On the miscible Rayleigh-Taylor instability: two and three dimensions

We investigate the miscible Rayleigh-Taylor (RT) instability in both 2 and 3 dimensions using direct numerical simulations, where the working fluid is assumed incompressible under the Boussinesq approximation. We first consider the case of randomly perturbed interfaces. With a variety of diagnostics, we develop a physical picture for the detailed temporal development of the mixed layer: We identify three distinct evolutionary phases in the development of the mixed layer, which can be related to detailed variations in the growth of the mixing zone. Our analysis provides an explanation for the observed differences between two and three-dimensional RT instability; the analysis also leads us to concentrate on the RT models which (1) work equally well for both laminar and turbulent flows, and (2) do not depend on turbulent scaling within the mixing layer between fluids. These candidate RT models are based on point sources within bubbles (or plumes) and interaction with each other (or the background flow). With this motivation, we examine the evolution of single plumes, and relate our numerical results (of single plumes) to a simple analytical model for plume evolution.Comment: 31 pages, 27 figures, to appear in November issue of JFM, 2001. For better figures: http://astro.uchicago.edu/~young/ps/jfmtry08.ps.

Simulations of Astrophysical Fluid Instabilities

We present direct numerical simulations of mixing at Rayleigh-Taylor unstable interfaces performed with the FLASH code, developed at the ASCI/Alliances Center for Astrophysical Thermonuclear Flashes at the University of Chicago. We present initial results of single-mode studies in two and three dimensions. Our results indicate that three-dimensional instabilities grow significantly faster than two-dimensional instabilities and that grid resolution can have a significant effect on instability growth rates. We also find that unphysical diffusive mixing occurs at the fluid interface, particularly in poorly resolved simulations.Comment: 3 pages, 1 figure. To appear in the proceedings of the 20th Texas Symposium on Relativistic Astrophysic

Optimal, scalable forward models for computing gravity anomalies

We describe three approaches for computing a gravity signal from a density anomaly. The first approach consists of the classical "summation" technique, whilst the remaining two methods solve the Poisson problem for the gravitational potential using either a Finite Element (FE) discretization employing a multilevel preconditioner, or a Green's function evaluated with the Fast Multipole Method (FMM). The methods utilizing the PDE formulation described here differ from previously published approaches used in gravity modeling in that they are optimal, implying that both the memory and computational time required scale linearly with respect to the number of unknowns in the potential field. Additionally, all of the implementations presented here are developed such that the computations can be performed in a massively parallel, distributed memory computing environment. Through numerical experiments, we compare the methods on the basis of their discretization error, CPU time and parallel scalability. We demonstrate the parallel scalability of all these techniques by running forward models with up to $10^8$ voxels on 1000's of cores.Comment: 38 pages, 13 figures; accepted by Geophysical Journal Internationa

Large-Scale Simulations of Clusters of Galaxies

We discuss some of the computational challenges encountered in simulating the evolution of clusters of galaxies. Eulerian adaptive mesh refinement (AMR) techniques can successfully address these challenges but are currently being used by only a few groups. We describe our publicly available AMR code, FLASH, which uses an object-oriented framework to manage its AMR library, physics modules, and automated verification. We outline the development of the FLASH framework to include collisionless particles, permitting it to be used for cluster simulation.Comment: 3 pages, 3 figures, to appear in Proceedings of the VII International Workshop on Advanced Computing and Analysis Techniques in Physics Research (ACAT 2000), Fermilab, Oct. 16-20, 200

On Validating an Astrophysical Simulation Code

We present a case study of validating an astrophysical simulation code. Our study focuses on validating FLASH, a parallel, adaptive-mesh hydrodynamics code for studying the compressible, reactive flows found in many astrophysical environments. We describe the astrophysics problems of interest and the challenges associated with simulating these problems. We describe methodology and discuss solutions to difficulties encountered in verification and validation. We describe verification tests regularly administered to the code, present the results of new verification tests, and outline a method for testing general equations of state. We present the results of two validation tests in which we compared simulations to experimental data. The first is of a laser-driven shock propagating through a multi-layer target, a configuration subject to both Rayleigh-Taylor and Richtmyer-Meshkov instabilities. The second test is a classic Rayleigh-Taylor instability, where a heavy fluid is supported against the force of gravity by a light fluid. Our simulations of the multi-layer target experiments showed good agreement with the experimental results, but our simulations of the Rayleigh-Taylor instability did not agree well with the experimental results. We discuss our findings and present results of additional simulations undertaken to further investigate the Rayleigh-Taylor instability.Comment: 76 pages, 26 figures (3 color), Accepted for publication in the ApJ

Brain Bases of Reading Fluency in Typical Reading and Impaired Fluency in Dyslexia

