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This article considers two algorithms of a finite-volume solver for the MHD equations with a real-gas equation of state (EOS). Both algorithms use a multistate form of the Harten–Lax–Van Leer approximate Riemann solver as formulated for MHD discontinuities. This solver is modified to use the generalized sound speed from the real-gas EOS. Two methods are tested: EOS evaluation at cell centers and flux interfaces where the former is more computationally efficient. A battery of 1-D and 2-D tests is employed: convergence of 1-D and 2-D linearized waves, shock tube Riemann problems, a 2-D nonlinear circularly polarized Alfven wave, and a 2-D magneto-Rayleigh–Taylor instability test. The cell-centered-EOS-evaluation algorithm produces unresolvable thermodynamic inconsistencies in the intermediate states leading to spurious solutions while the flux-interface EOS evaluation algorithm robustly produces the correct solution. The linearized wave tests show that this inconsistency is associated with the magnetosonic waves and the magneto-Rayleigh–Taylor instability test demonstrates simulation results, where the spurious solution leads to an unphysical simulation.

Interleukin-17A (IL17A) plays a critical role in the development of numerous autoimmune diseases, including psoriasis. The clinical success of IL17A neutralizing biologics in psoriasis has underlined its importance as a drug discovery target. While many studies have focused on the differentiation and trafficking of IL17A producing T-helper 17 cells, less is known about IL17A-initiated signaling events in stromal and parenchymal cells leading to psoriatic phenotypes. We sought to discover signaling nodes downstream of IL17A contributing to disease pathogenesis. Using IL17A and tumor necrosis factor α (TNF) to stimulate primary human epidermal keratinocytes, we employed two different phenotypic screening approaches. First, a library of ∼22000 annotated compounds was screened for reduced secretion of the pro-inflammatory chemokine IL8. Second, a library of 729 kinases was screened in a pooled format by utilizing CRISPR-Cas9 and monitoring IL8 intracellular staining. The highest-ranking novel hits identified in both screens were the bromodomain and extra-terminal domain (BET) family proteins and bromodomain-containing protein 2 (BRD2), respectively. Comparison of BRD2, BRD3, and BRD4 silencing with siRNA and CRISPR confirmed that BRD2 was responsible for mediating IL8 production. Pan-BRD inhibitors and BRD2 knockout also reduced IL17A/TNF-mediated CXC motif chemokines 1/2/6 (CXCL1/2/6) and granulocyte colony stimulating factor (G-CSF) production. In RNA-Seq analysis, 438 IL17A/TNF dependent genes were reduced in BRD2-deficient primary keratinocytes. KEGG pathway analysis of these genes showed enrichment in TNF signaling and rheumatoid arthritis relevant genes. Moreover, a number of genes important for keratinocyte homeostasis and cornification were dysregulated in BRD2-deficient keratinocytes. In IL17A/TNF/IL22 stimulated three-dimensional organotypic raft cultures, pan-BRD inhibition reduced inflammatory factor production but elicited aberrant cornification, consistent with RNA-Seq analysis. These studies highlight a novel role for BRDs and BRD2 in particular in IL17A-mediated inflammatory signaling.

The aim of the study was to assess the feasibility of using a superb microvascular imaging-based vascular index (SMI-VI) for evaluating adult hepatic steatosis. We prospectively compared liver parenchyma SMI-VI (color pixels/total pixels in the region of interest), portal vein velocity, hepatic artery Doppler parameters (peak systolic velocity, end diastolic velocity, resistive index) and serum lipid and alanine aminotransferase (ALT) levels between 16 normal livers and 34 steatotic livers using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as the reference. On the basis of a two-tailed t-test, differences in SMI-VI, portal vein velocity, MRI-PDFF and ALT between normal (MRI-PDFF5%) and steatotic (MRI-PDFF ≥5%) livers were statistically significant (p0.02), whereas hepatic artery Doppler parameters and triglyceride levels were not (p0.05). We observed an inverse correlation of SMI-VI with MRI-PDFF (r = -0.88). With 0.19 as the best cutoff value, the area under the receiver operating characteristic curve, sensitivity and specificity of SMI-VI for determining ≥mild (MRI-PDFF ≥5%) non-alcoholic fatty liver disease (NAFLD) were 0.95, 96% and 94%, respectively. Our results indicate the feasibility of using SMI-VI to assess adult hepatic steatosis. SMI-VI is a potential surrogate marker in the screening for NAFLD.

