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At least 1,567 records · Page 87

Comparing two correlated C indices with right‐censored survival outcome: a one‐shot nonparametric approach

The area under the receiver operating characteristic curve is often used as a summary index of the diagnostic ability in evaluating biomarkers when the clinical outcome (truth) is binary. When the clinical outcome is right‐censored survival time, the C index, motivated as an extension of area under the receiver operating characteristic curve, has been proposed by Harrell as a measure of concordance between a predictive biomarker and the right‐censored survival outcome. In this work, we investigate methods for statistical comparison of two diagnostic or predictive systems, of which they could either be two biomarkers or two fixed algorithms, in terms of their C indices. We adopt a U ‐statistics‐based C estimator that is asymptotically normal and develop a nonparametric analytical approach to estimate the variance of the C estimator and the covariance of two C estimators. A z ‐score test is then constructed to compare the two C indices. We validate our one‐shot nonparametric method via simulation studies in terms of the type I error rate and power. We also compare our one‐shot method with resampling methods including the jackknife and the bootstrap. Simulation results show that the proposed one‐shot method provides almost unbiased variance estimations and has satisfactory type I error control and power. Finally, we illustrate the use of the proposed method with an example from the Framingham Heart Study. Copyright © 2014 John Wiley & Sons, Ltd.

Kang, Le↗

Developmental regulation of RNA processing by Rbfox proteins

The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3’UTRs, and pre-miRNAs hairpin structures. These versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing. Complex Rbfox expression is encoded in large genes encompassing multiple promoters and alternative splicing options that govern spatiotemporal expression of structurally distinct and tissue-specific protein isoforms with different classes of RNA targets. Nuclear Rbfox1 is a candidate master regulator that binds intronic UGCAUG elements to impact splicing efficiency of target alternative exons, many in transcripts for other splicing regulators. Tissue-specificity of Rbfox-mediated alternative splicing is executed by combinatorial regulation through the integrated activity of Rbfox proteins and synergistic or antagonistic splicing factors. Studies in animal models show that Rbfox1-related genes are critical for diverse developmental processes including germ cell differentiation and memory in Drosophila, neuronal migration and function in mouse brain, myoblast fusion and skeletal muscle function, and normal heart function. Finally, genetic and biochemical evidence suggest that aberrations in Rbfox-regulated circuitry are risk factors for multiple human disorders, especially neurodevelopmental disorders including epilepsy and autism, and cardiac hypertrophy.

59 BASIC BIOLOGICAL SCIENCES↗

Photocathodes

Photocathodes were at the heart of quantum physics development in the early twentieth century and are still used in high technologies devices like night-vision goggles, photomultiplier tubes and particle accelerators. The simplest form of photocathode is a metallic surface,negatively biased,from which electrons are extracted by energetic photons. After a brief description of the photocathode preparation, this chapter will present the latest developments and limitations of metallic and semiconductor photocathodes.

Liu, Wei↗

Twelve Ways to Fool the Masses When Giving Parallel-in-Time Results

Getting good speedup—let alone high parallel efficiency—for parallel-in-time (PinT) integration examples can be frustratingly difficult. The high complexity and large number of parameters in PinT methods can easily (and unintentionally) lead to numerical experiments that overestimate the algorithm’s performance. In the tradition of Bailey’s article “Twelve ways to fool the masses when giving performance results on parallel computers”, we discuss and demonstrate pitfalls to avoid when evaluating the performance of PinT methods. Despite being written in a light-hearted tone, this paper is intended to raise awareness that there are many ways to unintentionally fool yourself and others and that by avoiding these fallacies more meaningful PinT performance results can be obtained.

97 MATHEMATICS AND COMPUTING↗

The Kokkos OpenMPTarget Backend: Implementation and Lessons Learned

As the supercomputing landscape diversifies, solutions such as Kokkos to write vendor agnostic applications and libraries have risen in popularity. Kokkos provides a programming model designed for performance portability, which allows developers to write a single source implementation that can run efficiently on various architectures. At its heart, Kokkos maps parallel algorithms to architecture and vendor specific backends written in lower level programming models such as CUDA and HIP. Another approach to writing vendor agnostic parallel code is using OpenMP’s directives based approach, which lets developers annotate code to express parallelism. It is implemented at the compiler level and is supported by all major high performance computing vendors, as well as the primary Open Source toolchains GNU and LLVM. Since its inception, Kokkos has used OpenMP to parallelize on CPU architectures. In this paper, we explore leveraging OpenMP for a GPU backend and discuss the challenges we encountered when mapping the Kokkos APIs and semantics to OpenMP target constructs. As an exemplar workload we chose a simple conjugate gradient solver for sparse matrices. We find that performance on NVIDIA and AMD GPUs varies widely based on details of the implementation strategy and the chosen compiler. Furthermore, the performance of the OpenMP implementations decreases with increasing complexity of the investigated algorithms.

