor-γ and fatty acid binding protein (FABP)4 transcripts were measured by quantitative real-time polymerase chain reaction; FABP4 protein accumulation was evaluated by flow cytometry; and Nile red/4′,6-diamidino-2-phenylindole (DAPI) ratios were measured in fluorescent microplate assay. Skin fibroblasts and MSCs from fat pad, cartilage and umbilical cord were used as controls. Results Oil red staining indicated considerable heterogeneity between BM donors and individual cells within the same culture. FABP4 transcript levels increased 100- to 5000-fold by day 21, with large donor variability observed. Flow cytometry revealed increasing intra-culture heterogeneity over time; more granular cells accumulated more FABP4 protein and Nile red fluorescence compared with less granular cells. Nile red increase in day-21 MSCs was ∼5- and 4-fold, measured by flow cytometry or microplate assay, respectively. MSC proliferation/apoptosis was accounted through the use of Nile red/DAPI ratios; adipogenesis levels in day-21 BM MSCs increased ∼13-fold, with significant correlations with oil red scoring observed for MSC from other sources. Conclusions Flow cytometry permits the study of MSC differentiation at the single-cell level and sorting more and less mature cells from mixed cell populations. The microplate assay with the use of the Nile red/DAPI ratio provides rapid quantitative measurements and could be used as a low-cost, high-throughput method to quality-control MSC batches from different tissue sources. PMID:23260089

Engineering Microbial Metabolite Dynamics and Heterogeneity.

PubMed

Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

2017-10-01

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the Redundant Verification and the Non-Redundant Verification on the Hydraulic Tomography

NASA Astrophysics Data System (ADS)

Wei, T. B.; Chen, Y. L.; Lin, H. R.; Huang, S. Y.; Yeh, T. C. J.; Wen, J. C.

2016-12-01

In the groundwater study, it estimated the heterogeneous spatial distribution of hydraulic Properties, there were many scholars use to hydraulic tomography (HT) from field site pumping tests to estimate inverse of heterogeneous spatial distribution of hydraulic Properties, to prove the most of most field site aquifer was heterogeneous hydrogeological parameters spatial distribution field. Many scholars had proposed a method of hydraulic tomography to estimate heterogeneous spatial distribution of hydraulic Properties of aquifer, the Huang et al. [2011] was used the non-redundant verification analysis of pumping wells changed, observation wells fixed on the inverse and the forward, to reflect the feasibility of the heterogeneous spatial distribution of hydraulic Properties of field site aquifer of the non-redundant verification analysis on steady-state model.From post literature, finding only in steady state, non-redundant verification analysis of pumping well changed location and observation wells fixed location for inverse and forward. But the studies had not yet pumping wells fixed or changed location, and observation wells fixed location for redundant verification or observation wells change location for non-redundant verification of the various combinations may to explore of influences of hydraulic tomography method. In this study, it carried out redundant verification method and non-redundant verification method for forward to influences of hydraulic tomography method in transient. And it discuss above mentioned in NYUST campus sites the actual case, to prove the effectiveness of hydraulic tomography methods, and confirmed the feasibility on inverse and forward analysis from analysis results.Keywords: Hydraulic Tomography, Redundant Verification, Heterogeneous, Inverse, Forward

Extraocular Muscles in Patients With Infantile Nystagmus

PubMed Central

Berg, Kathleen T.; Hunter, David G.; Bothun, Erick D.; Antunes-Foschini, Rosalia; McLoon, Linda K.

2013-01-01

Objective To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control. Clinical Relevance Improved understanding of the etiology of nystagmus may direct future diagnostic and treatment strategies. PMID:22411664

Assessing the heterogeneity level in lipid nanoparticles for siRNA delivery: size-based separation, compositional heterogeneity, and impact on bioperformance.

PubMed

Zhang, Jingtao; Pei, Yi; Zhang, Hangchun; Wang, Lei; Arrington, Leticia; Zhang, Ye; Glass, Angela; Leone, Anthony M

2013-01-07

A primary consideration when developing lipid nanoparticle (LNP) based small interfering RNA (siRNA) therapeutics is formulation polydispersity or heterogeneity. The level of heterogeneity of physicochemical properties within a pharmaceutical batch could greatly affect the bioperformance, quality, and ability of a manufacturer to consistently control and reproduce the formulations. This article studied the heterogeneity in the size, composition, and in vitro performance of siRNA containing LNPs, by conducting preparative scale fractionation using a sephacryl S-1000 based size-exclusion chromatography (SEC) method. Eight LNPs with size in the range of 60-190 nm were first evaluated by the SEC method for size polydispersity characterization, and it was found that LNPs in the range of 60-150 nm could be well-resolved. Two LNPs (LNP A and LNP B) with similar bulk properties were fractionated, and fractions were studied in-depth for potential presence of polydispersity in size, composition, and in vitro silencing, as well as cytotoxicity. LNP A was deemed to be monodisperse following results of a semipreparative SEC fractionation that showed similar size, chemical composition, in vitro silencing activity, and cytotoxicity across the fractions. Therefore, LNP A represents a relatively homogeneous formulation and offers less of a challenge in its pharmaceutical development. In contrast, LNP B fractions were shown to be significantly more polydisperse in size distribution. Interestingly, LNP B SEC fractions also exhibited profound compositional variations (e.g., 5 fold difference in N/P ratio and 3 fold difference in lipid composition) along with up to 40 fold differences in the in vitro silencing activity. The impact of LNP size and formulation composition on in vitro performance is also discussed. The present results demonstrate the complexity and potential for presence of heterogeneity in LNP-based siRNA drug products. This underscores the need for tools that yield a detailed characterization of LNP formulations. This capability in tandem with the pursuit of improved formulation and process design can lead to more facile development of LNP-based siRNA pharmaceuticals of higher quality.

A numerical homogenization method for heterogeneous, anisotropic elastic media based on multiscale theory

DOE PAGES

Gao, Kai; Chung, Eric T.; Gibson, Richard L.; ...

2015-06-05

The development of reliable methods for upscaling fine scale models of elastic media has long been an important topic for rock physics and applied seismology. Several effective medium theories have been developed to provide elastic parameters for materials such as finely layered media or randomly oriented or aligned fractures. In such cases, the analytic solutions for upscaled properties can be used for accurate prediction of wave propagation. However, such theories cannot be applied directly to homogenize elastic media with more complex, arbitrary spatial heterogeneity. We therefore propose a numerical homogenization algorithm based on multiscale finite element methods for simulating elasticmore » wave propagation in heterogeneous, anisotropic elastic media. Specifically, our method used multiscale basis functions obtained from a local linear elasticity problem with appropriately defined boundary conditions. Homogenized, effective medium parameters were then computed using these basis functions, and the approach applied a numerical discretization that is similar to the rotated staggered-grid finite difference scheme. Comparisons of the results from our method and from conventional, analytical approaches for finely layered media showed that the homogenization reliably estimated elastic parameters for this simple geometry. Additional tests examined anisotropic models with arbitrary spatial heterogeneity where the average size of the heterogeneities ranged from several centimeters to several meters, and the ratio between the dominant wavelength and the average size of the arbitrary heterogeneities ranged from 10 to 100. Comparisons to finite-difference simulations proved that the numerical homogenization was equally accurate for these complex cases.« less

Hybrid massively parallel fast sweeping method for static Hamilton-Jacobi equations

NASA Astrophysics Data System (ADS)

Detrixhe, Miles; Gibou, Frédéric

2016-10-01

The fast sweeping method is a popular algorithm for solving a variety of static Hamilton-Jacobi equations. Fast sweeping algorithms for parallel computing have been developed, but are severely limited. In this work, we present a multilevel, hybrid parallel algorithm that combines the desirable traits of two distinct parallel methods. The fine and coarse grained components of the algorithm take advantage of heterogeneous computer architecture common in high performance computing facilities. We present the algorithm and demonstrate its effectiveness on a set of example problems including optimal control, dynamic games, and seismic wave propagation. We give results for convergence, parallel scaling, and show state-of-the-art speedup values for the fast sweeping method.

Generic, network schema agnostic sparse tensor factorization for single-pass clustering of heterogeneous information networks

PubMed Central

Meng, Qinggang; Deng, Su; Huang, Hongbin; Wu, Yahui; Badii, Atta

2017-01-01

Heterogeneous information networks (e.g. bibliographic networks and social media networks) that consist of multiple interconnected objects are ubiquitous. Clustering analysis is an effective method to understand the semantic information and interpretable structure of the heterogeneous information networks, and it has attracted the attention of many researchers in recent years. However, most studies assume that heterogeneous information networks usually follow some simple schemas, such as bi-typed networks or star network schema, and they can only cluster one type of object in the network each time. In this paper, a novel clustering framework is proposed based on sparse tensor factorization for heterogeneous information networks, which can cluster multiple types of objects simultaneously in a single pass without any network schema information. The types of objects and the relations between them in the heterogeneous information networks are modeled as a sparse tensor. The clustering issue is modeled as an optimization problem, which is similar to the well-known Tucker decomposition. Then, an Alternating Least Squares (ALS) algorithm and a feasible initialization method are proposed to solve the optimization problem. Based on the tensor factorization, we simultaneously partition different types of objects into different clusters. The experimental results on both synthetic and real-world datasets have demonstrated that our proposed clustering framework, STFClus, can model heterogeneous information networks efficiently and can outperform state-of-the-art clustering algorithms as a generally applicable single-pass clustering method for heterogeneous network which is network schema agnostic. PMID:28245222

Generic, network schema agnostic sparse tensor factorization for single-pass clustering of heterogeneous information networks.

PubMed

Wu, Jibing; Meng, Qinggang; Deng, Su; Huang, Hongbin; Wu, Yahui; Badii, Atta

2017-01-01

Heterogeneous information networks (e.g. bibliographic networks and social media networks) that consist of multiple interconnected objects are ubiquitous. Clustering analysis is an effective method to understand the semantic information and interpretable structure of the heterogeneous information networks, and it has attracted the attention of many researchers in recent years. However, most studies assume that heterogeneous information networks usually follow some simple schemas, such as bi-typed networks or star network schema, and they can only cluster one type of object in the network each time. In this paper, a novel clustering framework is proposed based on sparse tensor factorization for heterogeneous information networks, which can cluster multiple types of objects simultaneously in a single pass without any network schema information. The types of objects and the relations between them in the heterogeneous information networks are modeled as a sparse tensor. The clustering issue is modeled as an optimization problem, which is similar to the well-known Tucker decomposition. Then, an Alternating Least Squares (ALS) algorithm and a feasible initialization method are proposed to solve the optimization problem. Based on the tensor factorization, we simultaneously partition different types of objects into different clusters. The experimental results on both synthetic and real-world datasets have demonstrated that our proposed clustering framework, STFClus, can model heterogeneous information networks efficiently and can outperform state-of-the-art clustering algorithms as a generally applicable single-pass clustering method for heterogeneous network which is network schema agnostic.

Development of Molecular Catalysts to Bridge the Gap between Heterogeneous and Homogeneous Catalysts

NASA Astrophysics Data System (ADS)

Ye, Rong

Catalysts, heterogeneous, homogeneous, and enzymatic, are comprised of nanometer-sized inorganic and/or organic components. They share molecular factors including charge, coordination, interatomic distance, bonding, and orientation of catalytically active atoms. By controlling the governing catalytic components and molecular factors, catalytic processes of a multichannel and multiproduct nature could be run in all three catalytic platforms to create unique end-products. Unifying the fields of catalysis is the key to achieving the goal of 100% selectivity in catalysis. Recyclable catalysts, especially those that display selective reactivity, are vital for the development of sustainable chemical processes. Among available catalyst platforms, heterogeneous catalysts are particularly well-disposed toward separation from the reaction mixture via filtration methods, which renders them readily recyclable. Furthermore, heterogeneous catalysts offer numerous handles - some without homogeneous analogues - for performance and selectivity optimization. These handles include nanoparticle size, pore profile of porous supports, surface ligands and interface with oxide supports, and flow rate through a solid catalyst bed. Despite these available handles, however, conventional heterogeneous catalysts are themselves often structurally heterogeneous compared to homogeneous catalysts, which complicates efforts to optimize and expand the scope of their reactivity and selectivity. Ongoing efforts are aimed to address the above challenge by heterogenizing homogeneous catalysts, which can be defined as the modification of homogeneous catalysts to render them in a separable (solid) phase from the starting materials and products. Specifically, we grow the small nanoclusters in dendrimers, a class of uniform polymers with the connectivity of fractal trees and generally radial symmetry. Thanks to their dense multivalency, shape persistence and structural uniformity, dendrimers have proven to be versatile scaffolds for the synthesis and stabilization of small nanoclusters. Then these dendrimer-encapsulated metal clusters (DEMCs) are adsorbed onto mesoporous silica. Through this method, we have achieved selective transformations that had been challenging to accomplish in a heterogeneous setting, e.g. pi-bond activation and aldol reactions. Extensive investigation into the catalytic systems under reaction conditions allowed us to correlate the structural features (e.g. oxidation states) of the catalysts and their activity. Moreover, we have demonstrated that supported DEMCs are also excellent catalysts for typical heterogeneous reactions, including hydrogenation and alkane isomerization. Critically, these investigations also confirmed that the supported DEMCs are heterogeneous and stable against leaching. Catalysts optimization is achieved through the modulation of various parameters. The clusters are oxidized (e.g., with PhICl2) or reduced (e.g., with H2) in situ. Changing the dendrimer properties (e.g., generation, terminal functional groups) is analogous to ligand modification in homogeneous catalysts, which affect both catalytic activity and selectivity. Similarly, pore size of the support is another factor in determining product distribution. In a flow reactor, the flow rate is adjusted to control the residence time of the starting material and intermediates, and thus the final product selectivity. Our approach to heterogeneous catalysis affords various advantages: (1) the catalyst system can tap into the reactivity typical to homogeneous catalysts, which conventional heterogeneous catalysts could not achieve; (2) unlike most homogeneous catalysts with comparable performance, the heterogenized homogeneous catalysts can be recycled; (3) improved activity or selectivity compared to conventional homogeneous catalysts is possible because of uniquely heterogeneous parameters for optimization. While localized surface plasmon resonance (LSPR) provides a powerful platform for nanoparticle catalysis, our studies suggest that in some cases interband transitions should be considered as an alternative mechanism of light-driven nanoparticle catalysis. The benefits already demonstrated by plasmonic nanostructures as catalysts provided the impetus for examining complementary activation modes based on the metal nanoparticle itself. Leveraging these transitions has the potential to provide a means to highly active catalysis modes that would otherwise be challenging to access. For example, for the preparation of highly active metal catalysts on a subnanosized scale is challenging, thus limiting their exploitation and study in catalysis. Our work suggests a novel and facile strategy for the formation of highly active gold nanocluster catalysts by light illumination of the interband transitions in the presence of the appropriate substrate.

A Weighting Method for Assessing Between-Site Heterogeneity in Causal Mediation Mechanism

ERIC Educational Resources Information Center

Qin, Xu; Hong, Guanglei

2017-01-01

When a multisite randomized trial reveals between-site variation in program impact, methods are needed for further investigating heterogeneous mediation mechanisms across the sites. We conceptualize and identify a joint distribution of site-specific direct and indirect effects under the potential outcomes framework. A method-of-moments procedure…

Controlling the joint local false discovery rate is more powerful than meta-analysis methods in joint analysis of summary statistics from multiple genome-wide association studies.

PubMed

Jiang, Wei; Yu, Weichuan

2017-02-15

In genome-wide association studies (GWASs) of common diseases/traits, we often analyze multiple GWASs with the same phenotype together to discover associated genetic variants with higher power. Since it is difficult to access data with detailed individual measurements, summary-statistics-based meta-analysis methods have become popular to jointly analyze datasets from multiple GWASs. In this paper, we propose a novel summary-statistics-based joint analysis method based on controlling the joint local false discovery rate (Jlfdr). We prove that our method is the most powerful summary-statistics-based joint analysis method when controlling the false discovery rate at a certain level. In particular, the Jlfdr-based method achieves higher power than commonly used meta-analysis methods when analyzing heterogeneous datasets from multiple GWASs. Simulation experiments demonstrate the superior power of our method over meta-analysis methods. Also, our method discovers more associations than meta-analysis methods from empirical datasets of four phenotypes. The R-package is available at: http://bioinformatics.ust.hk/Jlfdr.html . eeyu@ust.hk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Imaging metabolic heterogeneity in cancer.

PubMed

Sengupta, Debanti; Pratx, Guillem

2016-01-06

As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

Phylogenetic Quantification of Intra-tumour Heterogeneity

PubMed Central

Schwarz, Roland F.; Trinh, Anne; Sipos, Botond; Brenton, James D.; Goldman, Nick; Markowetz, Florian

2014-01-01

Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data. PMID:24743184

Thermal phenomena under microwave field in the organic synthesis processes: Application to the Diels Alder reaction

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

Saillard, R.; Poux, M.; Audhuy-Peaudecerf, M.

1996-12-31

The influence of the microwave heating on chemical reactions were investigated. The kinetic of the Diels Alder reaction were studied under microwave irradiation at a frequency of 2.45 GHz in a single mode cavity and were compared to the kinetic obtained by a conventional heating. Experiments were carried out in a liquid solvent in order to have a better control of the medium temperature measurement. In a second part, the presence of a catalytic solid phase was introduced. Some thermal fluctuations which are due to an heterogeneity of the electric field were detected in the medium. They reduce the precisionmore » of the results and cause problems of experimental reproducibility. A thermoluminescent material allow a good visualization of these phenomena. In addition, the profiles of the electric field intensity were modelled by a 2D finite elements method in the reactor in the presence of a solvent. Despite the small size of the sample and the use of a monomode cavity which both limited the heterogeneities of the medium temperature, the authors showed a great heterogeneity of the electric field intensity and as a result the heterogeneity of the temperature in their sample. In order to avoid these phenomena which induce a lack of reproducibility, a stirring device was developed. The values of the kinetics obtained under the 2 heating modes with the introduction of the stirring device. So, it induces a good control of the medium temperature. All those investigations prompted the authors to the conclusion that there is no difference between microwave heating and a classical heating in the studied reaction.« less

Biologically Relevant Heterogeneity: Metrics and Practical Insights

PubMed Central

Gough, A; Stern, AM; Maier, J; Lezon, T; Shun, T-Y; Chennubhotla, C; Schurdak, ME; Haney, SA; Taylor, DL

2017-01-01

Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications including basic biomedical research, drug discovery, diagnostics and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high throughput workflow. This review and perspective emphasizes the experimental methods that capture multiplexed cell level data, as well as the need for standard metrics of the spatial, temporal and population components of heterogeneity. A recommendation is made for the adoption of a set of three heterogeneity indices that can be implemented in any high throughput workflow to optimize the decision-making process. In addition, a pairwise mutual information method is suggested as an approach to characterizing the spatial features of heterogeneity, especially in tissue-based imaging. Furthermore, metrics for temporal heterogeneity are in the early stages of development. Example studies indicate that the analysis of functional phenotypic heterogeneity can be exploited to guide decisions in the interpretation of biomedical experiments, drug discovery, diagnostics and the design of optimal therapeutic strategies for individual patients. PMID:28231035

Building Community Around Hydrologic Data Models Within CUAHSI

NASA Astrophysics Data System (ADS)

Maidment, D.

2007-12-01

The Consortium of Universities for the Advancement of Hydrologic Science, Inc (CUAHSI) has a Hydrologic Information Systems project which aims to provide better data access and capacity for data synthesis for the nation's water information, both that collected by academic investigators and that collected by water agencies. These data include observations of streamflow, water quality, groundwater levels, weather and climate and aquatic biology. Each water agency or research investigator has a unique method of formatting their data (syntactic heterogeneity) and describing their variables (semantic heterogeneity). The result is a large agglomeration of data in many formats and descriptions whose full content is hard to interpret and analyze. CUAHSI is helping to resolve syntactic heterogeneity through the development of WaterML, a standard XML markup language for communicating water observations data through web services, and a standard relational database structure for archiving data called the Observations Data Model. Variables in these data archiving and communicating systems are indexed against a controlled vocabulary of descriptive terms to provide the capacity to synthesize common data types from disparate data sources.

The paradox of sham therapy and placebo effect in osteopathy

PubMed Central

Cerritelli, Francesco; Verzella, Marco; Cicchitti, Luca; D’Alessandro, Giandomenico; Vanacore, Nicola

2016-01-01

Abstract Background: Placebo, defined as “false treatment,” is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as “sham therapy.” In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness. Methods: A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Results: A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed. Conclusion: High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings. PMID:27583913

Advancing current approaches to disease management evaluation: capitalizing on heterogeneity to understand what works and for whom.

PubMed

Elissen, Arianne M J; Adams, John L; Spreeuwenberg, Marieke; Duimel-Peeters, Inge G P; Spreeuwenberg, Cor; Linden, Ariel; Vrijhoef, Hubertus J M

2013-03-14

Evaluating large-scale disease management interventions implemented in actual health care settings is a complex undertaking for which universally accepted methods do not exist. Fundamental issues, such as a lack of control patients and limited generalizability, hamper the use of the 'gold-standard' randomized controlled trial, while methodological shortcomings restrict the value of observational designs. Advancing methods for disease management evaluation in practice is pivotal to learn more about the impact of population-wide approaches. Methods must account for the presence of heterogeneity in effects, which necessitates a more granular assessment of outcomes. This paper introduces multilevel regression methods as valuable techniques to evaluate 'real-world' disease management approaches in a manner that produces meaningful findings for everyday practice. In a worked example, these methods are applied to retrospectively gathered routine health care data covering a cohort of 105,056 diabetes patients who receive disease management for type 2 diabetes mellitus in the Netherlands. Multivariable, multilevel regression models are fitted to identify trends in clinical outcomes and correct for differences in characteristics of patients (age, disease duration, health status, diabetes complications, smoking status) and the intervention (measurement frequency and range, length of follow-up). After a median one year follow-up, the Dutch disease management approach was associated with small average improvements in systolic blood pressure and low-density lipoprotein, while a slight deterioration occurred in glycated hemoglobin. Differential findings suggest that patients with poorly controlled diabetes tend to benefit most from disease management in terms of improved clinical measures. Additionally, a greater measurement frequency was associated with better outcomes, while longer length of follow-up was accompanied by less positive results. Despite concerted efforts to adjust for potential sources of confounding and bias, there ultimately are limits to the validity and reliability of findings from uncontrolled research based on routine intervention data. While our findings are supported by previous randomized research in other settings, the trends in outcome measures presented here may have alternative explanations. Further practice-based research, perhaps using historical data to retrospectively construct a control group, is necessary to confirm results and learn more about the impact of population-wide disease management.

Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

PubMed

Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

2017-07-01

Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Improved STARFM with Help of an Unmixing-Based Method to Generate High Spatial and Temporal Resolution Remote Sensing Data in Complex Heterogeneous Regions.

PubMed

Xie, Dengfeng; Zhang, Jinshui; Zhu, Xiufang; Pan, Yaozhong; Liu, Hongli; Yuan, Zhoumiqi; Yun, Ya

2016-02-05

Remote sensing technology plays an important role in monitoring rapid changes of the Earth's surface. However, sensors that can simultaneously provide satellite images with both high temporal and spatial resolution haven't been designed yet. This paper proposes an improved spatial and temporal adaptive reflectance fusion model (STARFM) with the help of an Unmixing-based method (USTARFM) to generate the high spatial and temporal data needed for the study of heterogeneous areas. The results showed that the USTARFM had higher accuracy than STARFM methods in two aspects of analysis: individual bands and of heterogeneity analysis. Taking the predicted NIR band as an example, the correlation coefficients (r) for the USTARFM, STARFM and unmixing methods were 0.96, 0.95, 0.90, respectively (p-value < 0.001); Root Mean Square Error (RMSE) values were 0.0245, 0.0300, 0.0401, respectively; and ERGAS values were 0.5416, 0.6507, 0.8737, respectively. The USTARM showed consistently higher performance than STARM when the degree of heterogeneity ranged from 2 to 10, highlighting that the use of this method provides the capacity to solve the data fusion problems faced when using STARFM. Additionally, the USTARFM method could help researchers achieve better performance than STARFM at a smaller window size from its heterogeneous land surface quantitative representation.

Analysis of messy data with heteroscedastic in mean models

NASA Astrophysics Data System (ADS)

Trianasari, Nurvita; Sumarni, Cucu

2016-02-01

In the analysis of the data, we often faced with the problem of data where the data did not meet some assumptions. In conditions of such data is often called data messy. This problem is a consequence of the data that generates outliers that bias or error estimation. To analyze the data messy, there are three approaches, namely standard analysis, transform data and data analysis methods rather than a standard. Simulations conducted to determine the performance of a third comparative test procedure on average often the model variance is not homogeneous. Data simulation of each scenario is raised as much as 500 times. Next, we do the analysis of the average comparison test using three methods, Welch test, mixed models and Welch-r test. Data generation is done through software R version 3.1.2. Based on simulation results, these three methods can be used for both normal and abnormal case (homoscedastic). The third method works very well on data balanced or unbalanced when there is no violation in the homogenity's assumptions variance. For balanced data, the three methods still showed an excellent performance despite the violation of the assumption of homogeneity of variance, with the requisite degree of heterogeneity is high. It can be shown from the level of power test above 90 percent, and the best to Welch method (98.4%) and the Welch-r method (97.8%). For unbalanced data, Welch method will be very good moderate at in case of heterogeneity positive pair with a 98.2% power. Mixed models method will be very good at case of highly heterogeneity was negative negative pairs with power. Welch-r method works very well in both cases. However, if the level of heterogeneity of variance is very high, the power of all method will decrease especially for mixed models methods. The method which still works well enough (power more than 50%) is Welch-r method (62.6%), and the method of Welch (58.6%) in the case of balanced data. If the data are unbalanced, Welch-r method works well enough in the case of highly heterogeneous positive positive or negative negative pairs, there power are 68.8% and 51% consequencly. Welch method perform well enough only in the case of highly heterogeneous variety of positive positive pairs with it is power of 64.8%. While mixed models method is good in the case of a very heterogeneous variety of negative partner with 54.6% power. So in general, when there is a variance is not homogeneous case, Welch method is applied to the data rank (Welch-r) has a better performance than the other methods.

Green's Function and Stress Fields in Stochastic Heterogeneous Continua

NASA Astrophysics Data System (ADS)

Negi, Vineet

Many engineering materials used today are heterogenous in composition e.g. Composites - Polymer Matrix Composites, Metal Matrix Composites. Even, conventional engineering materials - metals, plastics, alloys etc. - may develop heterogeneities, like inclusions and residual stresses, during the manufacturing process. Moreover, these materials may also have intrinsic heterogeneities at a nanoscale in the form of grain boundaries in metals, crystallinity in amorphous polymers etc. While, the homogenized constitutive models for these materials may be satisfactory at a macroscale, recent studies of phenomena like fatigue failure, void nucleation, size-dependent brittle-ductile transition in polymeric nanofibers reveal a major play of micro/nanoscale physics in these phenomena. At this scale, heterogeneities in a material may no longer be ignored. Thus, this demands a study into the effects of various material heterogeneities. In this work, spatial heterogeneities in two material properties - elastic modulus and yield stress - have been investigated separately. The heterogeneity in the elastic modulus is studied in the context of Green's function. The Stochastic Finite Element method is adopted to get the mean statistics of the Green's function defined on a stochastic heterogeneous 2D infinite space. A study of the elastic-plastic transition in a domain having stochastic heterogenous yield stress was done using Mont-Carlo methods. The statistics for various stress and strain fields during the transition were obtained. Further, the effects of size of the domain and the strain-hardening rate on the stress fields during the heterogeneous elastic-plastic transition were investigated. Finally, a case is made for the role of the heterogenous elastic-plastic transition in damage nucleation and growth.

Heterogeneous structure and its effect on properties and electrochemical behavior of ion-exchange membrane

NASA Astrophysics Data System (ADS)

Ariono, D.; Khoiruddin; Subagjo; Wenten, I. G.

2017-02-01

Generally, commercially available ion-exchange membrane (IEM) can be classified into homogeneous and heterogeneous membranes. The classification is based on degree of heterogeneity in membrane structure. It is well known that the heterogeneity greatly affects the properties of IEM, such as conductivity, permselectivity, chemical and mechanical stability. The heterogeneity also influences ionic and electrical current transfer behavior of IEM-based processes during their operation. Therefore, understanding the role of heterogeneity in IEM properties is important to provide preliminary information on their operability and applicability. In this paper, the heterogeneity and its effect on IEM properties are reviewed. Some models for describing the heterogeneity of IEM and methods for characterizing the degree of heterogeneity are discussed. In addition, the influence of heterogeneity on the performance of IEM-based processes and their electrochemical behavior are described.

Large-scale replication and heterogeneity in Parkinson disease genetic loci

PubMed Central

Ioannidis, John P.A.; Aasly, Jan O.; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M.; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pramstaller, Peter P.; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Satake, Wataru; Silburn, Peter A.; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

2012-01-01

Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14–1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology® 2012;79:659–667 PMID:22786590

Risk of myocardial infarction and stroke in bipolar disorder: a systematic review and exploratory meta-analysis

PubMed Central

Prieto, M.L.; Cuéllar-Barboza, A.B.; Bobo, W.V.; Roger, V.L.; Bellivier, F.; Leboyer, M.; West, C.P.; Frye, M.A.

2016-01-01

Objective To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder. Method A systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 – May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random-effects meta-analysis. Results Five cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta-analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96–1.24, P = 0.20; I2 = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29–2.35; P = 0.0003; I2 = 83%). Conclusion There may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features. PMID:24850482

Epstein-Barr Virus and Gastric Cancer Risk: A Meta-analysis With Meta-regression of Case-control Studies.

PubMed

Bae, Jong-Myon; Kim, Eun Hee

2016-03-01

Research on how the risk of gastric cancer increases with Epstein-Barr virus (EBV) infection is lacking. In a systematic review that investigated studies published until September 2014, the authors did not calculate the summary odds ratio (SOR) due to heterogeneity across studies. Therefore, we include here additional studies published until October 2015 and conduct a meta-analysis with meta-regression that controls for the heterogeneity among studies. Using the studies selected in the previously published systematic review, we formulated lists of references, cited articles, and related articles provided by PubMed. From the lists, only case-control studies that detected EBV in tissue samples were selected. In order to control for the heterogeneity among studies, subgroup analysis and meta-regression were performed. In the 33 case-control results with adjacent non-cancer tissue, the total number of test samples in the case and control groups was 5280 and 4962, respectively. In the 14 case-control results with normal tissue, the total number of test samples in case and control groups was 1393 and 945, respectively. Upon meta-regression, the type of control tissue was found to be a statistically significant variable with regard to heterogeneity. When the control tissue was normal tissue of healthy individuals, the SOR was 3.41 (95% CI, 1.78 to 6.51; I-squared, 65.5%). The results of the present study support the argument that EBV infection increases the risk of gastric cancer. In the future, age-matched and sex-matched case-control studies should be conducted.

GSEH: A Novel Approach to Select Prostate Cancer-Associated Genes Using Gene Expression Heterogeneity.

PubMed

Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun

2018-01-01

When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

DTIC Science & Technology

2002-07-01

mutation in these 0 1 patients.74,89,92-95 HPRT mutant frequencies appear Controls Heterogeneous to be elevated in xeroderma pigmentosum patients, Cancer...forth), it is difficult toxic mechanism, although methods to detect pos - to predict the fate ofachemicalin abiological system, sible agents acting...specific. Thus, a genotoxic effect, po - importance of the original dose. Such studies are tentially contributing to carcinogenesis, can occur in complicated

Unit-bar migration and bar-trough deposition: impacts on hydraulic conductivity and grain size heterogeneity in a sandy streambed

NASA Astrophysics Data System (ADS)

Korus, Jesse T.; Gilmore, Troy E.; Waszgis, Michele M.; Mittelstet, Aaron R.

2018-03-01

The hydrologic function of riverbeds is greatly dependent upon the spatiotemporal distribution of hydraulic conductivity and grain size. Vertical hydraulic conductivity ( K v) is highly variable in space and time, and controls the rate of stream-aquifer interaction. Links between sedimentary processes, deposits, and K v heterogeneity have not been well established from field studies. Unit bars are building blocks of fluvial deposits and are key to understanding controls on heterogeneity. This study links unit bar migration to K v and grain size variability in a sand-dominated, low-sinuosity stream in Nebraska (USA) during a single 10-day hydrologic event. An incipient bar formed parallel to the thalweg and was highly permeable and homogenous. During high flow, this bar was submerged under 10-20 cm of water and migrated 100 m downstream and toward the channel margin, where it became markedly heterogeneous. Low- K v zones formed in the subsequent heterogeneous bar downstream of the original 15-40-cm-thick bar front and past abandoned bridge pilings. These low- K v zones correspond to a discontinuous 1-cm layer of fine sand and silt deposited in the bar trough. Findings show that K v heterogeneity relates chiefly to the deposition of suspended materials in low-velocity zones downstream of the bar and obstructions, and to their subsequent burial by migration of the bar during high flow. Deposition of the unit bar itself, although it emplaced the vast majority of the sediment volume, was secondary to bar-trough deposition as a control on the overall pattern of heterogeneity.

Heterogeneous recurrence monitoring and control of nonlinear stochastic processes

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

Yang, Hui, E-mail: huiyang@usf.edu; Chen, Yun

Recurrence is one of the most common phenomena in natural and engineering systems. Process monitoring of dynamic transitions in nonlinear and nonstationary systems is more concerned with aperiodic recurrences and recurrence variations. However, little has been done to investigate the heterogeneous recurrence variations and link with the objectives of process monitoring and anomaly detection. Notably, nonlinear recurrence methodologies are based on homogeneous recurrences, which treat all recurrence states in the same way as black dots, and non-recurrence is white in recurrence plots. Heterogeneous recurrences are more concerned about the variations of recurrence states in terms of state properties (e.g., valuesmore » and relative locations) and the evolving dynamics (e.g., sequential state transitions). This paper presents a novel approach of heterogeneous recurrence analysis that utilizes a new fractal representation to delineate heterogeneous recurrence states in multiple scales, including the recurrences of both single states and multi-state sequences. Further, we developed a new set of heterogeneous recurrence quantifiers that are extracted from fractal representation in the transformed space. To that end, we integrated multivariate statistical control charts with heterogeneous recurrence analysis to simultaneously monitor two or more related quantifiers. Experimental results on nonlinear stochastic processes show that the proposed approach not only captures heterogeneous recurrence patterns in the fractal representation but also effectively monitors the changes in the dynamics of a complex system.« less

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

A Meta-Analysis of the Convergent Validity of Self-Control Measures

PubMed Central

Duckworth, Angela Lee; Kern, Margaret L.

2011-01-01

There is extraordinary diversity in how the construct of self-control is operationalized in research studies. We meta-analytically examined evidence of convergent validity among executive function, delay of gratification, and self- and informant-report questionnaire measures of self-control. Overall, measures demonstrated moderate convergence (rrandom = .27 [95% CI = .24, .30]; rfixed = .34 [.33, .35], k = 282 samples, N = 33,564 participants), although there was substantial heterogeneity in the observed correlations. Correlations within and across types of self-control measures were strongest for informant-report questionnaires and weakest for executive function tasks. Questionnaires assessing sensation seeking impulses could be distinguished from questionnaires assessing processes of impulse regulation. We conclude that self-control is a coherent but multidimensional construct best assessed using multiple methods. PMID:21643479

Promoted Iron Nanocrystals Obtained via Ligand Exchange as Active and Selective Catalysts for Synthesis Gas Conversion

PubMed Central

2017-01-01

Colloidal synthesis routes have been recently used to fabricate heterogeneous catalysts with more controllable and homogeneous properties. Herein a method was developed to modify the surface composition of colloidal nanocrystal catalysts and to purposely introduce specific atoms via ligands and change the catalyst reactivity. Organic ligands adsorbed on the surface of iron oxide catalysts were exchanged with inorganic species such as Na2S, not only to provide an active surface but also to introduce controlled amounts of Na and S acting as promoters for the catalytic process. The catalyst composition was optimized for the Fischer–Tropsch direct conversion of synthesis gas into lower olefins. At industrially relevant conditions, these nanocrystal-based catalysts with controlled composition were more active, selective, and stable than catalysts with similar composition but synthesized using conventional methods, possibly due to their homogeneity of properties and synergic interaction of iron and promoters. PMID:28824820

Advanced nodal neutron diffusion method with space-dependent cross sections: ILLICO-VX

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

Rajic, H.L.; Ougouag, A.M.

1987-01-01

Advanced transverse integrated nodal methods for neutron diffusion developed since the 1970s require that node- or assembly-homogenized cross sections be known. The underlying structural heterogeneity can be accurately accounted for in homogenization procedures by the use of heterogeneity or discontinuity factors. Other (milder) types of heterogeneity, burnup-induced or due to thermal-hydraulic feedback, can be resolved by explicitly accounting for the spatial variations of material properties. This can be done during the nodal computations via nonlinear iterations. The new method has been implemented in the code ILLICO-VX (ILLICO variable cross-section method). Numerous numerical tests were performed. As expected, the convergence ratemore » of ILLICO-VX is lower than that of ILLICO, requiring approx. 30% more outer iterations per k/sub eff/ computation. The methodology has also been implemented as the NOMAD-VX option of the NOMAD, multicycle, multigroup, two- and three-dimensional nodal diffusion depletion code. The burnup-induced heterogeneities (space dependence of cross sections) are calculated during the burnup steps.« less

3D Transient Hydraulic Tomography (3DTHT): An Efficient Field and Modeling Method for High-Resolution Estimation of Aquifer Heterogeneity

NASA Astrophysics Data System (ADS)

Barrash, W.; Cardiff, M. A.; Kitanidis, P. K.

