Clocking Femtosecond Collisional Dynamics via Resonant X-Ray Spectroscopy.

Electron-ion collisional dynamics is of fundamental importance in determining plasma transport properties, nonequilibrium plasma evolution, and electron damage in diffraction imaging applications using bright x-ray free-electron lasers (FELs). Here we describe the first experimental measurements of ultrafast electron impact collisional ionization dynamics using resonant core-hole spectroscopy in a solid-density magnesium plasma, created and diagnosed with the Linac Coherent Light Source x-ray FEL. By resonantly pumping the 1s→2p transition in highly charged ions within an optically thin plasma, we have measured how off-resonance charge states are populated via collisional processes on femtosecond time scales. We present a collisional cross section model that matches our results and demonstrates how the cross sections are enhanced by dense-plasma effects including continuum lowering. Nonlocal thermodynamic equilibrium collisional radiative simulations show excellent agreement with the experimental results and provide new insight on collisional ionization and three-body-recombination processes in the dense-plasma regime.

Creation and diagnosis of a solid-density plasma with an X-ray free-electron laser.

Matter with a high energy density (>10(5) joules per cm(3)) is prevalent throughout the Universe, being present in all types of stars and towards the centre of the giant planets; it is also relevant for inertial confinement fusion. Its thermodynamic and transport properties are challenging to measure, requiring the creation of sufficiently long-lived samples at homogeneous temperatures and densities. With the advent of the Linac Coherent Light Source (LCLS) X-ray laser, high-intensity radiation (>10(17) watts per cm(2), previously the domain of optical lasers) can be produced at X-ray wavelengths. The interaction of single atoms with such intense X-rays has recently been investigated. An understanding of the contrasting case of intense X-ray interaction with dense systems is important from a fundamental viewpoint and for applications. Here we report the experimental creation of a solid-density plasma at temperatures in excess of 10(6) kelvin on inertial-confinement timescales using an X-ray free-electron laser. We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the timescales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.

Benchmark Experiment for Photoionized Plasma Emission from Accretion-Powered X-Ray Sources.

The interpretation of x-ray spectra emerging from x-ray binaries and active galactic nuclei accreted plasmas relies on complex physical models for radiation generation and transport in photoionized plasmas. These models have not been sufficiently experimentally validated. We have developed a highly reproducible benchmark experiment to study spectrum formation from a photoionized silicon plasma in a regime comparable to astrophysical plasmas. Ionization predictions are higher than inferred from measured absorption spectra. Self-emission measured at adjustable column densities tests radiation transport effects, demonstrating that the resonant Auger destruction assumption used to interpret black hole accretion spectra is inaccurate.

Measurements of the K-Shell Opacity of a Solid-Density Magnesium Plasma Heated by an X-Ray Free-Electron Laser.

We present measurements of the spectrally resolved x rays emitted from solid-density magnesium targets of varying sub-µm thicknesses isochorically heated by an x-ray laser. The data exhibit a largely thickness-independent source function, allowing the extraction of a measure of the opacity to K-shell x rays within well-defined regimes of electron density and temperature, extremely close to local thermodynamic equilibrium conditions. The deduced opacities at the peak of the Kα transitions of the ions are consistent with those predicted by detailed atomic-kinetics calculations.

Observation of Reverse Saturable Absorption of an X-ray Laser.

A nonlinear absorber in which the excited state absorption is larger than the ground state can undergo a process called reverse saturable absorption. It is a well-known phenomenon in laser physics in the optical regime, but is more difficult to generate in the x-ray regime, where fast nonradiative core electron transitions typically dominate the population kinetics during light matter interactions. Here, we report the first observation of decreasing x-ray transmission in a solid target pumped by intense x-ray free electron laser pulses. The measurement has been made below the K-absorption edge of aluminum, and the x-ray intensity ranges are 10^{16} -10^{17} W/cm^{2}. It has been confirmed by collisional radiative population kinetic calculations, underscoring the fast spectral modulation of the x-ray pulses and charge states relevant to the absorption and transmission of x-ray photons. The processes shown through detailed simulations are consistent with reverse saturable absorption, which would be the first observation of this phenomena in the x-ray regime. These light matter interactions provide a unique opportunity to investigate optical transport properties in the extreme state of matters, as well as affording the potential to regulate ultrafast x-ray free-electron laser pulses.

Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells.

Saturable absorption of an x-ray free-electron-laser heated solid-density aluminum plasma.

High-intensity x-ray pulses from an x-ray free-electron laser are used to heat and probe a solid-density aluminum sample. The photon-energy-dependent transmission of the heating beam is studied through the use of a photodiode. Saturable absorption is observed, with the resulting transmission differing significantly from the cold case, in good agreement with atomic-kinetics simulations.

Shot-to-shot intensity and wavefront stability of high-harmonic generation.

We report on the shot-to-shot stability of intensity and spatial phase of high-harmonic generation (HHG). The intensity stability is measured for each high-harmonic (HH) order with a spectrometer. Additionally, the spatial phase is measured with an XUV wavefront sensor for a single HH order measured in a single shot, which according to our knowledge was not reported before with a Hartmann wavefront sensor. Furthermore, we compare the single-shot measurement of the spatial phase with time-integrated measurements and we show that the XUV wavefront sensor is a useful tool to simultaneously optimize the spatial phase and intensity of HHG within the available HHG parameter range used in this study.

Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

Observations of the effect of ionization-potential depression in hot dense plasma.