This manuscript presents verification cases that are developed to study the electrothermal instability (ETI). Specific verification cases are included to ensure that the unit physics components necessary to model the ETI are accurate, providing a path for fluid-based codes to effectively simulate ETI in the linear and nonlinear growth regimes. Two software frameworks with different algorithmic approaches are compared for accuracy in their ability to simulate diffusion of a magnetic field, linear growth of the ETI, and a fully nonlinear ETI evolution. The nonlinear ETI simulations show early time agreement, with some differences emerging, as noted in the wavenumber spectrum, late into the nonlinear development of ETI. A sensitivity study explores the role of equation-of-state (EOS), vacuum density, and vacuum resistivity. EOS and vacuum resistivity are found to be the most critical factors in the modeling of nonlinear ETI development., 14 pages, 14 figures, To be published in the journal of High Energy Density Physics

The semi-implicit leapfrog time-discretization is a workhorse algorithm for initial-value MHD codes to bridge between vastly separated time scales. Inclusion of atomic interactions with neutrals breaks the functional structure of the MHD equations that exploited by the leapfrog. We address how to best integrate atomic physics into the semi-implicit leapfrog. Following the Crank-Nicolson method, one approach is to time-center the atomic interactions in the linear solver and use a Newton method to include the nonlinear contributions. Alternatively, another family of methods are based on operator-splitting the terms associated with the atomic interactions using a Strang-splitting technique. These methods naturally break equations into constituent ODE and PDE parts and preserve the structure exploited by the semi-implicit leapfrog. We study the accuracy and efficiency of these methods through a battery of 0D and 1D cases and show that a second-order-in-time Douglas-Rachford inspired coupling between the ODE and PDE advances is effective in reducing the time-discretization error to be comparable to that of Crank-Nicolson with Newton iteration of the nonlinear terms. Splitting ODE and PDE parts results in independent matrix solves for each field which reduces the computational cost considerably and provides parallelization over species relative to Crank-Nicolson.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability.

AimsTo discuss whether Discharge summaries include important information to community mental health teams .To identify patterns and produce recommendations for change by Quality improvement methods .MethodA convenience sample was selected of the first 5 patient discharges from each of the 6 adult inpatient wards at St Charles Hospital. This represented a total of 30 reviewed summaries. Outcome items were generated following discussion with community psychiatric colleagues based on those aspects of an admission thought to be of most use to a community mental health team. These were; reason for admission, diagnosis, circumstances of admission, progress on the ward, risk assessment, physical health, legal status on discharge, discharge medication, discharge management plan, contact details. Basic identification was also recorded as was the ward and date of dischargeResult•Only 3.3% (1/30) of discharge summaries were complete of all items.•However 23.3% (7/30) were almost complete, failing to record only a single item, and a further 2 missing only 2 of 10 items. There was a bimodal distribution (Graph 1).•Seven (7/30) discharge summaries provided no information. Of these, four (4/7) discharge summaries were written in the progress notes directly, rather than using the discharge summary proforma.•The ‘reason for admission’ item was a clear low outlier with only 2/30 reporting this piece of information. For a number of cases, this was recorded unhelpfully as “in crisis”.ConclusionThere was limited evidence of systemic patterns,however some wards showed internal stark differences with some summaries complete or almost complete and others empty.The key findings from this report are the high number of discharge summaries which have either no responses to them (7/30). This may indicate that the writer did not know how to use the current discharge template, and therefore support with using this is indicated. For those with a very low (7/30) number of item responses, we might conclude that these discharge summaries were written by someone with knowledge of using the system, but for another reason did not complete the majority of the items asked, and for this reasons are not immediately clear. Similarly, as highlighted above the main low outlying result relates to the apparent widespread practise of writing “in crisis” as the ‘reason for admission’, unfortunately to community teams this is an unhelpful and self-evident response.