2012-12-01

The distribution of hydraulic conductivity (K) is a major control on groundwater flow and contaminant transport. Our limited ability to determine 3D heterogeneous distributions of K is a major reason for increased costs and uncertainties associated with virtually all aspects of groundwater contamination management (e.g., site investigations, risk assessments, remediation method selection/design/operation, monitoring system design/operation). Hydraulic tomography (HT) is an emerging method for directly estimating the spatially variable distribution of K - in a similar fashion to medical or geophysical imaging. Here we present results from 3D transient field-scale experiments (3DTHT) which capture the heterogeneous K distribution in a permeable, moderately heterogeneous, coarse fluvial unconfined aquifer at the Boise Hydrogeophysical Research Site (BHRS). The results are verified against high-resolution K profiles from multi-level slug tests at BHRS wells. The 3DTHT field system for well instrumentation and data acquisition/feedback is fully modular and portable, and the in-well packer-and-port system is easily assembled and disassembled without expensive support equipment or need for gas pressurization. Tests are run for 15-20 min and the aquifer is allowed to recover while the pumping equipment is repositioned between tests. The tomographic modeling software developed uses as input observations of temporal drawdown behavior from each of numerous zones isolated in numerous observation wells during a series of pumping tests conducted from numerous isolated intervals in one or more pumping wells. The software solves for distributed K (as well as storage parameters Ss and Sy, if desired) and estimates parameter uncertainties using: a transient 3D unconfined forward model in MODFLOW, the adjoint state method for calculating sensitivities (Clemo 2007), and the quasi-linear geostatistical inverse method (Kitanidis 1995) for the inversion. We solve for K at >100,000 sub-m3 (1m x 1m x 0.6m) locations in a 60m x 60m x 18m modeled volume of the BHRS, with the primary investigated volume approximately 12m x 8m x 16m. Computing times are reasonable on high-end desktop computers or small clusters; we are investigating additional efficiency improvements with massive parallelization. Results from complete coverage (1m-length zones) in one pumping well and five observation wells provide a basis for evaluating method resolution capabilities by comparing K statistics from solutions with all tests and observations against partial test and observation coverage, and against independent K measurements at wells with multi-level slug tests. From these analyses we show that 3DTHT compares well with slug test results, and high-resolution information on heterogeneity is lost rapidly with reduction in test or observation coverage.

An improved recommendation algorithm via weakening indirect linkage effect

NASA Astrophysics Data System (ADS)

Chen, Guang; Qiu, Tian; Shen, Xiao-Quan

2015-07-01

We propose an indirect-link-weakened mass diffusion method (IMD), by considering the indirect linkage and the source object heterogeneity effect in the mass diffusion (MD) recommendation method. Experimental results on the MovieLens, Netflix, and RYM datasets show that, the IMD method greatly improves both the recommendation accuracy and diversity, compared with a heterogeneity-weakened MD method (HMD), which only considers the source object heterogeneity. Moreover, the recommendation accuracy of the cold objects is also better elevated in the IMD than the HMD method. It suggests that eliminating the redundancy induced by the indirect linkages could have a prominent effect on the recommendation efficiency in the MD method. Project supported by the National Natural Science Foundation of China (Grant No. 11175079) and the Young Scientist Training Project of Jiangxi Province, China (Grant No. 20133BCB23017).

Imaging oxygen distribution in marine sediments. The importance of bioturbation and sediment heterogeneity.

PubMed

Pischedda, L; Poggiale, J C; Cuny, P; Gilbert, F

2008-06-01

The influence of sediment oxygen heterogeneity, due to bioturbation, on diffusive oxygen flux was investigated. Laboratory experiments were carried out with 3 macrobenthic species presenting different bioturbation behaviour patterns: the polychaetes Nereis diversicolor and Nereis virens, both constructing ventilated galleries in the sediment column, and the gastropod Cyclope neritea, a burrowing species which does not build any structure. Oxygen two-dimensional distribution in sediments was quantified by means of the optical planar optode technique. Diffusive oxygen fluxes (mean and integrated) and a variability index were calculated on the captured oxygen images. All species increased sediment oxygen heterogeneity compared to the controls without animals. This was particularly noticeable with the polychaetes because of the construction of more or less complex burrows. Integrated diffusive oxygen flux increased with oxygen heterogeneity due to the production of interface available for solute exchanges between overlying water and sediments. This work shows that sediment heterogeneity is an important feature of the control of oxygen exchanges at the sediment-water interface.

Graphic report of the results from propensity score method analyses.

PubMed

Shrier, Ian; Pang, Menglan; Platt, Robert W

2017-08-01

To increase transparency in studies reporting propensity scores by using graphical methods that clearly illustrate (1) the number of participant exclusions that occur as a consequence of the analytic strategy and (2) whether treatment effects are constant or heterogeneous across propensity scores. We applied graphical methods to a real-world pharmacoepidemiologic study that evaluated the effect of initiating statin medication on the 1-year all-cause mortality post-myocardial infarction. We propose graphical methods to show the consequences of trimming and matching on the exclusion of participants from the analysis. We also propose the use of meta-analytical forest plots to show the magnitude of effect heterogeneity. A density plot with vertical lines demonstrated the proportion of subjects excluded because of trimming. A frequency plot with horizontal lines demonstrated the proportion of subjects excluded because of matching. An augmented forest plot illustrates the amount of effect heterogeneity present in the data. Our proposed techniques present additional and useful information that helps readers understand the sample that is analyzed with propensity score methods and whether effect heterogeneity is present. Copyright © 2017 Elsevier Inc. All rights reserved.

Acknowledging patient heterogeneity in economic evaluation : a systematic literature review.

PubMed

Grutters, Janneke P C; Sculpher, Mark; Briggs, Andrew H; Severens, Johan L; Candel, Math J; Stahl, James E; De Ruysscher, Dirk; Boer, Albert; Ramaekers, Bram L T; Joore, Manuela A

2013-02-01

Patient heterogeneity is the part of variability that can be explained by certain patient characteristics (e.g. age, disease stage). Population reimbursement decisions that acknowledge patient heterogeneity could potentially save money and increase population health. To date, however, economic evaluations pay only limited attention to patient heterogeneity. The objective of the present paper is to provide a comprehensive overview of the current knowledge regarding patient heterogeneity within economic evaluation of healthcare programmes. A systematic literature review was performed to identify methodological papers on the topic of patient heterogeneity in economic evaluation. Data were obtained using a keyword search of the PubMed database and manual searches. Handbooks were also included. Relevant data were extracted regarding potential sources of patient heterogeneity, in which of the input parameters of an economic evaluation these occur, methods to acknowledge patient heterogeneity and specific concerns associated with this acknowledgement. A total of 20 articles and five handbooks were included. The relevant sources of patient heterogeneity (demographics, preferences and clinical characteristics) and the input parameters where they occurred (baseline risk, treatment effect, health state utility and resource utilization) were combined in a framework. Methods were derived for the design, analysis and presentation phases of an economic evaluation. Concerns related mainly to the danger of false-positive results and equity issues. By systematically reviewing current knowledge regarding patient heterogeneity within economic evaluations of healthcare programmes, we provide guidance for future economic evaluations. Guidance is provided on which sources of patient heterogeneity to consider, how to acknowledge them in economic evaluation and potential concerns. The improved acknowledgement of patient heterogeneity in future economic evaluations may well improve the efficiency of healthcare.

Availability and temporal heterogeneity of water supply affect the vertical distribution and mortality of a belowground herbivore and consequently plant growth.

PubMed

Tsunoda, Tomonori; Kachi, Naoki; Suzuki, Jun-Ichirou

2014-01-01

We examined how the volume and temporal heterogeneity of water supply changed the vertical distribution and mortality of a belowground herbivore, and consequently affected plant biomass. Plantago lanceolata (Plantaginaceae) seedlings were grown at one per pot under different combinations of water volume (large or small volume) and heterogeneity (homogeneous water conditions, watered every day; heterogeneous conditions, watered every 4 days) in the presence or absence of a larva of the belowground herbivorous insect, Anomala cuprea (Coleoptera: Scarabaeidae). The larva was confined in different vertical distributions to top feeding zone (top treatment), middle feeding zone (middle treatment), or bottom feeding zone (bottom treatment); alternatively no larva was introduced (control treatment) or larval movement was not confined (free treatment). Three-way interaction between water volume, heterogeneity, and the herbivore significantly affected plant biomass. With a large water volume, plant biomass was lower in free treatment than in control treatment regardless of heterogeneity. Plant biomass in free treatment was as low as in top treatment. With a small water volume and in free treatment, plant biomass was low (similar to that under top treatment) under homogeneous water conditions but high under heterogeneous ones (similar to that under middle or bottom treatment). Therefore, there was little effect of belowground herbivory on plant growth under heterogeneous water conditions. In other watering regimes, herbivores would be distributed in the shallow soil and reduced root biomass. Herbivore mortality was high with homogeneous application of a large volume or heterogeneous application of a small water volume. Under the large water volume, plant biomass was high in pots in which the herbivore had died. Thus, the combinations of water volume and heterogeneity affected plant growth via the change of a belowground herbivore.

3D highly heterogeneous thermal model of pineal gland in-vitro study for electromagnetic exposure using finite volume method

NASA Astrophysics Data System (ADS)

Cen, Wei; Hoppe, Ralph; Lu, Rongbo; Cai, Zhaoquan; Gu, Ning

2017-08-01

In this paper, the relationship between electromagnetic power absorption and temperature distributions inside highly heterogeneous biological samples was accurately determinated using finite volume method. An in-vitro study on pineal gland that is responsible for physiological activities was for the first time simulated to illustrate effectiveness of the proposed method.

Heterogeneous Compression of Large Collections of Evolutionary Trees.

PubMed

Matthews, Suzanne J

2015-01-01

Compressing heterogeneous collections of trees is an open problem in computational phylogenetics. In a heterogeneous tree collection, each tree can contain a unique set of taxa. An ideal compression method would allow for the efficient archival of large tree collections and enable scientists to identify common evolutionary relationships over disparate analyses. In this paper, we extend TreeZip to compress heterogeneous collections of trees. TreeZip is the most efficient algorithm for compressing homogeneous tree collections. To the best of our knowledge, no other domain-based compression algorithm exists for large heterogeneous tree collections or enable their rapid analysis. Our experimental results indicate that TreeZip averages 89.03 percent (72.69 percent) space savings on unweighted (weighted) collections of trees when the level of heterogeneity in a collection is moderate. The organization of the TRZ file allows for efficient computations over heterogeneous data. For example, consensus trees can be computed in mere seconds. Lastly, combining the TreeZip compressed (TRZ) file with general-purpose compression yields average space savings of 97.34 percent (81.43 percent) on unweighted (weighted) collections of trees. Our results lead us to believe that TreeZip will prove invaluable in the efficient archival of tree collections, and enables scientists to develop novel methods for relating heterogeneous collections of trees.

Effect of Fructose on Glycemic Control in Diabetes

PubMed Central

Cozma, Adrian I.; Sievenpiper, John L.; de Souza, Russell J.; Chiavaroli, Laura; Ha, Vanessa; Wang, D. David; Mirrahimi, Arash; Yu, Matt E.; Carleton, Amanda J.; Di Buono, Marco; Jenkins, Alexandra L.; Leiter, Lawrence A.; Wolever, Thomas M.S.; Beyene, Joseph; Kendall, Cyril W.C.; Jenkins, David J.A.

2012-01-01

OBJECTIVE The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA1c) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic. Trial quality was assessed by the Heyland methodological quality score (MQS). RESULTS Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD −0.25 [95% CI −0.46 to −0.04]; P = 0.02) with significant intertrial heterogeneity (I2 = 63%; P = 0.001). This reduction is equivalent to a ∼0.53% reduction in HbA1c. Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point. CONCLUSIONS Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required. PMID:22723585

A custom correlation coefficient (CCC) approach for fast identification of multi-SNP association patterns in genome-wide SNPs data.

PubMed

Climer, Sharlee; Yang, Wei; de las Fuentes, Lisa; Dávila-Román, Victor G; Gu, C Charles

2014-11-01

Complex diseases are often associated with sets of multiple interacting genetic factors and possibly with unique sets of the genetic factors in different groups of individuals (genetic heterogeneity). We introduce a novel concept of custom correlation coefficient (CCC) between single nucleotide polymorphisms (SNPs) that address genetic heterogeneity by measuring subset correlations autonomously. It is used to develop a 3-step process to identify candidate multi-SNP patterns: (1) pairwise (SNP-SNP) correlations are computed using CCC; (2) clusters of so-correlated SNPs identified; and (3) frequencies of these clusters in disease cases and controls compared to identify disease-associated multi-SNP patterns. This method identified 42 candidate multi-SNP associations with hypertensive heart disease (HHD), among which one cluster of 22 SNPs (six genes) included 13 in SLC8A1 (aka NCX1, an essential component of cardiac excitation-contraction coupling) and another of 32 SNPs had 29 from a different segment of SLC8A1. While allele frequencies show little difference between cases and controls, the cluster of 22 associated alleles were found in 20% of controls but no cases and the other in 3% of controls but 20% of cases. These suggest that both protective and risk effects on HHD could be exerted by combinations of variants in different regions of SLC8A1, modified by variants from other genes. The results demonstrate that this new correlation metric identifies disease-associated multi-SNP patterns overlooked by commonly used correlation measures. Furthermore, computation time using CCC is a small fraction of that required by other methods, thereby enabling the analyses of large GWAS datasets. © 2014 WILEY PERIODICALS, INC.

A custom correlation coefficient (CCC) approach for fast identification of multi-SNP association patterns in genome-wide SNPs data

PubMed Central

Climer, Sharlee; Yang, Wei; de las Fuentes, Lisa; Dávila-Román, Victor G.; Gu, C. Charles

2014-01-01

Complex diseases are often associated with sets of multiple interacting genetic factors and possibly with unique sets of the genetic factors in different groups of individuals (genetic heterogeneity). We introduce a novel concept of Custom Correlation Coefficient (CCC) between single nucleotide polymorphisms (SNPs) that address genetic heterogeneity by measuring subset correlations autonomously. It is used to develop a 3-step process to identify candidate multi-SNP patterns: (1) pairwise (SNP-SNP) correlations are computed using CCC; (2) clusters of so-correlated SNPs identified; and (3) frequencies of these clusters in disease cases and controls compared to identify disease-associated multi-SNP patterns. This method identified 42 candidate multi-SNP associations with hypertensive heart disease (HHD), among which one cluster of 22 SNPs (6 genes) included 13 in SLC8A1 (aka NCX1, an essential component of cardiac excitation-contraction coupling) and another of 32 SNPs had 29 from a different segment of SLC8A1. While allele frequencies show little difference between cases and controls, the cluster of 22 associated alleles were found in 20% of controls but no cases and the other in 3% of controls but 20% of cases. These suggest that both protective and risk effects on HHD could be exerted by combinations of variants in different regions of SLC8A1, modified by variants from other genes. The results demonstrate that this new correlation metric identifies disease-associated multi-SNP patterns overlooked by commonly used correlation measures. Furthermore, computation time using CCC is a small fraction of that required by other methods, thereby enabling the analyses of large GWAS datasets. PMID:25168954

An FPGA-based heterogeneous image fusion system design method

NASA Astrophysics Data System (ADS)

Song, Le; Lin, Yu-chi; Chen, Yan-hua; Zhao, Mei-rong

2011-08-01

Taking the advantages of FPGA's low cost and compact structure, an FPGA-based heterogeneous image fusion platform is established in this study. Altera's Cyclone IV series FPGA is adopted as the core processor of the platform, and the visible light CCD camera and infrared thermal imager are used as the image-capturing device in order to obtain dualchannel heterogeneous video images. Tailor-made image fusion algorithms such as gray-scale weighted averaging, maximum selection and minimum selection methods are analyzed and compared. VHDL language and the synchronous design method are utilized to perform a reliable RTL-level description. Altera's Quartus II 9.0 software is applied to simulate and implement the algorithm modules. The contrast experiments of various fusion algorithms show that, preferably image quality of the heterogeneous image fusion can be obtained on top of the proposed system. The applied range of the different fusion algorithms is also discussed.

Grain Structure Control of Additively Manufactured Metallic Materials

PubMed Central

Faierson, Eric J.

2017-01-01

Grain structure control is challenging for metal additive manufacturing (AM). Grain structure optimization requires the control of grain morphology with grain size refinement, which can improve the mechanical properties of additive manufactured components. This work summarizes methods to promote fine equiaxed grains in both the additive manufacturing process and subsequent heat treatment. Influences of temperature gradient, solidification velocity and alloy composition on grain morphology are discussed. Equiaxed solidification is greatly promoted by introducing a high density of heterogeneous nucleation sites via powder rate control in the direct energy deposition (DED) technique or powder surface treatment for powder-bed techniques. Grain growth/coarsening during post-processing heat treatment can be restricted by presence of nano-scale oxide particles formed in-situ during AM. Grain refinement of martensitic steels can also be achieved by cyclic austenitizing in post-processing heat treatment. Evidently, new alloy powder design is another sustainable method enhancing the capability of AM for high-performance components with desirable microstructures.

Development of an Intelligent Monitoring and Control System for a Heterogeneous Numerical Propulsion System Simulation

NASA Technical Reports Server (NTRS)

Reed, John A.; Afjeh, Abdollah A.; Lewandowski, Henry; Homer, Patrick T.; Schlichting, Richard D.

1996-01-01

The NASA Numerical Propulsion System Simulation (NPSS) project is exploring the use of computer simulation to facilitate the design of new jet engines. Several key issues raised in this research are being examined in an NPSS-related research project: zooming, monitoring and control, and support for heterogeneity. The design of a simulation executive that addresses each of these issues is described. In this work, the strategy of zooming, which allows codes that model at different levels of fidelity to be integrated within a single simulation, is applied to the fan component of a turbofan propulsion system. A prototype monitoring and control system has been designed for this simulation to support experimentation with expert system techniques for active control of the simulation. An interconnection system provides a transparent means of connecting the heterogeneous systems that comprise the prototype.

WE-E-17A-06: Assessing the Scale of Tumor Heterogeneity by Complete Hierarchical Segmentation On MRI

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

Gensheimer, M; Trister, A; Ermoian, R

2014-06-15

Purpose: In many cancers, intratumoral heterogeneity exists in vascular and genetic structure. We developed an algorithm which uses clinical imaging to interrogate different scales of heterogeneity. We hypothesize that heterogeneity of perfusion at large distance scales may correlate with propensity for disease recurrence. We applied the algorithm to initial diagnosis MRI of rhabdomyosarcoma patients to predict recurrence. Methods: The Spatial Heterogeneity Analysis by Recursive Partitioning (SHARP) algorithm recursively segments the tumor image. The tumor is repeatedly subdivided, with each dividing line chosen to maximize signal intensity difference between the two subregions. This process continues to the voxel level, producing segmentsmore » at multiple scales. Heterogeneity is measured by comparing signal intensity histograms between each segmented region and the adjacent region. We measured the scales of contrast enhancement heterogeneity of the primary tumor in 18 rhabdomyosarcoma patients. Using Cox proportional hazards regression, we explored the influence of heterogeneity parameters on relapse-free survival (RFS). To compare with existing methods, fractal and Haralick texture features were also calculated. Results: The complete segmentation produced by SHARP allows extraction of diverse features, including the amount of heterogeneity at various distance scales, the area of the tumor with the most heterogeneity at each scale, and for a given point in the tumor, the heterogeneity at different scales. 10/18 rhabdomyosarcoma patients suffered disease recurrence. On contrast-enhanced MRI, larger scale of maximum signal intensity heterogeneity, relative to tumor diameter, predicted for shorter RFS (p=0.05). Fractal dimension, fractal fit, and three Haralick features did not predict RFS (p=0.09-0.90). Conclusion: SHARP produces an automatic segmentation of tumor regions and reports the amount of heterogeneity at various distance scales. In rhabdomyosarcoma, RFS was shorter when the primary tumor exhibited larger scale of heterogeneity on contrast-enhanced MRI. If validated on a larger dataset, this imaging biomarker could be useful to help personalize treatment.« less

Hybrid massively parallel fast sweeping method for static Hamilton–Jacobi equations

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

Detrixhe, Miles, E-mail: mdetrixhe@engineering.ucsb.edu; University of California Santa Barbara, Santa Barbara, CA, 93106; Gibou, Frédéric, E-mail: fgibou@engineering.ucsb.edu

The fast sweeping method is a popular algorithm for solving a variety of static Hamilton–Jacobi equations. Fast sweeping algorithms for parallel computing have been developed, but are severely limited. In this work, we present a multilevel, hybrid parallel algorithm that combines the desirable traits of two distinct parallel methods. The fine and coarse grained components of the algorithm take advantage of heterogeneous computer architecture common in high performance computing facilities. We present the algorithm and demonstrate its effectiveness on a set of example problems including optimal control, dynamic games, and seismic wave propagation. We give results for convergence, parallel scaling,more » and show state-of-the-art speedup values for the fast sweeping method.« less

Distributed containment control of heterogeneous fractional-order multi-agent systems with communication delays

NASA Astrophysics Data System (ADS)

Yang, Hongyong; Han, Fujun; Zhao, Mei; Zhang, Shuning; Yue, Jun

2017-08-01

Because many networked systems can only be characterized with fractional-order dynamics in complex environments, fractional-order calculus has been studied deeply recently. When diverse individual features are shown in different agents of networked systems, heterogeneous fractional-order dynamics will be used to describe the complex systems. Based on the distinguishing properties of agents, heterogeneous fractional-order multi-agent systems (FOMAS) are presented. With the supposition of multiple leader agents in FOMAS, distributed containment control of FOMAS is studied in directed weighted topologies. By applying Laplace transformation and frequency domain theory of the fractional-order operator, an upper bound of delays is obtained to ensure containment consensus of delayed heterogenous FOMAS. Consensus results of delayed FOMAS in this paper can be extended to systems with integer-order models. Finally, numerical examples are used to verify our results.

Metaplot: A Novel Stata Graph for Assessing Heterogeneity at a Glance

PubMed Central

Poorolajal, J; Mahmoodi, M; Majdzadeh, R; Fotouhi, A

2010-01-01

Background: Heterogeneity is usually a major concern in meta-analysis. Although there are some statistical approaches for assessing variability across studies, here we present a new approach to heterogeneity using “MetaPlot” that investigate the influence of a single study on the overall heterogeneity. Methods: MetaPlot is a two-way (x, y) graph, which can be considered as a complementary graphical approach for testing heterogeneity. This method shows graphically as well as numerically the results of an influence analysis, in which Higgins’ I2 statistic with 95% (Confidence interval) CI are computed omitting one study in each turn and then are plotted against reciprocal of standard error (1/SE) or “precision”. In this graph, “1/SE” lies on x axis and “I2 results” lies on y axe. Results: Having a first glance at MetaPlot, one can predict to what extent omission of a single study may influence the overall heterogeneity. The precision on x-axis enables us to distinguish the size of each trial. The graph describes I2 statistic with 95% CI graphically as well as numerically in one view for prompt comparison. It is possible to implement MetaPlot for meta-analysis of different types of outcome data and summary measures. Conclusion: This method presents a simple graphical approach to identify an outlier and its effect on overall heterogeneity at a glance. We wish to suggest MetaPlot to Stata experts to prepare its module for the software. PMID:23113013

Study on the ownership balance and the efficiency of mixed ownership enterprises from the perspective of heterogeneous shareholders

PubMed Central

Yin, Zhujia; Liu, Lijuan; Wang, Haidong

2018-01-01

Based on the database data of Chinese industrial enterprises from 2000 to 2007 and the LP method, this paper measures the total factor productivity of enterprises and investigates the effect of different mixed ownership forms on enterprises’ efficiency and the effect of heterogeneous ownership balance on the mixed ownership enterprises’ efficiency. The state-owned enterprise and mixed ownership enterprise are identified by the enterprise’s paid-up capital. The results show that, on the whole, for the mixed ownership enterprise, the higher the diversification degree of the shareholders is, the higher the efficiency becomes, and in different types of industries, the mixed forms of shareholders have different effects on the efficiency of enterprises. The heterogeneous ownership balance and the enterprise efficiency show nonlinear U-type relationships. Both the higher and lower heterogeneous ownership balance degrees will promote the enterprise’s efficiency. However, when the ownership balance degree is in the range of [0.2 0.5], the increase in ownership balance will lead to the decline of enterprise efficiency. Therefore, when introducing non-state-owned capital, state-owned enterprises should take full account of their own characteristics by rationally controlling the shareholding ratio of non-state-owned capital and play the positive role of a mixed ownership structure in corporate governance with appropriate ownership balances. PMID:29614126

Solving the Puzzle of Metastasis: The Evolution of Cell Migration in Neoplasms

PubMed Central

Chen, Jun; Sprouffske, Kathleen; Huang, Qihong; Maley, Carlo C.

2011-01-01

Background Metastasis represents one of the most clinically important transitions in neoplastic progression. The evolution of metastasis is a puzzle because a metastatic clone is at a disadvantage in competition for space and resources with non-metastatic clones in the primary tumor. Metastatic clones waste some of their reproductive potential on emigrating cells with little chance of establishing metastases. We suggest that resource heterogeneity within primary tumors selects for cell migration, and that cell emigration is a by-product of that selection. Methods and Findings We developed an agent-based model to simulate the evolution of neoplastic cell migration. We simulated the essential dynamics of neoangiogenesis and blood vessel occlusion that lead to resource heterogeneity in neoplasms. We observed the probability and speed of cell migration that evolves with changes in parameters that control the degree of spatial and temporal resource heterogeneity. Across a broad range of realistic parameter values, increasing degrees of spatial and temporal heterogeneity select for the evolution of increased cell migration and emigration. Conclusions We showed that variability in resources within a neoplasm (e.g. oxygen and nutrients provided by angiogenesis) is sufficient to select for cells with high motility. These cells are also more likely to emigrate from the tumor, which is the first step in metastasis and the key to the puzzle of metastasis. Thus, we have identified a novel potential solution to the puzzle of metastasis. PMID:21556134

Effect of lithological heterogeneity of bitumen sandstones on SAGD reservoir development

NASA Astrophysics Data System (ADS)

Korolev, E. A.; Usmanov, S. A.; Nikolaev, D. S.; Gabdelvaliyeva, R. R.

2018-05-01

The article describes the heavy oil field developed by the SAGD method. While development planning all the heterogeneity of the reservoir is must be taken into account. The objective of this work is to identify the distribution of lithological heterogeneities and their influence on oil production. For this reason, the studies of core samples were conducted and the heterogeneity was identified. Then properties and approximate geometry of lithological objects were studied. Also the effect of the heterogeneity on the heat propagation and production of fluid were analyzed. In the end, recommendations were made for the study of such heterogeneities on other deposits with similar geology

Modelling Geomechanical Heterogeneity of Rock Masses Using Direct and Indirect Geostatistical Conditional Simulation Methods

NASA Astrophysics Data System (ADS)

Eivazy, Hesameddin; Esmaieli, Kamran; Jean, Raynald

2017-12-01

An accurate characterization and modelling of rock mass geomechanical heterogeneity can lead to more efficient mine planning and design. Using deterministic approaches and random field methods for modelling rock mass heterogeneity is known to be limited in simulating the spatial variation and spatial pattern of the geomechanical properties. Although the applications of geostatistical techniques have demonstrated improvements in modelling the heterogeneity of geomechanical properties, geostatistical estimation methods such as Kriging result in estimates of geomechanical variables that are not fully representative of field observations. This paper reports on the development of 3D models for spatial variability of rock mass geomechanical properties using geostatistical conditional simulation method based on sequential Gaussian simulation. A methodology to simulate the heterogeneity of rock mass quality based on the rock mass rating is proposed and applied to a large open-pit mine in Canada. Using geomechanical core logging data collected from the mine site, a direct and an indirect approach were used to model the spatial variability of rock mass quality. The results of the two modelling approaches were validated against collected field data. The study aims to quantify the risks of pit slope failure and provides a measure of uncertainties in spatial variability of rock mass properties in different areas of the pit.

Chloride Transport in Heterogeneous Formation

NASA Astrophysics Data System (ADS)

Mukherjee, A.; Holt, R. M.

2017-12-01

The chloride mass balance (CMB) is a commonly-used method for estimating groundwater recharge. Observations of the vertical distribution of pore-water chloride are related to the groundwater infiltration rates (i.e. recharge rates). In CMB method, the chloride distribution is attributed mainly to the assumption of one dimensional piston flow. In many places, however, the vertical distribution of chloride will be influenced by heterogeneity, leading to horizontal movement of infiltrating waters. The impact of heterogeneity will be particularly important when recharge is locally focused. When recharge is focused in an area, horizontal movement of chloride-bearing waters, coupled with upward movement driven by evapotranspiration, may lead to chloride bulges that could be misinterpreted if the CMB method is used to estimate recharge. We numerically simulate chloride transport and evaluate the validity of the CMB method in highly heterogeneous systems. This simulation is conducted for the unsaturated zone of Ogallala, Antlers, and Gatuna (OAG) formations in Andrews County, Texas. A two dimensional finite element model will show the movement of chloride through heterogeneous systems. We expect to see chloride bulges not only close to the surface but also at depths characterized by horizontal or upward movement. A comparative study of focused recharge estimates in this study with available recharge data will be presented.

Spatial processes decouple management from objectives in a heterogeneous landscape: predator control as a case study.

PubMed

Mahoney, Peter J; Young, Julie K; Hersey, Kent R; Larsen, Randy T; McMillan, Brock R; Stoner, David C

2018-04-01

Predator control is often implemented with the intent of disrupting top-down regulation in sensitive prey populations. However, ambiguity surrounding the efficacy of predator management, as well as the strength of top-down effects of predators in general, is often exacerbated by the spatially implicit analytical approaches used in assessing data with explicit spatial structure. Here, we highlight the importance of considering spatial context in the case of a predator control study in south-central Utah. We assessed the spatial match between aerial removal risk in coyotes (Canis latrans) and mule deer (Odocoileus hemionus) resource selection during parturition using a spatially explicit, multi-level Bayesian model. With our model, we were able to evaluate spatial congruence between management action (i.e., coyote removal) and objective (i.e., parturient deer site selection) at two distinct scales: the level of the management unit and the individual coyote removal. In the case of the former, our results indicated substantial spatial heterogeneity in expected congruence between removal risk and parturient deer site selection across large areas, and is a reflection of logistical constraints acting on the management strategy and differences in space use between the two species. At the level of the individual removal, we demonstrated that the potential management benefits of a removed coyote were highly variable across all individuals removed and in many cases, spatially distinct from parturient deer resource selection. Our methods and results provide a means of evaluating where we might anticipate an impact of predator control, while emphasizing the need to weight individual removals based on spatial proximity to management objectives in any assessment of large-scale predator control. Although we highlight the importance of spatial context in assessments of predator control strategy, we believe our methods are readily generalizable in any management or large-scale experimental framework where spatial context is likely an important driver of outcomes. © 2018 by the Ecological Society of America.

Coffee consumption modifies risk of estrogen-receptor negative breast cancer

PubMed Central

2011-01-01

Introduction Breast cancer is a complex disease and may be sub-divided into hormone-responsive (estrogen receptor (ER) positive) and non-hormone-responsive subtypes (ER-negative). Some evidence suggests that heterogeneity exists in the associations between coffee consumption and breast cancer risk, according to different estrogen receptor subtypes. We assessed the association between coffee consumption and postmenopausal breast cancer risk in a large population-based study (2,818 cases and 3,111 controls), overall, and stratified by ER tumour subtypes. Methods Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated using the multivariate logistic regression models fitted to examine breast cancer risk in a stratified case-control analysis. Heterogeneity among ER subtypes was evaluated in a case-only analysis, by fitting binary logistic regression models, treating ER status as a dependent variable, with coffee consumption included as a covariate. Results In the Swedish study, coffee consumption was associated with a modest decrease in overall breast cancer risk in the age-adjusted model (OR> 5 cups/day compared to OR≤ 1 cup/day: 0.80, 95% CI: 0.64, 0.99, P trend = 0.028). In the stratified case-control analyses, a significant reduction in the risk of ER-negative breast cancer was observed in heavy coffee drinkers (OR> 5 cups/day compared to OR≤ 1 cup/day : 0.43, 95% CI: 0.25, 0.72, P trend = 0.0003) in a multivariate-adjusted model. The breast cancer risk reduction associated with higher coffee consumption was significantly higher for ER-negative compared to ER-positive tumours (P heterogeneity (age-adjusted) = 0.004). Conclusions A high daily intake of coffee was found to be associated with a statistically significant decrease in ER-negative breast cancer among postmenopausal women. PMID:21569535

Relationship between -889 C/T polymorphism in interleukin-1A gene and risk of chronic periodontitis: Evidence from a meta-analysis with new published findings

PubMed Central

da Silva, Felipe-Rodolfo-Pereira; Guimarães-Vasconcelos, Any-Carolina-Cardoso; de-Carvalho-França, Luiz-Felipe; di-Lenardo, David; Rodrigues, Luana-Silva; Barreto-do-Nascimento, Maria-Luísa-Lima

2017-01-01

Background Periodontitis results from an inflammatory response caused by accumulative microorganisms in periodontal sites. Several factors are involved in pathogenesis of periodontitis, for example the -889 C/T polymorphism in interleukin-1A gene. This study aimed to evaluate the relationship between this polymorphism and risk of development of chronic periodontitis by a meta-analysis based in new published findings. Material and Methods Thereunto a review in literature was performed in the electronic biomedical and education databases (Cochrane Library, Google Scholar, MEDLINE and PubMed) to studies published before August 2, 2015, the abstracts were evaluated and the data extraction performed by two calibrated examiners. The calculations of the meta-analysis were obtained through statistical software Review Manager version 5.2 with calculation of Odds Ratio (OR), heterogeneity (I²) and Funnel plots with P <0.05. Results In overall, twenty-one case/control studies were selected with 2,174 patients with chronic periodontitis and 1, 756 controls. The meta-analysis showed T allele was associated with chronic periodontitis (OR = 1.22, 95% CI: 1.09, 1.36, P = 0.0004) with decreased value to heterogeneity (I² = 15%, P = 0.28). TT genotype was associated to patients with chronic periodontitis (OR = 1.40, 95% CI: 1.07, 1.83, P = 0.01). No publication bias was found in this meta-analysis by asymmetry in Funnel plots. Conclusions This meta-analysis with 2,174 patients with chronic periodontitis and 1, 756 controls evidenced the -889 C/T polymorphism is associated to risk of development of chronic periodontitis with no significant value to heterogeneity to allelic evaluation. Key words:Alleles, odds ratio, periodontal disease, cytokines. PMID:27918732

A comprehensive tractography study of patients with bipolar disorder and their unaffected siblings.

PubMed

Sprooten, Emma; Barrett, Jennifer; McKay, D Reese; Knowles, Emma E; Mathias, Samuel R; Winkler, Anderson M; Brumbaugh, Margaret S; Landau, Stefanie; Cyr, Lindsay; Kochunov, Peter; Glahn, David C

2016-10-01

Diffusion tensor imaging studies show reductions in fractional anisotropy (FA) in individuals with bipolar disorder and their unaffected siblings. However, the use of various analysis methods is an important source of between-study heterogeneity. Using tract-based spatial statistics, we previously demonstrated widespread FA reductions in patients and unaffected relatives. To better interpret the neuroanatomical pattern of this previous finding and to assess the influence of methodological heterogeneity, we here applied tractography to the same sample. Diffusion-weighted images were acquired for 96 patients, 69 unaffected siblings and 56 controls. We applied TRACULA, an extension of a global probabilistic tractography algorithm, to automatically segment 18 major fiber tracts. Average FA within each tract and at each cross-section along each tract was compared between groups. Patients had reduced FA compared to healthy controls and their unaffected siblings in general, and in particular in the parietal part of the superior longitudinal fasciculus. In unaffected siblings, FA was nominally reduced compared to controls in the corpus callosum. Point-wise analyses indicated that similar effects were present along extended sections, but with variable effect sizes. Current symptom severity negatively correlated with FA in several fronto-limbic association tracts. The differential sensitivity of analysis techniques likely explains between-study heterogeneity in anatomical localization of FA reductions. The present tractography analysis confirms the presence of overall FA reductions in patients with bipolar disorder, which are most pronounced in the superior longitudinal fasciculus. Unaffected siblings may display similar, albeit more subtle and anatomically restricted FA reductions. Hum Brain Mapp 37:3474-3485, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome☆

PubMed Central

Radulescu, Eugenia; Minati, Ludovico; Ganeshan, Balaji; Harrison, Neil A.; Gray, Marcus A.; Beacher, Felix D.C.C.; Chatwin, Chris; Young, Rupert C.D.; Critchley, Hugo D.

2013-01-01

Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD. PMID:24179823

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

PubMed Central

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-01-01

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. PMID:28639575

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review

PubMed Central

Demarzo, Marcelo M.P.; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R.; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-01-01

PURPOSE Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I2 = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I2 = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I2 = 0; P >.05). CONCLUSIONS Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID:26553897

Advancing current approaches to disease management evaluation: capitalizing on heterogeneity to understand what works and for whom

PubMed Central

2013-01-01

Background Evaluating large-scale disease management interventions implemented in actual health care settings is a complex undertaking for which universally accepted methods do not exist. Fundamental issues, such as a lack of control patients and limited generalizability, hamper the use of the ‘gold-standard’ randomized controlled trial, while methodological shortcomings restrict the value of observational designs. Advancing methods for disease management evaluation in practice is pivotal to learn more about the impact of population-wide approaches. Methods must account for the presence of heterogeneity in effects, which necessitates a more granular assessment of outcomes. Methods This paper introduces multilevel regression methods as valuable techniques to evaluate ‘real-world’ disease management approaches in a manner that produces meaningful findings for everyday practice. In a worked example, these methods are applied to retrospectively gathered routine health care data covering a cohort of 105,056 diabetes patients who receive disease management for type 2 diabetes mellitus in the Netherlands. Multivariable, multilevel regression models are fitted to identify trends in clinical outcomes and correct for differences in characteristics of patients (age, disease duration, health status, diabetes complications, smoking status) and the intervention (measurement frequency and range, length of follow-up). Results After a median one year follow-up, the Dutch disease management approach was associated with small average improvements in systolic blood pressure and low-density lipoprotein, while a slight deterioration occurred in glycated hemoglobin. Differential findings suggest that patients with poorly controlled diabetes tend to benefit most from disease management in terms of improved clinical measures. Additionally, a greater measurement frequency was associated with better outcomes, while longer length of follow-up was accompanied by less positive results. Conclusions Despite concerted efforts to adjust for potential sources of confounding and bias, there ultimately are limits to the validity and reliability of findings from uncontrolled research based on routine intervention data. While our findings are supported by previous randomized research in other settings, the trends in outcome measures presented here may have alternative explanations. Further practice-based research, perhaps using historical data to retrospectively construct a control group, is necessary to confirm results and learn more about the impact of population-wide disease management. PMID:23497125

The Effects of Realistic Geological Heterogeneity on Seismic Modeling: Applications in Shear Wave Generation and Near-Surface Tunnel Detection

NASA Astrophysics Data System (ADS)

Sherman, Christopher Scott

Naturally occurring geologic heterogeneity is an important, but often overlooked, aspect of seismic wave propagation. This dissertation presents a strategy for modeling the effects of heterogeneity using a combination of geostatistics and Finite Difference simulation. In the first chapter, I discuss my motivations for studying geologic heterogeneity and seis- mic wave propagation. Models based upon fractal statistics are powerful tools in geophysics for modeling heterogeneity. The important features of these fractal models are illustrated using borehole log data from an oil well and geomorphological observations from a site in Death Valley, California. A large part of the computational work presented in this disserta- tion was completed using the Finite Difference Code E3D. I discuss the Python-based user interface for E3D and the computational strategies for working with heterogeneous models developed over the course of this research. The second chapter explores a phenomenon observed for wave propagation in heteroge- neous media - the generation of unexpected shear wave phases in the near-source region. In spite of their popularity amongst seismic researchers, approximate methods for modeling wave propagation in these media, such as the Born and Rytov methods or Radiative Trans- fer Theory, are incapable of explaining these shear waves. This is primarily due to these method's assumptions regarding the coupling of near-source terms with the heterogeneities and mode conversion. To determine the source of these shear waves, I generate a suite of 3D synthetic heterogeneous fractal geologic models and use E3D to simulate the wave propaga- tion for a vertical point force on the surface of the models. I also present a methodology for calculating the effective source radiation patterns from the models. The numerical results show that, due to a combination of mode conversion and coupling with near-source hetero- geneity, shear wave energy on the order of 10% of the compressional wave energy may be generated within the shear radiation node of the source. Interestingly, in some cases this shear wave may arise as a coherent pulse, which may be used to improve seismic imaging efforts. In the third and fourth chapters, I discuss the results of a numerical analysis and field study of seismic near-surface tunnel detection methods. Detecting unknown tunnels and voids, such as old mine workings or solution cavities in karst terrain, is a challenging prob- lem in geophysics and has implications for geotechnical design, public safety, and domestic security. Over the years, a number of different geophysical methods have been developed to locate these objects (microgravity, resistivity, seismic diffraction, etc.), each with varying results. One of the major challenges facing these methods is understanding the influence of geologic heterogeneity on their results, which makes this problem a natural extension of the modeling work discussed in previous chapters. In the third chapter, I present the results of a numerical study of surface-wave based tunnel detection methods. The results of this analysis show that these methods are capable of detecting a void buried within one wavelength of the surface, with size potentially much less than one wavelength. In addition, seismic surface- wave based detection methods are effective in media with moderate heterogeneity (epsilon < 5 %), and in fact, this heterogeneity may serve to increase the resolution of these methods. In the fourth chapter, I discuss the results of a field study of tunnel detection methods at a site within the Black Diamond Mines Regional Preserve, near Antioch California. I use a com- bination of surface wave backscattering, 1D surface wave attenuation, and 2D attenuation tomography to locate and determine the condition of two tunnels at this site. These results compliment the numerical study in chapter 3 and highlight their usefulness for detecting tunnels at other sites.