Although the neural systems supporting single word reading are well studied, there are limited direct comparisons between typical and dyslexic readers of the neural correlates of reading fluency. Reading fluency deficits are a persistent behavioral marker of dyslexia into adulthood. The current study identified the neural correlates of fluent reading in typical and dyslexic adult readers, using sentences presented in a word-by-word format in which single words were presented sequentially at fixed rates. Sentences were presented at slow, medium, and fast rates, and participants were asked to decide whether each sentence did or did not make sense semantically. As presentation rates increased, participants became less accurate and slower at making judgments, with comprehension accuracy decreasing disproportionately for dyslexic readers. In-scanner performance on the sentence task correlated significantly with standardized clinical measures of both reading fluency and phonological awareness. Both typical readers and readers with dyslexia exhibited widespread, bilateral increases in activation that corresponded to increases in presentation rate. Typical readers exhibited significantly larger gains in activation as a function of faster presentation rates than readers with dyslexia in several areas, including left prefrontal and left superior temporal regions associated with semantic retrieval and semantic and phonological representations. Group differences were more extensive when behavioral differences between conditions were equated across groups. These findings suggest a brain basis for impaired reading fluency in dyslexia, specifically a failure of brain regions involved in semantic retrieval and semantic and phonological representations to become fully engaged for comprehension at rapid reading rates

Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact

Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new opportunity; however, their use has highlighted other issues: the vascular normalization compared to a vessel pruning to promote the delivery of an active cancer immunotherapy and the development of resistance to immunotherapy which leads to a better selection of patients as candidates for ICIs. Nevertheless, the combination of antiangiogenic therapy plus ICIs represents an intriguing approach with high potential to improve the survival of these patients. Waiting for results from ongoing clinical trials, this review depicts the current knowledge about the resistance to antiangiogenic drugs in HCC. It could also provide updated information to clinicians focusing on the most effective combinations or sequential approaches in this regard, based on molecular mechanisms

Enhanced Active Safety Through Integrated Autonomous Drifting and Direct Yaw Moment Control via Nonlinear Model Predictive Control

The introduction of active safety systems and advanced driver assistance systems has enhanced the control authority over the vehicle dynamics through specialized actuators, enabling, for instance, independent wheel torque control. During emergency situations, these systems step in to aid the driver by limiting vehicle response to a stable and controllable range of low longitudinal tire slips and slip angles. This approach makes vehicle behavior predictable and manageable for the average human driver; however, it is conservative in case of driving automation. In fact, past research has shown that exceeding the operational boundaries of conventional active safety systems enables trajectories that are otherwise unattainable. This paper presents a nonlinear model predictive controller (NMPC) for path tracking (PT), which integrates steering, front-to-total longitudinal tire force distribution, and direct yaw moment actuation, and can operate beyond the limit of handling, e.g., to induce drift, if this is beneficial to PT. Simulation results of emergency conditions in an intersection scenario highlight that the proposed solution provides significant safety improvements, when compared to the concurrent operation of PT algorithms and the current generation of vehicle stability controllers

Risk Prediction in Acute Calculous Cholecystitis: A Systematic Review and Meta-analysis of Prognostic Factors and Predictive Models

BACKGROUND: Laparoscopic cholecystectomy is the main treatment of acute cholecystitis. Although considered relatively safe, it carries 6%–9% risk of major complications and 0.1%–1% risk of mortality. There is no consensus regarding the evaluation of the preoperative risks, and the management of patients with acute cholecystitis is usually guided by surgeon's personal preferences. We assessed the best method to identify patients with acute cholecystitis who are at high risk of complications and mortality. METHODS: We performed a systematic review of studies that reported the preoperative prediction of outcomes in people with acute cholecystitis. We searched the Cochrane Library, MEDLINE, EMBASE, WHO ICTRP, ClinicalTrials.gov, and Science Citation Index Expanded until April 27, 2019. We performed a meta-analysis when possible. RESULTS: Six thousand eight hundred twenty-seven people were included in one or more analyses in 12 studies. Tokyo guidelines 2013 (TG13) predicted mortality (two studies; Grade 3 versus Grade 1: odds ratio [OR] 5.08, 95% confidence interval [CI] 2.79–9.26). Gender predicted conversion to open cholecystectomy (two studies; OR 1.59, 95% CI 1.06–2.39). None of the factors reported in at least two studies had significant predictive ability of major or minor complications. CONCLUSION: There is significant uncertainty in the ability of prognostic factors and risk prediction models in predicting outcomes in people with acute calculous cholecystitis. Based on studies of high risk of bias, TG13 Grade 3 severity may be associated with greater mortality than Grade 1. Early referral of such patients to high-volume specialist centers should be considered. Further well-designed prospective studies are necessary

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

Purpose Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS. Patients and methods One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity. Results Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02). Conclusions Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival