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This paper discusses a strategy to initialize a two-dimensional (2D) Reynolds-averaged Navier–Stokes model [LANL's Besnard–Harlow–Rauenzahn (BHR) model] in order to describe an unsteady transitional Richtmyer–Meshkov (RM)-induced flow observed in on-going high-energy-density ensemble experiments performed on the OMEGA-EP facility. The experiments consist of a nominal single-mode perturbation (initial amplitude a 0 ≈ 10 and wavelength λ = 100 μ m) with target-to-target variations in the surface roughness subjected to the RM instability with delayed Rayleigh–Taylor in a heavy-to-light configuration. Our strategy leverages high-resolution three-dimensional (3D) implicit large eddy simulations (ILES) simulations to initialize BHR-relevant parameters and subsequently validate the 2D BHR results against the 3D ILES simulations. A suite of five 3D ILES simulations corresponding to five experimental target profiles is undertaken to generate an ensemble dataset. Using ensemble averages from the 3D simulations to initialize the turbulent kinetic energy in the BHR model (K0) demonstrates the ability of the model to predict the time evolution of the interface as well as the density-specific-volume covariance, b. To quantify the sensitivity of the BHR results to the choice of K0 and the initial turbulent length scale, S0, we execute a parameter sweep spanning four orders of magnitude for both S0 and K0, generating a parameter space consisting of 26 simulations. The Pearson's correlation coefficient is used as a measure of discrepancy between the 2D BHR and 3D ILES simulations and reveals that the ranges 8 ≲ S 0 ≲ 20 μ m and 109 ≲ K 0 ≲ 10 10 cm2/s2 produce predictions that agree best with the 3D ILES results. [ABSTRACT FROM AUTHOR]

Inertial confinement fusion (ICF) and high-energy density (HED) physics experiments experience complicated forcing for instability growth and mix due to the ubiquitous presence of multiple shocks interacting with perturbations on multiple material interfaces. One common driver of instability growth is successive shocks from the same direction. However, there is a severe lack of analytic work and modeling validation for same-sided successive shocks since they are extremely difficult to achieve with conventional (non-HED) drivers. Successive shocks access a large instability parameter space; idealized fluid theory [K. O. Mikaelian, Phys. Rev. A 31, 410 (1985)] predicts 15 different interface evolution scenarios for a sinusoidal perturbation. Growth becomes more complex for multi-mode, compressible HED systems. The Mshock campaign is the first experiment in any fluid regime to probe a wide portion of successive shock parameter space. This is enabled by our development of a hybrid direct/indirect drive platform capable of creating independently controllable successive shocks on the National Ignition Facility. These experiments have delivered the first data capable of rigorously challenging our models and their ability to accurately capture Richtmyer–Meshkov growth under successive shocks. Single-mode and two-mode experiments have successfully demonstrated the ability to access and control the various growth scenarios of the shocked interface, including re-inversion, freeze out, and continued growth. Simulations and theoretical modeling are shown to accurately capture the experimental observations in the linear growth phase, giving us confidence in our ICF/HED design codes. [ABSTRACT FROM AUTHOR]

The "Decel" platform at Sandia National Laboratories investigates the Richtmyer–Meshkov instability (RMI) in converging geometry under high energy density conditions [Knapp et al., Phys. Plasmas 27, 092707 (2020)]. In Decel, the Z machine magnetically implodes a cylindrical beryllium liner filled with liquid deuterium, launching a converging shock toward an on-axis beryllium rod machined with sinusoidal perturbations. The passage of the shock deposits vorticity along the Be/D2 interface, causing the perturbations to grow. In this paper, we present platform improvements along with recent experimental results. To improve the stability of the imploding liner to the magneto Rayleigh–Taylor instability, we modified its acceleration history by shortening the Z electrical current pulse. Next, we introduce a "split rod" configuration that allows two axial modes to be fielded simultaneously in different axial locations along the rod, doubling our data per experiment. We then demonstrate that asymmetric slots in the return current structure modify the magnetic drive pressure on the surface of the liner, advancing the evolution on one side of the rod by multiple ns compared to its 180° counterpart. This effectively enables two snapshots of the instability at different stages of evolution per radiograph with small deviations of the cross-sectional profile of the rod from the circular. Using this platform, we acquired RMI data at 272 and 157 μm wavelengths during the single shock stage. Finally, we demonstrate the utility of these data for benchmarking simulations by comparing calculations using ALEGRA MHD and RageRunner. [ABSTRACT FROM AUTHOR]

In this paper, we report on a crystal based x-ray imaging system fielded at the OMEGA EP laser facility. This new system has a pointing accuracy of +/100 μm, a temporal resolution down to 100 ps (depending on backlighter characteristics), variable magnification, and a spatial resolution of 21.9 µm at the object plane at a magnification of 15×. The system is designed to use a crystal along the crystal plane that satisfies the Bragg condition for the x ray of interest. The thin crystal is then bent into a spherical geometry and attached to a glass backing substrate to hold it in the diagnostic, and the x rays are imaged onto a charge coupled device. We report on data acquired with the new Los Alamos National Laboratory supplied spherical quartz crystal to image the Mn He-α 6.15 keV line emission. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a novel experimental platform for the study of the Richtmyer–Meshkov instability in a cylindrically converging geometry using a magnetically driven cylindrical piston. Magnetically driven solid liner implosions are used to launch a shock into a liquid deuterium working fluid and, ultimately, into an on-axis rod with a pre-imposed perturbation. The shock front trajectory is tracked through the working fluid and up to the point of impacting the rod through the use of on axis photonic Doppler velocimetry. This configuration allows for precise characterization of the shock state as it impacts the perturbed rod interface. Monochromatic x-ray radiography is used to measure the post-shock interface evolution and rod density profile. The ALEGRA MHD model is used to simulate the dynamics of the experiment in one dimension. We show that late in time the perturbation growth becomes non-linear as evidenced by the observation of high-order harmonics, up to n = 5. Two dimensional simulations performed using a combination of the GORGON MHD code and the xRAGE radiation hydrodynamics code suggest that the late time non-linear growth is modified by convergence effects as the bubbles and spikes experience differences in the pressure of the background flow. [ABSTRACT FROM AUTHOR]

A hydrodynamic shear mixing layer experiment at the National Ignition Facility had previously demonstrated Eulerian scaling of integrated, late-time quantities, including turbulent kinetic energy. In this manuscript, the experiment is repeated with new materials. Using the new dataset, we demonstrate that Euler-number scalings hold not just for late time, but dynamically throughout the experiment, for measurements in all three spatial dimensions. Incorporating the dynamic scaling leads to an enhanced calculation that the heavier of the two scaled experiments has approached three generations of mergers of its primary instability's structures and a consistent observation of such a merger in action in the lighter of the two scaled experiments. Furthermore, the improved scrutiny of the time evolution of instability structures leads to sharper estimates of turbulent kinetic energy, including a demonstration of different behaviors correlating with surface roughness (quantitatively consistent with transitions between laminar and turbulent initial states), as predicted by a Reynolds-averaged turbulent model, which evidently correctly handles the differing shock-roughness interactions to drive its internal state of the model into different regimes. Altogether, a picture arises of the analytical improvements in treating these variations (of times, densities, and roughnesses) as a unified whole and of multiple ways by which deviations from the scaling could indicate an onset of non-hydrodynamic behavior. Such deviations were not expected for these experiments (which models correctly indicated would remain hydrodynamic) but could be introduced by, for example, imposing external fields or increasing drive energy to test conditions relevant to inertial confinement fusion or other high-energy-density experiments. [ABSTRACT FROM AUTHOR]

A shock incident on an interface will cause any initial perturbations on that interface to grow. When the shock front is parallel to the interface, the perturbations grow due to the Richtmyer-Meshkov (RM) process. When there is some tilt between the shock front and the interface, shear flow will result across the postshock interface. Recent experiments on the OMEGA EP laser have studied the hydrodynamic instability growth which results from a supported shock interacting with a sinusoidally perturbed, oblique interface. The observed instability growth was dominated by Richtmyer-Meshkov at early times but became Kelvin-Helmholtz (KH)-like at late times. Previously, this instability growth was described using an analytic model for the deposition of baroclinic vorticity on the interface by a shock combined with a discrete vortex model. Here, we utilize the same baroclinic vorticity deposition model in conjunction with a desingularized, periodic Birkhoff-Rott equation to model instability evolution. The Birkhoff-Rott equation takes into account the vorticity distribution along the interface, whereas the discrete vortex model assumed that all vorticity over each wavelength of the perturbation is confined to a point. We compare the new model to xRAGE simulations and experiments. The model is found to overpredict both the instability growth and shear across the interface by about a factor of two, but correctly predicts that the growth is RM-like at early times and KH-like at late times. [ABSTRACT FROM AUTHOR]

In this work, we discuss simulations, along with a benchmarking experiment, performed using the xRAGE code which demonstrate the ability of a laser model to predict laser-driven, high-energy-density shock hydrodynamics with good fidelity. This directly contributes to our ability to model hydrodynamic-instability dynamics produced by a laser drive typical of those available at OMEGA, OMEGA-EP, NIF, and similar facilities. In particular, we show how the laser model is essential for predicting deceleration-phase Rayleigh-Taylor arising from laser turn-off. We do this using the experimental case of a seeded single-mode perturbation. Then, we turn to a seeded multimode perturbation to show how the above result permits us to access the modeling of hydrodynamic mixing, a topic of interest for future work. [ABSTRACT FROM AUTHOR]

The LANL Shear Campaign uses millimeter-scale initially solid shock tubes on the National Ignition Facility to conduct high-energy-density hydrodynamic plasma experiments, capable of reaching energy densities exceeding 100 kJ/cm3. These shock-tube experiments have for the first time reproduced spontaneously emergent coherent structures due to shear-based fluid instabilities [i.e., Kelvin-Helmholtz (KH)], demonstrating hydrodynamic scaling over 8 orders of magnitude in time and velocity. The KH vortices, referred to as “rollers,” and the secondary instabilities, referred to as “ribs,” are used to understand the turbulent kinetic energy contained in the system. Their evolution is used to understand the transition to turbulence and that transition's dependence on initial conditions. Experimental results from these studies are well modeled by the RAGE (Radiation Adaptive Grid Eulerian) hydro-code using the Besnard-Harlow-Rauenzahn turbulent mix model. Information inferred from both the experimental data and the mix model allows us to demonstrate that the specific Turbulent Kinetic Energy (sTKE) in the layer, as calculated from the plan-view structure data, is consistent with the mixing width growth and the RAGE simulations of sTKE. [ABSTRACT FROM AUTHOR]

The Rayleigh-Taylor (RT) instability is a common occurrence in nature, notably in astrophysical systems like supernovae, where it serves to mix the dense layers of the interior of an exploding star with the low-density stellar wind surrounding it, and in inertial confinement fusion experiments, where it mixes cooler materials with the central hot spot in an imploding capsule and stifles the desired nuclear reactions. In both of these examples, the radiative flux generated by strong shocks in the system may play a role in partially stabilizing RT instabilities. Here, we present experiments performed on the National Ignition Facility, designed to isolate and study the role of radiation and heat conduction from a shock front in the stabilization of hydrodynamic instabilities. By varying the laser power delivered to a shock-tube target with an embedded, unstable interface, the radiative fluxes generated at the shock front could be controlled. We observe decreased RT growth when the shock significantly heats the medium around it, in contrast to a system where the shock did not produce significant heating. Both systems are modeled with a modified set of buoyancy-drag equations accounting for ablative stabilization, and the experimental results are consistent with ablative stabilization when the shock is radiative. This result has important implications for our understanding of astrophysical radiative shocks and supernova radiative hydrodynamics [Kuranz et al., Nature Communications 9(1), 1564 (2018)]. [ABSTRACT FROM AUTHOR]

Energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh--Taylor instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh--Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger than the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants. [ABSTRACT FROM AUTHOR]