Computational accelerator physics has changed and broadened over the last decade or so. Part of the change is due to the advent of multiple ways of parallel computing. Another part comes from algorithmic developments. The multiple ways of parallel computing include distributed memory parallelism and on-chip parallelism, with the latter coming from architectures (CPU and GPU) having multiple processing elements (cores or streaming multiprocessors) and wide vector (SIMD) instruction units. The basics of these new architectures and their application to computational accelerator physics are briefly reviewed. Algorithmic advances in the select areas of spin tracking, cavity calculations, plasma acceleration, and electron cooling are also reviewed. In some cases the algorithms provide increased fidelity improving the overall accuracy, while in other cases, such as controlled dispersion, the algorithms provide increased fidelity by better modeling the essential physical interaction. Finally, the use of computational frameworks, which provide the basic computational infrastructure, while allowing the capability developer to concentrate on the math and physics, is reviewed in the context of the Vorpal application, which has found use across accelerator physics and many other fields.

The extended-MHD NIMROD code (Sovinec C.R. and King J.R. 2010 J. Comput. Phys. 229 5803) is used to simulate the dynamics of an edge harmonic oscillation (EHO) in quiescent H-mode (QH-mode) DIII-D (Luxon J.L. 2002 Nucl. Fusion 42 614) discharge 163 518. EHOs observed in non-linear MHD simulations have n = 1 and n = 2 as dominant modes akin the DIII-D experiment. Kinetic equilibrium reconstructions during the time of the fully-developed EHO include the effect of the MHD profile relaxation and are found below the stability boundary. This paper discusses methods to include additional instability drives to the experimental equilibria in order to trigger EHO formation. The experimental equilibrium for the DIII-D discharge 163 518 is modified to include two levels of instability drive by increasing the experimental pressure gradient. In order to do a more direct comparison of the simulation results with the experiment, a synthetic BES diagnostic is used to compute cross-correlation and cross-power spectral densities associated with the simulated density perturbations. It is shown that the amplitude of the experimental density perturbations is between the computed density perturbation amplitude for the two levels of instability drive. The synthetic cross-power spectral density shows a transition from a double to a single peak in frequency when the BES analysis shifts from near the LCFS towards the steep gradient region of the pedestal. This observation is similar to the experiment, but the first peak frequency for the weak instability drive is found below the experimental frequencies, and the second peak for the strong instability drive is found above the experimental peak frequencies. However, these peak frequencies are in agreement with the local flow estimate and a MHD turbulence bursty behavior in the simulations with the strong instability drive.

Although individual athletic performance generally tends to peak in the evening, individuals who exhibit a strong diurnal preference perform better closer to their circadian peak. Time-of-day performance effects are influenced by circadian phenotype (diurnal preference and chronotype—sleep-wake patterns), homeostatic energy reserves and, potentially, genotype, yet little is known about how these factors influence physiological effort. Here, we investigate the effects of time of day, diurnal preference, chronotype, and 'PER3' (a circadian clock gene) genotype on both effort and performance in a population of Division I collegiate swimmers (n = 27). Participants competed in 200m time trials at 7:00 and 19:00 and were sampled pre- and post-trial for salivary α-amylase levels (as a measure of physiological effort), allowing for per-individual measures of performance and physiological effort. Hair samples were collected for genotype analysis (a variable-number tandem-repeat (VNTR) and a single nucleotide polymorphism (SNP) in 'PER3'). Our results indicate significant and parallel time-of-day by circadian phenotype effects on swim performance and effort; evening-type swimmers swam on average 6% slower with 50% greater α-amylase levels in the morning than they did in the evening, and morning types required 5–7 times more effort in the evening trial to achieve the same performance result as the morning trial. In addition, our results suggest that these performance effects may be influenced by gene (circadian clock gene PER3 variants) by environment (time of day) interactions. Participants homozygous for the 'PER3' 4,4 length variant (rs57875989) or who possess a single G-allele at 'PER3' SNP rs228697 swam 3–6% slower in the morning. Overall, these results suggest that intra-individual variation in athletic performance and effort with time of day is associated with circadian phenotype and 'PER3' genotype.