Linnorm: improved statistical analysis for single cell RNA-seq expression data

PubMed Central

Yip, Shun H.; Wang, Panwen; Kocher, Jean-Pierre A.; Sham, Pak Chung

2017-01-01

Abstract Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy. PMID:28981748

Structure and Filling Characteristics of Paleokarst Reservoirs in the Northern Tarim Basin, Revealed by Outcrop, Core and Borehole Images

NASA Astrophysics Data System (ADS)

Tian, Fei; Lu, Xinbian; Zheng, Songqing; Zhang, Hongfang; Rong, Yuanshuai; Yang, Debin; Liu, Naigui

2017-06-01

The Ordovician paleokarst reservoirs in the Tahe oilfield, with burial depths of over 5300 m, experienced multiple phases of geologic processes and exhibit strong heterogeneity. Core testing can be used to analyse the characteristics of typical points at the centimetre scale, and seismic datasets can reveal the macroscopic outlines of reservoirs at the >10-m scale. However, neither method can identify caves, cave fills and fractures at the meter scale. Guided by outcrop investigations and calibrations based on core sample observations, this paper describes the interpretation of high longitudinal resolution borehole images, the identification of the characteristics of caves, cave fills (sedimentary, breccia and chemical fills) and fractures in single wells, and the identification of structures and fill characteristics at the meter scale in the strongly heterogeneous paleokarst reservoirs. The paleogeomorphology, a major controlling factor in the distribution of paleokarst reservoirs, was also analysed. The results show that one well can penetrate multiple cave layers of various sizes and that the caves are filled with multiple types of fill. The paleogeomorphology can be divided into highlands, slopes and depressions, which controlled the structure and fill characteristics of the paleokarst reservoirs. The results of this study can provide fundamental meter-scale datasets for interpreting detailed geologic features of deeply buried paleocaves, can be used to connect core- and seismic-scale interpretations, and can provide support for the recognition and development of these strongly heterogeneous reservoirs.

Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data-driven method.

PubMed

Bora, Emre; Aydın, Aydan; Saraç, Tuğba; Kadak, Muhammed Tayyib; Köse, Sezen

2017-02-01

Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first-degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low-scoring" and a "high-scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low-scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321-326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix.

PubMed

Saito, Akira; Numata, Yasushi; Hamada, Takuya; Horisawa, Tomoyoshi; Cosatto, Eric; Graf, Hans-Peter; Kuroda, Masahiko; Yamamoto, Yoichiro

2016-01-01

Recent developments in molecular pathology and genetic/epigenetic analysis of cancer tissue have resulted in a marked increase in objective and measurable data. In comparison, the traditional morphological analysis approach to pathology diagnosis, which can connect these molecular data and clinical diagnosis, is still mostly subjective. Even though the advent and popularization of digital pathology has provided a boost to computer-aided diagnosis, some important pathological concepts still remain largely non-quantitative and their associated data measurements depend on the pathologist's sense and experience. Such features include pleomorphism and heterogeneity. In this paper, we propose a method for the objective measurement of pleomorphism and heterogeneity, using the cell-level co-occurrence matrix. Our method is based on the widely used Gray-level co-occurrence matrix (GLCM), where relations between neighboring pixel intensity levels are captured into a co-occurrence matrix, followed by the application of analysis functions such as Haralick features. In the pathological tissue image, through image processing techniques, each nucleus can be measured and each nucleus has its own measureable features like nucleus size, roundness, contour length, intra-nucleus texture data (GLCM is one of the methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In this approach the most important point is how to define the neighborhood of each nucleus. We define three types of neighborhoods of a nucleus, then create the co-occurrence matrix and apply Haralick feature functions. In each image pleomorphism and heterogeneity are then determined quantitatively. For our method, one pixel corresponds to one nucleus feature, and we therefore named our method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for several nucleus features. CFLCM is showed as a useful quantitative method for pleomorphism and heterogeneity on histopathological image analysis.

Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

PubMed Central

Morton, Lindsay M.; Slager, Susan L.; Cerhan, James R.; Wang, Sophia S.; Vajdic, Claire M.; Skibola, Christine F.; Bracci, Paige M.; de Sanjosé, Silvia; Smedby, Karin E.; Chiu, Brian C. H.; Zhang, Yawei; Mbulaiteye, Sam M.; Monnereau, Alain; Turner, Jennifer J.; Clavel, Jacqueline; Adami, Hans-Olov; Chang, Ellen T.; Glimelius, Bengt; Hjalgrim, Henrik; Melbye, Mads; Crosignani, Paolo; di Lollo, Simonetta; Miligi, Lucia; Nanni, Oriana; Ramazzotti, Valerio; Rodella, Stefania; Costantini, Adele Seniori; Stagnaro, Emanuele; Tumino, Rosario; Vindigni, Carla; Vineis, Paolo; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Cocco, Pierluigi; Foretova, Lenka; Maynadié, Marc; Nieters, Alexandra; Staines, Anthony; Colt, Joanne S.; Cozen, Wendy; Davis, Scott; de Roos, Anneclaire J.; Hartge, Patricia; Rothman, Nathaniel; Severson, Richard K.; Holly, Elizabeth A.; Call, Timothy G.; Feldman, Andrew L.; Habermann, Thomas M.; Liebow, Mark; Blair, Aaron; Cantor, Kenneth P.; Kane, Eleanor V.; Lightfoot, Tracy; Roman, Eve; Smith, Alex; Brooks-Wilson, Angela; Connors, Joseph M.; Gascoyne, Randy D.; Spinelli, John J.; Armstrong, Bruce K.; Kricker, Anne; Holford, Theodore R.; Lan, Qing; Zheng, Tongzhang; Orsi, Laurent; Dal Maso, Luigino; Franceschi, Silvia; La Vecchia, Carlo; Negri, Eva; Serraino, Diego; Bernstein, Leslie; Levine, Alexandra; Friedberg, Jonathan W.; Kelly, Jennifer L.; Berndt, Sonja I.; Birmann, Brenda M.; Clarke, Christina A.; Flowers, Christopher R.; Foran, James M.; Kadin, Marshall E.; Paltiel, Ora; Weisenburger, Dennis D.; Linet, Martha S.; Sampson, Joshua N.

2014-01-01

Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. Methods We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case–control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). Results Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10−4), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10−4). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Conclusions Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility. PMID:25174034

Systematic review: conservative treatments for secondary lymphedema

PubMed Central

2012-01-01

Background Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments. Methods We searched MEDLINE®, EMBASE®, Cochrane Central Register of Controlled Trials®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies. Results Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain). Conclusions The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems. PMID:22216837

The paradox of sham therapy and placebo effect in osteopathy: A systematic review.

PubMed

Cerritelli, Francesco; Verzella, Marco; Cicchitti, Luca; D'Alessandro, Giandomenico; Vanacore, Nicola

2016-08-01

Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as "sham therapy." In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness. A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed. High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings.

Critical design of heterogeneous catalysts for biomass valorization: current thrust and emerging prospects

DOE PAGES

De, Sudipta; Dutta, Saikat; Saha, Basudeb

2016-01-01

Catalysis in the heterogeneous phase plays a crucial role in the valorization of biorenewable substrates with controlled reactivity, efficient mechanical process separation, greater recyclability and minimization of environmental effects.

Mathematically Gifted in the Heterogeneously Grouped Mathematics Classroom: What Is a Teacher to Do?

ERIC Educational Resources Information Center

Reed, Catherine Finlayson

2004-01-01

Differentiation provides one method by which teachers can provide appropriate challenges at appropriate levels for all learners in a heterogeneously grouped mathematics classroom, where the range of abilities and interests can be wide. This article considers a heterogeneously grouped high school geometry class where differentiation is practiced.…

Access Scheme for Controlling Mobile Agents and its Application to Share Medical Information.

PubMed

Liao, Yu-Ting; Chen, Tzer-Shyong; Chen, Tzer-Long; Chung, Yu-Fang; Chen, Yu- Xin; Hwang, Jen-Hung; Wang, Huihui; Wei, Wei

2016-05-01

This study is showing the advantage of mobile agents to conquer heterogeneous system environments and contribute to a virtual integrated sharing system. Mobile agents will collect medical information from each medical institution as a method to achieve the medical purpose of data sharing. Besides, this research also provides an access control and key management mechanism by adopting Public key cryptography and Lagrange interpolation. The safety analysis of the system is based on a network attacker's perspective. The achievement of this study tries to improve the medical quality, prevent wasting medical resources and make medical resources access to appropriate configuration.

InfoSymbiotics/DDDAS - The power of Dynamic Data Driven Applications Systems for New Capabilities in Environmental -, Geo-, and Space- Sciences

NASA Astrophysics Data System (ADS)

Darema, F.

2016-12-01

InfoSymbiotics/DDDAS embodies the power of Dynamic Data Driven Applications Systems (DDDAS), a concept whereby an executing application model is dynamically integrated, in a feed-back loop, with the real-time data-acquisition and control components, as well as other data sources of the application system. Advanced capabilities can be created through such new computational approaches in modeling and simulations, and in instrumentation methods, and include: enhancing the accuracy of the application model; speeding-up the computation to allow faster and more comprehensive models of a system, and create decision support systems with the accuracy of full-scale simulations; in addition, the notion of controlling instrumentation processes by the executing application results in more efficient management of application-data and addresses challenges of how to architect and dynamically manage large sets of heterogeneous sensors and controllers, an advance over the static and ad-hoc ways of today - with DDDAS these sets of resources can be managed adaptively and in optimized ways. Large-Scale-Dynamic-Data encompasses the next wave of Big Data, and namely dynamic data arising from ubiquitous sensing and control in engineered, natural, and societal systems, through multitudes of heterogeneous sensors and controllers instrumenting these systems, and where opportunities and challenges at these "large-scales" relate not only to data size but the heterogeneity in data, data collection modalities, fidelities, and timescales, ranging from real-time data to archival data. In tandem with this important dimension of dynamic data, there is an extended view of Big Computing, which includes the collective computing by networked assemblies of multitudes of sensors and controllers, this range from the high-end to the real-time seamlessly integrated and unified, and comprising the Large-Scale-Big-Computing. InfoSymbiotics/DDDAS engenders transformative impact in many application domains, ranging from the nano-scale to the terra-scale and to the extra-terra-scale. The talk will address opportunities for new capabilities together with corresponding research challenges, with illustrative examples from several application areas including environmental sciences, geosciences, and space sciences.

Spatiotemporal Analysis of Malaria in Urban Ahmedabad (Gujarat), India: Identification of Hot Spots and Risk Factors for Targeted Intervention

PubMed Central

Parizo, Justin; Sturrock, Hugh J. W.; Dhiman, Ramesh C.; Greenhouse, Bryan

2016-01-01

The world population, especially in developing countries, has experienced a rapid progression of urbanization over the last half century. Urbanization has been accompanied by a rise in cases of urban infectious diseases, such as malaria. The complexity and heterogeneity of the urban environment has made study of specific urban centers vital for urban malaria control programs, whereas more generalizable risk factor identification also remains essential. Ahmedabad city, India, is a large urban center located in the state of Gujarat, which has experienced a significant Plasmodium vivax and Plasmodium falciparum disease burden. Therefore, a targeted analysis of malaria in Ahmedabad city was undertaken to identify spatiotemporal patterns of malaria, risk factors, and methods of predicting future malaria cases. Malaria incidence in Ahmedabad city was found to be spatially heterogeneous, but temporally stable, with high spatial correlation between species. Because of this stability, a prediction method utilizing historic cases from prior years and seasons was used successfully to predict which areas of Ahmedabad city would experience the highest malaria burden and could be used to prospectively target interventions. Finally, spatial analysis showed that normalized difference vegetation index, proximity to water sources, and location within Ahmedabad city relative to the dense urban core were the best predictors of malaria incidence. Because of the heterogeneity of urban environments and urban malaria itself, the study of specific large urban centers is vital to assist in allocating resources and informing future urban planning. PMID:27382081

Vaccine effects on heterogeneity in susceptibility and implications for population health management

USGS Publications Warehouse

Langwig, Kate E.; Wargo, Andrew R.; Jones, Darbi R.; Viss, Jessie R.; Rutan, Barbara J.; Egan, Nicholas A.; Sá-Guimarães, Pedro; Min Sun Kim,; Kurath, Gael; Gomes, M. Gabriela M.; Lipsitch, Marc; Bansal, Shweta; Pettigrew, Melinda M.

2017-01-01

Heterogeneity in host susceptibility is a key determinant of infectious disease dynamics but is rarely accounted for in assessment of disease control measures. Understanding how susceptibility is distributed in populations, and how control measures change this distribution, is integral to predicting the course of epidemics with and without interventions. Using multiple experimental and modeling approaches, we show that rainbow trout have relatively homogeneous susceptibility to infection with infectious hematopoietic necrosis virus and that vaccination increases heterogeneity in susceptibility in a nearly all-or-nothing fashion. In a simple transmission model with an R0 of 2, the highly heterogeneous vaccine protection would cause a 35 percentage-point reduction in outbreak size over an intervention inducing homogenous protection at the same mean level. More broadly, these findings provide validation of methodology that can help to reduce biases in predictions of vaccine impact in natural settings and provide insight into how vaccination shapes population susceptibility.

A software architecture for multidisciplinary applications: Integrating task and data parallelism

NASA Technical Reports Server (NTRS)

Chapman, Barbara; Mehrotra, Piyush; Vanrosendale, John; Zima, Hans

1994-01-01

Data parallel languages such as Vienna Fortran and HPF can be successfully applied to a wide range of numerical applications. However, many advanced scientific and engineering applications are of a multidisciplinary and heterogeneous nature and thus do not fit well into the data parallel paradigm. In this paper we present new Fortran 90 language extensions to fill this gap. Tasks can be spawned as asynchronous activities in a homogeneous or heterogeneous computing environment; they interact by sharing access to Shared Data Abstractions (SDA's). SDA's are an extension of Fortran 90 modules, representing a pool of common data, together with a set of Methods for controlled access to these data and a mechanism for providing persistent storage. Our language supports the integration of data and task parallelism as well as nested task parallelism and thus can be used to express multidisciplinary applications in a natural and efficient way.

Electroformation of Janus and patchy capsules

NASA Astrophysics Data System (ADS)

Rozynek, Zbigniew; Mikkelsen, Alexander; Dommersnes, Paul; Fossum, Jon Otto

2014-05-01

Janus and patchy particles have designed heterogeneous surfaces that consist of two or several patches with different materials properties. These particles are emerging as building blocks for a new class of soft matter and functional materials. Here we introduce a route for forming heterogeneous capsules by producing highly ordered jammed colloidal shells of various shapes with domains of controlled size and composition. These structures combine the functionalities offered by Janus or patchy particles, and those given by permeable shells such as colloidosomes. The simple assembly route involves the synergetic action of electro-hydrodynamic flow and electro-coalescence. We demonstrate that the method is robust and straightforwardly extendable to production of multi-patchy capsules. This forms a starting point for producing patchy colloidosomes with domains of anisotropic chemical surface properties, permeability or mixed liquid-solid phase domains, which could be exploited to produce functional emulsions, light and hollow supra-colloidosome structures, or scaffolds.

Modeling the spatio-temporal heterogeneity in the PM10-PM2.5 relationship

NASA Astrophysics Data System (ADS)

Chu, Hone-Jay; Huang, Bo; Lin, Chuan-Yao

2015-02-01

This paper explores the spatio-temporal patterns of particulate matter (PM) in Taiwan based on a series of methods. Using fuzzy c-means clustering first, the spatial heterogeneity (six clusters) in the PM data collected between 2005 and 2009 in Taiwan are identified and the industrial and urban areas of Taiwan (southwestern, west central, northwestern, and northern Taiwan) are found to have high PM concentrations. The PM10-PM2.5 relationship is then modeled with global ordinary least squares regression, geographically weighted regression (GWR), and geographically and temporally weighted regression (GTWR). The GTWR and GWR produce consistent results; however, GTWR provides more detailed information of spatio-temporal variations of the PM10-PM2.5 relationship. The results also show that GTWR provides a relatively high goodness of fit and sufficient space-time explanatory power. In particular, the PM2.5 or PM10 varies with time and space, depending on weather conditions and the spatial distribution of land use and emission patterns in local areas. Such information can be used to determine patterns of spatio-temporal heterogeneity in PM that will allow the control of pollutants and the reduction of public exposure.

An Overview of Meta-Analyses of Danhong Injection for Unstable Angina.

PubMed

Zhang, Xiaoxia; Wang, Hui; Chang, Yanxu; Wang, Yuefei; Lei, Xiang; Fu, Shufei; Zhang, Junhua

2015-01-01

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved.

An Overview of Meta-Analyses of Danhong Injection for Unstable Angina

PubMed Central

Zhang, Xiaoxia; Chang, Yanxu; Wang, Yuefei; Lei, Xiang; Fu, Shufei; Zhang, Junhua

2015-01-01

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved. PMID:26539221

Output Consensus of Heterogeneous Linear Multi-Agent Systems by Distributed Event-Triggered/Self-Triggered Strategy.

PubMed

Hu, Wenfeng; Liu, Lu; Feng, Gang

2016-09-02

This paper addresses the output consensus problem of heterogeneous linear multi-agent systems. We first propose a novel distributed event-triggered control scheme. It is shown that, with the proposed control scheme, the output consensus problem can be solved if two matrix equations are satisfied. Then, we further propose a novel self-triggered control scheme, with which continuous monitoring is avoided. By introducing a fixed timer into both event- and self-triggered control schemes, Zeno behavior can be ruled out for each agent. The effectiveness of the event- and self-triggered control schemes is illustrated by an example.

Research on distributed heterogeneous data PCA algorithm based on cloud platform

NASA Astrophysics Data System (ADS)

Zhang, Jin; Huang, Gang

2018-05-01

Principal component analysis (PCA) of heterogeneous data sets can solve the problem that centralized data scalability is limited. In order to reduce the generation of intermediate data and error components of distributed heterogeneous data sets, a principal component analysis algorithm based on heterogeneous data sets under cloud platform is proposed. The algorithm performs eigenvalue processing by using Householder tridiagonalization and QR factorization to calculate the error component of the heterogeneous database associated with the public key to obtain the intermediate data set and the lost information. Experiments on distributed DBM heterogeneous datasets show that the model method has the feasibility and reliability in terms of execution time and accuracy.

The Effect of Vitamins on Glaucoma: A Systematic Review and Meta-Analysis

PubMed Central

Schouten, Jan S. A. G.; Webers, Carroll A. B.

2018-01-01

Background: The aim of is to determine the association of vitamins with glaucoma by performing a systematic review and meta-analyses. Methods: Studies on the relation of vitamins and glaucoma published up to December 2017 were identified in the PubMed and Embase database. Data on vitamins (method of assessment), glaucoma (type and method of assessment), study characteristics and quality were recorded. In case of multiple studies for one nutrient a meta-analysis was performed. Results: A total of 629 articles were identified of which 36 were included in the systematic review. The meta-analysis included five of them (940 open-angle glaucoma (OAG) cases and 123,697 controls in total) and resulted in an odds ratio [95% confidence interval] (OR [95% CI]) of 0.58 [0.37–0.91] for dietary vitamin A, though heterogeneity was high (I2 = 51%). After omitting studies that contributed significantly to the heterogeneity, the pooled OR [95% CI] was 0.45 [0.30–0.68] for dietary vitamin A on OAG (I2 = 0%). For vitamin B1, C and E no significant association with OAG was found (OR [95% CI]: 0.84 [0.47–1.51]; 0.68 [0.38–1.22]; 0.95 [0.75–1.19]; respectively). However, after addressing heterogeneity, vitamin C showed a protective effect as well. Especially, foods high in these vitamins (e.g., dark green vegetables) were protective for OAG. Conclusions: Dietary intake of vitamin A and C showed a beneficial association with OAG; however, findings on blood levels of vitamins do not show a clear relation with OAG. PMID:29547516

Applicable or non-applicable: investigations of clinical heterogeneity in systematic reviews.

PubMed

Chess, Laura E; Gagnier, Joel J

2016-02-17

Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. The most recent 100 systematic reviews from the top five journals in medicine-JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine-and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81% of Cochrane reviews and 90% of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1% of non-Cochrane reviews and 8% of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very few studies mentioned clinician training, compliance, brand, co-interventions, dose route, ethnicity, prognostic markers and psychosocial variables as covariates to investigate as potentially clinically heterogeneous. Addressing aspects of clinical heterogeneity was not different between Cochrane and non-Cochrane reviews. The ability to quantify and compare the clinical differences of trials within a meta-analysis is crucial to determining its applicability and use in clinical practice. Despite Cochrane Collaboration emphasis on methodology, the proportion of reviews that assess clinical heterogeneity is less than those of non-Cochrane reviews. Our assessment reveals that there is room for improvement in assessing clinical heterogeneity in both Cochrane and non-Cochrane reviews.

Origin and analysis of microbial population heterogeneity in bioprocesses.

PubMed

Müller, Susann; Harms, Hauke; Bley, Thomas

2010-02-01

Heterogeneity of industrial production cultures is accepted to a certain degree; however, the underlying mechanisms are seldom perceived or included in the development of new bioprocess control strategies. Population heterogeneity and its basics, perceptible in the diverse proficiency of cells, begins with asymmetric birth and is found to recess during the life cycle. Since inefficient subpopulations have significant impact on the productivity of industrial cultures, cellular heterogeneity needs to be detected and quantified by using high speed detection tools like flow cytometry. Possible origins of population heterogeneity, sophisticated fluorescent techniques for detection of individual cell states, and cutting-edge Omics-technologies for extended information beyond the resolution of fluorescent labelling are highlighted.

Operational control of large-sized polymer composite units of U-profile circular beam type by X-ray method

NASA Astrophysics Data System (ADS)

Kavalerov, B. V.; Anoshkin, A. N.; Osokin, V. M.; Tretyakov, A. A.; Potrakhov, N. N.; Bessonov, V. B.; Obodovskiy, A. V.

2018-02-01

The advantages of using the method of microfocus radiography in the non-destructive testing of aviation products are considered in the paper, using the example of a circular beam of a U-shaped profile made of polymer composite materials. The basic types of characteristic defects of parts arising in such a type are described both in the process of their manufacture and in the process of their exploitation, namely interlayer delaminations, pores and folds. Peculiarities of obtaining pseudo-volumetric images, which allow to increase the informativity about the structure of the object of control, as well as to identify the arising heterogeneities are given. A model of a robotic system is described that makes it possible to realize a small or multi-angle survey scheme, and, in particular, to carry out tomographic studies.

Characterization of Heterogeneities Controlling Transport and Fate of Pollutants in Unconsolidated Sand and Gravel Aquifers: Second Year Report

DTIC Science & Technology

1993-06-30

of Scientific Research, Air Force Systems Command, USAF, under grant number AFOSR 91-0298. The views and conclusions contained in this document are...investigations of pulse-test methods were carried out during this year. The first involved the application of the principles of tomography, which has proven to be...a multilayered reservoir: SPE Formation Eval., v. 2, no. 3, pp. 261-283. Ellis, V.D., 1987, Well Logging for Earth Scientists : Elsevier Science

Effect of heterogeneity and anisotropy related to the construction method on transfer processes in waste rock piles.

PubMed

Lahmira, Belkacem; Lefebvre, René; Aubertin, Michel; Bussière, Bruno

2016-01-01

Waste rock piles producing acid mine drainage (AMD) are partially saturated systems involving multiphase (gas and liquid) flow and coupled transfer processes. Their internal structure and heterogeneous properties are inherited from their wide-ranging material grain sizes, their modes of deposition, and the underlying topography. This paper aims at assessing the effect of physical heterogeneity and anisotropy of waste rock piles on the physical processes involved in the generation of AMD. Generic waste rock pile conditions were represented with the numerical simulator TOUGH AMD based on those found at the Doyon mine waste rock pile (Canada). Models included four randomly distributed material types (coarse, intermediate, fine and very fine-grained). The term "randomly" as used in this study means that the vertical profile and spatial distribution of materials in waste rock piles (internal structure) defy stratigraphy principles applicable to natural sediments (superposition and continuity). The materials have different permeability and capillary properties, covering the typical range of materials found in waste rock piles. Anisotropy with a larger horizontal than vertical permeability was used to represent the effect of pile construction by benches, while the construction by end-dumping was presumed to induce a higher vertical than horizontal permeability. Results show that infiltrated precipitation preferentially flows in fine-grained materials, which remain almost saturated, whereas gas flows preferentially through the most permeable coarse materials, which have higher volumetric gas saturation. Anisotropy, which depends on pile construction methods, often controls global gas flow paths. Construction by benches favours lateral air entry close to the pile slope, whereas end-dumping leads to air entry from the surface to the interior of the pile by secondary gas convection cells. These results can be useful to construct and rehabilitate waste rock piles to minimize AMD, while controlling gas flow and oxygen supply. Copyright © 2015 Elsevier B.V. All rights reserved.

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

PubMed

Christophorou, D; Funakoshi, N; Duny, Y; Valats, J-C; Bismuth, M; Pineton De Chambrun, G; Daures, J-P; Blanc, P

2015-04-01

The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use. © 2015 John Wiley & Sons Ltd.

Determining heterogeneous slip activity on multiple slip systems from single crystal orientation pole figures

DOE PAGES

Pagan, Darren C.; Miller, Matthew P.

2016-09-01

A new experimental method to determine heterogeneity of shear strains associated with crystallographic slip in the bulk of ductile, crystalline materials is outlined. The method quantifies the time resolved evolution of misorientation within plastically deforming crystals using single crystal orientation pole figures (SCPFs) measured in-situ with X-ray diffraction. A multiplicative decomposition of the crystal kinematics is used to interpret the distributions of lattice plane orientation observed on the SCPFs in terms of heterogeneous slip activity (shear strains) on multiple slip systems. Here, to show the method’s utility, the evolution of heterogeneous slip is quantified in a silicon single crystal plasticallymore » deformed at high temperature at multiple load steps, with slip activity in sub-volumes of the crystal analyzed simultaneously.« less

Temporal Heterogeneity and the Value of Slowness in Robotic Systems

DTIC Science & Technology

2015-11-01

DIMENSIONS OF HETEROGENEITY By now, we have become reasonably good at designing distributed control strategies for teams of networked agents in order...possible is the recent emergence of a relatively mature theory of how to coordinate control decisions across teams of networked agents. In fact...Loris, illustrated in Figure 2. Figure 2: Slow mammals that serve as bio-inspiration for SlowBot Behavior [Wikipedia] Top: Tree

A weighted U statistic for association analyses considering genetic heterogeneity.

PubMed

Wei, Changshuai; Elston, Robert C; Lu, Qing

2016-07-20

Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical Efficacy and Safety of Pamidronate Therapy on Bone Mass Density in Early Post-Renal Transplant Period: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Zijie; Han, Zhijian; Tao, Jun; Lu, Pei; Liu, Xuzhong; Wang, Jun; Wu, Bian; Huang, Zhengkai; Yin, Changjun; Tan, Ruoyun; Gu, Min

2014-01-01

Introduction The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. Materials and Methods A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate. Results Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD)  = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD  = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD  = −3.101 [−5.33, −0.89]; serum calcium: SMD  = 2.18 [−0.8, 5.16]; serum iPTH: SMD  = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. Conclusions This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate. PMID:25265508

Parallelizing Compiler Framework and API for Power Reduction and Software Productivity of Real-Time Heterogeneous Multicores

NASA Astrophysics Data System (ADS)

Hayashi, Akihiro; Wada, Yasutaka; Watanabe, Takeshi; Sekiguchi, Takeshi; Mase, Masayoshi; Shirako, Jun; Kimura, Keiji; Kasahara, Hironori

Heterogeneous multicores have been attracting much attention to attain high performance keeping power consumption low in wide spread of areas. However, heterogeneous multicores force programmers very difficult programming. The long application program development period lowers product competitiveness. In order to overcome such a situation, this paper proposes a compilation framework which bridges a gap between programmers and heterogeneous multicores. In particular, this paper describes the compilation framework based on OSCAR compiler. It realizes coarse grain task parallel processing, data transfer using a DMA controller, power reduction control from user programs with DVFS and clock gating on various heterogeneous multicores from different vendors. This paper also evaluates processing performance and the power reduction by the proposed framework on a newly developed 15 core heterogeneous multicore chip named RP-X integrating 8 general purpose processor cores and 3 types of accelerator cores which was developed by Renesas Electronics, Hitachi, Tokyo Institute of Technology and Waseda University. The framework attains speedups up to 32x for an optical flow program with eight general purpose processor cores and four DRP(Dynamically Reconfigurable Processor) accelerator cores against sequential execution by a single processor core and 80% of power reduction for the real-time AAC encoding.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

PubMed

Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan; Desler, Claus; Regnell, Christine Elisabeth; Larsen, Steen; Rasmussen, Lene Juel; Dela, Flemming; Bergersen, Linda Hildegard; Lauritzen, Martin

2018-01-01

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB m/m ) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB m/m hippocampus, but not in CSB m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian inversion analysis of nonlinear dynamics in surface heterogeneous reactions.

PubMed

Omori, Toshiaki; Kuwatani, Tatsu; Okamoto, Atsushi; Hukushima, Koji

2016-09-01

It is essential to extract nonlinear dynamics from time-series data as an inverse problem in natural sciences. We propose a Bayesian statistical framework for extracting nonlinear dynamics of surface heterogeneous reactions from sparse and noisy observable data. Surface heterogeneous reactions are chemical reactions with conjugation of multiple phases, and they have the intrinsic nonlinearity of their dynamics caused by the effect of surface-area between different phases. We adapt a belief propagation method and an expectation-maximization (EM) algorithm to partial observation problem, in order to simultaneously estimate the time course of hidden variables and the kinetic parameters underlying dynamics. The proposed belief propagation method is performed by using sequential Monte Carlo algorithm in order to estimate nonlinear dynamical system. Using our proposed method, we show that the rate constants of dissolution and precipitation reactions, which are typical examples of surface heterogeneous reactions, as well as the temporal changes of solid reactants and products, were successfully estimated only from the observable temporal changes in the concentration of the dissolved intermediate product.

Microfluidic-Assisted Production of Size-Controlled Superparamagnetic Iron Oxide Nanoparticles-Loaded Poly(methyl methacrylate) Nanohybrids.

PubMed

Ding, Shukai; Attia, Mohamed F; Wallyn, Justine; Taddei, Chiara; Serra, Christophe A; Anton, Nicolas; Kassem, Mohamad; Schmutz, Marc; Er-Rafik, Meriem; Messaddeq, Nadia; Collard, Alexandre; Yu, Wei; Giordano, Michele; Vandamme, Thierry F

2018-02-06

In this paper, superparamagnetic iron oxide nanoparticles (SPIONs, around 6 nm) encapsulated in poly(methyl methacrylate) nanoparticles (PMMA NPs) with controlled sizes ranging from 100 to 200 nm have been successfully produced. The hybrid polymeric NPs were prepared following two different methods: (1) nanoprecipitation and (2) nanoemulsification-evaporation. These two methods were implemented in two different microprocesses based on the use of an impact jet micromixer and an elongational-flow microemulsifier. SPIONs-loaded PMMA NPs synthesized by the two methods presented completely different physicochemical properties. The polymeric NPs prepared with the micromixer-assisted nanoprecipitation method showed a heterogeneous dispersion of SPIONs inside the polymer matrix, an encapsulation efficiency close to 100 wt %, and an irregular shape. In contrast, the polymeric NPs prepared with the microfluidic-assisted nanoemulsification-evaporation method showed a homogeneous dispersion, an almost complete encapsulation, and a spherical shape. The properties of the polymeric NPs have been characterized by dynamic light scattering, thermogravimetric analysis, and transmission electron microscope. In vitro cytotoxicity assays were also performed on the nanohybrids and pure PMMA NPs.

A Method To Ensure Heterogeneous Mixing of Grade 9 Classes.

ERIC Educational Resources Information Center

Brydges, Bruce

This paper presents outcomes of a practicum that was designed to address a need that was created when the Ministry of Education in Ontario, Canada, mandated that all grade 9 classes be "destreamed." A review of educational literature found no methods for ensuring that classes are truly heterogeneously mixed. The practicum was designed to…

The research of some polygraphic paper samples's polarization characteristics

NASA Astrophysics Data System (ADS)

Gavryliak, Mykhailo S.; Dobrovolskyi, Yuriy G.; Motrych, Artem V.; Arkhelyuk, Alexander D.

2018-01-01

Methods of investigation the polarization characteristics of certain types of polygraph paper were described. The most effective method for estimation of the characteristic features of optical heterogeneities of polygraph paper was proposed. The greatest sensitivity to the structural organization of optical heterogeneities of paper was observed for linearly polarized light beams with 90 degree polarization azimuth.

Digital Microdroplet Ejection Technology-Based Heterogeneous Objects Prototyping

PubMed Central

Yang, Jiquan; Feng, Chunmei; Yang, Jianfei; Zhu, Liya; Guo, Aiqing

2016-01-01

An integrate fabrication framework is presented to build heterogeneous objects (HEO) using digital microdroplets injecting technology and rapid prototyping. The heterogeneous materials part design and manufacturing method in structure and material was used to change the traditional process. The net node method was used for digital modeling that can configure multimaterials in time. The relationship of material, color, and jetting nozzle was built. The main important contributions are to combine the structure, material, and visualization in one process and give the digital model for manufacture. From the given model, it is concluded that the method is effective for HEO. Using microdroplet rapid prototyping and the model given in the paper HEO could be gotten basically. The model could be used in 3D biomanufacturing. PMID:26981110

Digital Microdroplet Ejection Technology-Based Heterogeneous Objects Prototyping.

PubMed

Li, Na; Yang, Jiquan; Feng, Chunmei; Yang, Jianfei; Zhu, Liya; Guo, Aiqing

2016-01-01

An integrate fabrication framework is presented to build heterogeneous objects (HEO) using digital microdroplets injecting technology and rapid prototyping. The heterogeneous materials part design and manufacturing method in structure and material was used to change the traditional process. The net node method was used for digital modeling that can configure multimaterials in time. The relationship of material, color, and jetting nozzle was built. The main important contributions are to combine the structure, material, and visualization in one process and give the digital model for manufacture. From the given model, it is concluded that the method is effective for HEO. Using microdroplet rapid prototyping and the model given in the paper HEO could be gotten basically. The model could be used in 3D biomanufacturing.

A technique for processing of planetary images with heterogeneous characteristics for estimating geodetic parameters of celestial bodies with the example of Ganymede

NASA Astrophysics Data System (ADS)

Zubarev, A. E.; Nadezhdina, I. E.; Brusnikin, E. S.; Karachevtseva, I. P.; Oberst, J.

2016-09-01

The new technique for generation of coordinate control point networks based on photogrammetric processing of heterogeneous planetary images (obtained at different time, scale, with different illumination or oblique view) is developed. The technique is verified with the example for processing the heterogeneous information obtained by remote sensing of Ganymede by the spacecraft Voyager-1, -2 and Galileo. Using this technique the first 3D control point network for Ganymede is formed: the error of the altitude coordinates obtained as a result of adjustment is less than 5 km. The new control point network makes it possible to obtain basic geodesic parameters of the body (axes size) and to estimate forced librations. On the basis of the control point network, digital terrain models (DTMs) with different resolutions are generated and used for mapping the surface of Ganymede with different levels of detail (Zubarev et al., 2015b).

Automated measurement of heterogeneity in CT images of healthy and diseased rat lungs using variogram analysis of an octree decomposition

PubMed Central

2014-01-01

Background Assessing heterogeneity in lung images can be an important diagnosis tool. We present a novel and objective method for assessing lung damage in a rat model of emphysema. We combined a three-dimensional (3D) computer graphics method–octree decomposition–with a geostatistics-based approach for assessing spatial relationships–the variogram–to evaluate disease in 3D computed tomography (CT) image volumes. Methods Male, Sprague-Dawley rats were dosed intratracheally with saline (control), or with elastase dissolved in saline to either the whole lung (for mild, global disease) or a single lobe (for severe, local disease). Gated 3D micro-CT images were acquired on the lungs of all rats at end expiration. Images were masked, and octree decomposition was performed on the images to reduce the lungs to homogeneous blocks of 2 × 2 × 2, 4 × 4 × 4, and 8 × 8 × 8 voxels. To focus on lung parenchyma, small blocks were ignored because they primarily defined boundaries and vascular features, and the spatial variance between all pairs of the 8 × 8 × 8 blocks was calculated as the square of the difference of signal intensity. Variograms–graphs of distance vs. variance–were constructed, and results of a least-squares-fit were compared. The robustness of the approach was tested on images prepared with various filtering protocols. Statistical assessment of the similarity of the three control rats was made with a Kruskal-Wallis rank sum test. A Mann-Whitney-Wilcoxon rank sum test was used to measure statistical distinction between individuals. For comparison with the variogram results, the coefficient of variation and the emphysema index were also calculated for all rats. Results Variogram analysis showed that the control rats were statistically indistinct (p = 0.12), but there were significant differences between control, mild global disease, and severe local disease groups (p < 0.0001). A heterogeneity index was calculated to describe the difference of an individual variogram from the control average. This metric also showed clear separation between dose groups. The coefficient of variation and the emphysema index, on the other hand, did not separate groups. Conclusion These results suggest the octree decomposition and variogram analysis approach may be a rapid, non-subjective, and sensitive imaging-based biomarker for characterizing lung disease. PMID:24393332

Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis.