Gayatri, Rahulkumar↗

Cyber-Infrastructure for Data-Intensive Geospatial Computing

With the recent advent of heterogeneous High-performance Computing (HPC) to handle EO “Big Data” workloads, there is a need for a unified Cyber-infrastructure (CI) platform that can bridge the best of many HPC worlds. In this chapter, we discuss such a CI platform being developed at Geographic Information Science and Technology (GIST) group using novel and innovative techniques, and emerging technologies that are scalable to large-scale supercomputers. The CI platform utilizes a wide variety of computing such as GPGPU, distributed, real-time and cluster computing, which are being brought together architecturally to enable data-driven analysis, scientific understanding of earth system models, and research collaboration. This development addresses the need for close integration of EO and other geospatial information in the face of growing volumes of the data, and facilitates spatio-temporal analysis of disparate and dynamic data streams. Horizontal scalability and linear throughput are supported in the heart of the platform itself. It is being used to support very broad application areas, ranging from high-resolution settlement mapping, national bioenergy infrastructure to urban information and mobility systems. The platform provides spatio-temporal decision support capabilities in planning, policy and operational missions for US federal agencies. Also, the platform is designed to be functionally and technologically sustainable for continued support of the US energy and environment mission for the coming decades.

Karthik, Rajasekar↗

Entanglement wedge reconstruction using the Petz map

At the heart of recent progress in AdS/CFT is the question of subregion duality, or entanglement wedge reconstruction: which part(s) of the boundary CFT are dual to a given subregion of the bulk? This question can be answered by appealing to the quantum error correcting properties of holography, and it was recently shown that robust bulk (entanglement wedge) reconstruction can be achieved using a universal recovery channel known as the twirled Petz map. In short, one can use the twirled Petz map to recover bulk data from a subset of the boundary. However, this map involves an averaging procedure over bulk and boundary modular time, and hence it can be somewhat intractable to evaluate in practice. We show that a much simpler channel, the Petz map, is sufficient for entanglement wedge reconstruction for any code space of fixed finite dimension – no twirling is required. Moreover, the error in the reconstruction will always be non-perturbatively small. From a quantum information perspective, we prove a general theorem extending the use of the Petz map as a general-purpose recovery channel to subsystem and operator algebra quantum error correction.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Loop amplitudes monodromy relations and color-kinematics duality

Color-kinematics duality is a remarkable conjectured property of gauge theory which, together with double copy, is at the heart of a wealth of new developments in scattering amplitudes. So far, its validity has been verified in most cases only empirically, with limited ab initio understanding beyond tree-level. In this paper we provide initial steps in a first-principle understanding of color-kinematics duality and double-copy at loop level, through a detailed analysis of the field-theory limit of the monodromy relations of string theory at one loop. In this limit, we dissect the type of Feynman graphs generated and the relations they obey. We find that graphs with contact-terms are unavoidable and are generated in the field theory limit of “bulk” contours which do not have a standard physical interpretation in string perturbation theory. We show how they are related to ambiguities in the definition of the loop momentum and that their role is precisely to cancel those ambiguities.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Strong- vs. weak-coupling pictures of jet quenching: a dry run using QED

High-energy partons (E >> T) traveling through a quark-gluon plasma lose energy by splitting via bremsstrahlung and pair production. Regardless of whether or not the quark-gluon plasma itself is strongly coupled, a vital question lying at the heart of philosophically different approaches to energy loss is whether the high-energy partons of an in-medium shower can be thought of as a collection of individual particles, or whether their coupling to each other is also so strong that a description as high-energy ``particles'' is inappropriate. We discuss some possible theorists' tests of this question for simple situations (e.g. an infinite, non-expanding plasma) using thought experiments and first-principles quantum field theory calculations (with some simplifying approximations). The physics of in-medium showers is substantially affected by the Landau-Pomeranchuk-Midgal (LPM) effect, and our proposed tests require use of what might be called ``next-to-leading order'' LPM results, which account for quantum interference between consecutive splittings. The complete set of such results is not yet available for QCD but is already available for the theory of large-N f QED. We therefore use large-N f QED as an example, presenting numerical results as a function of N f alpha, where alpha is the strength of the coupling at the relevant high-energy scale characterizing splittings of the high-energy particles.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Tissue Distribution of Mercury in the Bodies of Wild American Alligators ( Alligator mississippiensis ) from a Coastal Marsh in Louisiana (USA)