We present an experiment using lasers to produce a shock pressure of >10 Mbar, which we then use to drive Richtmyer-Meshkov and Rayleigh-Taylor growth at a 2D multimode perturbed interface. Key features of this platform are that we can precisely reproduce the perturbation from iteration to iteration of the experiment, facilitating analysis, and that the lasers allow us to produce very strong shocks, creating a plasma state in the system. We also implement a Bayesian technique to analyze the multimode spectra. This technique enables us to draw quantitative conclusions about the spectrum, even in the presence of significant noise. For instance, we measure the signal contained in the seeded modes over time, as well as the transition of the initial growth rate of these modes into the overall saturation behavior of the spectrum. [ABSTRACT FROM AUTHOR]

The counter-propagating shear campaign is examining instability growth and its transition to turbulence in the high-energy-density physics regime using a laser-driven counter-propagating flow platform. In these experiments, we observe consistent complex break-up of and structure growth in a tracer layer placed at the shear flow interface during the instability growth phase. We present a wavelet-transform based analysis technique capable of characterizing the scale- and directionalityresolved average intensity perturbations in static radiographs of the experiment. This technique uses the complete spatial information available in each radiograph to describe the structure evolution. We designed this analysis technique to generate a two-dimensional power spectrum for each radiograph from which we can recover information about structure widths, amplitudes, and orientations. The evolution of the distribution of power in the spectra for an experimental series is a potential metric for quantifying the structure size evolution as well as a system's evolution towards isotropy. [ABSTRACT FROM AUTHOR]

Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k- type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varying two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. We also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths. [ABSTRACT FROM AUTHOR]

An indirectly-driven shock tube experiment fielded on the National Ignition Facility (NIF) was used to create a high-energy-density hydrodynamics platform at unprecedented scale. Scaling up a shear-induced mixing experiment previously fielded at OMEGA, the NIF shear platform drives 130 µm/ns shocks into a CH foam-filled shock tube (~ 60 mg/cc) with interior dimensions of 1.5 mm diameter and 5 mm length. The pulse-shaping capabilities of the NIF are used to extend the drive for >10 ns, and the large interior tube volumes are used to isolate physics-altering edge effects from the region of interest. The scaling of the experiment to the NIF allows for considerable improvement in maximum driving time of hydrodynamics, in fidelity of physics under examination, and in diagnostic clarity. Details of the experimental platform and post-shot simulations used in the analysis of the platform-qualifying data are presented. Hydrodynamic scaling is used to compare shear data from OMEGA with that from NIF, suggesting a possible change in the dimensionality of the instability at late times from one platform to the other. [ABSTRACT FROM AUTHOR]

A very large area (7.5 mm²) laser-driven x-ray backlighter, termed the Big Area BackLighter (BABL) has been developed for the National Ignition Facility (NIF) to support high energy density experiments. The BABL provides an alternative to Pinhole-Apertured point-projection Backlighting (PABL) for a large field of view. This bypasses the challenges for PABL in the equatorial plane of the NIF target chamber where space is limited because of the unconverted laser light that threatens the diagnostic aperture, the backlighter foil, and the pinhole substrate. A transmission experiment using 132 kJ of NIF laser energy at a maximum intensity of 8.52 x 1014 W/cm² illuminating the BABL demonstrated good conversion efficiency of >3.5% into K-shell emission producing ~4.6 kJ of high energy x rays, while yielding high contrast images with a highly uniform background that agree well with 2D simulated spectra and spatial profiles. [ABSTRACT FROM AUTHOR]

We report on the novel integration of streaked radiography into a counter-flowing High Energy Density (HED) shear environment that continually measures a growing mix layer of Al separating two low-density CH foams. Measurements of the mix width allow us to validate compressible turbulence models and with streaked imaging, make this possible with a minimal number of experiments on large laser facilities. In this paper, we describe how the HED counter-flowing shear layer is created and diagnosed with streaked radiography. We then compare the streaked data to previous two-dimensional, single frame radiography and radiation hydrodynamic simulations of the experiment with inline compressible turbulent mix models. [ABSTRACT FROM AUTHOR]

The counterpropagating shear experiment has previously demonstrated the ability to create regions of shock-driven shear, balanced symmetrically in pressure, and experiencing minimal net drift. This allows for the creation of a high-Mach-number high-energy-density shear environment. New data from the counterpropagating shear campaign is presented, and both hydrocode modeling and theoretical analysis in the context of a Reynolds-averaged-Navier-Stokes model suggest turbulent dissipation of energy from the supersonic flow bounding the layer is a significant driver in its expansion. A theoretical minimum shear flow Mach number threshold is suggested for substantial thermal-turbulence coupling. [ABSTRACT FROM AUTHOR]

A theory of shocks dominated by radiation energy flux in optically mixed thin-upstream thick-downstream systems, in which the temperature immediately ahead and some short distance behind the shock front are equilibrated by radiation transport, is presented. This theory is applied to determine properties of the normal and oblique radiative shock, followed by applications to interactions when radiative and polytropic shocks are present in the same system. Comparison with experimental data is presented. [ABSTRACT FROM AUTHOR]

The radiative precursor of a sufficiently fast shock has been observed to drive the vaporization of shock tube material ahead of the shock. The resulting expansion drives a converging blast wave into the gas volume of the tube. The effects of this wall shock may be observed and correlated with primary shock parameters. We demonstrate this process in experiments performed on the Omega Laser Facility, launching shocks propagating through xenon with speeds above 100 km/s driven by ablation pressures of approximately 50 Mbars. Wall shocks in laser experiments, in which the principal shock waves themselves should not be radiative, are also reported—in which the wall shocks have been launched by some other early energy source. [ABSTRACT FROM AUTHOR]

Objective: To analyse the levels of interleukin-6 (IL-6) in the synovial fluids and sera of patients with osteoarthritis (OA) and to identify the IL-6-secreting cells. Methods: Serum, synovial fluid, synovial tissue, and articular cartilage samples were collected from 49 OA patients with end-stage knee or hip OA who underwent joint replacement surgery. Serum and synovial fluid levels of IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and IL-6-secreting cells were identified by immunohistochemistry. Results: Eight out of 49 patients (16%) exhibited elevated IL-6 levels in the synovial fluids, averaging at 2022±526 pg/mL, while the levels in the rest of the patients averaged at 132±19 pg/mL. The sera levels of all patients were comparable in the 10 pg/mL range. Immunohistochemical analyses revealed plasma cells in the synovial lining of the high producers as the source of IL-6. Conclusions: Synovial fluid IL-6 levels may help to classify OA patients and may point to a subgroup with a particular impact from their immune system. [ABSTRACT FROM AUTHOR]

We derive a model describing vorticity deposition on a high-Atwood number interface with a sinusoidal perturbation by an oblique shock propagating from a heavy into a light material. Limiting cases of the model result in vorticity distributions that lead to Richtmyer-Meshkov and Kelvin-Helmholtz instability growth. For certain combinations of perturbation amplitude, wavelength, and tilt of the shock, a regime is found in which discrete, co-aligned, vortices are deposited on the interface. The subsequent interface evolution is described by a discrete vortex model, which is found to agree well with both RAGE simulations and experiments at early times. [ABSTRACT FROM AUTHOR]

Using a large volume high-energy-density fluid shear experiment (8.5 cm3) at the National Ignition Facility, we have demonstrated for the first time the ability to significantly alter the evolution of a supersonic sheared mixing layer by controlling the initial conditions of that layer. By altering the initial surface roughness of the tracer foil, we demonstrate the ability to transition the shear mixing layer from a highly ordered system of coherent structures to a randomly ordered system with a faster growing mix layer, indicative of strong mixing in the layer at a temperature of several tens of electron volts and at near solid density. Simulations using a turbulent-mix model show good agreement with the experimental results and poor agreement without turbulent mix. [ABSTRACT FROM AUTHOR]

Coherent emergent structures have been observed in a high-energy-density supersonic mixing layer experiment. A millimeter-scale shock tube uses lasers to drive Mbar shocks into the tube volume. The shocks are driven into initially solid foam (60 mg/cm³) hemicylinders separated by an Al or Ti metal tracer strip; the components are vaporized by the drive. Before the experiment disassembles, the shocks cross at the tube center, creating a very fast (U> 200 km/s) shear-unstable zone. After several nanoseconds, an expanding mixing layer is measured, and after 10+ ns we observe the appearance of streamwise-periodic, spanwise-aligned rollers associated with the primary Kelvin-Helmholtz instability of mixing layers. We additionally image roller pairing and spanwise-periodic streamwise-aligned filaments associated with secondary instabilities. New closures are derived to connect length scales of these structures to estimates of fluctuating velocity data otherwise unobtainable in the high-energy-density environment. This analysis indicates shear-induced specific turbulent energies 10³-104 times higher than the nearest conventional experiments. Because of difficulties in continuously driving systems under these conditions and the harshness of the experimental environment limiting the usable diagnostics, clear evidence of these developing structures has never before been observed in this regime. [ABSTRACT FROM AUTHOR]

In a turbulence experiment conducted at the Omega Laser Facility [Boehly et al., Opt. Commun. 133, 495 (1997)]], regions of 60 mg/cc foam are separated by an aluminum plate running the length of a 1.6 mm shock tube. Two counter-propagating laser-driven shocks are used to create a high speed, ΔV=140 km/s shear flow environment, sustained for ∼10 ns, while canceling the transverse pressure gradient across the interface. The spreading of the aluminum by shear-instability-induced mixing is measured by x-ray radiography. The width of the mix region is compared to simulations. Reynolds numbers >=4×105 are achieved within the layer. Following the onset of shear, we observe striations corresponding to the dominant mode growth and their transition through non-linear structures to developed turbulence. [ABSTRACT FROM AUTHOR]

We report an experimental and computational study investigating the effects of laser preheat on the hydrodynamic behavior of a material layer. In particular, we find that perturbation of the surface of the layer results in a complex interaction, in which the bulk of the layer develops density, pressure, and temperature structure and in which the surface experiences instability-like behavior, including mode coupling. A uniform one-temperature preheat model is used to reproduce the experimentally observed behavior, and we find that this model can be used to capture the evolution of the layer, while also providing evidence of complexities in the preheat behavior. This result has important consequences for inertially confined fusion plasmas, which can be difficult to diagnose in detail, as well as for laser hydrodynamics experiments, which generally depend on assumptions about initial conditions in order to interpret their results. [ABSTRACT FROM AUTHOR]

Background: Immune cell dysfunction is a central part of immune paralysis in sepsis. Granulocyte concentrate (GC) transfusions can induce tissue damage via local effects of neutrophils. The hypothesis of an extracorporeal plasma treatment with granulocytes is to show beneficial effects with fewer side effects. Clinical trials with standard GC have supported this approach. This ex vivo study investigated the functional properties of purified granulocyte preparations during the extracorporeal plasma treatment., Methods: Purified GC were stored for up to 3 days and compared with standard GC in an immune cell perfusion therapy model. The therapy consists of a plasma separation device and an extracorporeal circuit. Plasma is perfused through the tubing system with donor immune cells of the GC, and only the treated plasma is filtered for re-transfusion. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Efficacy of granulocytes regarding phagocytosis, oxidative burst as well as cell viability and metabolic parameters were assessed., Results: In pGC, the metabolic surrogate parameters of cell functionality showed comparable courses even after a storage period of 72 h. In particular, glucose and oxygen consumption were lower after extended storage. The course of lactate dehydrogenase concentration yields no indication of cell impairment in the extracorporeal circulation. The cells were viable throughout the entire study period and exhibited preserved phagocytosis and oxidative burst functionality., Conclusion: The granulocytes demonstrated full functionality in the 6 h extracorporeal circuits after 3 days storage and in septic shock plasma. This is demonstrating the functionality of the system and encourages further clinical studies., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Immune cell dysfunction plays a central role in sepsis-associated immune paralysis. The transfusion of healthy donor immune cells, i.e., granulocyte concentrates (GC) potentially induces tissue damage via local effects of neutrophils. Initial clinical trials using standard donor GC in a strictly extracorporeal bioreactor system for treatment of septic shock patients already provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cells using plasma filters. In this ex vivo study, we demonstrate the functional characteristics of a simplified extracorporeal therapy system using purified granulocyte preparations., Methods: Purified GC were used in an immune cell perfusion model prefilled with human donor plasma simulating a 6-h treatment. The extracorporeal circuit consisted of a blood circuit and a plasma circuit with 3 plasma filters (PF). PF1 is separating the plasma from the patient's blood. Plasma is then perfused through PF2 containing donor immune cells and used in a dead-end mode. The filtrated plasma is finally retransfused to the blood circuit. PF3 is included in the plasma backflow as a redundant safety measure. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Phagocytosis activity, oxidative burst and cell viability as well as cytokine release and metabolic parameters of purified GCs were assessed., Results: Cells were viable throughout the study period and exhibited well-preserved functionality and efficient metabolic activity. Course of lactate dehydrogenase and free hemoglobin concentration yielded no indication of cell impairment. The capability of the cells to secret various cytokines was preserved. Of particular interest is equivalence in performance of the cells on day 1 and day 3, demonstrating the sustained shelf life and performance of the immune cells in the purified GCs., Conclusion: Results demonstrate the suitability of a simplified extracorporeal system. Furthermore, granulocytes remain viable and highly active during a 6-h treatment even after storage for 3 days supporting the treatment of septic patients with this system in advanced clinical trials., (© 2022. The Author(s).)