Recent results from experiments and simulation [1], [2] of magnetically driven pulsed power liners have explored the role of the early-time electrothermal instability in the evolution of the magneto-Rayleigh-Taylor instability. Our focus will be on understanding the development of such instabilities and the potential stabilization mechanisms, which we expect could play a significant role in supporting the success of the MagLIF (Magnetized Liner Inertial Fusion) program. MagLIF is a particularly promising emerging concept for producing fusion energy in amounts greater than breakeven. Better understanding of magnetoRayleigh-Taylor instabilities through advanced modeling will improve the MagLIF concept. Experiments have shown that studies of high-energy density plasmas from wire-array implosions require physics modeling that goes well beyond simple models such as ideal magnetohydrodynamics. The goal of this work is to provide increased understanding of these experiments by employing simulations with a multifluid extended-MHD model, which uses kinetic closures for thermal conductivity, resistivity, and viscosity. We will use codes easily available to the wider research community, including university students, with a secondary goal of providing the community with well-benchmarked tools capable of advanced modeling of high-energy-density plasmas. This proposal also pioneers a hybrid fluid-kinetic modeling approach that is applicable to other high-energydensity physics scenarios.

Methods are described that extend fields from reconstructed equilibria to include scrape-off-layer current through extrapolated parametrized and experimental fits. The extrapolation includes both the effects of the toroidal-field and pressure gradients which produce scrape-off-layer current after recomputation of the Grad-Shafranov solution. To quantify the degree that inclusion of scrape-off-layer current modifies the equilibrium, the $\chi$-squared goodness-of-fit parameter is calculated for cases with and without scrape-off-layer current. The change in $\chi$-squared is found to be minor when scrape-off-layer current is included however flux surfaces are shifted by up to 3 cm. The impact on edge modes of these scrape-off-layer modifications is also found to be small and the importance of these methods to nonlinear computation is discussed., Comment: 14 pages

The extended-MHD NIMROD code [C.R. Sovinec and J.R. King, J. Comput. Phys. 229, 5803 (2010)] models broadband-MHD activity from a reconstruction of a quiescent H-mode shot on the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)]. Computations with the reconstructed toroidal and poloidal ion flows exhibit low-n perturbations (n=1-5) that grow and saturate into a turbulent-like MHD state. The workflow used to project the reconstructed state onto the NIMROD basis functions re-solves the Grad-Shafranov equation and extrapolates profiles to include scrape-off-layer currents. Evaluation of the transport from the turbulent-like MHD state leads to a relaxation of the density and temperature profiles., Comment: 8 pages

Extended-MHD modeling of DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)] quiescent H-mode (QH-mode) discharges with nonlinear NIMROD [C. R. Sovinec et al., J. Comput. Phys. 195, 355 (2004)] simulations saturates into a turbulent state but does not saturate when the steady-state flow inferred from measurements is not included. This is consistent with the experimental observations of the quiescent regime on DIII-D. The simulation with flow develops into a saturated turbulent state where the n=1 and 2 toroidal modes become dominant through an inverse cascade. Each mode in the range of n=1-5 is dominant at a different time. Consistent with experimental observations during QH-mode, the simulated state leads to large particle transport relative to the thermal transport. Analysis shows that the amplitude and phase of the density and temperature perturbations differ resulting in greater fluctuation-induced convective particle transport relative to the convective thermal transport. Comparison to magnetic-coil measurements shows that rotation frequencies differ between the simulation and experiment, which indicates that more sophisticated extended-MHD two-fluid modeling is required., Comment: 11 pages, 10 figures, manuscript associated with invited talk at APS-DPP Annual Meeting, 2016, in San Jose

A temporally staggered algorithm for advancing solutions of the two-fluid plasma model is analyzed with von Neumann's method and with differential approximation. The implicit leapfrog algorithm [C.R. Sovinec et al., J. Phys. Conf. Series 16 (2005) 25-34] is found to be numerically stable at arbitrarily large time-step when the advective, Hall, and gyroviscous terms are temporally centered in their respective advances and the coefficient of the semi-implicit operator meets the criterion found for basic hyperbolic systems. Numerical instability with forward or backward differencing of advection is evident as an ill-posed equation in the differential approximation for a simplified system. At large time-step, the accuracy of the algorithm is comparable to that of the Crank-Nicolson method for all plane waves except the parallel mode that is sensitive to the ion cyclotron resonance. An implementation reproduces theoretical results on the transition from resistive magnetohydrodynamics to two-fluid reconnection in a sheared-slab linear tearing mode. A nonlinear three-dimensional computation in toroidal geometry shows an increasing exponentiation rate of kinetic energy as magnetic reconnection from an internal kink mode changes from current-sheet to 'X-point' geometry.