Total mercury (THg) concentrations were measured in wild alligators inhabiting a coastal marsh in southern Louisiana, to determine the tissue distribution of THg among various body organs and tissue compartments. Concentrations of THg in claws and dermal tail scutes were compared to those in blood, brain, gonad, heart, kidney, liver, and skeletal muscle to determine if the former tissues, commonly available by non-lethal sampling, could be used as measures of body burdens in various internal organs. Mercury was found in all body organs and tissue compartments. However, overall, THg concentrations measured in alligators were below the FDA action level for fish consumption and were comparable to previous data reported from southwestern Louisiana. Here, our results suggest consumption of meat from alligators found in this region may be of little public health concern. However, the extended period of time between sampling (in this study) and the present-day highlight the need for continuous, additional, and more recent sampling to ensure consumer safety. Total mercury concentrations were highest in the kidney (3.18 ± 0.69 mg/kg dw) and liver (3.12 ± 0.76 mg/kg dw). THg levels in non-lethal samples (blood, claws, and dermal tail scutes) were positively correlated with all tissue THg concentrations (blood: R 2 = 0.513 – 0.988; claw: R 2 = 0.347 – 0.637, scutes: R 2 = 0.333 – 0.649). Because THg concentrations from blood, claws, and scutes were correlated with those of the internal organs, non-lethal sampling methods may be a viable method of estimating levels of THg in other body tissues.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Transcatheter Arterial Embolization for Postoperative Bleeding Following Abdominal Surgery

PurposeWe aimed to estimate the usefulness of transcatheter arterial embolization (TAE) in patients with postoperative abdominal hemorrhage and to evaluate the effects of pancreatic fistula on clinical outcomes and angiographic findings.Materials and MethodsWe enrolled 22 patients (20 males and 2 females; mean age 63 years; range 25–86 years), who underwent transarterial angiography for postoperative hemorrhage after abdominal surgery. This group corresponded to 28 procedures. Technical and clinical success rates were calculated, and clinical findings and outcomes were compared between patients with and without a pancreatic fistula.ResultsPre-interventional CT was performed in all patients before first angiography, and the location of the bleeding was identified in all but one patient. Active arterial bleeding, identified by extravasation of contrast agent (n = 12), pseudoaneurysm formation (n = 12), and arterial wall irregularity (n = 2) were detected in 28 angiographic procedures, and embolization was performed in 26 instances. Various embolization techniques such as isolation, packing, embolization, and stentgraft implantation were performed. The technical and clinical success rates were 96% (25/26 procedures) and 82% (18/22 patients), respectively. In hemodynamically unstable patients (shock index: heart rate/systolic blood pressure > 1), a 92% (12/13 cases) technical success rate was achieved. There were no significant differences in any evaluated parameters between patients with and without pancreatic fistula.ConclusionTAE is a safe and effective for treating postoperative hemorrhage even in patients with hemodynamic instability and pancreatic fistula. Additionally, pre-interventional CT is useful for effective, consecutive interventions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Applying the principles of isotope analysis in plant and animal ecology to forensic science in the Americas

Forensic science is an applied science that helps investigators answer questions at the heart of a crime: Who, What, When, Where, and How. As part of that process, forensic practitioners use basic laws of chemistry and physics to examine evidence and theories of origin to interpret said evidence. Ecological research has had an extraordinary impact on forensic science through the development and application of a specialized measurement technique useful for examining evidence that appears chemically and physically identical: stable isotope analysis. In this review, we examine the proven utility of stable isotope analysis in forensic settings from an ecological perspective, concentrating on work from the Americas completed within the last three decades. Our primary focus is on the interpretation of stable isotope ratios using plant and animal physiological models for “source inference,” although we also recognize that sample-to-sample comparison of stable isotope ratios can be useful in many forensic settings. Examples of the forensic application of stable isotope analysis cover the gamut, from cotton used in counterfeit bills to anthrax shipped through the U.S. Postal Service, from beer adulterated with cheap adjuncts to human remains discovered in shallow graves and never identified. Recent methodological developments—including isotope analysis of specific compounds, multiple elements, and radioisotopes—and the generation of isotope landscapes, or isoscapes, approaches for data interpretation promises that stable isotope analysis will continue to be used in forensic settings for another three decades… and beyond.