PubMed

Tse, Genevieve; Eslick, Guy D

2016-02-01

Evidence suggests that soy foods have chemoprotective properties that may reduce the risk of certain cancers such as breast and prostate cancer. However, data involving gastrointestinal (GI) have been limited, and the evidence remains controversial. This study aims to determine the potential relationship between dietary soy intake and GI cancer risk with an evaluation of the effects of isoflavone as an active soy constituent. Relevant studies were identified after literature search via electronic databases through May 2014. Subgroup analysis for isoflavone intake (studies n = 10) was performed. Covariants including gender types, anatomical subsites and preparation methods were also evaluated. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random effects model. Twenty-two case-control and 18 cohort studies were included for meta-analysis, which contained a total of 633,476 participants and 13,639 GI cancer cases. The combined OR was calculated as 0.93 (95% CI 0.87-0.99; p value heterogeneity = 0.01), showing only a slight decrease in risk, the association was stronger for colon cancer (OR 0.92; 95% CI 0.96-0.99; p value heterogeneity = 0.163) and colorectal cancer (CRC) (OR 0.92; 95% CI 0.87-0.97; p value heterogeneity = 0.3). Subgroup analysis for isoflavone intake showed a statistically significant risk reduction with a risk estimate of 0.73 (95% CI 0.59-0.92; p value heterogeneity = 0), and particularly for CRC (OR 0.76; 95% CI 0.59-0.98; p value heterogeneity = 0). This study provides evidence that soy intake as a food group is only associated with a small reduction in GI cancer risk. Separate analysis for dietary isoflavone intakes suggests a stronger inverse association.

Partial volume correction of PET-imaged tumor heterogeneity using expectation maximization with a spatially varying point spread function

PubMed Central

Barbee, David L; Flynn, Ryan T; Holden, James E; Nickles, Robert J; Jeraj, Robert

2010-01-01

Tumor heterogeneities observed in positron emission tomography (PET) imaging are frequently compromised of partial volume effects which may affect treatment prognosis, assessment, or future implementations such as biologically optimized treatment planning (dose painting). This paper presents a method for partial volume correction of PET-imaged heterogeneous tumors. A point source was scanned on a GE Discover LS at positions of increasing radii from the scanner’s center to obtain the spatially varying point spread function (PSF). PSF images were fit in three dimensions to Gaussian distributions using least squares optimization. Continuous expressions were devised for each Gaussian width as a function of radial distance, allowing for generation of the system PSF at any position in space. A spatially varying partial volume correction (SV-PVC) technique was developed using expectation maximization (EM) and a stopping criterion based on the method’s correction matrix generated for each iteration. The SV-PVC was validated using a standard tumor phantom and a tumor heterogeneity phantom, and was applied to a heterogeneous patient tumor. SV-PVC results were compared to results obtained from spatially invariant partial volume correction (SINV-PVC), which used directionally uniform three dimensional kernels. SV-PVC of the standard tumor phantom increased the maximum observed sphere activity by 55 and 40% for 10 and 13 mm diameter spheres, respectively. Tumor heterogeneity phantom results demonstrated that as net changes in the EM correction matrix decreased below 35%, further iterations improved overall quantitative accuracy by less than 1%. SV-PVC of clinically observed tumors frequently exhibited changes of ±30% in regions of heterogeneity. The SV-PVC method implemented spatially varying kernel widths and automatically determined the number of iterations for optimal restoration, parameters which are arbitrarily chosen in SINV-PVC. Comparing SV-PVC to SINV-PVC demonstrated that similar results could be reached using both methods, but large differences result for the arbitrary selection of SINV-PVC parameters. The presented SV-PVC method was performed without user intervention, requiring only a tumor mask as input. Research involving PET-imaged tumor heterogeneity should include correcting for partial volume effects to improve the quantitative accuracy of results. PMID:20009194

Linnorm: improved statistical analysis for single cell RNA-seq expression data.

PubMed

Yip, Shun H; Wang, Panwen; Kocher, Jean-Pierre A; Sham, Pak Chung; Wang, Junwen

2017-12-15

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Stochastic multi-scale models of competition within heterogeneous cellular populations: Simulation methods and mean-field analysis.

PubMed

Cruz, Roberto de la; Guerrero, Pilar; Spill, Fabian; Alarcón, Tomás

2016-10-21

We propose a modelling framework to analyse the stochastic behaviour of heterogeneous, multi-scale cellular populations. We illustrate our methodology with a particular example in which we study a population with an oxygen-regulated proliferation rate. Our formulation is based on an age-dependent stochastic process. Cells within the population are characterised by their age (i.e. time elapsed since they were born). The age-dependent (oxygen-regulated) birth rate is given by a stochastic model of oxygen-dependent cell cycle progression. Once the birth rate is determined, we formulate an age-dependent birth-and-death process, which dictates the time evolution of the cell population. The population is under a feedback loop which controls its steady state size (carrying capacity): cells consume oxygen which in turn fuels cell proliferation. We show that our stochastic model of cell cycle progression allows for heterogeneity within the cell population induced by stochastic effects. Such heterogeneous behaviour is reflected in variations in the proliferation rate. Within this set-up, we have established three main results. First, we have shown that the age to the G1/S transition, which essentially determines the birth rate, exhibits a remarkably simple scaling behaviour. Besides the fact that this simple behaviour emerges from a rather complex model, this allows for a huge simplification of our numerical methodology. A further result is the observation that heterogeneous populations undergo an internal process of quasi-neutral competition. Finally, we investigated the effects of cell-cycle-phase dependent therapies (such as radiation therapy) on heterogeneous populations. In particular, we have studied the case in which the population contains a quiescent sub-population. Our mean-field analysis and numerical simulations confirm that, if the survival fraction of the therapy is too high, rescue of the quiescent population occurs. This gives rise to emergence of resistance to therapy since the rescued population is less sensitive to therapy. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intermediate Scale Laboratory Testing to Understand Mechanisms of Capillary and Dissolution Trapping during Injection and Post-Injection of CO 2 in Heterogeneous Geological Formations

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

Illangasekare, Tissa; Trevisan, Luca; Agartan, Elif

2015-03-31

Carbon Capture and Storage (CCS) represents a technology aimed to reduce atmospheric loading of CO 2 from power plants and heavy industries by injecting it into deep geological formations, such as saline aquifers. A number of trapping mechanisms contribute to effective and secure storage of the injected CO 2 in supercritical fluid phase (scCO 2) in the formation over the long term. The primary trapping mechanisms are structural, residual, dissolution and mineralization. Knowledge gaps exist on how the heterogeneity of the formation manifested at all scales from the pore to the site scales affects trapping and parameterization of contributing mechanismsmore » in models. An experimental and modeling study was conducted to fill these knowledge gaps. Experimental investigation of fundamental processes and mechanisms in field settings is not possible as it is not feasible to fully characterize the geologic heterogeneity at all relevant scales and gathering data on migration, trapping and dissolution of scCO 2. Laboratory experiments using scCO 2 under ambient conditions are also not feasible as it is technically challenging and cost prohibitive to develop large, two- or three-dimensional test systems with controlled high pressures to keep the scCO 2 as a liquid. Hence, an innovative approach that used surrogate fluids in place of scCO 2 and formation brine in multi-scale, synthetic aquifers test systems ranging in scales from centimeter to meter scale developed used. New modeling algorithms were developed to capture the processes controlled by the formation heterogeneity, and they were tested using the data from the laboratory test systems. The results and findings are expected to contribute toward better conceptual models, future improvements to DOE numerical codes, more accurate assessment of storage capacities, and optimized placement strategies. This report presents the experimental and modeling methods and research results.« less

Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder.

PubMed

Kessler, R C; van Loo, H M; Wardenaar, K J; Bossarte, R M; Brenner, L A; Ebert, D D; de Jonge, P; Nierenberg, A A; Rosellini, A J; Sampson, N A; Schoevers, R A; Wilcox, M A; Zaslavsky, A M

2017-02-01

Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful. We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalised) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments. Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention v. control) or differential treatment outcomes (i.e., intervention A v. intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalised treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials. Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment studies, applying and refining these models in subsequent pragmatic trials, carrying out pooled secondary analyses to extract the maximum amount of information from these coordinated studies, and using this information to focus future discovery efforts in the segment of the patient population in which continued uncertainty about treatment response exists.

A loosely coupled framework for terminology controlled distributed EHR search for patient cohort identification in clinical research.

PubMed

Zhao, Lei; Lim Choi Keung, Sarah N; Taweel, Adel; Tyler, Edward; Ogunsina, Ire; Rossiter, James; Delaney, Brendan C; Peterson, Kevin A; Hobbs, F D Richard; Arvanitis, Theodoros N

2012-01-01

Heterogeneous data models and coding schemes for electronic health records present challenges for automated search across distributed data sources. This paper describes a loosely coupled software framework based on the terminology controlled approach to enable the interoperation between the search interface and heterogeneous data sources. Software components interoperate via common terminology service and abstract criteria model so as to promote component reuse and incremental system evolution.

Control of finite critical behaviour in a small-scale social system

NASA Astrophysics Data System (ADS)

Daniels, Bryan C.; Krakauer, David C.; Flack, Jessica C.

2017-02-01

Many adaptive systems sit near a tipping or critical point. For systems near a critical point small changes to component behaviour can induce large-scale changes in aggregate structure and function. Criticality can be adaptive when the environment is changing, but entails reduced robustness through sensitivity. This tradeoff can be resolved when criticality can be tuned. We address the control of finite measures of criticality using data on fight sizes from an animal society model system (Macaca nemestrina, n=48). We find that a heterogeneous, socially organized system, like homogeneous, spatial systems (flocks and schools), sits near a critical point; the contributions individuals make to collective phenomena can be quantified; there is heterogeneity in these contributions; and distance from the critical point (DFC) can be controlled through biologically plausible mechanisms exploiting heterogeneity. We propose two alternative hypotheses for why a system decreases the distance from the critical point.

Organizational heterogeneity of vertebrate genomes.

PubMed

Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

2012-01-01

Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

A new time domain random walk method for solute transport in 1-D heterogeneous media

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

Banton, O.; Delay, F.; Porel, G.

A new method to simulate solute transport in 1-D heterogeneous media is presented. This time domain random walk method (TDRW), similar in concept to the classical random walk method, calculates the arrival time of a particle cloud at a given location (directly providing the solute breakthrough curve). The main advantage of the method is that the restrictions on the space increments and the time steps which exist with the finite differences and random walk methods are avoided. In a homogeneous zone, the breakthrough curve (BTC) can be calculated directly at a given distance using a few hundred particles or directlymore » at the boundary of the zone. Comparisons with analytical solutions and with the classical random walk method show the reliability of this method. The velocity and dispersivity calculated from the simulated results agree within two percent with the values used as input in the model. For contrasted heterogeneous media, the random walk can generate high numerical dispersion, while the time domain approach does not.« less

Field Effect Modulation of Heterogeneous Charge Transfer Kinetics at Back-Gated Two-Dimensional MoS2 Electrodes.

PubMed

Wang, Yan; Kim, Chang-Hyun; Yoo, Youngdong; Johns, James E; Frisbie, C Daniel

2017-12-13

The ability to improve and to modulate the heterogeneous charge transfer kinetics of two-dimensional (2D) semiconductors, such as MoS 2 , is a major challenge for electrochemical and photoelectrochemical applications of these materials. Here we report a continuous and reversible physical method for modulating the heterogeneous charge transfer kinetics at a monolayer MoS 2 working electrode supported on a SiO 2 /p-Si substrate. The heavily doped p-Si substrate serves as a back gate electrode; application of a gate voltage (V BG ) to p-Si tunes the electron occupation in the MoS 2 conduction band and shifts the conduction band edge position relative to redox species dissolved in electrolyte in contact with the front side of the MoS 2 . The gate modulation of both charge density and energy band alignment impacts charge transfer kinetics as measured by cyclic voltammetry (CV). Specifically, cyclic voltammograms combined with numerical simulations suggest that the standard heterogeneous charge transfer rate constant (k 0 ) for MoS 2 in contact with the ferrocene/ferrocenium (Fc 0/+ ) redox couple can be modulated by over 2 orders of magnitude from 4 × 10 -6 to 1 × 10 -3 cm/s, by varying V BG . In general, the field effect offers the potential to tune the electrochemical properties of 2D semiconductors, opening up new possibilities for fundamental studies of the relationship between charge transfer kinetics and independently controlled electronic band alignment and band occupation.

Genetic Heterogeneity of Self-Reported Ancestry Groups in an Admixed Brazilian Population

PubMed Central

Lins, Tulio C; Vieira, Rodrigo G; Abreu, Breno S; Gentil, Paulo; Moreno-Lima, Ricardo; Oliveira, Ricardo J; Pereira, Rinaldo W

2011-01-01

Background Population stratification is the main source of spurious results and poor reproducibility in genetic association findings. Population heterogeneity can be controlled for by grouping individuals in ethnic clusters; however, in admixed populations, there is evidence that such proxies do not provide efficient stratification control. The aim of this study was to evaluate the relation of self-reported with genetic ancestry and the statistical risk of grouping an admixed sample based on self-reported ancestry. Methods A questionnaire that included an item on self-reported ancestry was completed by 189 female volunteers from an admixed Brazilian population. Individual genetic ancestry was then determined by genotyping ancestry informative markers. Results Self-reported ancestry was classified as white, intermediate, and black. The mean difference among self-reported groups was significant for European and African, but not Amerindian, genetic ancestry. Pairwise fixation index analysis revealed a significant difference among groups. However, the increase in the chance of type 1 error was estimated to be 14%. Conclusions Self-reporting of ancestry was not an appropriate methodology to cluster groups in a Brazilian population, due to high variance at the individual level. Ancestry informative markers are more useful for quantitative measurement of biological ancestry. PMID:21498954

Innovative Sol-Gel Routes for the Bottom-up Preparation of Heterogeneous Catalysts.

PubMed

Debecker, Damien P

2017-12-11

Heterogeneous catalysts can be prepared by different methods offering various levels of control on the final properties of the solid. In this account, we exemplify bottom-up preparation routes that are based on the sol-gel chemistry and allow to tailor some decisive properties of solid catalysts. First, an emulsion templating strategy is shown to lead to macrocellular self-standing monoliths with a macroscopic 3D structure. The latter can be used as catalyst or catalyst supports in flow chemistry, without requiring any subsequent shaping step. Second, the aerosol-assisted sol-gel process allows for the one-step and continuous production of porous mixed oxides. Tailored textural properties can be obtained together with an excellent control on composition and homogeneity. Third, the application of non-hydrolytic sol-gel routes, in the absence of water, leads to mixed oxides with outstanding textural properties and with peculiar surface chemistry. In all cases, the resulting catalytic performance can be correlated with the specificities of the preparation routes presented. This is exemplified in catalytic reactions in the fields of biomass conversion, petro chemistry, enantioselective organic synthesis, and air pollution mitigation. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bias of apparent tracer ages in heterogeneous environments.

PubMed

McCallum, James L; Cook, Peter G; Simmons, Craig T; Werner, Adrian D

2014-01-01

The interpretation of apparent ages often assumes that a water sample is composed of a single age. In heterogeneous aquifers, apparent ages estimated with environmental tracer methods do not reflect mean water ages because of the mixing of waters from many flow paths with different ages. This is due to nonlinear variations in atmospheric concentrations of the tracer with time resulting in biases of mixed concentrations used to determine apparent ages. The bias of these methods is rarely reported and has not been systematically evaluated in heterogeneous settings. We simulate residence time distributions (RTDs) and environmental tracers CFCs, SF6 , (85) Kr, and (39) Ar in synthetic heterogeneous confined aquifers and compare apparent ages to mean ages. Heterogeneity was simulated as both K-field variance (σ(2) ) and structure. We demonstrate that an increase in heterogeneity (increase in σ(2) or structure) results in an increase in the width of the RTD. In low heterogeneity cases, widths were generally on the order of 10 years and biases generally less than 10%. In high heterogeneity cases, widths can reach 100 s of years and biases can reach up to 100%. In cases where the temporal variations of atmospheric concentration of individual tracers vary, different patterns of bias are observed for the same mean age. We show that CFC-12 and CFC-113 ages may be used to correct for the mean age if analytical errors are small. © 2013, National Ground Water Association.

Adaptive adjustment of the randomization ratio using historical control data.

PubMed

Hobbs, Brian P; Carlin, Bradley P; Sargent, Daniel J

2013-01-01

Prospective trial design often occurs in the presence of 'acceptable' historical control data. Typically, these data are only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al., succeeded a similar trial reported by Saltz et al., and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS), characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial's frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure lead to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on preexisting information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare.

Dissecting cancer evolution at the macro-heterogeneity and micro-heterogeneity scale.

PubMed

Barber, Louise J; Davies, Matthew N; Gerlinger, Marco

2015-02-01

Intratumour heterogeneity complicates biomarker discovery and treatment personalization, and pervasive cancer evolution is a key mechanism leading to therapy failure and patient death. Thus, understanding subclonal heterogeneity architectures and cancer evolution processes is critical for the development of effective therapeutic approaches which can control or thwart cancer evolutionary plasticity. Current insights into heterogeneity are mainly limited to the macroheterogeneity level, established by cancer subclones that have undergone significant clonal expansion. Novel single cell sequencing and blood-based subclonal tracking technologies are enabling detailed insights into microheterogeneity and the dynamics of clonal evolution. We assess how this starts to delineate the rules governing cancer evolution and novel angles for more effective therapeutic intervention. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

PubMed Central

2011-01-01

Background Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Methods Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. Results The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively). No SNP reached genome-wide significance in the combined analyses of all the panels. Conclusions This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations. PMID:21995314

Blasting methods for heterogeneous rocks in hillside open-pit mines with high and steep slopes

NASA Astrophysics Data System (ADS)

Chen, Y. J.; Chang, Z. G.; Chao, X. H.; Zhao, J. F.

2017-06-01

In the arid desert areas in Xinjiang, most limestone quarries are hillside open-pit mines (OPMs) where the limestone is hard, heterogeneous, and fractured, and can be easily broken into large blocks by blasting. This study tried to find effective technical methods for blasting heterogeneous rocks in such quarries based on an investigation into existing problems encountered in actual mining at Hongshun Limestone Quarry in Xinjiang. This study provided blasting schemes for hillside OPMs with different heights and slopes. These schemes involve the use of vertical deep holes, oblique shallow holes, and downslope hole-by-hole sublevel or simultaneous detonation techniques. In each bench, the detonations of holes in a detonation unit occur at intervals of 25-50 milliseconds. The research findings can offer technical guidance on how to blast heterogeneous rocks in hillside limestone quarries.

Heterogeneity and frequency of BRAF mutations in primary melanoma: Comparison between molecular methods and immunohistochemistry

PubMed Central

Bruno, William; Martinuzzi, Claudia; Andreotti, Virginia; Pastorino, Lorenza; Spagnolo, Francesco; Dalmasso, Bruna; Cabiddu, Francesco; Gualco, Marina; Ballestrero, Alberto; Bianchi-Scarrà, Giovanna; Queirolo, Paola

2017-01-01

Finding the best technique to identify BRAF mutations with a high sensitivity and specificity is mandatory for accurate patient selection for target therapy. BRAF mutation frequency ranges from 40 to 60% depending on melanoma clinical characteristics and detection technique used. Intertumoral heterogeneity could lead to misinterpretation of BRAF mutational status; this is especially important if testing is performed on primary specimens, when metastatic lesions are unavailable. Aim of this study was to identify the best combination of methods for detecting BRAF mutations (among peptide nucleic acid – PNA-clamping real-time PCR, immunohistochemistry and capillary sequencing) and investigate BRAF mutation heterogeneity in a series of 100 primary melanomas and a subset of 25 matched metastatic samples. Overall, we obtained a BRAF mutation frequency of 62%, based on the combination of at least two techniques. Concordance between mutation status in primary and metastatic tumor was good but not complete (67%), when agreement of at least two techniques were considered. Next generation sequencing was used to quantify the threshold of detected mutant alleles in discordant samples. Combining different methods excludes that the observed heterogeneity is technique-based. We propose an algorithm for BRAF mutation testing based on agreement between immunohistochemistry and PNA; a third molecular method could be added in case of discordance of the results. Testing the primary tumor when the metastatic sample is unavailable is a good option if at least two methods of detection are used, however the presence of intertumoral heterogeneity or the occurrence of additional primaries should be carefully considered. PMID:28039443

Automation of multi-agent control for complex dynamic systems in heterogeneous computational network

NASA Astrophysics Data System (ADS)

Oparin, Gennady; Feoktistov, Alexander; Bogdanova, Vera; Sidorov, Ivan

2017-01-01

The rapid progress of high-performance computing entails new challenges related to solving large scientific problems for various subject domains in a heterogeneous distributed computing environment (e.g., a network, Grid system, or Cloud infrastructure). The specialists in the field of parallel and distributed computing give the special attention to a scalability of applications for problem solving. An effective management of the scalable application in the heterogeneous distributed computing environment is still a non-trivial issue. Control systems that operate in networks, especially relate to this issue. We propose a new approach to the multi-agent management for the scalable applications in the heterogeneous computational network. The fundamentals of our approach are the integrated use of conceptual programming, simulation modeling, network monitoring, multi-agent management, and service-oriented programming. We developed a special framework for an automation of the problem solving. Advantages of the proposed approach are demonstrated on the parametric synthesis example of the static linear regulator for complex dynamic systems. Benefits of the scalable application for solving this problem include automation of the multi-agent control for the systems in a parallel mode with various degrees of its detailed elaboration.

Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

PubMed Central

Ouellette, Marie-Hélène

2016-01-01

The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis. PMID:27821782

Impact of mechanical heterogeneity on joint density in a welded ignimbrite

NASA Astrophysics Data System (ADS)

Soden, A. M.; Lunn, R. J.; Shipton, Z. K.

2016-08-01

Joints are conduits for groundwater, hydrocarbons and hydrothermal fluids. Robust fluid flow models rely on accurate characterisation of joint networks, in particular joint density. It is generally assumed that the predominant factor controlling joint density in layered stratigraphy is the thickness of the mechanical layer where the joints occur. Mechanical heterogeneity within the layer is considered a lesser influence on joint formation. We analysed the frequency and distribution of joints within a single 12-m thick ignimbrite layer to identify the controls on joint geometry and distribution. The observed joint distribution is not related to the thickness of the ignimbrite layer. Rather, joint initiation, propagation and termination are controlled by the shape, spatial distribution and mechanical properties of fiamme, which are present within the ignimbrite. The observations and analysis presented here demonstrate that models of joint distribution, particularly in thicker layers, that do not fully account for mechanical heterogeneity are likely to underestimate joint density, the spatial variability of joint distribution and the complex joint geometries that result. Consequently, we recommend that characterisation of a layer's compositional and material properties improves predictions of subsurface joint density in rock layers that are mechanically heterogeneous.

Enhanced biodegradation by hydraulic heterogeneities in petroleum hydrocarbon plumes.

PubMed

Bauer, Robert D; Rolle, Massimo; Bauer, Sebastian; Eberhardt, Christina; Grathwohl, Peter; Kolditz, Olaf; Meckenstock, Rainer U; Griebler, Christian

2009-02-27

In case of dissolved electron donors and acceptors, natural attenuation of organic contaminant plumes in aquifers is governed by hydrodynamic mixing and microbial activity. Main objectives of this work were (i) to determine whether aerobic and anaerobic biodegradation in porous sediments is controlled by transverse dispersion, (ii) to elucidate the effect of sediment heterogeneity on mixing and biodegradation, and (iii) to search for degradation-limiting factors. Comparative experiments were conducted in two-dimensional sediment microcosms. Aerobic toluene and later ethylbenzene degradation by Pseudomonas putida strain F1 was initially followed in a plume developing from oxic to anoxic conditions and later under steady-state mixing-controlled conditions. Competitive anaerobic degradation was then initiated by introduction of the denitrifying strain Aromatoleum aromaticum EbN1. In homogeneous sand, aerobic toluene degradation was clearly controlled by dispersive mixing. Similarly, under denitrifying conditions, microbial activity was located at the plume's fringes. Sediment heterogeneity caused flow focusing and improved the mixing of reactants. Independent from the electron accepting process, net biodegradation was always higher in the heterogeneous setting with a calculated efficiency plus of 23-100% as compared to the homogeneous setup. Flow and reactive transport model simulations were performed in order to interpret and evaluate the experimental results.

Altered Error-Related Activity in Patients with Schizophrenia

ERIC Educational Resources Information Center

Koch, Kathrin; Wagner, Gerd; Schultz, Christoph; Schachtzabel, Claudia; Nenadic, Igor; Axer, Martina; Reichenbach, Jurgen R.; Sauer, Heinrich; Schlosser, Ralf G. M.

2009-01-01

Deficits in working memory (WM) and executive cognitive control are core features of schizophrenia. However, findings regarding functional activation strengths are heterogeneous, partly due to differences in task demands and behavioral performance. Previous investigators proposed integrating these heterogeneous findings into a comprehensive model…

SU-E-T-626: Accuracy of Dose Calculation Algorithms in MultiPlan Treatment Planning System in Presence of Heterogeneities

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

Moignier, C; Huet, C; Barraux, V

Purpose: Advanced stereotactic radiotherapy (SRT) treatments require accurate dose calculation for treatment planning especially for treatment sites involving heterogeneous patient anatomy. The purpose of this study was to evaluate the accuracy of dose calculation algorithms, Raytracing and Monte Carlo (MC), implemented in the MultiPlan treatment planning system (TPS) in presence of heterogeneities. Methods: First, the LINAC of a CyberKnife radiotherapy facility was modeled with the PENELOPE MC code. A protocol for the measurement of dose distributions with EBT3 films was established and validated thanks to comparison between experimental dose distributions and calculated dose distributions obtained with MultiPlan Raytracing and MCmore » algorithms as well as with the PENELOPE MC model for treatments planned with the homogenous Easycube phantom. Finally, bones and lungs inserts were used to set up a heterogeneous Easycube phantom. Treatment plans with the 10, 7.5 or the 5 mm field sizes were generated in Multiplan TPS with different tumor localizations (in the lung and at the lung/bone/soft tissue interface). Experimental dose distributions were compared to the PENELOPE MC and Multiplan calculations using the gamma index method. Results: Regarding the experiment in the homogenous phantom, 100% of the points passed for the 3%/3mm tolerance criteria. These criteria include the global error of the method (CT-scan resolution, EBT3 dosimetry, LINAC positionning …), and were used afterwards to estimate the accuracy of the MultiPlan algorithms in heterogeneous media. Comparison of the dose distributions obtained in the heterogeneous phantom is in progress. Conclusion: This work has led to the development of numerical and experimental dosimetric tools for small beam dosimetry. Raytracing and MC algorithms implemented in MultiPlan TPS were evaluated in heterogeneous media.« less

Cell adhesion heterogeneity reinforces tumour cell dissemination: novel insights from a mathematical model.

PubMed

Reher, David; Klink, Barbara; Deutsch, Andreas; Voss-Böhme, Anja

2017-08-11

Cancer cell invasion, dissemination, and metastasis have been linked to an epithelial-mesenchymal transition (EMT) of individual tumour cells. During EMT, adhesion molecules like E-cadherin are downregulated and the decrease of cell-cell adhesion allows tumour cells to dissociate from the primary tumour mass. This complex process depends on intracellular cues that are subject to genetic and epigenetic variability, as well as extrinsic cues from the local environment resulting in a spatial heterogeneity in the adhesive phenotype of individual tumour cells. Here, we use a novel mathematical model to study how adhesion heterogeneity, influenced by intrinsic and extrinsic factors, affects the dissemination of tumour cells from an epithelial cell population. The model is a multiscale cellular automaton that couples intracellular adhesion receptor regulation with cell-cell adhesion. Simulations of our mathematical model indicate profound effects of adhesion heterogeneity on tumour cell dissemination. In particular, we show that a large variation of intracellular adhesion receptor concentrations in a cell population reinforces cell dissemination, regardless of extrinsic cues mediated through the local cell density. However, additional control of adhesion receptor concentration through the local cell density, which can be assumed in healthy cells, weakens the effect. Furthermore, we provide evidence that adhesion heterogeneity can explain the remarkable differences in adhesion receptor concentrations of epithelial and mesenchymal phenotypes observed during EMT and might drive early dissemination of tumour cells. Our results suggest that adhesion heterogeneity may be a universal trigger to reinforce cell dissemination in epithelial cell populations. This effect can be at least partially compensated by a control of adhesion receptor regulation through neighbouring cells. Accordingly, our findings explain how both an increase in intra-tumour adhesion heterogeneity and the loss of control through the local environment can promote tumour cell dissemination. This article was reviewed by Hanspeter Herzel, Thomas Dandekar and Marek Kimmel.

Using Length of Stay to Control for Unobserved Heterogeneity When Estimating Treatment Effect on Hospital Costs with Observational Data: Issues of Reliability, Robustness, and Usefulness.

PubMed

May, Peter; Garrido, Melissa M; Cassel, J Brian; Morrison, R Sean; Normand, Charles

2016-10-01

To evaluate the sensitivity of treatment effect estimates when length of stay (LOS) is used to control for unobserved heterogeneity when estimating treatment effect on cost of hospital admission with observational data. We used data from a prospective cohort study on the impact of palliative care consultation teams (PCCTs) on direct cost of hospital care. Adult patients with an advanced cancer diagnosis admitted to five large medical and cancer centers in the United States between 2007 and 2011 were eligible for this study. Costs were modeled using generalized linear models with a gamma distribution and a log link. We compared variability in estimates of PCCT impact on hospitalization costs when LOS was used as a covariate, as a sample parameter, and as an outcome denominator. We used propensity scores to account for patient characteristics associated with both PCCT use and total direct hospitalization costs. We analyzed data from hospital cost databases, medical records, and questionnaires. Our propensity score weighted sample included 969 patients who were discharged alive. In analyses of hospitalization costs, treatment effect estimates are highly sensitive to methods that control for LOS, complicating interpretation. Both the magnitude and significance of results varied widely with the method of controlling for LOS. When we incorporated intervention timing into our analyses, results were robust to LOS-controls. Treatment effect estimates using LOS-controls are not only suboptimal in terms of reliability (given concerns over endogeneity and bias) and usefulness (given the need to validate the cost-effectiveness of an intervention using overall resource use for a sample defined at baseline) but also in terms of robustness (results depend on the approach taken, and there is little evidence to guide this choice). To derive results that minimize endogeneity concerns and maximize external validity, investigators should match and analyze treatment and comparison arms on baseline factors only. Incorporating intervention timing may deliver results that are more reliable, more robust, and more useful than those derived using LOS-controls. © Health Research and Educational Trust.

Challenges of CAC in Heterogeneous Wireless Cognitive Networks

NASA Astrophysics Data System (ADS)

Wang, Jiazheng; Fu, Xiuhua

Call admission control (CAC) is known as an effective functionality in ensuring the QoS of wireless networks. The vision of next generation wireless networks has led to the development of new call admission control (CAC) algorithms specifically designed for heterogeneous wireless Cognitive networks. However, there will be a number of challenges created by dynamic spectrum access and scheduling techniques associated with the cognitive systems. In this paper for the first time, we recommend that the CAC policies should be distinguished between primary users and secondary users. The classification of different methods of cac policies in cognitive networks contexts is proposed. Although there have been some researches within the umbrella of Joint CAC and cross-layer optimization for wireless networks, the advent of the cognitive networks adds some additional problems. We present the conceptual models for joint CAC and cross-layer optimization respectively. Also, the benefit of Cognition can only be realized fully if application requirements and traffic flow contexts are determined or inferred in order to know what modes of operation and spectrum bands to use at each point in time. The process model of Cognition involved per-flow-based CAC is presented. Because there may be a number of parameters on different levels affecting a CAC decision and the conditions for accepting or rejecting a call must be computed quickly and frequently, simplicity and practicability are particularly important for designing a feasible CAC algorithm. In a word, a more thorough understanding of CAC in heterogeneous wireless cognitive networks may help one to design better CAC algorithms.

A physiology-based model describing heterogeneity in glucose metabolism: the core of the Eindhoven Diabetes Education Simulator (E-DES).

PubMed

Maas, Anne H; Rozendaal, Yvonne J W; van Pul, Carola; Hilbers, Peter A J; Cottaar, Ward J; Haak, Harm R; van Riel, Natal A W

2015-03-01

Current diabetes education methods are costly, time-consuming, and do not actively engage the patient. Here, we describe the development and verification of the physiological model for healthy subjects that forms the basis of the Eindhoven Diabetes Education Simulator (E-DES). E-DES shall provide diabetes patients with an individualized virtual practice environment incorporating the main factors that influence glycemic control: food, exercise, and medication. The physiological model consists of 4 compartments for which the inflow and outflow of glucose and insulin are calculated using 6 nonlinear coupled differential equations and 14 parameters. These parameters are estimated on 12 sets of oral glucose tolerance test (OGTT) data (226 healthy subjects) obtained from literature. The resulting parameter set is verified on 8 separate literature OGTT data sets (229 subjects). The model is considered verified if 95% of the glucose data points lie within an acceptance range of ±20% of the corresponding model value. All glucose data points of the verification data sets lie within the predefined acceptance range. Physiological processes represented in the model include insulin resistance and β-cell function. Adjusting the corresponding parameters allows to describe heterogeneity in the data and shows the capabilities of this model for individualization. We have verified the physiological model of the E-DES for healthy subjects. Heterogeneity of the data has successfully been modeled by adjusting the 4 parameters describing insulin resistance and β-cell function. Our model will form the basis of a simulator providing individualized education on glucose control. © 2014 Diabetes Technology Society.

A Modular Environment for Geophysical Inversion and Run-time Autotuning using Heterogeneous Computing Systems

NASA Astrophysics Data System (ADS)

Myre, Joseph M.

Heterogeneous computing systems have recently come to the forefront of the High-Performance Computing (HPC) community's interest. HPC computer systems that incorporate special purpose accelerators, such as Graphics Processing Units (GPUs), are said to be heterogeneous. Large scale heterogeneous computing systems have consistently ranked highly on the Top500 list since the beginning of the heterogeneous computing trend. By using heterogeneous computing systems that consist of both general purpose processors and special- purpose accelerators, the speed and problem size of many simulations could be dramatically increased. Ultimately this results in enhanced simulation capabilities that allows, in some cases for the first time, the execution of parameter space and uncertainty analyses, model optimizations, and other inverse modeling techniques that are critical for scientific discovery and engineering analysis. However, simplifying the usage and optimization of codes for heterogeneous computing systems remains a challenge. This is particularly true for scientists and engineers for whom understanding HPC architectures and undertaking performance analysis may not be primary research objectives. To enable scientists and engineers to remain focused on their primary research objectives, a modular environment for geophysical inversion and run-time autotuning on heterogeneous computing systems is presented. This environment is composed of three major components: 1) CUSH---a framework for reducing the complexity of programming heterogeneous computer systems, 2) geophysical inversion routines which can be used to characterize physical systems, and 3) run-time autotuning routines designed to determine configurations of heterogeneous computing systems in an attempt to maximize the performance of scientific and engineering codes. Using three case studies, a lattice-Boltzmann method, a non-negative least squares inversion, and a finite-difference fluid flow method, it is shown that this environment provides scientists and engineers with means to reduce the programmatic complexity of their applications, to perform geophysical inversions for characterizing physical systems, and to determine high-performing run-time configurations of heterogeneous computing systems using a run-time autotuner.

Research Results Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

NASA Astrophysics Data System (ADS)

2009-01-01

Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

State-of-the-art Nanofabrication in Catalysis.

PubMed

Karim, Waiz; Tschupp, Simon A; Herranz, Juan; Schmidt, Thomas J; Ekinci, Yasin; van Bokhovenac, Jeroen A

2017-04-26

We present recent developments in top-down nanofabrication that have found application in catalysis research. To unravel the complexity of catalytic systems, the design and use of models with control of size, morphology, shape and inter-particle distances is a necessity. The study of well-defined and ordered nanoparticles on a support contributes to the understanding of complex phenomena that govern reactions in heterogeneous and electro-catalysis. We review the strengths and limitations of different nanolithography methods such as electron beam lithography (EBL), photolithography, extreme ultraviolet (EUV) lithography and colloidal lithography for the creation of such highly tunable catalytic model systems and their applications in catalysis. Innovative strategies have enabled particle sizes reaching dimensions below 10 nm. It is now possible to create pairs of particles with distance controlled with an extremely high precision in the order of one nanometer. We discuss our approach to study these model systems at the single-particle level using X-ray absorption spectroscopy and show new ways to fabricate arrays of single nanoparticles or nanoparticles in pairs over a large area using EBL and EUV-achromatic Talbot lithography. These advancements have provided new insights into the active sites in metal catalysts and enhanced the understanding of the role of inter-particle interactions and catalyst supports, such as in the phenomenon of hydrogen spillover. We present a perspective on future directions for employing top-down nanofabrication in heterogeneous and electrocatalysis. The rapid development in nanofabrication and characterization methods will continue to have an impact on understanding of complex catalytic processes.

HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case-control studies.

PubMed

Lu, Su; Wang, Zhanwei; Liu, Hong; Hao, Xishan

2010-12-01

Proto-oncogene HER2 (also known as erbB-2 or neu) plays an important role in the carcinogenesis and the prognosis of breast cancer. Many epidemiological studies have been conducted to explore the association between the HER2 Ile655Val polymorphism and breast cancer risk. However, inconsistency existed in the results. Therefore, we performed a meta-analysis of 27 published case-control studies including 11,504 cases and 12,538 controls. We assessed the strength of the association by crude odds ratios (ORs) with 95% confidence intervals (CIs) and reached a result that HER2 Ile655Val polymorphism was associated with an increased breast cancer risk in overall populations (for Ile/Val vs. Ile/Ile: OR = 1.05, 95% CI = 1.00-1.12, P = 0.07 for heterogeneity; for the dominant model Ile/Val + Val/Val vs. Ile/Ile: OR = 1.10, 95% CI = 1.01-1.20, P = 0.01 for heterogeneity). In subgroup analysis by ethnicity, we found a significant association among Africans (for Val/Val vs. Ile/Ile: OR = .78, 95% CI = 1.94-39.72, P = 0.35 for heterogeneity; for the recessive model Val/Val vs. Ile/Val +Ile/Ile: OR = 8.60, 95% CI = 1.92-38.48, P = 0.31 for heterogeneity) and Asians (for Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01-1.39, P = 0.41 for heterogeneity; for the dominant model Val/Val + Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01-1.38, P = 0.27 for heterogeneity). In conclusion, our meta-analysis suggests that HER2 Ile 655Val polymorphism may contribute to breast cancer risk.