Background: Use of donor granulocyte concentrate (GC) has been limited due to its short storage time of 6-24 h, which is partially due to residual red blood cells (RBCs) and platelets and the resulting lactate production leading to an acidotic milieu. To increase this storage time, we developed a closed system procedure compatible with standard blood bank technologies to remove RBC and platelets and to enrich the GC., Methods: Standard GCs (sGCs) were sedimented, washed twice with 0.9% sodium chloride (NaCl), and resuspended in blood group-identical fresh frozen plasma. The resulting purified GCs (pGCs) were then stored in platelet bags at a cell concentration of about 5 × 10 7  ± 1.8 × 10 7 leukocytes/ml without agitation at room temperature for up to 72 h. Cell count and viability, pH, blood gases, phagocytosis, and oxidative burst were monitored daily., Results: A significant reduction in RBC (98%) through sedimentation, and platelets (96%) by washing, purified the white blood cell (WBC) population and enriched the granulocytes to 96% of the WBC in the pGC. After 72 h of storage, over 90% of the initial WBC count of pGC remained, was viable (≥97%), and the granulocytes exhibited a high phagocytosis and oxidative burst functionality, comparable to sGC after 24 h., Conclusion: Purification extends the maximum storage period of GC from 24 to 72 h and may therefore improve the availability of GC and its clinical use., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

In this work, we present results from experiments capable of producing and measuring the propagation of multiple successive, copropagating shocks across an unstable planar interface, where the shocks are independently driven and separately controllable, enabling the study of this important phenomenon. Copropagating shocks play a significant role in a wide range of systems involving stratified media subject to a shock, and exhibit different physical characteristics compared to counterpropagating shocks. Existing techniques, however, preclude copropagating shocks, so experiments to date have been limited to the study of counterpropagating shocks. We address this previous limitation and open a physical parameter space for study using a new hohlraum platform on the National Ignition Facility. Initial experimental results are presented together with comparisons from numerical simulations.

A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Purpose. Drug-induced liver injury (DILI) is the most common cause of liver injury and a serious clinical problem; antimycotics are involved in approximately 3% of all DILI cases. The hepatotoxicity of many drugs, including the antimycotics, is poorly screened in human models. Methods. In a standardized assay the cytotoxicity on hepatocytes of different concentrations ( C max, 5x C max, and 10x C max) of the antimycotics used for systemic infections was tested. Anidulafungin (ANI), liposomal amphotericerin B (L-AmB), caspofungin (CASPO), fluconazole (FLUCO), and voriconazole (VORI) were incubated with HepG2/C3A cells. After incubation, the viability of cells (XTT test, LDH release, trypan blue staining), the synthesis of albumin, the cytochrome 1A2 activity, and the cell death (DNA fragmentation) were determined. Kruskal-Wallis and Mann-Whitney tests were used for statistical analyses. Results. L-AmB, ANI, and CASPO showed a mild hepatotoxicity in the C max concentrations. Higher concentrations of anidulafungin led to a severe impairment of hepatocyte viability and function. The azoles FLUCO and VORI had a higher hepatotoxic potential in all concentrations. Conclusion. Antimycotics, especially azoles, used for systemic infections should be given with caution in patient with liver insufficiency or liver failure or high risk for this; therefore, therapeutic drug monitoring should be used. Further studies with this approach are encouraged.

Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

Background: There is controversy regarding whether in-hospital time delay to appendectomy in children with appendicitis affects risk for perforation., Objective: Our aim was to evaluate the impact of time delay from emergency department (ED) presentation to operating room (OR) appendectomy on rates of developing appendiceal perforation in children who present with computed tomography (CT)-confirmed, uncomplicated (no radiographic evidence of perforation) appendicitis., Methods: We conducted a retrospective case review of 248 consecutive children aged ≤18 years with CT-confirmed uncomplicated appendicitis during a 4-year period., Results: There were 149 males and 99 females, all received subsequent appendectomy. Despite all receiving ED parenteral antibiotic therapy, 54 (22%) developed in-hospital appendiceal perforation (surgeon operative observation or pathologist histologic analysis). No patient developed perforation when appendectomy was performed within 9 h after ED presentation; the rate of perforation was approximately sixfold greater in those with in-hospital delay >9 h (25%) vs. ≤9 h (4.6%). The rate of developing perforation increased to 21% during hours 9-24, and 41% after 24 h. Regression analysis showed three factors were significantly associated with developing perforation: longer mean time delay from ED presentation to OR appendectomy, presence of fever, and presence of an appendicolith. The risk for developing perforation increased by 1.10 for each hour of time delay from ED presentation to OR appendectomy; the estimated odds ratios for developing perforation per interval of in-hospital delay were 2.05 at 8 h, 4.22 at 16 h, and 8.67 at 24 h., Conclusions: Increasing in-hospital time delay from ED presentation to OR appendectomy is associated with increased risk for developing appendiceal perforation in children who present with CT-documented uncomplicated appendicitis. Risk is approximately sixfold greater in those who experience delay >9 h vs. those whose delay is ≤9 h. Antibiotic therapy does not reliably prevent progression of the disease. Appendectomy should be considered an urgent procedure to maximize outcomes and prevent complications associated with appendix perforation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To analyse the levels of interleukin-6 (IL-6) in the synovial fluids and sera of patients with osteoarthritis (OA) and to identify the IL-6-secreting cells., Methods: Serum, synovial fluid, synovial tissue, and articular cartilage samples were collected from 49 OA patients with end-stage knee or hip OA who underwent joint replacement surgery. Serum and synovial fluid levels of IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and IL-6-secreting cells were identified by immunohistochemistry., Results: Eight out of 49 patients (16%) exhibited elevated IL-6 levels in the synovial fluids, averaging at 2022+/-526 pg/mL, while the levels in the rest of the patients averaged at 132+/-19 pg/mL. The sera levels of all patients were comparable in the 10 pg/mL range. Immunohistochemical analyses revealed plasma cells in the synovial lining of the high producers as the source of IL-6., Conclusions: Synovial fluid IL-6 levels may help to classify OA patients and may point to a subgroup with a particular impact from their immune system.

Weight gain in schizophrenic patients during chemotherapy was first reported with chlorpromazine. Since then other antipsychotic drugs have exhibited this effect, while some have reduced weight. A retrospective review of 78 schizophrenic patients revealed that thiothixene, fluphenazine, haloperidol, and thioridazine produced a mean weight gain and loxapine a mean weight loss after 12 and 36 weeks of treatment. The ability of an effective antipsychotic drug, such as loxapine, to prevent weight gain or to produce weight loss offers a clinical advantage in the treatment of those schizophrenic patients where weight gain should be a problem.