Chesson, Lesley A.↗

Fluid–Structure Interaction Analysis of Papillary Muscle Forces Using a Comprehensive Mitral Valve Model with 3D Chordal Structure

Numerical models of native heart valves are being used to study valve biomechanics to aid design and development of repair procedures and replacement devices. These models have evolved from simple two-dimensional approximations to complex three-dimensional, fully coupled fluid-structure interaction (FSI) systems. Such simulations are useful for predicting the mechanical and hemodynamic loading on implanted valve devices. A current challenge for improving the accuracy of these predictions is choosing and implementing modeling boundary conditions. In order to address this challenge, we are utilizing an advanced in-vitro system to validate FSI conditions for the mitral valve system. Explanted ovine mitral valves were mounted in an in vitro setup, and structural data for the mitral valve was acquired with *CT. Experimental data from the in-vitro ovine mitral valve system were used to validate the computational model. As the valve closes, the hemodynamic data, high speed lea et dynamics, and force vectors from the in-vitro system were compared to the results of the FSI simulation computational model. The total force of 2.6 N per papillary muscle is matched by the computational model. In vitro and in vivo force measurements are important in validating and adjusting material parameters in computational models. The simulations can then be used to answer questions that are otherwise not possible to investigate experimentally. This work is important to maximize the validity of computational models of not just the mitral valve, but any biomechanical aspect using computational simulation in designing medical devices.

Comprehensive Computational Model↗

Multiscale Modeling in the Clinic: Drug Design and Development

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

Clancy, Colleen E.↗

A Case for Electron-Astrophysics

Abstract The smallest characteristic scales, at which electron dynamics determines the plasma behaviour, are the next frontier in space and astrophysical plasma research. The analysis of astrophysical processes at these scales lies at the heart of the research theme of electron-astrophysics. Electron scales are the ultimate bottleneck for dissipation of plasma turbulence, which is a fundamental process not understood in the electron-kinetic regime. In addition, plasma electrons often play an important role for the spatial transfer of thermal energy due to the high heat flux associated with their velocity distribution. The regulation of this electron heat flux is likewise not understood. By focussing on these and other fundamental electron processes, the research theme of electron-astrophysics links outstanding science questions of great importance to the fields of space physics, astrophysics, and laboratory plasma physics. In this White Paper, submitted to ESA in response to the Voyage 2050 call, we review a selection of these outstanding questions, discuss their importance, and present a roadmap for answering them through novel space-mission concepts.

79 ASTRONOMY AND ASTROPHYSICS↗

BRAHMS-Sensitive Bolometer Arrays for the SPICA Imaging Polarimetry

A high-sensitivity cryogenic sub-millimetre camera is planned for the SPICA space observatory. At the heart of this instrument, new all-silicon bolometer arrays integrate in pixel instrumental polarimetry capabilities.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Porous Media Characterization Using Minkowski Functionals: Theories, Applications and Future Directions

Porous materials are ubiquitous, from biological tissues (skin, cartilage, bones, heart tissue), to manufactured materials (paper, functional porous materials, batteries, drug delivery systems, diapers), to environmental materials (rocks, soils, plants). Because these materials are composed of multiple phases, the effects of flow, heat transfer, chemical reactions, and deformations including swelling and shrinking are more complex than that for a single phase such as a gas, liquid, or solid. The realization that porous materials, regardless of the application, have commonalities in modeling approaches, experimental methods, and numerical methods was the impetus of this journal, Transport in Porous Media (founded by Jacob Bear in 1986) and of the International Society for Porous Media (InterPore, interpore.org), which at its roots, originated in 2006. The growth of TIPM and of InterPore mirrors the explosive interest in porous media research that is now recognized as a field of research in and of itself. It is in the honor of InterPore’s 10th anniversary, celebrated at the InterPore 10th Annual Meeting and Jubilee in 2018 in New Orleans, USA, that this special issue was conceived.

Armstrong, Ryan T. (ORCID:0000000164317902)↗