Fourier Transformed Infra-Red Imaging of Femoral Neck Bone: Reduced Heterogeneity of Mineral-to-Matrix and Carbonate-to-Phosphate and more Variable Crystallinity in Treatment-Naïve Fracture Cases compared to Fracture-Free Controls

PubMed Central

Gourion-Arsiquaud, Samuel; Lukashova, Lyudmilla; Power, Jon; Loveridge, Nigel; Reeve, Jonathan; Boskey, Adele L.

2012-01-01

After age 60 hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier Transform Infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and non-fractured bones. Whole femoral neck cross sections, divided into quadrants along the neck’s axis, from 10 women with hip fracture and 10 cadaveric controls were studied using FTIRI and micro-computed Tomography. Although 3-dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix ratio was reduced in the cases of hip fracture, confirming previous reports. New findings were that the FTIRI microscopic variation (heterogeneity) of the mineral-to-matrix ratio was substantially reduced in the fracture group as was the heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity of crystallinity was increased. Increased variation of crystallinity was statistically associated with reduced variation of the carbonate-to-phosphate ratio. Anatomical variation in these properties between the different femoral neck quadrants was reduced in the fracture group compared to controls. While our treatment-naïve patients had reduced rather than increased bending resistance, these changes in heterogeneity associated with hip fracture are in another way comparable to the effects of experimental bisphosphonate therapy, which decreases heterogeneity and other indicators of bone’s toughness as a material. PMID:22865771

Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls.

PubMed

Gourion-Arsiquaud, Samuel; Lukashova, Lyudmilla; Power, Jon; Loveridge, Nigel; Reeve, Jonathan; Boskey, Adele L

2013-01-01

After the age of 60 years, hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced bone mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier transform infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and nonfractured bones. Whole femoral neck cross sections, divided into quadrants along the neck's axis, from 10 women with hip fracture and 10 cadaveric controls were studied using FTIRI and micro-computed tomography. Although 3-dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix ratio was reduced in the cases of hip fracture, confirming previous reports. New findings were that the FTIRI microscopic variation (heterogeneity) of the mineral-to-matrix ratio was substantially reduced in the fracture group as was the heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity of crystallinity was increased. Increased variation of crystallinity was statistically associated with reduced variation of the carbonate-to-phosphate ratio. Anatomical variation in these properties between the different femoral neck quadrants was reduced in the fracture group compared with controls. Although our treatment-naive patients had reduced rather than increased bending resistance, these changes in heterogeneity associated with hip fracture are in another way comparable to the effects of experimental bisphosphonate therapy, which decreases heterogeneity and other indicators of bone's toughness as a material. Copyright © 2013 American Society for Bone and Mineral Research.

An Efficient Multiscale Finite-Element Method for Frequency-Domain Seismic Wave Propagation

DOE PAGES

Gao, Kai; Fu, Shubin; Chung, Eric T.

2018-02-13

The frequency-domain seismic-wave equation, that is, the Helmholtz equation, has many important applications in seismological studies, yet is very challenging to solve, particularly for large geological models. Iterative solvers, domain decomposition, or parallel strategies can partially alleviate the computational burden, but these approaches may still encounter nontrivial difficulties in complex geological models where a sufficiently fine mesh is required to represent the fine-scale heterogeneities. We develop a novel numerical method to solve the frequency-domain acoustic wave equation on the basis of the multiscale finite-element theory. We discretize a heterogeneous model with a coarse mesh and employ carefully constructed high-order multiscalemore » basis functions to form the basis space for the coarse mesh. Solved from medium- and frequency-dependent local problems, these multiscale basis functions can effectively capture themedium’s fine-scale heterogeneity and the source’s frequency information, leading to a discrete system matrix with a much smaller dimension compared with those from conventional methods.We then obtain an accurate solution to the acoustic Helmholtz equation by solving only a small linear system instead of a large linear system constructed on the fine mesh in conventional methods.We verify our new method using several models of complicated heterogeneities, and the results show that our new multiscale method can solve the Helmholtz equation in complex models with high accuracy and extremely low computational costs.« less

An Efficient Multiscale Finite-Element Method for Frequency-Domain Seismic Wave Propagation

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

Gao, Kai; Fu, Shubin; Chung, Eric T.

The frequency-domain seismic-wave equation, that is, the Helmholtz equation, has many important applications in seismological studies, yet is very challenging to solve, particularly for large geological models. Iterative solvers, domain decomposition, or parallel strategies can partially alleviate the computational burden, but these approaches may still encounter nontrivial difficulties in complex geological models where a sufficiently fine mesh is required to represent the fine-scale heterogeneities. We develop a novel numerical method to solve the frequency-domain acoustic wave equation on the basis of the multiscale finite-element theory. We discretize a heterogeneous model with a coarse mesh and employ carefully constructed high-order multiscalemore » basis functions to form the basis space for the coarse mesh. Solved from medium- and frequency-dependent local problems, these multiscale basis functions can effectively capture themedium’s fine-scale heterogeneity and the source’s frequency information, leading to a discrete system matrix with a much smaller dimension compared with those from conventional methods.We then obtain an accurate solution to the acoustic Helmholtz equation by solving only a small linear system instead of a large linear system constructed on the fine mesh in conventional methods.We verify our new method using several models of complicated heterogeneities, and the results show that our new multiscale method can solve the Helmholtz equation in complex models with high accuracy and extremely low computational costs.« less

Development of at-line assay to monitor charge variants of MAbs during production.

PubMed

St Amand, M M; Ogunnaike, B A; Robinson, A S

2014-01-01

One major challenge currently facing the biopharmaceutical industry is to understand how MAb microheterogeneity affects therapeutic efficacy, potency, immunogenicity, and clearance. MAb micro-heterogeneity can result from post-translational modifications such as sialylation, galactosylation, C-terminal lysine cleavage, glycine amidation, and tryptophan oxidation, each of which can generate MAb charge variants; such heterogeneity can affect pharmacokinetics (PK) considerably. Implementation of appropriate on-line quality control strategies may help to regulate bioprocesses, thus enabling more homogenous material with desired post-translational modifications and PK behavior. However, one major restriction to implementation of quality control strategies is the availability of techniques for obtaining on-line or at-line measurements of these attributes. In this work, we describe the development of an at-line assay to separate MAb charge variants in near real-time, which could ultimately be used to implement on-line quality control strategies for MAb production. The assay consists of a 2D-HPLC method with sequential in-line Protein A and WCX-10 HPLC column steps. To perform the 2D-HPLC assay at-line, the two columns steps were integrated into a single method using a novel system configuration that allowed parallel flow over column 1 or column 2 or sequential flow from column 1 to column 2. A bioreactor system was also developed such that media samples could be removed automatically from bioreactor vessels during production and delivered to the 2D-HPLC for analysis. With this at-line HPLC assay, we have demonstrated that MAb microheterogeneity occurs throughout the cell cycle whether the host cell line is grown under different or the same nominal culture conditions. © 2013 American Institute of Chemical Engineers.

Probability and Cumulative Density Function Methods for the Stochastic Advection-Reaction Equation

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

Barajas-Solano, David A.; Tartakovsky, Alexandre M.

We present a cumulative density function (CDF) method for the probabilistic analysis of $d$-dimensional advection-dominated reactive transport in heterogeneous media. We employ a probabilistic approach in which epistemic uncertainty on the spatial heterogeneity of Darcy-scale transport coefficients is modeled in terms of random fields with given correlation structures. Our proposed CDF method employs a modified Large-Eddy-Diffusivity (LED) approach to close and localize the nonlocal equations governing the one-point PDF and CDF of the concentration field, resulting in a $(d + 1)$ dimensional PDE. Compared to the classsical LED localization, the proposed modified LED localization explicitly accounts for the mean-field advectivemore » dynamics over the phase space of the PDF and CDF. To illustrate the accuracy of the proposed closure, we apply our CDF method to one-dimensional single-species reactive transport with uncertain, heterogeneous advection velocities and reaction rates modeled as random fields.« less

A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

PubMed

Li, Qi-Gang; He, Yong-Han; Wu, Huan; Yang, Cui-Ping; Pu, Shao-Yan; Fan, Song-Qing; Jiang, Li-Ping; Shen, Qiu-Shuo; Wang, Xiao-Xiong; Chen, Xiao-Qiong; Yu, Qin; Li, Ying; Sun, Chang; Wang, Xiangting; Zhou, Jumin; Li, Hai-Peng; Chen, Yong-Bin; Kong, Qing-Peng

2017-01-01

Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both in vitro and in vivo , to be crucial in tumorigenesis, e.g., alcohol metabolism ( ADH1B ), chromosome remodeling ( NCAPH ) and complement system ( Adipsin ). Together, we present a sharper tool to navigate large-scale expression data and gain new mechanistic insights into tumorigenesis.

The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome.

PubMed

Caswell, Deborah R; Swanton, Charles

2017-07-18

The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes. Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse. Heterogeneity may fuel metastasis through the selection of rare, aggressive, somatically altered cells. However, extreme levels of chromosomal instability, which contribute to intratumour heterogeneity, are associated with improved patient outcomes, suggesting a delicate balance between high and low levels of genome instability. We review evidence that intratumour heterogeneity influences tumour evolution, including metastasis, drug resistance, and the immune response. We discuss the prevalence of tumour heterogeneity, and how it can be initiated and sustained by external and internal forces. Understanding tumour evolution and metastasis could yield novel therapies that leverage the immune system to control emerging tumour neo-antigens.

A View on Future Building System Modeling and Simulation

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

Wetter, Michael

This chapter presents what a future environment for building system modeling and simulation may look like. As buildings continue to require increased performance and better comfort, their energy and control systems are becoming more integrated and complex. We therefore focus in this chapter on the modeling, simulation and analysis of building energy and control systems. Such systems can be classified as heterogeneous systems because they involve multiple domains, such as thermodynamics, fluid dynamics, heat and mass transfer, electrical systems, control systems and communication systems. Also, they typically involve multiple temporal and spatial scales, and their evolution can be described bymore » coupled differential equations, discrete equations and events. Modeling and simulating such systems requires a higher level of abstraction and modularisation to manage the increased complexity compared to what is used in today's building simulation programs. Therefore, the trend towards more integrated building systems is likely to be a driving force for changing the status quo of today's building simulation programs. Thischapter discusses evolving modeling requirements and outlines a path toward a future environment for modeling and simulation of heterogeneous building systems.A range of topics that would require many additional pages of discussion has been omitted. Examples include computational fluid dynamics for air and particle flow in and around buildings, people movement, daylight simulation, uncertainty propagation and optimisation methods for building design and controls. For different discussions and perspectives on the future of building modeling and simulation, we refer to Sahlin (2000), Augenbroe (2001) and Malkawi and Augenbroe (2004).« less

Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review

PubMed Central

Gorton, Hayley C; Webb, Roger T; Kapur, Navneet; Ashcroft, Darren M

2016-01-01

Objectives To establish which non-psychotropic medications have been assessed in relation to risk of suicide or attempted suicide in observational studies, document reported associations and consider study strengths and limitations. Design Systematic review. Methods Four databases (Embase, Medline, PsycINFO and International Pharmaceutical Abstracts) were searched from 1990 to June 2014, and reference lists of included articles were hand-searched. Case–control, cohort and case only studies which reported suicide or attempted suicide in association with any non-psychotropic medication were included. Outcome measures The outcomes eligible for inclusion were suicide and attempted suicide, as defined by the authors of the included study. Results Of 11 792 retrieved articles, 19 were eligible for inclusion. Five studies considered cardiovascular medication and antiepileptics; two considered leukotriene receptor antagonists, isotretinoin and corticosteroids; one assessed antibiotics and another assessed varenicline. An additional study compared multiple medications prescribed to suicide cases versus controls. There was marked heterogeneity in study design, outcome and exposure classification, and control for confounding factors; particularly comorbid mental and physical illness. No increased risk was associated with cardiovascular medications, but associations with other medications remained inconclusive and meta-analysis was inappropriate due to study heterogeneity. Conclusions Whether non-psychotropic medications are associated with increased risk of suicide or attempted suicide remains largely unknown. Robust identification of suicide outcomes and control of comorbidities could improve quantification of risk associated with non-psychotropic medication, beyond that conferred by underlying physical and mental illnesses. PMID:26769782

Area-averaged evapotranspiration over a heterogeneous land surface: aggregation of multi-point EC flux measurements with a high-resolution land-cover map and footprint analysis

NASA Astrophysics Data System (ADS)

Xu, Feinan; Wang, Weizhen; Wang, Jiemin; Xu, Ziwei; Qi, Yuan; Wu, Yueru

2017-08-01

The determination of area-averaged evapotranspiration (ET) at the satellite pixel scale/model grid scale over a heterogeneous land surface plays a significant role in developing and improving the parameterization schemes of the remote sensing based ET estimation models and general hydro-meteorological models. The Heihe Watershed Allied Telemetry Experimental Research (HiWATER) flux matrix provided a unique opportunity to build an aggregation scheme for area-averaged fluxes. On the basis of the HiWATER flux matrix dataset and high-resolution land-cover map, this study focused on estimating the area-averaged ET over a heterogeneous landscape with footprint analysis and multivariate regression. The procedure is as follows. Firstly, quality control and uncertainty estimation for the data of the flux matrix, including 17 eddy-covariance (EC) sites and four groups of large-aperture scintillometers (LASs), were carefully done. Secondly, the representativeness of each EC site was quantitatively evaluated; footprint analysis was also performed for each LAS path. Thirdly, based on the high-resolution land-cover map derived from aircraft remote sensing, a flux aggregation method was established combining footprint analysis and multiple-linear regression. Then, the area-averaged sensible heat fluxes obtained from the EC flux matrix were validated by the LAS measurements. Finally, the area-averaged ET of the kernel experimental area of HiWATER was estimated. Compared with the formerly used and rather simple approaches, such as the arithmetic average and area-weighted methods, the present scheme is not only with a much better database, but also has a solid grounding in physics and mathematics in the integration of area-averaged fluxes over a heterogeneous surface. Results from this study, both instantaneous and daily ET at the satellite pixel scale, can be used for the validation of relevant remote sensing models and land surface process models. Furthermore, this work will be extended to the water balance study of the whole Heihe River basin.

In search of causal variants: refining disease association signals using cross-population contrasts.

PubMed

Saccone, Nancy L; Saccone, Scott F; Goate, Alison M; Grucza, Richard A; Hinrichs, Anthony L; Rice, John P; Bierut, Laura J

2008-08-29

Genome-wide association (GWA) using large numbers of single nucleotide polymorphisms (SNPs) is now a powerful, state-of-the-art approach to mapping human disease genes. When a GWA study detects association between a SNP and the disease, this signal usually represents association with a set of several highly correlated SNPs in strong linkage disequilibrium. The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up. We implemented a systematic method for testing association across diverse population samples having differing histories and LD patterns, using a logistic regression framework. The hypothesis is that important underlying biological mechanisms are shared across human populations, and we can filter correlated variants by testing for heterogeneity of genetic effects in different population samples. This approach formalizes the descriptive comparison of p-values that has typified similar cross-population fine-mapping studies to date. We applied this method to correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-American samples. Of the 10 SNPs genotyped in the r2 > or = 0.8 bin for rs16969968, three demonstrated significant cross-population heterogeneity and are filtered from priority follow-up; the remaining SNPs include rs16969968 (heterogeneity p = 0.75). Though the power to filter out rs16969968 is reduced due to the difference in allele frequency in the two groups, the results nevertheless focus attention on a smaller group of SNPs that includes the non-synonymous SNP rs16969968, which retains a similar effect size (odds ratio) across both population samples. Filtering out SNPs that demonstrate cross-population heterogeneity enriches for variants more likely to be important and causative. Our approach provides an important and effective tool to help interpret results from the many GWA studies now underway.

First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

PubMed Central

Sandercock, J; Parmar, M K B; Torri, V; Qian, W

2002-01-01

Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer. British Journal of Cancer (2002) 87, 815–824. doi:10.1038/sj.bjc.6600567 www.bjcancer.com © 2002 Cancer Research UK PMID:12373593

Link prediction based on nonequilibrium cooperation effect

NASA Astrophysics Data System (ADS)

Li, Lanxi; Zhu, Xuzhen; Tian, Hui

2018-04-01

Link prediction in complex networks has become a common focus of many researchers. But most existing methods concentrate on neighbors, and rarely consider degree heterogeneity of two endpoints. Node degree represents the importance or status of endpoints. We describe the large-degree heterogeneity as the nonequilibrium between nodes. This nonequilibrium facilitates a stable cooperation between endpoints, so that two endpoints with large-degree heterogeneity tend to connect stably. We name such a phenomenon as the nonequilibrium cooperation effect. Therefore, this paper proposes a link prediction method based on the nonequilibrium cooperation effect to improve accuracy. Theoretical analysis will be processed in advance, and at the end, experiments will be performed in 12 real-world networks to compare the mainstream methods with our indices in the network through numerical analysis.

Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts.

PubMed

Alberti, K P; Guthmann, J P; Fermon, F; Nargaye, K D; Grais, R F

2008-03-01

Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.

A Comparison of Traditional, Step-Path, and Geostatistical Techniques in the Stability Analysis of a Large Open Pit

NASA Astrophysics Data System (ADS)

Mayer, J. M.; Stead, D.

2017-04-01

With the increased drive towards deeper and more complex mine designs, geotechnical engineers are often forced to reconsider traditional deterministic design techniques in favour of probabilistic methods. These alternative techniques allow for the direct quantification of uncertainties within a risk and/or decision analysis framework. However, conventional probabilistic practices typically discretize geological materials into discrete, homogeneous domains, with attributes defined by spatially constant random variables, despite the fact that geological media display inherent heterogeneous spatial characteristics. This research directly simulates this phenomenon using a geostatistical approach, known as sequential Gaussian simulation. The method utilizes the variogram which imposes a degree of controlled spatial heterogeneity on the system. Simulations are constrained using data from the Ok Tedi mine site in Papua New Guinea and designed to randomly vary the geological strength index and uniaxial compressive strength using Monte Carlo techniques. Results suggest that conventional probabilistic techniques have a fundamental limitation compared to geostatistical approaches, as they fail to account for the spatial dependencies inherent to geotechnical datasets. This can result in erroneous model predictions, which are overly conservative when compared to the geostatistical results.

Nonparametric Bayesian clustering to detect bipolar methylated genomic loci.

PubMed

Wu, Xiaowei; Sun, Ming-An; Zhu, Hongxiao; Xie, Hehuang

2015-01-16

With recent development in sequencing technology, a large number of genome-wide DNA methylation studies have generated massive amounts of bisulfite sequencing data. The analysis of DNA methylation patterns helps researchers understand epigenetic regulatory mechanisms. Highly variable methylation patterns reflect stochastic fluctuations in DNA methylation, whereas well-structured methylation patterns imply deterministic methylation events. Among these methylation patterns, bipolar patterns are important as they may originate from allele-specific methylation (ASM) or cell-specific methylation (CSM). Utilizing nonparametric Bayesian clustering followed by hypothesis testing, we have developed a novel statistical approach to identify bipolar methylated genomic regions in bisulfite sequencing data. Simulation studies demonstrate that the proposed method achieves good performance in terms of specificity and sensitivity. We used the method to analyze data from mouse brain and human blood methylomes. The bipolar methylated segments detected are found highly consistent with the differentially methylated regions identified by using purified cell subsets. Bipolar DNA methylation often indicates epigenetic heterogeneity caused by ASM or CSM. With allele-specific events filtered out or appropriately taken into account, our proposed approach sheds light on the identification of cell-specific genes/pathways under strong epigenetic control in a heterogeneous cell population.

The impact of heterogeneity in individual frailty on the dynamics of mortality.

PubMed

Vaupel, J W; Manton, K G; Stallard, E

1979-08-01

Life table methods are developed for populations whose members differ in their endowment for longevity. Unlike standard methods, which ignore such heterogeneity, these methods use different calculations to construct cohort, period, and individual life tables. The results imply that standard methods overestimate current life expectancy and potential gains in life expectancy from health and safety interventions, while underestimating rates of individual aging, past progress in reducing mortality, and mortality differentials between pairs of populations. Calculations based on Swedish mortality data suggest that these errors may be important, especially in old age.

Statistically Validated Networks in Bipartite Complex Systems

PubMed Central

Tumminello, Michele; Miccichè, Salvatore; Lillo, Fabrizio; Piilo, Jyrki; Mantegna, Rosario N.

2011-01-01

Many complex systems present an intrinsic bipartite structure where elements of one set link to elements of the second set. In these complex systems, such as the system of actors and movies, elements of one set are qualitatively different than elements of the other set. The properties of these complex systems are typically investigated by constructing and analyzing a projected network on one of the two sets (for example the actor network or the movie network). Complex systems are often very heterogeneous in the number of relationships that the elements of one set establish with the elements of the other set, and this heterogeneity makes it very difficult to discriminate links of the projected network that are just reflecting system's heterogeneity from links relevant to unveil the properties of the system. Here we introduce an unsupervised method to statistically validate each link of a projected network against a null hypothesis that takes into account system heterogeneity. We apply the method to a biological, an economic and a social complex system. The method we propose is able to detect network structures which are very informative about the organization and specialization of the investigated systems, and identifies those relationships between elements of the projected network that cannot be explained simply by system heterogeneity. We also show that our method applies to bipartite systems in which different relationships might have different qualitative nature, generating statistically validated networks in which such difference is preserved. PMID:21483858

Integration of Heterogeneous Bibliographic Information through Data Abstractions.

ERIC Educational Resources Information Center

Breazeal, Juliette Ow

This study examines the integration of heterogeneous bibliographic information resources from geographically distributed locations in an automated, unified, and controlled way using abstract data types called "classes" through the Message-Object Model defined in Smalltalk-80 software. The concept of achieving data consistency by…

Spatiotemporal Heterogeneity Analysis of Hemorrhagic Fever with Renal Syndrome in China Using Geographically Weighted Regression Models

PubMed Central

Li, Shujuan; Ren, Hongyan; Hu, Wensheng; Lu, Liang; Xu, Xinliang; Zhuang, Dafang; Liu, Qiyong

2014-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in China. The identification of the spatiotemporal pattern of HFRS will provide a foundation for the effective control of the disease. Based on the incidence of HFRS, as well as environmental factors, and social-economic factors of China from 2005–2012, this paper identified the spatiotemporal characteristics of HFRS distribution and the factors that impact this distribution. The results indicate that the spatial distribution of HFRS had a significant, positive spatial correlation. The spatiotemporal heterogeneity was affected by the temperature, precipitation, humidity, NDVI of January, NDVI of August for the previous year, land use, and elevation in 2005–2009. However, these factors did not explain the spatiotemporal heterogeneity of HFRS incidences in 2010–2012. Spatiotemporal heterogeneity of provincial HFRS incidences and its relation to environmental factors would provide valuable information for hygiene authorities to design and implement effective measures for the prevention and control of HFRS in China. PMID:25429681

Vaccine Effects on Heterogeneity in Susceptibility and Implications for Population Health Management

PubMed Central

Wargo, Andrew R.; Jones, Darbi R.; Viss, Jessie R.; Rutan, Barbara J.; Egan, Nicholas A.; Sá-Guimarães, Pedro; Kim, Min Sun; Kurath, Gael; Gomes, M. Gabriela M.

2017-01-01

ABSTRACT Heterogeneity in host susceptibility is a key determinant of infectious disease dynamics but is rarely accounted for in assessment of disease control measures. Understanding how susceptibility is distributed in populations, and how control measures change this distribution, is integral to predicting the course of epidemics with and without interventions. Using multiple experimental and modeling approaches, we show that rainbow trout have relatively homogeneous susceptibility to infection with infectious hematopoietic necrosis virus and that vaccination increases heterogeneity in susceptibility in a nearly all-or-nothing fashion. In a simple transmission model with an R0 of 2, the highly heterogeneous vaccine protection would cause a 35 percentage-point reduction in outbreak size over an intervention inducing homogenous protection at the same mean level. More broadly, these findings provide validation of methodology that can help to reduce biases in predictions of vaccine impact in natural settings and provide insight into how vaccination shapes population susceptibility. PMID:29162706

Arcade: A Web-Java Based Framework for Distributed Computing

NASA Technical Reports Server (NTRS)

Chen, Zhikai; Maly, Kurt; Mehrotra, Piyush; Zubair, Mohammad; Bushnell, Dennis M. (Technical Monitor)

2000-01-01

Distributed heterogeneous environments are being increasingly used to execute a variety of large size simulations and computational problems. We are developing Arcade, a web-based environment to design, execute, monitor, and control distributed applications. These targeted applications consist of independent heterogeneous modules which can be executed on a distributed heterogeneous environment. In this paper we describe the overall design of the system and discuss the prototype implementation of the core functionalities required to support such a framework.

Quantitative CT scans of lung parenchymal pathology in premature infants ages 0-6 years.

PubMed

Spielberg, David R; Walkup, Laura L; Stein, Jill M; Crotty, Eric J; Rattan, Mantosh S; Hossain, Md Monir; Brody, Alan S; Woods, Jason C

2018-03-01

Bronchopulmonary dysplasia (BPD) is a common, heterogeneous disease in premature infants. We hypothesized that quantitative CT techniques could assess lung parenchymal heterogeneity in BPD patients across a broad age range and demonstrate how pathologies change over time. A cross-sectional, retrospective study of children age 0-6 years with non-contrast chest CT scans was conducted. BPD subjects met NICHD/NHLBI diagnostic criteria for BPD and were excluded for congenital lung/airway abnormalities or other known/suspected pulmonary diagnoses; control subjects were not premature and had normal CT scan findings. Radiologic opacities, lucencies, and spatial heterogeneity were quantified via: 1) thresholding using CT-attenuation (HU); 2) manual segmentation; and 3) Ochiai reader-scoring system. Clinical outcomes included BPD severity by NICHD/NHLBI criteria, respiratory support at NICU discharge, wheezing, and respiratory exacerbations. Heterogeneity (standard deviation) of lung attenuation in BPD was significantly greater than in controls (difference 36.4 HU [26.1-46.7 HU], P < 0.001); the difference between the groups decreased 0.58 HU per month of age (0.08-1.07 HU per month, P = 0.02). BPD patients had greater amounts of opacities and lucencies than controls except with automated quantification of lucencies. Cross-sectionally, lucencies per Ochiai score and opacities per manual segmentation decreased with time. No approach measured a statistically significant relationship to BPD clinical severity. Opacities, lucencies, and overall heterogeneity of lungs via quantitative CT can distinguish BPD patients from healthy controls, and these abnormalities decrease with age across BPD patients. Defining BPD severity by clinical outcomes such as respiratory support at several time points (vs a single time point, per current guidelines) may be meaningful. © 2017 Wiley Periodicals, Inc.

Phenotypic and genetic heterogeneity among subjects with mild airflow obstruction in COPDGene.

PubMed

Lee, Jin Hwa; Cho, Michael H; McDonald, Merry-Lynn N; Hersh, Craig P; Castaldi, Peter J; Crapo, James D; Wan, Emily S; Dy, Jennifer G; Chang, Yale; Regan, Elizabeth A; Hardin, Megan; DeMeo, Dawn L; Silverman, Edwin K

2014-10-01

Chronic obstructive pulmonary disease (COPD) is characterized by marked phenotypic heterogeneity. Most previous studies have focused on COPD subjects with FEV1 < 80% predicted. We investigated the clinical and genetic heterogeneity in subjects with mild airflow limitation in spirometry grade 1 defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD 1). Data from current and former smokers participating in the COPDGene Study (NCT00608764) were analyzed. K-means clustering was performed to explore subtypes within 794 GOLD 1 subjects. For all subjects with GOLD 1 and with each cluster, a genome-wide association study and candidate gene testing were performed using smokers with normal lung function as a control group. Combinations of COPD genome-wide significant single nucleotide polymorphisms (SNPs) were tested for association with FEV1 (% predicted) in GOLD 1 and in a combined group of GOLD 1 and smoking control subjects. K-means clustering of GOLD 1 subjects identified putative "near-normal", "airway-predominant", "emphysema-predominant" and "lowest FEV1% predicted" subtypes. In non-Hispanic whites, the only SNP nominally associated with GOLD 1 status relative to smoking controls was rs7671167 (FAM13A) in logistic regression models with adjustment for age, sex, pack-years of smoking, and genetic ancestry. The emphysema-predominant GOLD 1 cluster was nominally associated with rs7671167 (FAM13A) and rs161976 (BICD1). The lowest FEV1% predicted cluster was nominally associated with rs1980057 (HHIP) and rs1051730 (CHRNA3). Combinations of COPD genome-wide significant SNPs were associated with FEV1 (% predicted) in a combined group of GOLD 1 and smoking control subjects. Our results indicate that GOLD 1 subjects show substantial clinical heterogeneity, which is at least partially related to genetic heterogeneity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low-energy Control of Electrical Turbulence in the Heart

PubMed Central

Luther, Stefan; Fenton, Flavio H.; Kornreich, Bruce G.; Squires, Amgad; Bittihn, Philip; Hornung, Daniel; Zabel, Markus; Flanders, James; Gladuli, Andrea; Campoy, Luis; Cherry, Elizabeth M.; Luther, Gisa; Hasenfuss, Gerd; Krinsky, Valentin I.; Pumir, Alain; Gilmour, Robert F.; Bodenschatz, Eberhard

2011-01-01

Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult due to the nonlinear interaction of excitation waves within a heterogeneous anatomical substrate1–4. Lacking a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation5–7. Here, we establish the relation between the response of the tissue to an electric field and the spatial distribution of heterogeneities of the scale-free coronary vascular structure. We show that in response to a pulsed electric field E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E), and a characteristic time τ for tissue depolarization that obeys a power law τ∝Eα. These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore efficient termination of fibrillation. Using this novel control strategy, we demonstrate, for the first time, low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and at the same time provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques. PMID:21753855

Levels of Red Blood Cell Fatty Acids in Patients With Psychosis, Their Unaffected Siblings, and Healthy Controls

PubMed Central

Medema, Suzanne; Mocking, Roel J. T.; Koeter, Maarten W. J.; Vaz, Frédéric M.; Meijer, Carin; de Haan, Lieuwe; van Beveren, Nico J. M.; Kahn, René; de Haan, Lieuwe; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Meijer, Carin; Myin-Germeys, Inez

2016-01-01

Background: Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. Methods: For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. Results: Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. Conclusions: We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients. PMID:26385764

Evaluating the Impact of Database Heterogeneity on Observational Study Results

PubMed Central

Madigan, David; Ryan, Patrick B.; Schuemie, Martijn; Stang, Paul E.; Overhage, J. Marc; Hartzema, Abraham G.; Suchard, Marc A.; DuMouchel, William; Berlin, Jesse A.

2013-01-01

Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results. PMID:23648805

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

PubMed

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Proteomic Methods of Detection and Quantification of Protein Toxins.

PubMed

Duracova, Miloslava; Klimentova, Jana; Fucikova, Alena; Dresler, Jiri

2018-02-28

Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins , Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis , Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album . The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents.

Proteomic Methods of Detection and Quantification of Protein Toxins

PubMed Central

Klimentova, Jana; Fucikova, Alena

2018-01-01

Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins, Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis, Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album. The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents. PMID:29495560

General expressions for downlink signal to interference and noise ratio in homogeneous and heterogeneous LTE-Advanced networks.

PubMed

Ali, Nora A; Mourad, Hebat-Allah M; ElSayed, Hany M; El-Soudani, Magdy; Amer, Hassanein H; Daoud, Ramez M

2016-11-01

The interference is the most important problem in LTE or LTE-Advanced networks. In this paper, the interference was investigated in terms of the downlink signal to interference and noise ratio (SINR). In order to compare the different frequency reuse methods that were developed to enhance the SINR, it would be helpful to have a generalized expression to study the performance of the different methods. Therefore, this paper introduces general expressions for the SINR in homogeneous and in heterogeneous networks. In homogeneous networks, the expression was applied for the most common types of frequency reuse techniques: soft frequency reuse (SFR) and fractional frequency reuse (FFR). The expression was examined by comparing it with previously developed ones in the literature and the comparison showed that the expression is valid for any type of frequency reuse scheme and any network topology. Furthermore, the expression was extended to include the heterogeneous network; the expression includes the problem of co-tier and cross-tier interference in heterogeneous networks (HetNet) and it was examined by the same method of the homogeneous one.

Laplacian normalization and random walk on heterogeneous networks for disease-gene prioritization.

PubMed

Zhao, Zhi-Qin; Han, Guo-Sheng; Yu, Zu-Guo; Li, Jinyan

2015-08-01

Random walk on heterogeneous networks is a recently emerging approach to effective disease gene prioritization. Laplacian normalization is a technique capable of normalizing the weight of edges in a network. We use this technique to normalize the gene matrix and the phenotype matrix before the construction of the heterogeneous network, and also use this idea to define the transition matrices of the heterogeneous network. Our method has remarkably better performance than the existing methods for recovering known gene-phenotype relationships. The Shannon information entropy of the distribution of the transition probabilities in our networks is found to be smaller than the networks constructed by the existing methods, implying that a higher number of top-ranked genes can be verified as disease genes. In fact, the most probable gene-phenotype relationships ranked within top 3 or top 5 in our gene lists can be confirmed by the OMIM database for many cases. Our algorithms have shown remarkably superior performance over the state-of-the-art algorithms for recovering gene-phenotype relationships. All Matlab codes can be available upon email request. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reply to Efford on ‘Integrating resource selection information with spatial capture-recapture’

USGS Publications Warehouse

Royle, Andy; Chandler, Richard; Sun, Catherine C.; Fuller, Angela K.

2014-01-01

3. A key point of Royle et al. (Methods in Ecology and Evolution, 2013, 4) was that active resource selection induces heterogeneity in encounter probability which, if unaccounted for, should bias estimates of population size or density. The models of Royle et al. (Methods in Ecology and Evolution, 2013, 4) and Efford (Methods in Ecology and Evolution, 2014, 000, 000) merely amount to alternative models of resource selection, and hence varying amounts of heterogeneity in encounter probability.

Method of assessing heterogeneity in images

DOEpatents

Jacob, Richard E.; Carson, James P.

2016-08-23

A method of assessing heterogeneity in images is disclosed. 3D images of an object are acquired. The acquired images may be filtered and masked. Iterative decomposition is performed on the masked images to obtain image subdivisions that are relatively homogeneous. Comparative analysis, such as variogram analysis or correlogram analysis, is performed of the decomposed images to determine spatial relationships between regions of the images that are relatively homogeneous.

Heterogeneity and anisotropy in the lithospheric mantle

NASA Astrophysics Data System (ADS)

Tommasi, Andréa; Vauchez, Alain

2015-10-01

The lithospheric mantle is intrinsically heterogeneous and anisotropic. These two properties govern the repartition of deformation, controlling intraplate strain localization and development of new plate boundaries. Geophysical and geological observations provide clues on the types, ranges, and characteristic length scales of heterogeneity and anisotropy in the lithospheric mantle. Seismic tomography points to variations in geothermal gradient and hence in rheological behavior at scales of hundreds of km. Seismic anisotropy data substantiate anisotropic physical properties consistent at scales of tens to hundreds of km. Receiver functions imply lateral and vertical heterogeneity at scales < 10 km, which might record gradients in composition or anisotropy. Observations on naturally deformed peridotites establish that compositional heterogeneity and Crystal Preferred Orientations (CPOs) are ubiquitous from the mm to the km scales. These data allow discussing the processes that produce/destroy heterogeneity and anisotropy and constraining the time scales over which they are active. This analysis highlights: (i) the role of deformation and reactive percolation of melts and fluids in producing compositional and structural heterogeneity and the feedbacks between these processes, (ii) the weak mechanical effect of mineralogical variations, and (iii) the low volumes of fine-grained microstructures and difficulty to preserve them. In contrast, olivine CPO and the resulting anisotropy of mechanical and thermal properties are only modified by deformation. Based on this analysis, we propose that strain localization at the plate scale is, at first order, controlled by large-scale variations in thermal structure and in CPO-induced anisotropy. In cold parts of the lithospheric mantle, grain size reduction may contribute to strain localization, but the low volume of fine-grained domains limits this effect.

A Deep Convolutional Coupling Network for Change Detection Based on Heterogeneous Optical and Radar Images.

PubMed

Liu, Jia; Gong, Maoguo; Qin, Kai; Zhang, Puzhao

2018-03-01

We propose an unsupervised deep convolutional coupling network for change detection based on two heterogeneous images acquired by optical sensors and radars on different dates. Most existing change detection methods are based on homogeneous images. Due to the complementary properties of optical and radar sensors, there is an increasing interest in change detection based on heterogeneous images. The proposed network is symmetric with each side consisting of one convolutional layer and several coupling layers. The two input images connected with the two sides of the network, respectively, are transformed into a feature space where their feature representations become more consistent. In this feature space, the different map is calculated, which then leads to the ultimate detection map by applying a thresholding algorithm. The network parameters are learned by optimizing a coupling function. The learning process is unsupervised, which is different from most existing change detection methods based on heterogeneous images. Experimental results on both homogenous and heterogeneous images demonstrate the promising performance of the proposed network compared with several existing approaches.

Cirrus Heterogeneity Effects on Cloud Optical Properties Retrieved with an Optimal Estimation Method from MODIS VIS to TIR Channels.

NASA Technical Reports Server (NTRS)

Fauchez, T.; Platnick, S.; Meyer, K.; Sourdeval, O.; Cornet, C.; Zhang, Z.; Szczap, F.

2016-01-01

This study presents preliminary results on the effect of cirrus heterogeneities on top-of-atmosphere (TOA) simulated radiances or reflectances for MODIS channels centered at 0.86, 2.21, 8.56, 11.01 and 12.03 micrometers , and on cloud optical properties retrieved with a research-level optimal estimation method (OEM). Synthetic cirrus cloud fields are generated using a 3D cloud generator (3DCLOUD) and radiances/reflectances are simulated using a 3D radiative transfer code (3DMCPOL). We find significant differences between the heterogeneity effects on either visible and near-infrared (VNIR) or thermal infrared (TIR) radiances. However, when both wavelength ranges are combined, heterogeneity effects are dominated by the VNIR horizontal radiative transport effect. As a result, small optical thicknesses are overestimated and large ones are underestimated. Retrieved effective diameter are found to be slightly affected, contrarily to retrievals using TIR channels only.