A vertex detector that can measure particles with charm or bottom quarks would dramatically expand the physics capability of the STAR detector at RHIC. To accomplish this, we are proposing to build the Heavy Flavor Tracker (HFT) using 2×2 cm Active Pixels Sensors (APS). Ten of these APS chips will be arranged on a ladder (0.28% of a radiation length) at radii of 1.5 and at 5.0 cm. We have examined several properties of APS chips, so that we can characterize the performance of this detector. Using 1.5 GeV/ c electrons, we have measured the charge collected and compared it to the expected charge. To achieve high efficiency, we have considered two different cluster finding algorithms and found that the choice of algorithm is dependent on noise level. We have demonstrated that a Scanning Electron Microscope can probe properties of an APS chip. In particular, we studied several position resolution algorithms. Finally, we studied the properties of pixel pitches from 5 to 30 μm.

Many problems of interest in plasma modelling are subject to the ‘tyranny of scales’, specifically, problems that encompass physical processes that operate on timescales that are separated by many orders of magnitude. Investigating such problems therefore requires the use of implicit time-integration schemes, which advance problem solutions on the timescale of interest, while incorporating the physics of the fast-timescales. One promising route to develop these implicit solvers is the combination of Jacobian-Free Newton-Krylov methods, combined with physics-based pre-conditioners based on Schur complement analysis of the physical system.

As part of an upper level undergraduate developmental biology course at the University of Minnesota Duluth, we developed a unit in which students carried out original research as part of a cooperative class project. Students had the opportunity to gain experience in the scientific method from experimental design all of the way through to the preparation of publication on their research that included text, figures, and tables. This kind of inquiry-based learning has been shown to have many benefits for students, including increased long-term learning and a better understanding of the process of scientific discovery. In our project, students designed experiments to explore why zebrafish typically spawn in the first few hours after the lights come on in the morning. The results of our experiments suggest that spawning still occurs when the dark-to-light transition is altered or absent. This is consistent with the work of others that demonstrates that rhythmic spawning behavior is regulated by an endogenous circadian clock. Our successes and failures carrying out original research as part of an undergraduate course should contribute to the growing approaches for using zebrafish to bring the excitement of experimental science to the classroom.

The linear, collisional, constant-ψ drift-tearing mode is analyzed for different regimes of the plasma-β, ion-skin-depth parameter space with an unreduced, extended-magnetohydrodynamic model. New dispersion relations are found at moderate plasma β and previous drift-tearing results are classified as applicable at small plasma β.

Drift and Hall effects on magnetic tearing, island evolution, and relaxation in pinch configurations are investigated using a non-reduced first-order finite-Larmor-radius (FLR) fluid model with the nonideal magnetohydrodynamics (MHD) with rotation, open discussion (NIMROD) code [C.R. Sovinec and J. R. King, J. Comput. Phys. 229, 5803 (2010)]. An unexpected result with a uniform pressure profile is a drift effect that reduces the growth rate when the ion sound gyroradius (ρs) is smaller than the tearing-layer width. This drift is present only with warm-ion FLR modeling, and analytics show that it arises from ∇B and poloidal curvature represented in the Braginskii gyroviscous stress. Nonlinear single-helicity computations with experimentally relevant ρs values show that the warm-ion gyroviscous effects reduce saturated-island widths. Computations with multiple nonlinearly interacting tearing fluctuations find that m = 1 core-resonant-fluctuation amplitudes are reduced by a factor of two relative to single-f...

The linear and nonlinear evolution of a single-helicity tearing mode in a cylindrical, force-free pinch are investigated using a fluid model with first-order finite-Larmor-radius corrections. Linear results computed with the nimrod [nonideal magnetohydrodynamics (MHD) with rotation, open discussion] code [Sovinec et al., J. Comput. Phys. 195, 355 (2004)] produce a regime at small ρs where the growth rate is reduced relative to resistive MHD, though the Hall term is not significant. The leading order contributions from ion gyroviscosity may be expressed as a drift associated with ∇B0 and poloidal curvature for experimentally relevant β=0.1, S~105-106 force-free equilibria. The heuristic analytical dispersion relation, γ4(γ-iω*gv)=γMHD5 where ω*gv is the gyroviscous drift frequency, confirms numerical results. The behavior of our cylindrical computations at large ρs corroborates previous analytic slab studies where an enhanced growth rate and radially localized Hall dynamo are predicted. Similar to previous...