Simulation study of axial ultrasound transmission in heterogeneous cortical bone model

NASA Astrophysics Data System (ADS)

Takano, Koki; Nagatani, Yoshiki; Matsukawa, Mami

2017-07-01

Ultrasound propagation in a heterogeneous cortical bone was studied. Using a bovine radius, the longitudinal wave velocity distribution in the axial direction was experimentally measured in the MHz range. The bilinear interpolation and piecewise cubic Hermite interpolation methods were applied to create a three-dimensional (3D) precise velocity model of the bone using experimental data. By assuming the uniaxial anisotropy of the bone, the distributions of all elastic moduli of a 3D heterogeneous model were estimated. The elastic finite-difference time-domain method was used to simulate axial ultrasonic wave propagation. The wave propagation in the initial model was compared with that in the thinner model, where the inner part of the cortical bone model was removed. The wave front of the first arriving signal (FAS) slightly depended on the heterogeneity in each model. Owing to the decrease in bone thickness, the propagation behavior also changed and the FAS velocity clearly decreased.

Integrating heterogeneous databases in clustered medic care environments using object-oriented technology

NASA Astrophysics Data System (ADS)

Thakore, Arun K.; Sauer, Frank

1994-05-01

The organization of modern medical care environments into disease-related clusters, such as a cancer center, a diabetes clinic, etc., has the side-effect of introducing multiple heterogeneous databases, often containing similar information, within the same organization. This heterogeneity fosters incompatibility and prevents the effective sharing of data amongst applications at different sites. Although integration of heterogeneous databases is now feasible, in the medical arena this is often an ad hoc process, not founded on proven database technology or formal methods. In this paper we illustrate the use of a high-level object- oriented semantic association method to model information found in different databases into an integrated conceptual global model that integrates the databases. We provide examples from the medical domain to illustrate an integration approach resulting in a consistent global view, without attacking the autonomy of the underlying databases.

Dynamical links between small- and large-scale mantle heterogeneity: Seismological evidence

NASA Astrophysics Data System (ADS)

Frost, Daniel A.; Garnero, Edward J.; Rost, Sebastian

2018-01-01

We identify PKP • PKP scattered waves (also known as P‧ •P‧) from earthquakes recorded at small-aperture seismic arrays at distances less than 65°. P‧ •P‧ energy travels as a PKP wave through the core, up into the mantle, then scatters back down through the core to the receiver as a second PKP. P‧ •P‧ waves are unique in that they allow scattering heterogeneities throughout the mantle to be imaged. We use array-processing methods to amplify low amplitude, coherent scattered energy signals and resolve their incoming direction. We deterministically map scattering heterogeneity locations from the core-mantle boundary to the surface. We use an extensive dataset with sensitivity to a large volume of the mantle and a location method allowing us to resolve and map more heterogeneities than have previously been possible, representing a significant increase in our understanding of small-scale structure within the mantle. Our results demonstrate that the distribution of scattering heterogeneities varies both radially and laterally. Scattering is most abundant in the uppermost and lowermost mantle, and a minimum in the mid-mantle, resembling the radial distribution of tomographically derived whole-mantle velocity heterogeneity. We investigate the spatial correlation of scattering heterogeneities with large-scale tomographic velocities, lateral velocity gradients, the locations of deep-seated hotspots and subducted slabs. In the lowermost 1500 km of the mantle, small-scale heterogeneities correlate with regions of low seismic velocity, high lateral seismic gradient, and proximity to hotspots. In the upper 1000 km of the mantle there is no significant correlation between scattering heterogeneity location and subducted slabs. Between 600 and 900 km depth, scattering heterogeneities are more common in the regions most remote from slabs, and close to hotspots. Scattering heterogeneities show an affinity for regions close to slabs within the upper 200 km of the mantle. The similarity between the distribution of large-scale and small-scale mantle structures suggests a dynamic connection across scales, whereby mantle heterogeneities of all sizes may be directed in similar ways by large-scale convective currents.

Adding Qualitative and Mixed Methods Research to Health Intervention Studies: Interacting With Differences.

PubMed

Johnson, R Burke; Schoonenboom, Judith

2016-04-01

The purpose of this article is to explain how to improve intervention designs, such as randomized controlled trials (RCTs), in health science research using a process philosophy and theory known as dialectical pluralism (DP). DP views reality as plural and uses dialectical, dialogical, and hermeneutical approaches to knowledge construction. Using DP and its "both/and" logic, and its attempt to produce new creative syntheses, researchers on heterogeneous teams can better dialogue with qualitative and mixed methods approaches, concepts, paradigms, methodologies, and methods to improve their intervention research studies. The concept of reflexivity is utilized but is expanded when it is a component of DP. Examples of strategies for identifying, inviting, and creating divergence and integrative strategies for producing strong mixed methods intervention studies are provided and illustrated using real-life examples. © The Author(s) 2015.

Heterogeneous Teams of Autonomous Vehicles: Advanced Sensing & Control

DTIC Science & Technology

2009-03-01

Final Technical 3. DATES COVERED (From To) 7/1/05-12/31708 4. TITLE AND SUBTITLE Heterogeneous Teams of Autonomous Vehicles Advanced Sensing...assimilating data from underwater and surface autonomous vehicles in addition to the usual sources of Eulerian and Lagrangian systems into a small scale

Estimation of blood flow heterogeneity in human skeletal muscle using intravascular tracer data: importance for modeling transcapillary exchange.

PubMed

Vicini, P; Bonadonna, R C; Lehtovirta, M; Groop, L C; Cobelli, C

1998-01-01

Distributed models of blood-tissue exchange are widely used to measure kinetic events of various solutes from multiple tracer dilution experiments. Their use requires, however, a careful description of blood flow heterogeneity along the capillary bed. Since they have mostly been applied in animal studies, direct measurement of the heterogeneity distribution was possible, e.g., with the invasive microsphere method. Here we apply distributed modeling to a dual tracer experiment in humans, performed using an intravascular (indocyanine green dye, subject to distribution along the vascular tree and confined to the capillary bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary transfer across the capillary membrane in the interstitial fluid) tracer. The goal is to measure relevant parameters of transcapillary exchange in human skeletal muscle. We show that assuming an accurate description of blood flow heterogeneity is crucial for modeling, and in particular that assuming for skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is inappropriate. The same reason prevents the use of the common method of estimating the input function of the distributed model via deconvolution, which assumes a known blood flow heterogeneity, either defined from literature or measured, when possible. We present a novel approach for the estimation of blood flow heterogeneity in each individual from the intravascular tracer data. When this newly estimated blood flow heterogeneity is used, a more satisfactory model fit is obtained and it is possible to reliably measure parameters of capillary membrane permeability-surface product and interstitial fluid volume describing transcapillary transfer in vivo.

Mass Spectrometry Imaging for the Investigation of Intratumor Heterogeneity.

PubMed

Balluff, B; Hanselmann, M; Heeren, R M A

2017-01-01

One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research. © 2017 Elsevier Inc. All rights reserved.

HPV-associated head and neck cancers in the Asia Pacific: A critical literature review & meta-analysis.

PubMed

Shaikh, Mushfiq Hassan; McMillan, Nigel A J; Johnson, Newell W

2015-12-01

Malignancies of the upper aero-digestive tract are a major public health problem, especially in the Asia Pacific. Certain Human papillomaviruses (HPVs) are well-established risk factors for carcinoma of the uterine cervix and for a subset of head and neck carcinomata: however their true importance in different populations and anatomical subsites remains unclear. The major risk factors in Asia Pacific remain smoked/smokeless tobacco, areca nut, alcohol abuse and poor diet, with limited evidence for HPVs. We review published studies of association of HPV with anatomical site-specific Head & Neck Squamous Cell Carcinoma (HNSCC) in these populations and attempt a meta-analysis. From MEDLINE/PubMed/WEB-of SCIENCE/EMBASE/Scopus databases we found 67 relevant studies with a total of 7280 cases: 15 case-control studies met our inclusion criteria for meta-analysis, totaling 1106 cases & 638 controls. HPV detection rates, sample site and size, and methods of tissue preservation and HPV detection were tabulated for each study. Studies were heterogeneous in terms of sample selection and method of detection of HPVs. Most were of limited quality. Averaging data from 67 studies of HNSCC, the prevalence of HPV of any subtype is approximately 36%. PCR (polymerase chain reaction) was the most used detection method and HPV16 the most common genotype reported. Meta-analyses of case-control studies from this region reveal significant heterogeneity but suggest higher HPV prevalence in oropharyngeal cancer (OR: 14.66; 95%CI: 6.09-35.26) compared to oral cavity cancer and laryngeal cancer; (OR: 4.06; 95%CI: 3.05-5.39 & OR: 3.23; 95%CI: 1.37-7.61) respectively. In view of the significant association of HPV with HNSCC, studies with accurate subsite classification and more sensitive detection methods are necessary. Accurate data from this geographical region are essential to inform public health policies and treatment decisions, especially as studies from Europe and North America reveal HPV-driven cancers to be less aggressive, permitting treatment de-intensification. Copyright © 2015 Elsevier Ltd. All rights reserved.

Facile large-scale synthesis of brain-like mesoporous silica nanocomposites via a selective etching process

NASA Astrophysics Data System (ADS)

Chen, Yu; Wang, Qihua; Wang, Tingmei

2015-10-01

The core-shell structured mesoporous silica nanomaterials (MSNs) are experiencing rapid development in many applications such as heterogeneous catalysis, bio-imaging and drug delivery wherein a large pore volume is desirable. We develop a one-pot method for large-scale synthesis of brain-like mesoporous silica nanocomposites based on the reasonable change of the intrinsic nature of the -Si-O-Si- framework of silica nanoparticles together with a selective etching strategy. The as-synthesized products show good monodispersion and a large pore volume of 1.0 cm3 g-1. The novelty of this approach lies in the use of an inorganic-organic hybrid layer to assist the creation of large-pore morphology on the outermost shell thereby promoting efficient mass transfer or storage. Importantly, the method is reliable and grams of products can be easily prepared. The morphology on the outermost silica shell can be controlled by simply adjusting the VTES-to-TEOS molar ratio (VTES: triethoxyvinylsilane, TEOS: tetraethyl orthosilicate) as well as the etching time. The as-synthesized products exhibit fluorescence performance by incorporating rhodamine B isothiocyanate (RITC) covalently into the inner silica walls, which provide potential application in bioimaging. We also demonstrate the applications of as-synthesized large-pore structured nanocomposites in drug delivery systems and stimuli-responsive nanoreactors for heterogeneous catalysis.The core-shell structured mesoporous silica nanomaterials (MSNs) are experiencing rapid development in many applications such as heterogeneous catalysis, bio-imaging and drug delivery wherein a large pore volume is desirable. We develop a one-pot method for large-scale synthesis of brain-like mesoporous silica nanocomposites based on the reasonable change of the intrinsic nature of the -Si-O-Si- framework of silica nanoparticles together with a selective etching strategy. The as-synthesized products show good monodispersion and a large pore volume of 1.0 cm3 g-1. The novelty of this approach lies in the use of an inorganic-organic hybrid layer to assist the creation of large-pore morphology on the outermost shell thereby promoting efficient mass transfer or storage. Importantly, the method is reliable and grams of products can be easily prepared. The morphology on the outermost silica shell can be controlled by simply adjusting the VTES-to-TEOS molar ratio (VTES: triethoxyvinylsilane, TEOS: tetraethyl orthosilicate) as well as the etching time. The as-synthesized products exhibit fluorescence performance by incorporating rhodamine B isothiocyanate (RITC) covalently into the inner silica walls, which provide potential application in bioimaging. We also demonstrate the applications of as-synthesized large-pore structured nanocomposites in drug delivery systems and stimuli-responsive nanoreactors for heterogeneous catalysis. Electronic supplementary information (ESI) available: The average particle size distribution of LPASN-1, LPASN-2 and LPASN-3; the wide-angle XRD pattern of LPASN-2/LPASN-3/LPASN-4; the catalytic properties of LPASN-PNIPAM at different temperatures (15 °C and 33 °C). See DOI: 10.1039/c5nr04123f

Identical synchronization of nonidentical oscillators: when only birds of different feathers flock together

NASA Astrophysics Data System (ADS)

Zhang, Yuanzhao; Motter, Adilson E.

2018-01-01

An outstanding problem in the study of networks of heterogeneous dynamical units concerns the development of rigorous methods to probe the stability of synchronous states when the differences between the units are not small. Here, we address this problem by presenting a generalization of the master stability formalism that can be applied to heterogeneous oscillators with large mismatches. Our approach is based on the simultaneous block diagonalization of the matrix terms in the variational equation, and it leads to dimension reduction that simplifies the original equation significantly. This new formalism allows the systematic investigation of scenarios in which the oscillators need to be nonidentical in order to reach an identical state, where all oscillators are completely synchronized. In the case of networks of identically coupled oscillators, this corresponds to breaking the symmetry of the system as a means to preserve the symmetry of the dynamical state— a recently discovered effect termed asymmetry-induced synchronization (AISync). Our framework enables us to identify communication delay as a new and potentially common mechanism giving rise to AISync, which we demonstrate using networks of delay-coupled Stuart-Landau oscillators. The results also have potential implications for control, as they reveal oscillator heterogeneity as an attribute that may be manipulated to enhance the stability of synchronous states.

Heterogeneities in Leishmania infantum Infection: Using Skin Parasite Burdens to Identify Highly Infectious Dogs

PubMed Central

Calvo-Bado, Leo; Garcez, Lourdes M.; Quinnell, Rupert J.

2014-01-01

Background The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs. PMID:24416460

Systems Science Methods in Public Health

PubMed Central

Luke, Douglas A.; Stamatakis, Katherine A.

2012-01-01

Complex systems abound in public health. Complex systems are made up of heterogeneous elements that interact with one another, have emergent properties that are not explained by understanding the individual elements of the system, persist over time and adapt to changing circumstances. Public health is starting to use results from systems science studies to shape practice and policy, for example in preparing for global pandemics. However, systems science study designs and analytic methods remain underutilized and are not widely featured in public health curricula or training. In this review we present an argument for the utility of systems science methods in public health, introduce three important systems science methods (system dynamics, network analysis, and agent-based modeling), and provide three case studies where these methods have been used to answer important public health science questions in the areas of infectious disease, tobacco control, and obesity. PMID:22224885

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

Yang, Y M; Bush, K; Han, B

Purpose: Accurate and fast dose calculation is a prerequisite of precision radiation therapy in modern photon and particle therapy. While Monte Carlo (MC) dose calculation provides high dosimetric accuracy, the drastically increased computational time hinders its routine use. Deterministic dose calculation methods are fast, but problematic in the presence of tissue density inhomogeneity. We leverage the useful features of deterministic methods and MC to develop a hybrid dose calculation platform with autonomous utilization of MC and deterministic calculation depending on the local geometry, for optimal accuracy and speed. Methods: Our platform utilizes a Geant4 based “localized Monte Carlo” (LMC) methodmore » that isolates MC dose calculations only to volumes that have potential for dosimetric inaccuracy. In our approach, additional structures are created encompassing heterogeneous volumes. Deterministic methods calculate dose and energy fluence up to the volume surfaces, where the energy fluence distribution is sampled into discrete histories and transported using MC. Histories exiting the volume are converted back into energy fluence, and transported deterministically. By matching boundary conditions at both interfaces, deterministic dose calculation account for dose perturbations “downstream” of localized heterogeneities. Hybrid dose calculation was performed for water and anthropomorphic phantoms. Results: We achieved <1% agreement between deterministic and MC calculations in the water benchmark for photon and proton beams, and dose differences of 2%–15% could be observed in heterogeneous phantoms. The saving in computational time (a factor ∼4–7 compared to a full Monte Carlo dose calculation) was found to be approximately proportional to the volume of the heterogeneous region. Conclusion: Our hybrid dose calculation approach takes advantage of the computational efficiency of deterministic method and accuracy of MC, providing a practical tool for high performance dose calculation in modern RT. The approach is generalizable to all modalities where heterogeneities play a large role, notably particle therapy.« less

DREAMing: a simple and ultrasensitive method for assessing intratumor epigenetic heterogeneity directly from liquid biopsies

PubMed Central

Pisanic, Thomas R.; Athamanolap, Pornpat; Poh, Weijie; Chen, Chen; Hulbert, Alicia; Brock, Malcolm V.; Herman, James G.; Wang, Tza-Huei

2015-01-01

Many cancers comprise heterogeneous populations of cells at primary and metastatic sites throughout the body. The presence or emergence of distinct subclones with drug-resistant genetic and epigenetic phenotypes within these populations can greatly complicate therapeutic intervention. Liquid biopsies of peripheral blood from cancer patients have been suggested as an ideal means of sampling intratumor genetic and epigenetic heterogeneity for diagnostics, monitoring and therapeutic guidance. However, current molecular diagnostic and sequencing methods are not well suited to the routine assessment of epigenetic heterogeneity in difficult samples such as liquid biopsies that contain intrinsically low fractional concentrations of circulating tumor DNA (ctDNA) and rare epigenetic subclonal populations. Here we report an alternative approach, deemed DREAMing (Discrimination of Rare EpiAlleles by Melt), which uses semi-limiting dilution and precise melt curve analysis to distinguish and enumerate individual copies of epiallelic species at single-CpG-site resolution in fractions as low as 0.005%, providing facile and inexpensive ultrasensitive assessment of locus-specific epigenetic heterogeneity directly from liquid biopsies. The technique is demonstrated here for the evaluation of epigenetic heterogeneity at p14ARF and BRCA1 gene-promoter loci in liquid biopsies obtained from patients in association with non-small cell lung cancer (NSCLC) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively. PMID:26304549

A simplified analytical dose calculation algorithm accounting for tissue heterogeneity for low-energy brachytherapy sources.

PubMed

Mashouf, Shahram; Lechtman, Eli; Beaulieu, Luc; Verhaegen, Frank; Keller, Brian M; Ravi, Ananth; Pignol, Jean-Philippe

2013-09-21

The American Association of Physicists in Medicine Task Group No. 43 (AAPM TG-43) formalism is the standard for seeds brachytherapy dose calculation. But for breast seed implants, Monte Carlo simulations reveal large errors due to tissue heterogeneity. Since TG-43 includes several factors to account for source geometry, anisotropy and strength, we propose an additional correction factor, called the inhomogeneity correction factor (ICF), accounting for tissue heterogeneity for Pd-103 brachytherapy. This correction factor is calculated as a function of the media linear attenuation coefficient and mass energy absorption coefficient, and it is independent of the source internal structure. Ultimately the dose in heterogeneous media can be calculated as a product of dose in water as calculated by TG-43 protocol times the ICF. To validate the ICF methodology, dose absorbed in spherical phantoms with large tissue heterogeneities was compared using the TG-43 formalism corrected for heterogeneity versus Monte Carlo simulations. The agreement between Monte Carlo simulations and the ICF method remained within 5% in soft tissues up to several centimeters from a Pd-103 source. Compared to Monte Carlo, the ICF methods can easily be integrated into a clinical treatment planning system and it does not require the detailed internal structure of the source or the photon phase-space.

Robust analysis of an underwater navigational strategy in electrically heterogeneous corridors.

PubMed

Dimble, Kedar D; Ranganathan, Badri N; Keshavan, Jishnu; Humbert, J Sean

2016-08-01

Obstacles and other global stimuli provide relevant navigational cues to a weakly electric fish. In this work, robust analysis of a control strategy based on electrolocation for performing obstacle avoidance in electrically heterogeneous corridors is presented and validated. Static output feedback control is shown to achieve the desired goal of reflexive obstacle avoidance in such environments in simulation and experimentation. The proposed approach is computationally inexpensive and readily implementable on a small scale underwater vehicle, making underwater autonomous navigation feasible in real-time.

Estimation of brood and nest survival: Comparative methods in the presence of heterogeneity

USGS Publications Warehouse

Manly, Bryan F.J.; Schmutz, Joel A.

2001-01-01

The Mayfield method has been widely used for estimating survival of nests and young animals, especially when data are collected at irregular observation intervals. However, this method assumes survival is constant throughout the study period, which often ignores biologically relevant variation and may lead to biased survival estimates. We examined the bias and accuracy of 1 modification to the Mayfield method that allows for temporal variation in survival, and we developed and similarly tested 2 additional methods. One of these 2 new methods is simply an iterative extension of Klett and Johnson's method, which we refer to as the Iterative Mayfield method and bears similarity to Kaplan-Meier methods. The other method uses maximum likelihood techniques for estimation and is best applied to survival of animals in groups or families, rather than as independent individuals. We also examined how robust these estimators are to heterogeneity in the data, which can arise from such sources as dependent survival probabilities among siblings, inherent differences among families, and adoption. Testing of estimator performance with respect to bias, accuracy, and heterogeneity was done using simulations that mimicked a study of survival of emperor goose (Chen canagica) goslings. Assuming constant survival for inappropriately long periods of time or use of Klett and Johnson's methods resulted in large bias or poor accuracy (often >5% bias or root mean square error) compared to our Iterative Mayfield or maximum likelihood methods. Overall, estimator performance was slightly better with our Iterative Mayfield than our maximum likelihood method, but the maximum likelihood method provides a more rigorous framework for testing covariates and explicity models a heterogeneity factor. We demonstrated use of all estimators with data from emperor goose goslings. We advocate that future studies use the new methods outlined here rather than the traditional Mayfield method or its previous modifications.

A Heterogeneous Network Based Method for Identifying GBM-Related Genes by Integrating Multi-Dimensional Data.

PubMed

Chen Peng; Ao Li

2017-01-01

The emergence of multi-dimensional data offers opportunities for more comprehensive analysis of the molecular characteristics of human diseases and therefore improving diagnosis, treatment, and prevention. In this study, we proposed a heterogeneous network based method by integrating multi-dimensional data (HNMD) to identify GBM-related genes. The novelty of the method lies in that the multi-dimensional data of GBM from TCGA dataset that provide comprehensive information of genes, are combined with protein-protein interactions to construct a weighted heterogeneous network, which reflects both the general and disease-specific relationships between genes. In addition, a propagation algorithm with resistance is introduced to precisely score and rank GBM-related genes. The results of comprehensive performance evaluation show that the proposed method significantly outperforms the network based methods with single-dimensional data and other existing approaches. Subsequent analysis of the top ranked genes suggests they may be functionally implicated in GBM, which further corroborates the superiority of the proposed method. The source code and the results of HNMD can be downloaded from the following URL: http://bioinformatics.ustc.edu.cn/hnmd/ .

Using sequential self-calibration method to identify conductivity distribution: Conditioning on tracer test data

USGS Publications Warehouse

Hu, B.X.; He, C.

2008-01-01

An iterative inverse method, the sequential self-calibration method, is developed for mapping spatial distribution of a hydraulic conductivity field by conditioning on nonreactive tracer breakthrough curves. A streamline-based, semi-analytical simulator is adopted to simulate solute transport in a heterogeneous aquifer. The simulation is used as the forward modeling step. In this study, the hydraulic conductivity is assumed to be a deterministic or random variable. Within the framework of the streamline-based simulator, the efficient semi-analytical method is used to calculate sensitivity coefficients of the solute concentration with respect to the hydraulic conductivity variation. The calculated sensitivities account for spatial correlations between the solute concentration and parameters. The performance of the inverse method is assessed by two synthetic tracer tests conducted in an aquifer with a distinct spatial pattern of heterogeneity. The study results indicate that the developed iterative inverse method is able to identify and reproduce the large-scale heterogeneity pattern of the aquifer given appropriate observation wells in these synthetic cases. ?? International Association for Mathematical Geology 2008.

Careflow Mining Techniques to Explore Type 2 Diabetes Evolution.

PubMed

Dagliati, Arianna; Tibollo, Valentina; Cogni, Giulia; Chiovato, Luca; Bellazzi, Riccardo; Sacchi, Lucia

2018-03-01

In this work we describe the application of a careflow mining algorithm to detect the most frequent patterns of care in a type 2 diabetes patients cohort. The applied method enriches the detected patterns with clinical data to define temporal phenotypes across the studied population. Novel phenotypes are discovered from heterogeneous data of 424 Italian patients, and compared in terms of metabolic control and complications. Results show that careflow mining can help to summarize the complex evolution of the disease into meaningful patterns, which are also significant from a clinical point of view.

Long-Term Efficacy of Psychosocial Treatments for Adults With Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review

PubMed Central

López-Pinar, Carlos; Martínez-Sanchís, Sonia; Carbonell-Vayá, Enrique; Fenollar-Cortés, Javier; Sánchez-Meca, Julio

2018-01-01

Background: Recent evidence suggests that psychosocial treatments, particularly cognitive-behavioral therapy (CBT), are effective interventions for adult attention deficit hyperactivity disorder (ADHD). The objective of this review was to determine the long-term efficacy of psychosocial interventions in improving clinically relevant variables, including ADHD core symptoms, clinical global impression (CGI), and global functioning. Methods: In total, nine randomized controlled trials and three uncontrolled single-group pretest-posttest studies were included. The data from these studies were combined using the inverse variance method. Heterogeneity and risk of bias were assessed. Subgroup analyses and meta-regressions were performed, to determine the influence of different potential moderator variables (risk of bias, medication status, follow-up length, therapy type and setting, and control group type) on effect size (ES) estimates. Results: Up to 680 of a total of 1,073 participants assessed pre-treatment were retained at follow-up. Treatment groups showed greater improvement than control groups in self-reported total ADHD symptoms, inattention, and hyperactivity/impulsivity, in addition to CGI and global functioning. Blind assessors also reported a large ES in within-subject outcomes. Studies using dialectical behavioral therapy (DBT) in a group setting, with active control matching, and that were rated as having an unclear risk of bias, achieved significantly lower ES estimates for most outcomes. Treatment effectiveness, according to the CGI measure, and global functioning were significantly increased when the percentage of medicated participants was greater. Conclusions: Our results indicate that the post-treatment gains reported in previous reviews are sustained for at least 12 months. Nevertheless, these results must be interpreted with caution, because of a high level of heterogeneity among studies and the risk of bias observed in the majority of outcomes. Thus, these findings indicate that psychological interventions are a highly valuable and stable clinical tool for the treatment of core symptoms and global functioning in adults with ADHD. PMID:29780342

Long-Term Efficacy of Psychosocial Treatments for Adults With Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review.

PubMed

López-Pinar, Carlos; Martínez-Sanchís, Sonia; Carbonell-Vayá, Enrique; Fenollar-Cortés, Javier; Sánchez-Meca, Julio

2018-01-01

Background: Recent evidence suggests that psychosocial treatments, particularly cognitive-behavioral therapy (CBT), are effective interventions for adult attention deficit hyperactivity disorder (ADHD). The objective of this review was to determine the long-term efficacy of psychosocial interventions in improving clinically relevant variables, including ADHD core symptoms, clinical global impression (CGI), and global functioning. Methods: In total, nine randomized controlled trials and three uncontrolled single-group pretest-posttest studies were included. The data from these studies were combined using the inverse variance method. Heterogeneity and risk of bias were assessed. Subgroup analyses and meta-regressions were performed, to determine the influence of different potential moderator variables (risk of bias, medication status, follow-up length, therapy type and setting, and control group type) on effect size (ES) estimates. Results: Up to 680 of a total of 1,073 participants assessed pre-treatment were retained at follow-up. Treatment groups showed greater improvement than control groups in self-reported total ADHD symptoms, inattention, and hyperactivity/impulsivity, in addition to CGI and global functioning. Blind assessors also reported a large ES in within-subject outcomes. Studies using dialectical behavioral therapy (DBT) in a group setting, with active control matching, and that were rated as having an unclear risk of bias, achieved significantly lower ES estimates for most outcomes. Treatment effectiveness, according to the CGI measure, and global functioning were significantly increased when the percentage of medicated participants was greater. Conclusions: Our results indicate that the post-treatment gains reported in previous reviews are sustained for at least 12 months. Nevertheless, these results must be interpreted with caution, because of a high level of heterogeneity among studies and the risk of bias observed in the majority of outcomes. Thus, these findings indicate that psychological interventions are a highly valuable and stable clinical tool for the treatment of core symptoms and global functioning in adults with ADHD.

NMR analysis of compositional heterogeneity in polysaccharides

USDA-ARS?s Scientific Manuscript database

Many copolysaccharides are compositionally heterogeneous, and the composition determined by the usual analytical or spectroscopic methods provides only an average value. For some polysaccharides, the NMR data contain copolymer sequence information, such as diad, triad, and tetrad sequence intensiti...

Drug concentration heterogeneity facilitates the evolution of drug resistance.

PubMed

Kepler, T B; Perelson, A S

1998-09-29

Pathogenic microorganisms use Darwinian processes to circumvent attempts at their control through chemotherapy. In the case of HIV-1 infection, in which drug resistance is a continuing problem, we show that in one-compartment systems, there is a relatively narrow window of drug concentrations that allows evolution of resistant variants. When the system is enlarged to two spatially distinct compartments held at different drug concentrations with transport of virus between them, the range of average drug concentrations that allow evolution of resistance is significantly increased. For high average drug concentrations, resistance is very unlikely to arise without spatial heterogeneity. We argue that a quantitative understanding of the role played by heterogeneity in drug levels and pathogen transport is crucial for attempts to control re-emergent infectious disease.

A fully-coupled discontinuous Galerkin spectral element method for two-phase flow in petroleum reservoirs

NASA Astrophysics Data System (ADS)

Taneja, Ankur; Higdon, Jonathan

2018-01-01

A high-order spectral element discontinuous Galerkin method is presented for simulating immiscible two-phase flow in petroleum reservoirs. The governing equations involve a coupled system of strongly nonlinear partial differential equations for the pressure and fluid saturation in the reservoir. A fully implicit method is used with a high-order accurate time integration using an implicit Rosenbrock method. Numerical tests give the first demonstration of high order hp spatial convergence results for multiphase flow in petroleum reservoirs with industry standard relative permeability models. High order convergence is shown formally for spectral elements with up to 8th order polynomials for both homogeneous and heterogeneous permeability fields. Numerical results are presented for multiphase fluid flow in heterogeneous reservoirs with complex geometric or geologic features using up to 11th order polynomials. Robust, stable simulations are presented for heterogeneous geologic features, including globally heterogeneous permeability fields, anisotropic permeability tensors, broad regions of low-permeability, high-permeability channels, thin shale barriers and thin high-permeability fractures. A major result of this paper is the demonstration that the resolution of the high order spectral element method may be exploited to achieve accurate results utilizing a simple cartesian mesh for non-conforming geological features. Eliminating the need to mesh to the boundaries of geological features greatly simplifies the workflow for petroleum engineers testing multiple scenarios in the face of uncertainty in the subsurface geology.

Automated Traffic Management System and Method

NASA Technical Reports Server (NTRS)

Glass, Brian J. (Inventor); Spirkovska, Liljana (Inventor); McDermott, William J. (Inventor); Reisman, Ronald J. (Inventor); Gibson, James (Inventor); Iverson, David L. (Inventor)

2000-01-01

A data management system and method that enables acquisition, integration, and management of real-time data generated at different rates, by multiple heterogeneous incompatible data sources. The system achieves this functionality by using an expert system to fuse data from a variety of airline, airport operations, ramp control, and air traffic control tower sources, to establish and update reference data values for every aircraft surface operation. The system may be configured as a real-time airport surface traffic management system (TMS) that electronically interconnects air traffic control, airline data, and airport operations data to facilitate information sharing and improve taxi queuing. In the TMS operational mode, empirical data shows substantial benefits in ramp operations for airlines, reducing departure taxi times by about one minute per aircraft in operational use, translating as $12 to $15 million per year savings to airlines at the Atlanta, Georgia airport. The data management system and method may also be used for scheduling the movement of multiple vehicles in other applications, such as marine vessels in harbors and ports, trucks or railroad cars in ports or shipping yards, and railroad cars in switching yards. Finally, the data management system and method may be used for managing containers at a shipping dock, stock on a factory floor or in a warehouse, or as a training tool for improving situational awareness of FAA tower controllers, ramp and airport operators, or commercial airline personnel in airfield surface operations.

A Review of Preventative Methods against Human Leishmaniasis Infection

PubMed Central

Stockdale, Lisa; Newton, Robert

2013-01-01

Background Leishmaniasis is an intracellular parasitic infection transmitted to humans via the sandfly. Approximately 350 million people are at risk of contracting the disease and an estimated 1.6 million new cases occur annually. Of the two main forms, visceral and cutaneous, the visceral form is fatal in 85–90% of untreated cases. Aims This literature review aims to identify and evaluate the current evidence base for the use of various preventative methods against human leishmaniasis. Methods A literature search was performed of the relevant database repositories for primary research conforming to a priori inclusion and exclusion criteria. Results A total of 84 controlled studies investigating 12 outcome measures were identified, implementing four broad categories of preventative interventions: animal reservoir control, vector population control, human reservoir control and a category for multiple concurrently implemented interventions. The primary studies investigated a heterogeneous mix of outcome measures using a range of different methods. Conclusions This review highlights an absence of research measuring human-specific outcomes (35% of the total) across all intervention categories. The apparent inability of study findings to be generalizable across different geographic locations, points towards gaps in knowledge regarding the biology of transmission of Leishmania in different settings. More research is needed which investigates human infection as the primary outcome measure as opposed to intermediate surrogate markers, with a focus on developing a human vaccine. PMID:23818997

Precise Control of Quantum Confinement in Cesium Lead Halide Perovskite Quantum Dots via Thermodynamic Equilibrium.

PubMed

Dong, Yitong; Qiao, Tian; Kim, Doyun; Parobek, David; Rossi, Daniel; Son, Dong Hee

2018-05-09

Cesium lead halide (CsPbX 3 ) nanocrystals have emerged as a new family of materials that can outperform the existing semiconductor nanocrystals due to their superb optical and charge-transport properties. However, the lack of a robust method for producing quantum dots with controlled size and high ensemble uniformity has been one of the major obstacles in exploring the useful properties of excitons in zero-dimensional nanostructures of CsPbX 3 . Here, we report a new synthesis approach that enables the precise control of the size based on the equilibrium rather than kinetics, producing CsPbX 3 quantum dots nearly free of heterogeneous broadening in their exciton luminescence. The high level of size control and ensemble uniformity achieved here will open the door to harnessing the benefits of excitons in CsPbX 3 quantum dots for photonic and energy-harvesting applications.

ρ-VOF: An interface sharpening method for gas-liquid flow simulation

NASA Astrophysics Data System (ADS)

Wang, Jiantao; Liu, Gang; Jiang, Xiong; Mou, Bin

2018-05-01

The study on simulation of compressible gas-liquid flow remains open. Popular methods are either confined to incompressible flow regime, or inevitably induce smear of the free interface. A new finite volume method for compressible two-phase flow simulation is contributed for this subject. First, the “heterogeneous equilibrium” assumption is introduced to the control volume, by hiring free interface reconstruction technology, the distribution of each component in the control volume is achieved. Next, AUSM+-up (advection upstream splitting method) scheme is employed to calculate the convective fluxes and pressure fluxes, with the contact discontinuity characteristic considered, followed by the update of the whole flow field. The new method features on density-based pattern and interface reconstruction technology from VOF (volume of fluid), thus we name it “ρ-VOF method”. Inherited from AUSM families and VOF, ρ-VOF behaves as an all-speed method, capable of simulating shock in gas-liquid flow, and preserving the sharpness of the free interface. Gas-liquid shock tube is simulated to evaluate the method, from which good agreement is obtained between the predicted results and those of the cited literature, meanwhile, sharper free interface is identified. Finally, the capability and validity of ρ-VOF method can be concluded in compressible gas-liquid flow simulation.

Probing messenger RNA conformational heterogeneity using single-molecule fluorescence anisotropy

NASA Astrophysics Data System (ADS)

Sinha, Deepak; Sastry, Srikanth; Shivashankar, G. V.

2006-03-01

In this letter we describe a method to probe biomolecular conformations and their dynamics at the single molecule level. We show, using fluorescence anisotropy based methods, that the hydrodynamic volume of biomolecules captures the intrinsic heterogeneity within a population. Population distributions of conformations and their dynamics are studied by making anisotropy measurements on one molecule at a time within a confocal volume. The mean anisotropy of mRNA is lowered on addition of salt while the spread remains the same. The intrinsic heterogeneity is revealed when conformational transitions are frozen, resulting in a drastic increase in the spread of the anisotropy. These studies reveal that mRNA samples a broad range of conformations.

A study of fracture phenomena in fiber composite laminates. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Konish, H. J., Jr.

1973-01-01

The extension of linear elastic fracture mechanics from ostensibly homogeneous isotropic metallic alloys to heterogeneous anisotropic advanced fiber composites is considered. It is analytically demonstrated that the effects of material anisotropy do not alter the principal characteristics exhibited by a crack in an isotropic material. The heterogeneity of fiber composites is experimentally shown to have a negligible effect on the behavior of a sufficiently long crack. A method is proposed for predicting the fracture strengths of a large class of composite laminates; the values predicted by this method show good agreement with limited experimental data. The limits imposed by material heterogeneity are briefly discussed, and areas for further study are recommended.

Two new methods to fit models for network meta-analysis with random inconsistency effects.

PubMed

Law, Martin; Jackson, Dan; Turner, Rebecca; Rhodes, Kirsty; Viechtbauer, Wolfgang

2016-07-28

Meta-analysis is a valuable tool for combining evidence from multiple studies. Network meta-analysis is becoming more widely used as a means to compare multiple treatments in the same analysis. However, a network meta-analysis may exhibit inconsistency, whereby the treatment effect estimates do not agree across all trial designs, even after taking between-study heterogeneity into account. We propose two new estimation methods for network meta-analysis models with random inconsistency effects. The model we consider is an extension of the conventional random-effects model for meta-analysis to the network meta-analysis setting and allows for potential inconsistency using random inconsistency effects. Our first new estimation method uses a Bayesian framework with empirically-based prior distributions for both the heterogeneity and the inconsistency variances. We fit the model using importance sampling and thereby avoid some of the difficulties that might be associated with using Markov Chain Monte Carlo (MCMC). However, we confirm the accuracy of our importance sampling method by comparing the results to those obtained using MCMC as the gold standard. The second new estimation method we describe uses a likelihood-based approach, implemented in the metafor package, which can be used to obtain (restricted) maximum-likelihood estimates of the model parameters and profile likelihood confidence intervals of the variance components. We illustrate the application of the methods using two contrasting examples. The first uses all-cause mortality as an outcome, and shows little evidence of between-study heterogeneity or inconsistency. The second uses "ear discharge" as an outcome, and exhibits substantial between-study heterogeneity and inconsistency. Both new estimation methods give results similar to those obtained using MCMC. The extent of heterogeneity and inconsistency should be assessed and reported in any network meta-analysis. Our two new methods can be used to fit models for network meta-analysis with random inconsistency effects. They are easily implemented using the accompanying R code in the Additional file 1. Using these estimation methods, the extent of inconsistency can be assessed and reported.

Degradation of bisphenol A in water by the heterogeneous photo-Fenton.

PubMed

Jiang, Chuanrui; Xu, Zhencheng; Guo, Qingwei; Zhuo, Qiongfang

2014-01-01

Bisphenol A (BPA) is a kind of a controversial endocrine disruptor, and is ubiquitous in environment. The degradation of BPA with the heterogeneous photo-Fenton system was demonstrated in this study. The Fe-Y molecular sieve catalyst was prepared with the ion exchange method, and it was characterized by X-ray radiation diffraction (XRD). The effects ofpH, initial concentration of H2O2, initial BPA concentration, and irradiation intensity on the degradation of BPA were investigated. The service life and iron solubility of catalyst were also tested. XRD test shows that the major phase of the Fe-Y catalyst was Fe2O3. The method of heterogeneous photo-Fenton with Fe-Y catalyst was superior to photolysis, photo-oxidation with only hydrogen, heterogeneous Fenton, and homogeneous photo-Fenton approaches. pH value had no obvious effects on BPA degradation over the range of 2.2-7.2. The initial concentration of H2O2 had an optimal value of 20 x 10(-4) mol/L. The decrease in initial concentration of BPA was favourable for degradation. The intensity of ultraviolet irradiation has no obvious effect on the BPA removal. The stability tests indicated that the Fe-Y catalyst can be reused and iron solubility concentration ranged from NA to 0.0062 mg/L. Based on the results, the heterogeneous photo-Fenton treatment is the available method for the degradation of BPA.

Modeling and scaleup of steamflood in a heterogeneous reservoir

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

Dehghani, K.; Basham, W.M.; Durlofsky, L.J.

1995-11-01

A series of simulation runs was conducted for different geostatistically derived cross-sectional models to study the degree of heterogeneity required for proper modeling of steamfloods in a thick, heavy-oil reservoir with thin diatomite barriers Different methods for coarsening the most detailed models were applied, and performance predictions for the coarsened and detailed models compared. Use of a general scaleup method provided the most accurate coarse grid models.

Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

PubMed

Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

2015-05-01

Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for Bone and Mineral Research.

Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials

PubMed Central

Yu, Hong; Chi, Dongmei; Wang, Siyang; Liu, Bin

2016-01-01

Objective To determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines. Methods MEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality. Results 5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I2=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I2=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I2=0%, respectively). Conclusions The current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit. PMID:26932135

LNAPL source zone delineation using soil gases in a heterogeneous silty-sand aquifer.

PubMed

Cohen, Grégory J V; Jousse, Florie; Luze, Nicolas; Höhener, Patrick; Atteia, Olivier

2016-09-01

Source delineation of hydrocarbon contaminated sites is of high importance for remediation work. However, traditional methods like soil core extraction and analysis or recent Membrane Interface Probe methods are time consuming and costly. Therefore, the development of an in situ method based on soil gas analysis can be interesting. This includes the direct measurement of volatile organic compounds (VOCs) in soil gas taken from gas probes using a PID (Photo Ionization Detector) and the analysis of other soil gases related to VOC degradation distribution (CH4, O2, CO2) or related to presence of Light Non-Aqueous Phase Liquid (LNAPL) as (222)Rn. However, in widespread heterogeneous formations, delineation by gas measurements becomes more challenging. The objective of this study is twofold: (i) to analyse the potential of several in situ gas measurement techniques in comparison to soil coring for LNAPL source delineation at a heterogeneous contaminated site where the techniques might be limited by a low diffusion potential linked to the presence of fine sands and silts, and (ii) to analyse the effect of vertical sediment heterogeneities on the performance of these gas measurement methods. Thus, five types of gases were analysed: VOCs, their three related degradation products O2, CO2 and CH4 and (222)Rn. Gas measurements were compared to independent LNAPL analysis by coring. This work was conducted at an old industrial site frequently contaminated by a Diesel-Fuel mixture located in a heterogeneous fine-grained aquifer. Results show that in such heterogeneous media migration of reactive gases like VOCs occurs only across small distances and the VOC concentrations sampled with gas probes are mainly related to local conditions rather than the presence of LNAPL below the gas probe. (222)Rn is not well correlated with LNAPL because of sediment heterogeneity. Oxygen, CO2, and especially CH4, have larger lengths of diffusion and give the clearest picture for LNAPL presence at this site even when the gas probe is somewhat distant. Copyright © 2016 Elsevier B.V. All rights reserved.

An electrical resistivity-based method for investigation of subsurface structure

NASA Astrophysics Data System (ADS)

Alves Meira Neto, A.; Litwin, D.; Troch, P. A. A.; Ferre, T. P. A.

2017-12-01

Resolving the spatial distribution of soil porosity within the subsurface is of great importance for understanding flow and transport within heterogeneous media. Additionally, porosity patterns can be associated with the availability of water and carbon dioxide that will drive geochemical reactions and constrain microbiological growth. The use of controlled experimentation has the potential to circumvent problems related to the external and internal variability of natural systems, while also allowing a higher degree of observability. In this study, we suggest an ERT-based method of retrieving porosity fields based on the application of Archie's law associated with an experimental procedure that can be used in laboratory-scale studies. We used a 2 cubic meter soil lysimeter, equipped with 238 electrodes distributed along its walls for testing the method. The lysimeter serves as a scaled-down version of the highly monitored artificial hillslopes at the Landscape Evolution Observatory (LEO) located at Biosphere 2 - University of Arizona. The capability of the ERT system in deriving spatially distributed patterns of porosity with respect to its several sources of uncertainty was numerically evaluated. The results will be used to produce an optimal experimental design and for assessing the reliability of experimental results. This novel approach has the potential to further resolve subsurface heterogeneity within the LEO project, and highlight the use of ERT-derived results for hydro-bio-geochemical studies.

Cause-specific mortality time series analysis: a general method to detect and correct for abrupt data production changes

PubMed Central

2011-01-01

Background Monitoring the time course of mortality by cause is a key public health issue. However, several mortality data production changes may affect cause-specific time trends, thus altering the interpretation. This paper proposes a statistical method that detects abrupt changes ("jumps") and estimates correction factors that may be used for further analysis. Methods The method was applied to a subset of the AMIEHS (Avoidable Mortality in the European Union, toward better Indicators for the Effectiveness of Health Systems) project mortality database and considered for six European countries and 13 selected causes of deaths. For each country and cause of death, an automated jump detection method called Polydect was applied to the log mortality rate time series. The plausibility of a data production change associated with each detected jump was evaluated through literature search or feedback obtained from the national data producers. For each plausible jump position, the statistical significance of the between-age and between-gender jump amplitude heterogeneity was evaluated by means of a generalized additive regression model, and correction factors were deduced from the results. Results Forty-nine jumps were detected by the Polydect method from 1970 to 2005. Most of the detected jumps were found to be plausible. The age- and gender-specific amplitudes of the jumps were estimated when they were statistically heterogeneous, and they showed greater by-age heterogeneity than by-gender heterogeneity. Conclusion The method presented in this paper was successfully applied to a large set of causes of death and countries. The method appears to be an alternative to bridge coding methods when the latter are not systematically implemented because they are time- and resource-consuming. PMID:21929756

Multiscale analysis and computation for flows in heterogeneous media

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

Efendiev, Yalchin; Hou, T. Y.; Durlofsky, L. J.

Our work in this project is aimed at making fundamental advances in multiscale methods for flow and transport in highly heterogeneous porous media. The main thrust of this research is to develop a systematic multiscale analysis and efficient coarse-scale models that can capture global effects and extend existing multiscale approaches to problems with additional physics and uncertainties. A key emphasis is on problems without an apparent scale separation. Multiscale solution methods are currently under active investigation for the simulation of subsurface flow in heterogeneous formations. These procedures capture the effects of fine-scale permeability variations through the calculation of specialized coarse-scalemore » basis functions. Most of the multiscale techniques presented to date employ localization approximations in the calculation of these basis functions. For some highly correlated (e.g., channelized) formations, however, global effects are important and these may need to be incorporated into the multiscale basis functions. Other challenging issues facing multiscale simulations are the extension of existing multiscale techniques to problems with additional physics, such as compressibility, capillary effects, etc. In our project, we explore the improvement of multiscale methods through the incorporation of additional (single-phase flow) information and the development of a general multiscale framework for flows in the presence of uncertainties, compressible flow and heterogeneous transport, and geomechanics. We have considered (1) adaptive local-global multiscale methods, (2) multiscale methods for the transport equation, (3) operator-based multiscale methods and solvers, (4) multiscale methods in the presence of uncertainties and applications, (5) multiscale finite element methods for high contrast porous media and their generalizations, and (6) multiscale methods for geomechanics. Below, we present a brief overview of each of these contributions.« less

Metaplot: a novel stata graph for assessing heterogeneity at a glance.

PubMed

Poorolajal, J; Mahmoodi, M; Majdzadeh, R; Fotouhi, A

2010-01-01

Heterogeneity is usually a major concern in meta-analysis. Although there are some statistical approaches for assessing variability across studies, here we present a new approach to heterogeneity using "MetaPlot" that investigate the influence of a single study on the overall heterogeneity. MetaPlot is a two-way (x, y) graph, which can be considered as a complementary graphical approach for testing heterogeneity. This method shows graphically as well as numerically the results of an influence analysis, in which Higgins' I(2) statistic with 95% (Confidence interval) CI are computed omitting one study in each turn and then are plotted against reciprocal of standard error (1/SE) or "precision". In this graph, "1/SE" lies on x axis and "I(2) results" lies on y axe. Having a first glance at MetaPlot, one can predict to what extent omission of a single study may influence the overall heterogeneity. The precision on x-axis enables us to distinguish the size of each trial. The graph describes I(2) statistic with 95% CI graphically as well as numerically in one view for prompt comparison. It is possible to implement MetaPlot for meta-analysis of different types of outcome data and summary measures. This method presents a simple graphical approach to identify an outlier and its effect on overall heterogeneity at a glance. We wish to suggest MetaPlot to Stata experts to prepare its module for the software.

Transport of Cryptosporidium parvum Oocysts in Charge Heterogeneous Porous Media: Microfluidics Experiment and Numerical Simulation

NASA Astrophysics Data System (ADS)

Liu, Y.; Meng, X.; Guo, Z.; Zhang, C.; Nguyen, T. H.; Hu, D.; Ji, J.; Yang, X.

2017-12-01

Colloidal attachment on charge heterogeneous grains has significant environmental implications for transport of hazardous colloids, such as pathogens, in the aquifer, where iron, manganese, and aluminium oxide minerals are the major source of surface charge heterogeneity of the aquifer grains. A patchwise surface charge model is often used to describe the surface charge heterogeneity of the grains. In the patchwise model, the colloidal attachment efficiency is linearly correlated with the fraction of the favorable patches (θ=λ(θf - θu)+θu). However, our previous microfluidic study showed that the attachment efficiency of oocysts of Cryptosporidium parvum, a waterborne protozoan parasite, was not linear correlated with the fraction of the favorable patches (λ). In this study, we developed a pore scale model to simulate colloidal transport and attachment on charge heterogeneous grains. The flow field was simulated using the LBM method and colloidal transport and attachment were simulated using the Lagrange particle tracking method. The pore scale model was calibrated with experimental results of colloidal and oocyst transport in microfluidic devices and was then used to simulate oocyst transport in charge heterogeneous porous media under a variety of environmental relative conditions, i.e. the fraction of favorable patchwise, ionic strength, and pH. The results of the pore scale simulations were used to evaluate the effect of surface charge heterogeneity on upscaling of oocyst transport from pore to continuum scale and to develop an applicable correlation between colloidal attachment efficiency and the fraction of the favorable patches.

The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes

PubMed Central

Jovanovski, Elena; Li, Dandan; Thanh Ho, Hoang Vi; Djedovic, Vladimir; Ruiz Marques, Any de Castro; Shishtar, Esra; Mejia, Sonia Blanco; Sievenpiper, John L.; de Souza, Russell J.; Duvnjak, Lea; Vuksan, Vladimir

2017-01-01

Abstract Background: Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation. Methods: The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic. Results: A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = –.01; [95%: –.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: –.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: –5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I2 ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of –.25 (95% CI: –.38, –.12; P <.001) for HbA1c (%). Conclusions: ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area. PMID:28538363

Sources of heterogeneity in studies of the BMI-mortality association.

PubMed

Peter, Raphael Simon; Nagel, Gabriele

2017-06-01

To date, the amount of heterogeneity among studies of the body mass index-mortality association attributable to differences in the age distribution and length of follow-up has not been quantified. Therefore, we wanted to quantify the amount of heterogeneity attributable to age and follow-up in results of studies on the body mass index-mortality relation. We used optima of the body mass index mortality association reported for 30 populations and performed meta-regression to estimate the amount of heterogeneity attributable to sex, ethnicity, mean age at baseline, percentage smokers, and length of follow-up. Ethnicity as single factor accounted for 36% (95% CI, 11-56%) of heterogeneity. Mean age and length of follow-up had an interactive effect and together accounted for 56% (95% CI, 24-74%) of the remaining heterogeneity. Sex did not significantly contribute to the heterogeneity, after controlling for ethnicity, age, and length of follow-up. A considerable amount of heterogeneity in studies of the body mass index-mortality association is attributable to ethnicity, age, and length of follow-up. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

PubMed Central

Trifan, Anca; Stanciu, Carol; Girleanu, Irina; Stoica, Oana Cristina; Singeap, Ana Maria; Maxim, Roxana; Chiriac, Stefan Andrei; Ciobica, Alin; Boiculese, Lucian

2017-01-01

AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal. PMID:29085200

Identifying sources of heterogeneity in capture probabilities: An example using the Great Tit Parus major

USGS Publications Warehouse

Senar, J.C.; Conroy, M.J.; Carrascal, L.M.; Domenech, J.; Mozetich, I.; Uribe, F.

1999-01-01

Heterogeneous capture probabilities are a common problem in many capture-recapture studies. Several methods of detecting the presence of such heterogeneity are currently available, and stratification of data has been suggested as the standard method to avoid its effects. However, few studies have tried to identify sources of heterogeneity, or whether there are interactions among sources. The aim of this paper is to suggest an analytical procedure to identify sources of capture heterogeneity. We use data on the sex and age of Great Tits captured in baited funnel traps, at two localities differing in average temperature. We additionally use 'recapture' data obtained by videotaping at feeder (with no associated trap), where the tits ringed with different colours were recorded. This allowed us to test whether individuals in different classes (age, sex and condition) are not trapped because of trap shyness or because o a reduced use of the bait. We used logistic regression analysis of the capture probabilities to test for the effects of age, sex, condition, location and 'recapture method. The results showed a higher recapture probability in the colder locality. Yearling birds (either males or females) had the highest recapture prob abilities, followed by adult males, while adult females had the lowest recapture probabilities. There was no effect of the method of 'recapture' (trap or video tape), which suggests that adult females are less often captured in traps no because of trap-shyness but because of less dependence on supplementary food. The potential use of this methodological approach in other studies is discussed.

Digital signaling decouples activation probability and population heterogeneity.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Lipniacki, Tomasz; Quake, Stephen R; Tay, Savaş

2015-10-21

Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Optimization and real-time control for laser treatment of heterogeneous soft tissues.

PubMed

Feng, Yusheng; Fuentes, David; Hawkins, Andrea; Bass, Jon M; Rylander, Marissa Nichole

2009-01-01

Predicting the outcome of thermotherapies in cancer treatment requires an accurate characterization of the bioheat transfer processes in soft tissues. Due to the biological and structural complexity of tumor (soft tissue) composition and vasculature, it is often very difficult to obtain reliable tissue properties that is one of the key factors for the accurate treatment outcome prediction. Efficient algorithms employing in vivo thermal measurements to determine heterogeneous thermal tissues properties in conjunction with a detailed sensitivity analysis can produce essential information for model development and optimal control. The goals of this paper are to present a general formulation of the bioheat transfer equation for heterogeneous soft tissues, review models and algorithms developed for cell damage, heat shock proteins, and soft tissues with nanoparticle inclusion, and demonstrate an overall computational strategy for developing a laser treatment framework with the ability to perform real-time robust calibrations and optimal control. This computational strategy can be applied to other thermotherapies using the heat source such as radio frequency or high intensity focused ultrasound.

Generalized multiscale finite-element method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

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

Gao, Kai; Fu, Shubin; Gibson, Richard L.

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

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

Gao, Kai, E-mail: kaigao87@gmail.com; Fu, Shubin, E-mail: shubinfu89@gmail.com; Gibson, Richard L., E-mail: gibson@tamu.edu

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Generalized multiscale finite-element method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

DOE PAGES

Gao, Kai; Fu, Shubin; Gibson, Richard L.; ...

2015-04-14

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Transmission X-ray scattering as a probe for complex liquid-surface structures

DOE PAGES

Fukuto, Masafumi; Yang, Lin; Nykypanchuk, Dmytro; ...

2016-01-28

The need for functional materials calls for increasing complexity in self-assembly systems. As a result, the ability to probe both local structure and heterogeneities, such as phase-coexistence and domain morphologies, has become increasingly important to controlling self-assembly processes, including those at liquid surfaces. The traditional X-ray scattering methods for liquid surfaces, such as specular reflectivity and grazing-incidence diffraction, are not well suited to spatially resolving lateral heterogeneities due to large illuminated footprint. A possible alternative approach is to use scanning transmission X-ray scattering to simultaneously probe local intermolecular structures and heterogeneous domain morphologies on liquid surfaces. To test the feasibilitymore » of this approach, transmission small- and wide-angle X-ray scattering (TSAXS/TWAXS) studies of Langmuir films formed on water meniscus against a vertically immersed hydrophilic Si substrate were recently carried out. First-order diffraction rings were observed in TSAXS patterns from a monolayer of hexagonally packed gold nanoparticles and in TWAXS patterns from a monolayer of fluorinated fatty acids, both as a Langmuir monolayer on water meniscus and as a Langmuir–Blodgett monolayer on the substrate. The patterns taken at multiple spots have been analyzed to extract the shape of the meniscus surface and the ordered-monolayer coverage as a function of spot position. These results, together with continual improvement in the brightness and spot size of X-ray beams available at synchrotron facilities, support the possibility of using scanning-probe TSAXS/TWAXS to characterize heterogeneous structures at liquid surfaces.« less

Joubert syndrome: A model for untangling recessive disorders with extreme genetic heterogeneity

PubMed Central

R, Bachmann-Gagescu; JC, Dempsey; IG, Phelps; BJ, O’Roak; DM, Knutzen; TC, Rue; GE, Ishak; CR, Isabella; N, Gorden; J, Adkins; EA, Boyle; N, de Lacy; D, O’Day; A, Alswaid; AR, Devi; L, Lingappa; C, Lourenço; L, Martorell; À, Garcia-Cazorla; H, Ozyürek; G, Haliloğlu; B, Tuysuz; M, Topçu; P, Chance; MA, Parisi; I, Glass; J, Shendure; D, Doherty

2016-01-01

Background Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances, and a distinctive mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS. Methods We sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion (CADD) algorithm with an optimized score cut-off. Results We identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a “pure JS” phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS-subtypes. Conclusion This work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes, and enable gene-specific treatments in the future. PMID:26092869

Using Polymer Alternating Gas to Enhance Oil Recovery in Heavy Oil

NASA Astrophysics Data System (ADS)

Yang, Yongzhi; Li, Weirong; Zhou, Tiyao; Dong, Zhenzhen

2018-02-01

CO2 has been used to recover oil for more than 40 years. Currently, about 43% of EOR production in U.S. is from CO2 flooding. CO2 flooding is a well-established EOR technique, but its density and viscosity nature are challenges for CO2 projects. Low density (0.5 to 0.8 g/cm3) causes gas to rise upward in reservoirs and bypass many lower portions of the reservoir. Low viscosity (0.02 to 0.08 cp) leads to poor volumetric sweep efficiency. So water-alternating-gas (WAG) method was used to control the mobility of CO2 and improve sweep efficiency. However, WAG process has some other problems in heavy oil reservoir, such as poor mobility ratio and gravity overriding. To examine the applicability of carbon dioxide to recover viscous oil from highly heterogeneous reservoirs, this study suggests a new EOR method--polymer-alternating gas (PAG) process. The process involves a combination of polymer flooding and CO2 injection. To confirm the effectiveness of PAG process in heavy oils, a reservoir model from Liaohe Oilfield is used to compare the technical and economic performance among PAG, WAG and polymer flooding. Simulation results show that PAG method would increase oil recovery over 10% compared with other EOR methods and PAG would be economically success based on assumption in this study. This study is the first to apply PAG to enhance oil recovery in heavy oil reservoir with highly heterogeneous. Besides, this paper provides detailed discussions and comparison about PAG with other EOR methods in this heavy oil reservoir.

Mesenchymal stem cells in maxillary sinus augmentation: A systematic review with meta-analysis

PubMed Central

Mangano, Francesco G; Colombo, Marco; Veronesi, Giovanni; Caprioglio, Alberto; Mangano, Carlo

2015-01-01

AIM: To investigate the effectiveness of mesenchymal stem cells (MSCs) in maxillary sinus augmentation (MSA), with various scaffold materials. METHODS: MEDLINE, EMBASE and SCOPUS were searched using keywords such as sinus graft, MSA, maxillary sinus lift, sinus floor elevation, MSC and cell-based, in different combinations. The searches included full text articles written in English, published over a 10-year period (2004-2014). Inclusion criteria were clinical/radiographic and histologic/ histomorphometric studies in humans and animals, on the use of MSCs in MSA. Meta-analysis was performed only for experimental studies (randomized controlled trials and controlled trials) involving MSA, with an outcome measurement of histologic evaluation with histomorphometric analysis reported. Mean and standard deviation values of newly formed bone from each study were used, and weighted mean values were assessed to account for the difference in the number of subjects among the different studies. To compare the results between the test and the control groups, the differences of regenerated bone in mean and 95% confidence intervals were calculated. RESULTS: Thirty-nine studies (18 animal studies and 21 human studies) published over a 10-year period (between 2004 and 2014) were considered to be eligible for inclusion in the present literature review. These studies demonstrated considerable variation with respect to study type, study design, follow-up, and results. Meta-analysis was performed on 9 studies (7 animal studies and 2 human studies). The weighted mean difference estimate from a random-effect model was 9.5% (95%CI: 3.6%-15.4%), suggesting a positive effect of stem cells on bone regeneration. Heterogeneity was measured by the I2 index. The formal test confirmed the presence of substantial heterogeneity (I2 = 83%, P < 0.0001). In attempt to explain the substantial heterogeneity observed, we considered a meta-regression model with publication year, support type (animal vs humans) and follow-up length (8 or 12 wk) as covariates. After adding publication year, support type and follow-up length to the meta-regression model, heterogeneity was no longer significant (I2 = 33%, P = 0.25). CONCLUSION: Several studies have demonstrated the potential for cell-based approaches in MSA; further clinical trials are needed to confirm these results. PMID:26240683

Vortex forcing model for turbulent flow over spanwise-heterogeneous topogrpahies: scaling arguments and similarity solution

NASA Astrophysics Data System (ADS)

Anderson, William; Yang, Jianzhi

2017-11-01

Spanwise surface heterogeneity beneath high-Reynolds number, fully-rough wall turbulence is known to induce mean secondary flows in the form of counter-rotating streamwise vortices. The secondary flows are a manifestation of Prandtl's secondary flow of the second kind - driven and sustained by spatial heterogeneity of components of the turbulent (Reynolds averaged) stress tensor. The spacing between adjacent surface heterogeneities serves as a control on the spatial extent of the counter-rotating cells, while their intensity is controlled by the spanwise gradient in imposed drag (where larger gradients associated with more dramatic transitions in roughness induce stronger cells). In this work, we have performed an order of magnitude analysis of the mean (Reynolds averaged) streamwise vorticity transport equation, revealing the scaling dependence of circulation upon spanwise spacing. The scaling arguments are supported by simulation data. Then, we demonstrate that mean streamwise velocity can be predicted a priori via a similarity solution to the mean streamwise vorticity transport equation. A vortex forcing term was used to represent the affects of spanwise topographic heterogeneity within the flow. Efficacy of the vortex forcing term was established with large-eddy simulation cases, wherein vortex forcing model parameters were altered to capture different values of spanwise spacing.

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

PubMed Central

Radovich, Milan; Clare, Susan E.; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A.; Solzak, Jeffrey P.; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V.; Rufenbarger, Connie; Lillemoe, Heather A.; Blosser, Rachel J.; Choi, Mi Ran; Sauder, Candice A.; Doxey, Diane; Henry, Jill E.; Hilligoss, Eric E.; Sakarya, Onur; Hyland, Fiona C.; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W.; Schneider, Bryan P.

2014-01-01

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER−,PR−,HER2−). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90% of TNBCs revealing an over-expressed central network. In conclusion, Use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos. PMID:24292813

The impact of capsaicin intake on risk of developing gastric cancers: a meta-analysis.

PubMed

Pabalan, Noel; Jarjanazi, Hamdi; Ozcelik, Hilmi

2014-09-01

Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls. We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome. The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity) < 0.0001-0.04). The homogeneous (P(heterogeneity) = 0.27-0.37) H. pylori (OR 0.60 and 1.69) effects were highly significant (P < 0.001) in the low and medium-high intake analyses, respectively. Given outcomes from the tests of interaction, high capsaicin intake is significantly different from the protection that low consumption offers. This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits.

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

PubMed

Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

2014-01-01

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

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

J. Zhou; H. Huang; M. Deo

Log and seismic data indicate that most shale formations have strong heterogeneity. Conventional analytical and semi-analytical fracture models are not enough to simulate the complex fracture propagation in these highly heterogeneous formation. Without considering the intrinsic heterogeneity, predicted morphology of hydraulic fracture may be biased and misleading in optimizing the completion strategy. In this paper, a fully coupling fluid flow and geomechanics hydraulic fracture simulator based on dual-lattice Discrete Element Method (DEM) is used to predict the hydraulic fracture propagation in heterogeneous reservoir. The heterogeneity of rock is simulated by assigning different material force constant and critical strain to differentmore » particles and is adjusted by conditioning to the measured data and observed geological features. Based on proposed model, the effects of heterogeneity at different scale on micromechanical behavior and induced macroscopic fractures are examined. From the numerical results, the microcrack will be more inclined to form at the grain weaker interface. The conventional simulator with homogeneous assumption is not applicable for highly heterogeneous shale formation.« less

Scaling properties of conduction velocity in heterogeneous excitable media

NASA Astrophysics Data System (ADS)

Shajahan, T. K.; Borek, Bartłomiej; Shrier, Alvin; Glass, Leon

2011-10-01

Waves of excitation through excitable media, such as cardiac tissue, can propagate as plane waves or break up to form reentrant spiral waves. In diseased hearts reentrant waves can be associated with fatal cardiac arrhythmias. In this paper we investigate the conditions that lead to wave break, reentry, and propagation failure in mathematical models of heterogeneous excitable media. Two types of heterogeneities are considered: sinks are regions in space in which the voltage is fixed at its rest value, and breaks are nonconducting regions with no-flux boundary conditions. We find that randomly distributed heterogeneities in the medium have a decremental effect on the velocity, and above a critical density of such heterogeneities the conduction fails. Using numerical and analytical methods we derive the general relationship among the conduction velocity, density of heterogeneities, diffusion coefficient, and the rise time of the excitation in both two and three dimensions. This work helps us understand the factors leading to reduced propagation velocity and the formation of spiral waves in heterogeneous excitable media.

Effectiveness of Xylitol in Reducing Dental Caries in Children.

PubMed

Marghalani, Abdullah A; Guinto, Emilie; Phan, Minhthu; Dhar, Vineet; Tinanoff, Norman

2017-03-15

The purpose of this study was to evaluate the effectiveness of xylitol in reducing dental caries in children compared to no treatment, a placebo, or preventive strategies. MEDLINE via PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 1, 1995 through Sept. 26, 2016 for randomized and controlled trials on children consuming xylitol for at least 12 months. The primary endpoint was caries reduction measured by mean decayed, missing, and filled primary and permanent surfaces/ teeth (dmfs/t, DMFS/T, respectively). The I2 and chi-square test for heterogeneity were used to detect trial heterogeneity. Meta-analyses were performed and quality was evaluated using GRADE profiler software. Analysis of five randomized controlled trials (RCTs) showed that xylitol had a small effect on reducing dental caries (standardized mean difference [SMD] equals -0.24; 95 percent confidence interval [CI] equals -0.48 to 0.01; P = 0.06) with a very low quality of evidence and considerable heterogeneity. Studies with higher xylitol doses (greater than four grams per day) demonstrated a medium caries reduction (SMD equals -0.54; 95 percent CI equals -1.14 to 0.05; P = 0.07), with these studies also having considerable heterogeneity and very low quality of evidence. The present systematic review examining the effectiveness of xylitol on caries incidence in children showed a small effect size in randomized controlled trials and a very low quality of evidence that makes preventive action of xylitol uncertain.

Three-dimensional modeling of nitrate-N transport in vadose zone: Roles of soil heterogeneity and groundwater flux.

PubMed

Akbariyeh, Simin; Bartelt-Hunt, Shannon; Snow, Daniel; Li, Xu; Tang, Zhenghong; Li, Yusong

2018-04-01

Contamination of groundwater from nitrogen fertilizers in agricultural lands is an important environmental and water quality management issue. It is well recognized that in agriculturally intensive areas, fertilizers and pesticides may leach through the vadose zone and eventually reach groundwater. While numerical models are commonly used to simulate fate and transport of agricultural contaminants, few models have considered a controlled field work to investigate the influence of soil heterogeneity and groundwater flow on nitrate-N distribution in both root zone and deep vadose zone. In this work, a numerical model was developed to simulate nitrate-N transport and transformation beneath a center pivot-irrigated corn field on Nebraska Management System Evaluation area over a three-year period. The model was based on a realistic three-dimensional sediment lithology, as well as carefully controlled irrigation and fertilizer application plans. In parallel, a homogeneous soil domain, containing the major sediment type of the site (i.e. sandy loam), was developed to conduct the same water flow and nitrate-N leaching simulations. Simulated nitrate-N concentrations were compared with the monitored nitrate-N concentrations in 10 multi-level sampling wells over a three-year period. Although soil heterogeneity was mainly observed from top soil to 3 m below the surface, heterogeneity controlled the spatial distribution of nitrate-N concentration. Soil heterogeneity, however, has minimal impact on the total mass of nitrate-N in the domain. In the deeper saturated zone, short-term variations of nitrate-N concentration correlated with the groundwater level fluctuations. Copyright © 2018 Elsevier B.V. All rights reserved.

Three-dimensional modeling of nitrate-N transport in vadose zone: Roles of soil heterogeneity and groundwater flux

NASA Astrophysics Data System (ADS)

Akbariyeh, Simin; Bartelt-Hunt, Shannon; Snow, Daniel; Li, Xu; Tang, Zhenghong; Li, Yusong

2018-04-01

Contamination of groundwater from nitrogen fertilizers in agricultural lands is an important environmental and water quality management issue. It is well recognized that in agriculturally intensive areas, fertilizers and pesticides may leach through the vadose zone and eventually reach groundwater. While numerical models are commonly used to simulate fate and transport of agricultural contaminants, few models have considered a controlled field work to investigate the influence of soil heterogeneity and groundwater flow on nitrate-N distribution in both root zone and deep vadose zone. In this work, a numerical model was developed to simulate nitrate-N transport and transformation beneath a center pivot-irrigated corn field on Nebraska Management System Evaluation area over a three-year period. The model was based on a realistic three-dimensional sediment lithology, as well as carefully controlled irrigation and fertilizer application plans. In parallel, a homogeneous soil domain, containing the major sediment type of the site (i.e. sandy loam), was developed to conduct the same water flow and nitrate-N leaching simulations. Simulated nitrate-N concentrations were compared with the monitored nitrate-N concentrations in 10 multi-level sampling wells over a three-year period. Although soil heterogeneity was mainly observed from top soil to 3 m below the surface, heterogeneity controlled the spatial distribution of nitrate-N concentration. Soil heterogeneity, however, has minimal impact on the total mass of nitrate-N in the domain. In the deeper saturated zone, short-term variations of nitrate-N concentration correlated with the groundwater level fluctuations.

Warped document image correction method based on heterogeneous registration strategies

NASA Astrophysics Data System (ADS)

Tong, Lijing; Zhan, Guoliang; Peng, Quanyao; Li, Yang; Li, Yifan

2013-03-01

With the popularity of digital camera and the application requirement of digitalized document images, using digital cameras to digitalize document images has become an irresistible trend. However, the warping of the document surface impacts on the quality of the Optical Character Recognition (OCR) system seriously. To improve the warped document image's vision quality and the OCR rate, this paper proposed a warped document image correction method based on heterogeneous registration strategies. This method mosaics two warped images of the same document from different viewpoints. Firstly, two feature points are selected from one image. Then the two feature points are registered in the other image base on heterogeneous registration strategies. At last, image mosaics are done for the two images, and the best mosaiced image is selected by OCR recognition results. As a result, for the best mosaiced image, the distortions are mostly removed and the OCR results are improved markedly. Experimental results show that the proposed method can resolve the issue of warped document image correction more effectively.

Catastrophe theory—one of the basic components in the analysis of the seismic response of rock mass to explosions

NASA Astrophysics Data System (ADS)

Khachay, OA; Khachay, OYu

2018-03-01

It is shown that the dynamic process of mining can be controlled using the catastrophe theory. The control parameters can be values of blasting energy and locations of explosions relative to an area under study or operation. The kinematic and dynamic parameters of the deformation waves, as well as the structural features of rock mass through which these waves pass act as internal parameters. The use of the analysis methods for short-term and medium-term forecast of rock mass condition with the control parameters only is insufficient in the presence of sharp heterogeneity. However, the joint use of qualitative recommendations of the catastrophe theory and spatial–temporal data of changes in the internal parameters of rock mass will allow accident prevention in the course of mining.

An adaptive critic-based scheme for consensus control of nonlinear multi-agent systems

NASA Astrophysics Data System (ADS)

Heydari, Ali; Balakrishnan, S. N.

2014-12-01

The problem of decentralised consensus control of a network of heterogeneous nonlinear systems is formulated as an optimal tracking problem and a solution is proposed using an approximate dynamic programming based neurocontroller. The neurocontroller training comprises an initial offline training phase and an online re-optimisation phase to account for the fact that the reference signal subject to tracking is not fully known and available ahead of time, i.e., during the offline training phase. As long as the dynamics of the agents are controllable, and the communication graph has a directed spanning tree, this scheme guarantees the synchronisation/consensus even under switching communication topology and directed communication graph. Finally, an aerospace application is selected for the evaluation of the performance of the method. Simulation results demonstrate the potential of the scheme.

Measuring and predicting reservoir heterogeneity in complex deposystems: The fluvial-deltaic Big Injun sandstone in West Virginia

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

Patchen, D.G.; Hohn, M.E.; Aminian, K.

1993-04-01

The purpose of this research is to develop techniques to measure and predict heterogeneities in oil reservoirs that are the products of complex deposystems. The unit chosen for study is the Lower Mississippian Big Injun sandstone, a prolific oil producer (nearly 60 fields) in West Virginia. This research effort has been designed and is being implemented as an integrated effort involving stratigraphy, structural geology, petrology, seismic study, petroleum engineering, modeling and geostatistics. Sandstone bodies are being mapped within their regional depositional systems, and then sandstone bodies are being classified in a scheme of relative heterogeneity to determine heterogeneity across depositionalmore » systems. Facies changes are being mapped within given reservoirs, and the environments of deposition responsible for each facies are being interpreted to predict the inherent relative heterogeneity of each facies. Structural variations will be correlated both with production, where the availability of production data will permit, and with variations in geologic and engineering parameters that affect production. A reliable seismic model of the Big Injun reservoirs in Granny Creek field is being developed to help interpret physical heterogeneity in that field. Pore types are being described and related to permeability, fluid flow and diagenesis, and petrographic data are being integrated with facies and depositional environments to develop a technique to use diagenesis as a predictive tool in future reservoir development. Another objective in the Big Injun study is to determine the effect of heterogeneity on fluid flow and efficient hydrocarbon recovery in order to improve reservoir management. Graphical methods will be applied to Big Injun production data and new geostatistical methods will be developed to detect regional trends in heterogeneity.« less

Measuring and predicting reservoir heterogeneity in complex deposystems: The fluvial-deltaic Big Injun sandstone in West Virginia. Annual report, September 20, 1991--September 20, 1992

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

Patchen, D.G.; Hohn, M.E.; Aminian, K.

1993-04-01

The purpose of this research is to develop techniques to measure and predict heterogeneities in oil reservoirs that are the products of complex deposystems. The unit chosen for study is the Lower Mississippian Big Injun sandstone, a prolific oil producer (nearly 60 fields) in West Virginia. This research effort has been designed and is being implemented as an integrated effort involving stratigraphy, structural geology, petrology, seismic study, petroleum engineering, modeling and geostatistics. Sandstone bodies are being mapped within their regional depositional systems, and then sandstone bodies are being classified in a scheme of relative heterogeneity to determine heterogeneity across depositionalmore » systems. Facies changes are being mapped within given reservoirs, and the environments of deposition responsible for each facies are being interpreted to predict the inherent relative heterogeneity of each facies. Structural variations will be correlated both with production, where the availability of production data will permit, and with variations in geologic and engineering parameters that affect production. A reliable seismic model of the Big Injun reservoirs in Granny Creek field is being developed to help interpret physical heterogeneity in that field. Pore types are being described and related to permeability, fluid flow and diagenesis, and petrographic data are being integrated with facies and depositional environments to develop a technique to use diagenesis as a predictive tool in future reservoir development. Another objective in the Big Injun study is to determine the effect of heterogeneity on fluid flow and efficient hydrocarbon recovery in order to improve reservoir management. Graphical methods will be applied to Big Injun production data and new geostatistical methods will be developed to detect regional trends in heterogeneity.« less

Catalase-Modulated Heterogeneous Fenton Reaction for Selective Cancer Cell Eradication: SnFe2O4 Nanocrystals as an Effective Reagent for Treating Lung Cancer Cells.

PubMed

Lee, Kuan-Ting; Lu, Yu-Jen; Mi, Fwu-Long; Burnouf, Thierry; Wei, Yi-Ting; Chiu, Shao-Chieh; Chuang, Er-Yuan; Lu, Shih-Yuan

2017-01-18

Heterogeneous Fenton reactions have been proven to be an effective and promising selective cancer cell treatment method. The key working mechanism for this method to achieve the critical therapeutic selectivity however remains unclear. In this study, we proposed and demonstrated for the first time the critical role played by catalase in realizing the therapeutic selectivity for the heterogeneous Fenton reaction-driven cancer cell treatment. The heterogeneous Fenton reaction, with the lattice ferric ions of the solid catalyst capable of converting H 2 O 2 to highly reactive hydroxyl radicals, can effectively eradicate cancer cells. In this study, SnFe 2 O 4 nanocrystals, a recently discovered outstanding heterogeneous Fenton catalyst, were applied for selective killing of lung cancer cells. The SnFe 2 O 4 nanocrystals, internalized into the cancer cells, can effectively convert endogenous H 2 O 2 into highly reactive hydroxyl radicals to invoke an intensive cytotoxic effect on the cancer cells. On the other hand, catalase, present at a significantly higher concentration in normal cells than in cancer cells, remarkably can impede the apoptotic cell death induced by the internalized SnFe 2 O 4 nanocrystals. According to the results obtained from the in vitro cytotoxicity study, the relevant oxidative attacks were effectively suppressed by the presence of normal physiological levels of catalase. The SnFe 2 O 4 nanocrystals were thus proved to effect apoptotic cancer cell death through the heterogeneous Fenton reaction and were benign to cells possessing normal physiological levels of catalase. The catalase modulation of the involved heterogeneous Fenton reaction plays the key role in achieving selective cancer cell eradication for the heterogeneous Fenton reaction-driven cancer cell treatment.

Probing Mantle Heterogeneity Across Spatial Scales

NASA Astrophysics Data System (ADS)

Hariharan, A.; Moulik, P.; Lekic, V.

2017-12-01

Inferences of mantle heterogeneity in terms of temperature, composition, grain size, melt and crystal structure may vary across local, regional and global scales. Probing these scale-dependent effects require quantitative comparisons and reconciliation of tomographic models that vary in their regional scope, parameterization, regularization and observational constraints. While a range of techniques like radial correlation functions and spherical harmonic analyses have revealed global features like the dominance of long-wavelength variations in mantle heterogeneity, they have limited applicability for specific regions of interest like subduction zones and continental cratons. Moreover, issues like discrepant 1-D reference Earth models and related baseline corrections have impeded the reconciliation of heterogeneity between various regional and global models. We implement a new wavelet-based approach that allows for structure to be filtered simultaneously in both the spectral and spatial domain, allowing us to characterize heterogeneity on a range of scales and in different geographical regions. Our algorithm extends a recent method that expanded lateral variations into the wavelet domain constructed on a cubed sphere. The isolation of reference velocities in the wavelet scaling function facilitates comparisons between models constructed with arbitrary 1-D reference Earth models. The wavelet transformation allows us to quantify the scale-dependent consistency between tomographic models in a region of interest and investigate the fits to data afforded by heterogeneity at various dominant wavelengths. We find substantial and spatially varying differences in the spectrum of heterogeneity between two representative global Vp models constructed using different data and methodologies. Applying the orthonormality of the wavelet expansion, we isolate detailed variations in velocity from models and evaluate additional fits to data afforded by adding such complexities to long-wavelength variations. Our method provides a way to probe and evaluate localized features in a multi-scale description of mantle heterogeneity.

Synthesis of a molecularly defined single-active site heterogeneous catalyst for selective oxidation of N-heterocycles.

PubMed

Zhang, Yujing; Pang, Shaofeng; Wei, Zhihong; Jiao, Haijun; Dai, Xingchao; Wang, Hongli; Shi, Feng

2018-04-13

Generally, a homogeneous catalyst exhibits good activity and defined active sites but it is difficult to recycle. Meanwhile, a heterogeneous catalyst can easily be reused but its active site is difficult to reveal. It is interesting to bridge the gap between homogeneous and heterogeneous catalysis via controllable construction of a heterogeneous catalyst containing defined active sites. Here, we report that a molecularly defined, single-active site heterogeneous catalyst has been designed and prepared via the oxidative polymerization of maleimide derivatives. These polymaleimide derivatives can be active catalysts for the selective oxidation of heterocyclic compounds to quinoline and indole via the recycling of -C=O and -C-OH groups, which was confirmed by tracing the reaction with GC-MS using maleimide as the catalyst and by FT-IR analysis with polymaleimide as the catalyst. These results might promote the development of heterogeneous catalysts with molecularly defined single active sites exhibiting a comparable activity to homogeneous catalysts.

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

PubMed Central

Chadeka, Evans Asena; Nagi, Sachiyo; Sunahara, Toshihiko; Cheruiyot, Ngetich Benard; Bahati, Felix; Ozeki, Yuriko; Inoue, Manabu; Osada-Oka, Mayuko; Okabe, Mayuko; Hirayama, Yukio; Changoma, Mwatasa; Adachi, Keishi; Mwende, Faith; Kikuchi, Mihoko; Nakamura, Risa; Kalenda, Yombo Dan Justin; Kaneko, Satoshi; Hirayama, Kenji; Shimada, Masaaki; Ichinose, Yoshio; Njenga, Sammy M.; Matsumoto, Sohkichi

2017-01-01

Background Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4–9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0–17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources. PMID:28863133

Spatial and seasonal variations of leaf area index (LAI) in subtropical secondary forests related to floristic composition and stand characters

NASA Astrophysics Data System (ADS)

Zhu, Wenjuan; Xiang, Wenhua; Pan, Qiong; Zeng, Yelin; Ouyang, Shuai; Lei, Pifeng; Deng, Xiangwen; Fang, Xi; Peng, Changhui

2016-07-01

Leaf area index (LAI) is an important parameter related to carbon, water, and energy exchange between canopy and atmosphere and is widely applied in process models that simulate production and hydrological cycles in forest ecosystems. However, fine-scale spatial heterogeneity of LAI and its controlling factors have yet to be fully understood in Chinese subtropical forests. We used hemispherical photography to measure LAI values in three subtropical forests (Pinus massoniana-Lithocarpus glaber coniferous and evergreen broadleaved mixed forests, Choerospondias axillaris deciduous broadleaved forests, and L. glaber-Cyclobalanopsis glauca evergreen broadleaved forests) from April 2014 to January 2015. Spatial heterogeneity of LAI and its controlling factors were analysed using geostatistical methods and the generalised additive models (GAMs) respectively. Our results showed that LAI values differed greatly in the three forests and their seasonal variations were consistent with plant phenology. LAI values exhibited strong spatial autocorrelation for the three forests measured in January and for the L. glaber-C. glauca forest in April, July, and October. Obvious patch distribution pattern of LAI values occurred in three forests during the non-growing period and this pattern gradually dwindled in the growing season. Stem number, crown coverage, proportion of evergreen conifer species on basal area basis, proportion of deciduous species on basal area basis, and forest types affected the spatial variations in LAI values in January, while stem number and proportion of deciduous species on basal area basis affected the spatial variations in LAI values in July. Floristic composition, spatial heterogeneity, and seasonal variations should be considered for sampling strategy in indirect LAI measurement and application of LAI to simulate functional processes in subtropical forests.

A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.

PubMed

Martin, Joanna; Walters, Raymond K; Demontis, Ditte; Mattheisen, Manuel; Lee, S Hong; Robinson, Elise; Brikell, Isabell; Ghirardi, Laura; Larsson, Henrik; Lichtenstein, Paul; Eriksson, Nicholas; Werge, Thomas; Mortensen, Preben Bo; Pedersen, Marianne Giørtz; Mors, Ole; Nordentoft, Merete; Hougaard, David M; Bybjerg-Grauholm, Jonas; Wray, Naomi R; Franke, Barbara; Faraone, Stephen V; O'Donovan, Michael C; Thapar, Anita; Børglum, Anders D; Neale, Benjamin M

2018-06-15

Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r g estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15). Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Ochratoxin A in raisins and currants: basic extraction procedure used in two small marketing surveys of the occurrence and control of the heterogeneity of the toxins in samples.

PubMed

Möller, T E; Nyberg, M

2003-11-01

A basic extraction procedure for analysis of ochratoxin A (OTA) in currants and raisins is described, as well as the occurrence of OTA and a control of heterogeneity of the toxin in samples bought for two small marketing surveys 1999/2000 and 2001/02. Most samples in the surveys were divided into two subsamples that were individually prepared as slurries and analysed separately. The limit of quantification for the method was estimated as 0.1 microg kg(-1) and recoveries of 85, 90 and 115% were achieved in recovery experiments at 10, 5 and 0.1 microg kg(-1), respectively. Of all 118 subsamples analysed in the surveys, 96 (84%) contained ochratoxin A at levels above the quantification level and five samples (4%) contained more than the European Community legislation of 10 microg kg(-1). The OTA concentrations found in the first survey were in the range < 0.1-19.0 microg kg(-1) with a median concentration of 0.9 microg kg(-1). In the 2001/02 study, the range was < 0.1-34.6 microg kg(-1) with a median of 0.2 microg kg(-1). Big differences were often achieved between individual subsamples of the original sample, which indicate a wide heterogeneous distribution of the toxin. Data from the repeatability test as well as recovery experiments from the same slurries showed that preparation of slurries as described here seemed to give a homogeneous and representative sample. The extraction with the basic sodium bicarbonate-methanol mixture used in the surveys gave similar or somewhat higher OTA values on some samples tested in a comparison with a weak phosphoric acid water-methanol extraction mixture.

The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses

PubMed Central

2011-01-01

Introduction Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA. Methods A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy. Results In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen. Conclusions Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy. PMID:21884589

Mapping Drought Sensitivity of Ecosystem Functioning in Mountainous Watersheds: Spatial Heterogeneity and Geological-Geomorphological Control

NASA Astrophysics Data System (ADS)

Wainwright, H. M.; Steefel, C. F.; Williams, K. H.; Hubbard, S. S.; Enquist, B. J.; Steltzer, H.; Sarah, T.

2016-12-01

Mountainous watersheds in the Upper Colorado River Basin play a critical role in supplying water and nutrients to western North America. Ecosystem functioning in those regions - including plant dynamics and biogeochemical cycling - is known to be limited by water availability. Under the climate change, early snowmelt and increasing temperature are expected to intensify the drought conditions in early growing seasons. Although the impact of early-season drought has been documented in plot-scale experiments, ascertaining its significance in mountainous watersheds is challenging given the highly heterogeneous nature of the systems with complex terrain and diverse plant functional types (PFTs). The objectives of this study are (1) to map the regions where the plant dynamics are relatively more sensitive to drought conditions based on historical satellite and climate data, and (2) to identify the environmental controls (e.g., geomorphology, elevation, geology, snow and PFT) on drought sensitivity. We characterize the spatial heterogeneity of drought sensitivity in four watersheds (a 15 x 15 km domain) near the Rocky Mountain Biological Laboratory in Colorado, USA. Following previous plot-scale studies, we first define the drought sensitivity based on annual peak NDVI (Landsat 5) and climatic datasets. Non-parametric tree-based machine learning methods are used to identify the significant environmental controls, using high-resolution LiDAR digital elevation map and peak snow-water-equivalent distribution from NASA airborne snow observatory. Results show that the drought sensitivity is negatively correlated with elevation, suggesting increased water limitations in lower elevation (less snow, higher temperature). The drought sensitivity is more spatially variable in shallow-rooted plant types, affected by local hydrological conditions. We also found geomorphological and geological controls, such as high sensitivity in the steep well-drained glacial moraine regions. Our results highlight the importance of geology and subsurface flow conditions, in addition to snow accumulation. In parallel, the remotely-sensed drought sensitivity can be used as a scalable metric to identify the vulnerable regions to the future climate change, as well as to inform future sampling and characterization.

Plasminogen Activator Inhibitor-1 4G/5G Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis

PubMed Central

Li, Yan-yan

2012-01-01

Background The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. Objective and Methods The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. Results The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). Conclusions In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD. PMID:22496752

Analytical methods for solving boundary value heat conduction problems with heterogeneous boundary conditions on lines. I - Review

NASA Astrophysics Data System (ADS)

Kartashov, E. M.

1986-10-01

Analytical methods for solving boundary value problems for the heat conduction equation with heterogeneous boundary conditions on lines, on a plane, and in space are briefly reviewed. In particular, the method of dual integral equations and summator series is examined with reference to stationary processes. A table of principal solutions to dual integral equations and pair summator series is proposed which presents the known results in a systematic manner. Newly obtained results are presented in addition to the known ones.

Electrokinetically driven microfluidic mixing with patchwise surface heterogeneity and AC applied electric field

NASA Astrophysics Data System (ADS)

Luo, Win-Jet; Yue, Cheng-Feng

2004-12-01

This paper investigates two-dimensional, time-dependent electroosmotic flows driven by an AC electric field via patchwise surface heterogeneities distributed along the microchannel walls. The time-dependent flow fields through the microchannel are simulated for various patchwise heterogeneous surface patterns using the backwards-Euler time stepping numerical method. Different heterogeneous surface patterns are found to create significantly different electrokinetic transport phenomena. It is shown that the presence of oppositely charged surface heterogeneities on the microchannel walls results in the formation of localized flow circulations within the bulk flow. These circulation regions grow and decay periodically in accordance with the applied periodic AC electric field intensity. The circulations provide an effective means of enhancing species mixing in the microchannel. A suitable design of the patchwise heterogeneous surface pattern permits the mixing channel length and the retention time required to attain a homogeneous solution to be reduced significantly.

Multispecies coexistence of trees in tropical forests: spatial signals of topographic niche differentiation increase with environmental heterogeneity.

PubMed

Brown, C; Burslem, D F R P; Illian, J B; Bao, L; Brockelman, W; Cao, M; Chang, L W; Dattaraja, H S; Davies, S; Gunatilleke, C V S; Gunatilleke, I A U N; Huang, J; Kassim, A R; Lafrankie, J V; Lian, J; Lin, L; Ma, K; Mi, X; Nathalang, A; Noor, S; Ong, P; Sukumar, R; Su, S H; Sun, I F; Suresh, H S; Tan, S; Thompson, J; Uriarte, M; Valencia, R; Yap, S L; Ye, W; Law, R

2013-08-07

Neutral and niche theories give contrasting explanations for the maintenance of tropical tree species diversity. Both have some empirical support, but methods to disentangle their effects have not yet been developed. We applied a statistical measure of spatial structure to data from 14 large tropical forest plots to test a prediction of niche theory that is incompatible with neutral theory: that species in heterogeneous environments should separate out in space according to their niche preferences. We chose plots across a range of topographic heterogeneity, and tested whether pairwise spatial associations among species were more variable in more heterogeneous sites. We found strong support for this prediction, based on a strong positive relationship between variance in the spatial structure of species pairs and topographic heterogeneity across sites. We interpret this pattern as evidence of pervasive niche differentiation, which increases in importance with increasing environmental heterogeneity.

Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity

PubMed Central

Zhong, Qing; Rüschoff, Jan H.; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J.; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J.; Rupp, Niels J.; Fankhauser, Christian; Buhmann, Joachim M.; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A.; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C.; Jochum, Wolfram; Wild, Peter J.

2016-01-01

Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility. PMID:27052161

Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

PubMed

Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

2016-04-07

Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.

Scaling impacts on environmental controls and spatial heterogeneity of soil organic carbon stocks

NASA Astrophysics Data System (ADS)

Mishra, U.; Riley, W. J.

2015-01-01

The spatial heterogeneity of land surfaces affects energy, moisture, and greenhouse gas exchanges with the atmosphere. However, representing heterogeneity of terrestrial hydrological and biogeochemical processes in earth system models (ESMs) remains a critical scientific challenge. We report the impact of spatial scaling on environmental controls, spatial structure, and statistical properties of soil organic carbon (SOC) stocks across the US state of Alaska. We used soil profile observations and environmental factors such as topography, climate, land cover types, and surficial geology to predict the SOC stocks at a 50 m spatial scale. These spatially heterogeneous estimates provide a dataset with reasonable fidelity to the observations at a sufficiently high resolution to examine the environmental controls on the spatial structure of SOC stocks. We upscaled both the predicted SOC stocks and environmental variables from finer to coarser spatial scales (s = 100, 200, 500 m, 1, 2, 5, 10 km) and generated various statistical properties of SOC stock estimates. We found different environmental factors to be statistically significant predictors at different spatial scales. Only elevation, temperature, potential evapotranspiration, and scrub land cover types were significant predictors at all scales. The strengths of control (the median value of geographically weighted regression coefficients) of these four environmental variables on SOC stocks decreased with increasing scale and were accurately represented using mathematical functions (R2 = 0.83-0.97). The spatial structure of SOC stocks across Alaska changed with spatial scale. Although the variance (sill) and unstructured variability (nugget) of the calculated variograms of SOC stocks decreased exponentially with scale, the correlation length (range) remained relatively constant across scale. The variance of predicted SOC stocks decreased with spatial scale over the range of 50 to ~ 500 m, and remained constant beyond this scale. The fitted exponential function accounted for 98% of variability in the variance of SOC stocks. We found moderately-accurate linear relationships between mean and higher-order moments of predicted SOC stocks (R2 ~ 0.55-0.63). Current ESMs operate at coarse spatial scales (50-100 km), and are therefore unable to represent environmental controllers and spatial heterogeneity of high-latitude SOC stocks consistent with observations. We conclude that improved understanding of the scaling behavior of environmental controls and statistical properties of SOC stocks can improve ESM land model benchmarking and perhaps allow representation of spatial heterogeneity of biogeochemistry at scales finer than those currently resolved by ESMs.

Scaling impacts on environmental controls and spatial heterogeneity of soil organic carbon stocks

NASA Astrophysics Data System (ADS)

Mishra, U.; Riley, W. J.

2015-07-01

The spatial heterogeneity of land surfaces affects energy, moisture, and greenhouse gas exchanges with the atmosphere. However, representing the heterogeneity of terrestrial hydrological and biogeochemical processes in Earth system models (ESMs) remains a critical scientific challenge. We report the impact of spatial scaling on environmental controls, spatial structure, and statistical properties of soil organic carbon (SOC) stocks across the US state of Alaska. We used soil profile observations and environmental factors such as topography, climate, land cover types, and surficial geology to predict the SOC stocks at a 50 m spatial scale. These spatially heterogeneous estimates provide a data set with reasonable fidelity to the observations at a sufficiently high resolution to examine the environmental controls on the spatial structure of SOC stocks. We upscaled both the predicted SOC stocks and environmental variables from finer to coarser spatial scales (s = 100, 200, and 500 m and 1, 2, 5, and 10 km) and generated various statistical properties of SOC stock estimates. We found different environmental factors to be statistically significant predictors at different spatial scales. Only elevation, temperature, potential evapotranspiration, and scrub land cover types were significant predictors at all scales. The strengths of control (the median value of geographically weighted regression coefficients) of these four environmental variables on SOC stocks decreased with increasing scale and were accurately represented using mathematical functions (R2 = 0.83-0.97). The spatial structure of SOC stocks across Alaska changed with spatial scale. Although the variance (sill) and unstructured variability (nugget) of the calculated variograms of SOC stocks decreased exponentially with scale, the correlation length (range) remained relatively constant across scale. The variance of predicted SOC stocks decreased with spatial scale over the range of 50 m to ~ 500 m, and remained constant beyond this scale. The fitted exponential function accounted for 98 % of variability in the variance of SOC stocks. We found moderately accurate linear relationships between mean and higher-order moments of predicted SOC stocks (R2 ∼ 0.55-0.63). Current ESMs operate at coarse spatial scales (50-100 km), and are therefore unable to represent environmental controllers and spatial heterogeneity of high-latitude SOC stocks consistent with observations. We conclude that improved understanding of the scaling behavior of environmental controls and statistical properties of SOC stocks could improve ESM land model benchmarking and perhaps allow representation of spatial heterogeneity of biogeochemistry at scales finer than those currently resolved by ESMs.

Scaling impacts on environmental controls and spatial heterogeneity of soil organic carbon stocks

DOE PAGES

Mishra, U.; Riley, W. J.

2015-07-02

The spatial heterogeneity of land surfaces affects energy, moisture, and greenhouse gas exchanges with the atmosphere. However, representing the heterogeneity of terrestrial hydrological and biogeochemical processes in Earth system models (ESMs) remains a critical scientific challenge. We report the impact of spatial scaling on environmental controls, spatial structure, and statistical properties of soil organic carbon (SOC) stocks across the US state of Alaska. We used soil profile observations and environmental factors such as topography, climate, land cover types, and surficial geology to predict the SOC stocks at a 50 m spatial scale. These spatially heterogeneous estimates provide a data setmore » with reasonable fidelity to the observations at a sufficiently high resolution to examine the environmental controls on the spatial structure of SOC stocks. We upscaled both the predicted SOC stocks and environmental variables from finer to coarser spatial scales ( s = 100, 200, and 500 m and 1, 2, 5, and 10 km) and generated various statistical properties of SOC stock estimates. We found different environmental factors to be statistically significant predictors at different spatial scales. Only elevation, temperature, potential evapotranspiration, and scrub land cover types were significant predictors at all scales. The strengths of control (the median value of geographically weighted regression coefficients) of these four environmental variables on SOC stocks decreased with increasing scale and were accurately represented using mathematical functions ( R 2 = 0.83–0.97). The spatial structure of SOC stocks across Alaska changed with spatial scale. Although the variance (sill) and unstructured variability (nugget) of the calculated variograms of SOC stocks decreased exponentially with scale, the correlation length (range) remained relatively constant across scale. The variance of predicted SOC stocks decreased with spatial scale over the range of 50 m to ~ 500 m, and remained constant beyond this scale. The fitted exponential function accounted for 98 % of variability in the variance of SOC stocks. We found moderately accurate linear relationships between mean and higher-order moments of predicted SOC stocks ( R 2 ∼ 0.55–0.63). Current ESMs operate at coarse spatial scales (50–100 km), and are therefore unable to represent environmental controllers and spatial heterogeneity of high-latitude SOC stocks consistent with observations. We conclude that improved understanding of the scaling behavior of environmental controls and statistical properties of SOC stocks could improve ESM land model benchmarking and perhaps allow representation of spatial heterogeneity of biogeochemistry at scales finer than those currently resolved by ESMs.« less

Scaling impacts on environmental controls and spatial heterogeneity of soil organic carbon stocks

DOE PAGES

Mishra, U.; Riley, W. J.

2015-01-01

The spatial heterogeneity of land surfaces affects energy, moisture, and greenhouse gas exchanges with the atmosphere. However, representing heterogeneity of terrestrial hydrological and biogeochemical processes in earth system models (ESMs) remains a critical scientific challenge. We report the impact of spatial scaling on environmental controls, spatial structure, and statistical properties of soil organic carbon (SOC) stocks across the US state of Alaska. We used soil profile observations and environmental factors such as topography, climate, land cover types, and surficial geology to predict the SOC stocks at a 50 m spatial scale. These spatially heterogeneous estimates provide a dataset with reasonablemore » fidelity to the observations at a sufficiently high resolution to examine the environmental controls on the spatial structure of SOC stocks. We upscaled both the predicted SOC stocks and environmental variables from finer to coarser spatial scales ( s = 100, 200, 500 m, 1, 2, 5, 10 km) and generated various statistical properties of SOC stock estimates. We found different environmental factors to be statistically significant predictors at different spatial scales. Only elevation, temperature, potential evapotranspiration, and scrub land cover types were significant predictors at all scales. The strengths of control (the median value of geographically weighted regression coefficients) of these four environmental variables on SOC stocks decreased with increasing scale and were accurately represented using mathematical functions ( R 2 = 0.83–0.97). The spatial structure of SOC stocks across Alaska changed with spatial scale. Although the variance (sill) and unstructured variability (nugget) of the calculated variograms of SOC stocks decreased exponentially with scale, the correlation length (range) remained relatively constant across scale. The variance of predicted SOC stocks decreased with spatial scale over the range of 50 to ~ 500 m, and remained constant beyond this scale. The fitted exponential function accounted for 98% of variability in the variance of SOC stocks. We found moderately-accurate linear relationships between mean and higher-order moments of predicted SOC stocks ( R 2 ~ 0.55–0.63). Current ESMs operate at coarse spatial scales (50–100 km), and are therefore unable to represent environmental controllers and spatial heterogeneity of high-latitude SOC stocks consistent with observations. We conclude that improved understanding of the scaling behavior of environmental controls and statistical properties of SOC stocks can improve ESM land model benchmarking and perhaps allow representation of spatial heterogeneity of biogeochemistry at scales finer than those currently resolved by ESMs.« less

Extending religion-health research to secular minorities: issues and concerns.

PubMed

Hwang, Karen; Hammer, Joseph H; Cragun, Ryan T

2011-09-01

Claims about religion's beneficial effects on physical and psychological health have received substantial attention in popular media, but empirical support for these claims is mixed. Many of these claims are tenuous because they fail to address basic methodological issues relating to construct validity, sampling methods or analytical problems. A more conceptual problem has to do with the near universal lack of atheist control samples. While many studies include samples of individuals classified as "low spirituality" or religious "nones", these groups are heterogeneous and contain only a fraction of members who would be considered truly secular. We illustrate the importance of including an atheist control group whenever possible in the religiosity/spirituality and health research and discuss areas for further investigation.

A multi-institutional study of independent calculation verification in inhomogeneous media using a simple and effective method of heterogeneity correction integrated with the Clarkson method.

PubMed

Jinno, Shunta; Tachibana, Hidenobu; Moriya, Shunsuke; Mizuno, Norifumi; Takahashi, Ryo; Kamima, Tatsuya; Ishibashi, Satoru; Sato, Masanori

2018-05-21

In inhomogeneous media, there is often a large systematic difference in the dose between the conventional Clarkson algorithm (C-Clarkson) for independent calculation verification and the superposition-based algorithms of treatment planning systems (TPSs). These treatment site-dependent differences increase the complexity of the radiotherapy planning secondary check. We developed a simple and effective method of heterogeneity correction integrated with the Clarkson algorithm (L-Clarkson) to account for the effects of heterogeneity in the lateral dimension, and performed a multi-institutional study to evaluate the effectiveness of the method. In the method, a 2D image reconstructed from computed tomography (CT) images is divided according to lines extending from the reference point to the edge of the multileaf collimator (MLC) or jaw collimator for each pie sector, and the radiological path length (RPL) of each line is calculated on the 2D image to obtain a tissue maximum ratio and phantom scatter factor, allowing the dose to be calculated. A total of 261 plans (1237 beams) for conventional breast and lung treatments and lung stereotactic body radiotherapy were collected from four institutions. Disagreements in dose between the on-site TPSs and a verification program using the C-Clarkson and L-Clarkson algorithms were compared. Systematic differences with the L-Clarkson method were within 1% for all sites, while the C-Clarkson method resulted in systematic differences of 1-5%. The L-Clarkson method showed smaller variations. This heterogeneity correction integrated with the Clarkson algorithm would provide a simple evaluation within the range of -5% to +5% for a radiotherapy plan secondary check.

Do goethite surfaces really control the transport and retention of multi-walled carbon nanotubes in chemically heterogeneous porous media?

USDA-ARS?s Scientific Manuscript database

Transport and retention behavior of multiwalled carbon nanotubes (MWCNTs) was studied in mixtures of negatively charged quartz sand (QS) and positively charged goethite-coated sand (GQS) to assess the role of chemical heterogeneity. The linear equilibrium sorption model provided a good description o...

Principles of E-network modelling of heterogeneous systems

NASA Astrophysics Data System (ADS)

Tarakanov, D.; Tsapko, I.; Tsapko, S.; Buldygin, R.

2016-04-01

The present article is concerned with the analytical and simulation modelling of heterogeneous technical systems using E-network mathematical apparatus (the expansion of Petri nets). The distinguishing feature of the given system is the presence of the module6 which identifies the parameters of the controlled object as well as the external environment.

Overeducation and Earnings within an Occupation: Controlling for Occupational Heterogeneity of Nurses

ERIC Educational Resources Information Center

Rubb, Stephen

2014-01-01

Using data from the 2004 National Sample Survey of Registered Nurses, the role of occupational heterogeneity in the standard overeducation-required-undereducation (ORU) earnings function introduced by Duncan and Hoffman [1981. "The incidence and wage effects of overeducation." "Economics of Education Review" 1, no. 1: 75-86] is…

Reservoir heterogeneity in Carboniferous sandstone of the Black Warrior basin. Final report

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

Kugler, R.L.; Pashin, J.C.; Carroll, R.E.

1994-04-01

Although oil production in the Black Warrior basin of Alabama is declining, additional oil may be produced through improved recovery strategies, such as waterflooding, chemical injection, strategic well placement, and infill drilling. High-quality characterization of reservoirs in the Black Warrior basin is necessary to utilize advanced technology to recover additional oil and to avoid premature abandonment of fields. This report documents controls on the distribution and producibility of oil from heterogeneous Carboniferous reservoirs in the Black Warrior basin of Alabama. The first part of the report summarizes the structural and depositional evolution of the Black Warrior basin and establishes themore » geochemical characteristics of hydrocarbon source rocks and oil in the basin. This second part characterizes facies heterogeneity and petrologic and petrophysical properties of Carter and Millerella sandstone reservoirs. This is followed by a summary of oil production in the Black Warrior basin and an evaluation of seven improved-recovery projects in Alabama. In the final part, controls on the producibility of oil from sandstone reservoirs are discussed in terms of a scale-dependent heterogeneity classification.« less

Instruments for preparation of heterogeneous catalysts by an impregnation method

NASA Astrophysics Data System (ADS)

Yamada, Yusuke; Akita, Tomoki; Ueda, Atsushi; Shioyama, Hiroshi; Kobayashi, Tetsuhiko

2005-06-01

Instruments for the preparation of heterogeneous catalysts in powder form have been developed. The instruments consist of powder dispensing robot and an automated liquid handling machine equipped with an ultrasonic and a vortex mixer. The combination of these two instruments achieves the catalyst preparation by incipient wetness and ion exchange methods. The catalyst library prepared with these instruments were tested for dimethyl ether steam reforming and characterized by transmission electron microscopy observations.

Economic evaluations of tobacco control mass media campaigns: a systematic review

PubMed Central

Atusingwize, Edwinah; Lewis, Sarah; Langley, Tessa

2015-01-01

Background International evidence shows that mass media campaigns are effective tobacco control interventions. However, they require substantial investment; a key question is whether their costs are justified by their benefits. The aim of this study was to systematically and comprehensively review economic evaluations of tobacco control mass media campaigns. Methods An electronic search of databases and grey literature was conducted to identify all published economic evaluations of tobacco control mass media campaigns. The authors reviewed studies independently and assessed the quality of studies using the Drummond 10-point checklist. A narrative synthesis was used to summarise the key features and quality of the identified studies. Results 10 studies met the inclusion criteria and were included in the review. All the studies included a cost effectiveness analysis, a cost utility analysis or both. The methods were highly heterogeneous, particularly in terms of the types of costs included. On the whole, studies were well conducted, but the interventions were often poorly described in terms of campaign content and intensity, and cost information was frequently inadequate. All studies concluded that tobacco control mass media campaigns are a cost effective public health intervention. Conclusions The evidence on the cost effectiveness of tobacco control mass media campaigns is limited, but of acceptable quality and consistently suggests that they offer good value for money. PMID:24985730

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

PubMed

Rose, Jonathan A; Wanner, Nicholas; Cheong, Hoi I; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

PubMed Central

Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations

PubMed Central

Band, Gavin; Le, Quang Si; Jostins, Luke; Pirinen, Matti; Kivinen, Katja; Jallow, Muminatou; Sisay-Joof, Fatoumatta; Bojang, Kalifa; Pinder, Margaret; Sirugo, Giorgio; Conway, David J.; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Taylor, Terrie; Ndila, Carolyne; Peshu, Norbert; Marsh, Kevin; Williams, Thomas N.; Alcock, Daniel; Andrews, Robert; Edkins, Sarah; Gray, Emma; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Schuldt, Kathrin; Clark, Taane G.; Small, Kerrin S.; Teo, Yik Ying; Kwiatkowski, Dominic P.; Rockett, Kirk A.; Barrett, Jeffrey C.; Spencer, Chris C. A.

2013-01-01

Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP–based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles. PMID:23717212

Statistical characterization of Earth’s heterogeneities from seismic scattering

NASA Astrophysics Data System (ADS)

Zheng, Y.; Wu, R.

2009-12-01

The distortion of a teleseismic wavefront carries information about the heterogeneities through which the wave propagates and it is manifestited as logarithmic amplitude (logA) and phase fluctuations of the direct P wave recorded by a seismic network. By cross correlating the fluctuations (e.g., logA-logA or phase-phase), we obtain coherence functions, which depend on spatial lags between stations and incident angles between the incident waves. We have mathematically related the depth-dependent heterogeneity spectrum to the observable coherence functions using seismic scattering theory. We will show that our method has sharp depth resolution. Using the HiNet seismic network data in Japan, we have inverted power spectra for two depth ranges, ~0-120km and below ~120km depth. The coherence functions formed by different groups of stations or by different groups of earthquakes at different back azimuths are similar. This demonstrates that the method is statistically stable and the inhomogeneities are statistically stationary. In both depth intervals, the trend of the spectral amplitude decays from large scale to small scale in a power-law fashion with exceptions at ~50km for the logA data. Due to the spatial spacing of the seismometers, only information from length scale 15km to 200km is inverted. However our scattering method provides new information on small to intermediate scales that are comparable to scales of the recycled materials and thus is complimentary to the global seismic tomography which reveals mainly large-scale heterogeneities on the order of ~1000km. The small-scale heterogeneities revealed here are not likely of pure thermal origin. Therefore, the length scale and strength of heterogeneities as a function of depth may provide important constraints in mechanical mixing of various components in the mantle convection.

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

PubMed

Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

Simultaneous Local Binary Feature Learning and Encoding for Homogeneous and Heterogeneous Face Recognition.

PubMed

Lu, Jiwen; Erin Liong, Venice; Zhou, Jie

2017-08-09

In this paper, we propose a simultaneous local binary feature learning and encoding (SLBFLE) approach for both homogeneous and heterogeneous face recognition. Unlike existing hand-crafted face descriptors such as local binary pattern (LBP) and Gabor features which usually require strong prior knowledge, our SLBFLE is an unsupervised feature learning approach which automatically learns face representation from raw pixels. Unlike existing binary face descriptors such as the LBP, discriminant face descriptor (DFD), and compact binary face descriptor (CBFD) which use a two-stage feature extraction procedure, our SLBFLE jointly learns binary codes and the codebook for local face patches so that discriminative information from raw pixels from face images of different identities can be obtained by using a one-stage feature learning and encoding procedure. Moreover, we propose a coupled simultaneous local binary feature learning and encoding (C-SLBFLE) method to make the proposed approach suitable for heterogeneous face matching. Unlike most existing coupled feature learning methods which learn a pair of transformation matrices for each modality, we exploit both the common and specific information from heterogeneous face samples to characterize their underlying correlations. Experimental results on six widely used face datasets are presented to demonstrate the effectiveness of the proposed method.

Steps towards incorporating heterogeneities into program theory: A case study of a data-driven approach.

PubMed

Sridharan, Sanjeev; Jones, Bobby; Caudill, Barry; Nakaima, April

2016-10-01

This paper describes a framework that can help refine program theory through data explorations and stakeholder dialogue. The framework incorporates the following steps: a recognition that program implementation might need to be multi-phased for a number of interventions, the need to take stock of program theory, the application of pattern recognition methods to help identify heterogeneous program mechanisms, and stakeholder dialogue to refine the program. As part of the data exploration, a method known as developmental trajectories is implemented to learn about heterogeneous trajectories of outcomes in longitudinal evaluations. This method identifies trajectory clusters and also can estimate different treatment impacts for the various groups. The framework is highlighted with data collected in an evaluation of an alcohol risk-reduction program delivered in a college fraternity setting. The framework discussed in the paper is informed by a realist focus on "what works for whom under what contexts." The utility of the framework in contributing to a dialogue on heterogeneous mechanism and subsequent implementation is described. The connection of the ideas in paper to a 'learning through principled discovery' approach is also described. Copyright © 2016. Published by Elsevier Ltd.

Patterns of Emphysema Heterogeneity

PubMed Central

Valipour, Arschang; Shah, Pallav L.; Gesierich, Wolfgang; Eberhardt, Ralf; Snell, Greg; Strange, Charlie; Barry, Robert; Gupta, Avina; Henne, Erik; Bandyopadhyay, Sourish; Raffy, Philippe; Yin, Youbing; Tschirren, Juerg; Herth, Felix J.F.

2016-01-01

Background Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥ 15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥ 30% difference in tissue destruction. Conclusion Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones. PMID:26430783

Effects of advanced life support versus basic life support on the mortality rates of patients with trauma in prehospital settings: a study protocol for a systematic review and meta-analysis

PubMed Central

Kondo, Yutaka; Fukuda, Tatsuma; Uchimido, Ryo; Hifumi, Toru; Hayashida, Kei

2017-01-01

Introduction Advanced life support (ALS) is thought to be associated with improved survival in prehospital trauma care when compared with basic life support (BLS). However, evidence on the benefits of prehospital ALS for patients with trauma is controversial. Therefore, we aim to clarify if ALS improves mortality in patients with trauma when compared with BLS by conducting a systematic review and meta-analysis of the recent literature. Methods and analysis We will perform searches in PubMed, Embase and the Cochrane Central Register of Controlled Trials for published observational studies, controlled before-and-after studies, randomised controlled trials and other controlled trials conducted in humans and published until March 2017. We will screen search results, assess study selection, extract data and assess the risk of bias in duplicate; disagreements will be resolved through discussions. Data from clinically homogeneous studies will be pooled using a random-effects meta-analysis, heterogeneity of effects will be assessed using the χ2 test of homogeneity, and any observed heterogeneity will be quantified using the I2 statistic. Last, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of the evidence. Ethics and dissemination Our study does not require ethical approval as it is based on findings of previously published articles. Results will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and publications for patient information. Trial registration number PROSPERO (International Prospective Register of Systematic Reviews) registration number CRD42017054389. PMID:29061611

Evaluation of Intersection Traffic Control Measures through Simulation

NASA Astrophysics Data System (ADS)

Asaithambi, Gowri; Sivanandan, R.

2015-12-01

Modeling traffic flow is stochastic in nature due to randomness in variables such as vehicle arrivals and speeds. Due to this and due to complex vehicular interactions and their manoeuvres, it is extremely difficult to model the traffic flow through analytical methods. To study this type of complex traffic system and vehicle interactions, simulation is considered as an effective tool. Application of homogeneous traffic models to heterogeneous traffic may not be able to capture the complex manoeuvres and interactions in such flows. Hence, a microscopic simulation model for heterogeneous traffic is developed using object oriented concepts. This simulation model acts as a tool for evaluating various control measures at signalized intersections. The present study focuses on the evaluation of Right Turn Lane (RTL) and Channelised Left Turn Lane (CLTL). A sensitivity analysis was performed to evaluate RTL and CLTL by varying the approach volumes, turn proportions and turn lane lengths. RTL is found to be advantageous only up to certain approach volumes and right-turn proportions, beyond which it is counter-productive. CLTL is found to be advantageous for lower approach volumes for all turn proportions, signifying the benefits of CLTL. It is counter-productive for higher approach volume and lower turn proportions. This study pinpoints the break-even points for various scenarios. The developed simulation model can be used as an appropriate intersection lane control tool for enhancing the efficiency of flow at intersections. This model can also be employed for scenario analysis and can be valuable to field traffic engineers in implementing vehicle-type based and lane-based traffic control measures.