The newly commissioned Orion laser system has been used to study dense plasmas created by a combination of short pulse laser heating and compression by laser driven shocks. Thus the plasma density was systematically varied between 1 and 10 g/cc by using aluminum samples buried in plastic foils or diamond sheets. The aluminum was heated to electron temperatures between 500 and 700 eV allowing the plasma conditions to be diagnosed by K-shell emission spectroscopy. The K-shell spectra show the effect of the ionization potential depression as a function of density. The data are compared to simulated spectra which account for the change in the ionization potential by the commonly used Stewart and Pyatt prescription and an alternative due to Ecker and Kröll suggested by recent x-ray free-electron laser experiments. The experimental data are in closer agreement with simulations using the model of Stewart and Pyatt.

Resonant Kα spectroscopy of solid-density aluminum plasmas.

The x-ray intensities made available by x-ray free electron lasers (FEL) open up new x-ray matter interaction channels not accessible with previous sources. We report here on the resonant generation of Kα emission, that is to say the production of copious Kα radiation by tuning the x-ray FEL pulse to photon energies below that of the K edge of a solid aluminum sample. The sequential absorption of multiple photons in the same atom during the 80 fs pulse, with photons creating L-shell holes and then one resonantly exciting a K-shell electron into one of these holes, opens up a channel for the Kα production, as well as the absorption of further photons. We demonstrate rich spectra of such channels, and investigate the emission produced by tuning the FEL energy to the K-L transitions of those highly charged ions that have transition energies below the K edge of the cold material. The spectra are sensitive to x-ray intensity dependent opacity effects, with ions containing L-shell holes readily reabsorbing the Kα radiation.

Direct measurements of the ionization potential depression in a dense plasma.

We have used the Linac Coherent Light Source to generate solid-density aluminum plasmas at temperatures of up to 180 eV. By varying the photon energy of the x rays that both create and probe the plasma, and observing the K-α fluorescence, we can directly measure the position of the K edge of the highly charged ions within the system. The results are found to disagree with the predictions of the extensively used Stewart-Pyatt model, but are consistent with the earlier model of Ecker and Kröll, which predicts significantly greater depression of the ionization potential.

Problem based review: pleuritic chest pain.

Pleuritic pain, a sharp discomfort near the chest wall exacerbated by inspiration is associated with a number of pathologies. Pulmonary embolus and infection are two common causes but diagnosis can often be challenging, both for experienced physicians and trainees. The underlying anatomy and pathophysiology of such pain and the most common aetiologies are presented. Clinical symptoms and signs that may arise alongside pleuritic pain are then discussed, followed by an introduction to the diagnostic tools such as the Wells’ score and current guidelines that can help to select the most appropriate investigation(s). Management of pulmonary embolism and other common causes of pleuritic pain are also discussed and highlighted by a clinical vignette.

Electronic structure of warm dense copper studied by ultrafast x-ray absorption spectroscopy.

We use time-resolved x-ray absorption spectroscopy to investigate the unoccupied electronic density of states of warm dense copper that is produced isochorically through the absorption of an ultrafast optical pulse. The temperature of the superheated electron-hole plasma, which ranges from 4000 to 10 000 K, was determined by comparing the measured x-ray absorption spectrum with a simulation. The electronic structure of warm dense copper is adequately described with the high temperature electronic density of state calculated by the density functional theory. The dynamics of the electron temperature is consistent with a two-temperature model, while a temperature-dependent electron-phonon coupling parameter is necessary.

Decay of cystalline order and equilibration during the solid-to-plasma transition induced by 20-fs microfocused 92-eV free-electron-laser pulses.

We have studied a solid-to-plasma transition by irradiating Al foils with the FLASH free electron laser at intensities up to 10(16) W/cm(2). Intense XUV self-emission shows spectral features that are consistent with emission from regions of high density, which go beyond single inner-shell photoionization of solids. Characteristic features of intrashell transitions allowed us to identify Auger heating of the electrons in the conduction band occurring immediately after the absorption of the XUV laser energy as the dominant mechanism. A simple model of a multicharge state inverse Auger effect is proposed to explain the target emission when the conduction band at solid density becomes more atomiclike as energy is transferred from the electrons to the ions. This allows one to determine, independent of plasma simulations, the electron temperature and density just after the decay of crystalline order and to characterize the early time evolution.

An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (Natrox™) on the Rates of Healing of Chronic DiAbetic Foot Ulcers (OTONAL Trial).

Natrox™ topical oxygen therapy (TOT) (Inotec AMD Ltd, Cambridgeshire, UK) employs a small battery-powered "oxygen generator" to concentrate atmospheric oxygen and feeds pure, moist, oxygen through a fine, soft tube to a dressing-like "oxygen distribution system", which is placed over the wound and is held in place by a conventional dressing. The aim was to determine the effectiveness of Natrox™ for non-healing diabetic foot ulcers (DFU) over a 3-month period.Longitudinal, single-arm, open prospective registry study using 12 weeks of TOT using a 4 week run-in period. 20 patients recruited to OTONAL had chronic DFU greater than 3 months duration or minor amputation sites with less than 50% healing in 4 weeks.There were 13 (65%) males and the mean age was 65.7 (±11.6) years. The mean glycated haemoglobin (HbA1c) was 6.9 (±1.3) mmol mol-1 and mean wound duration before TOT was 114 (±79.1) days. 18/20 (90.0%) patients had concomitant lower limb revascularization angioplasty for chronic limb threatening ischaemia. The mean size of the foot ulcer at baseline was 11.3 ± 14.8 cm2 and mean transcutaneous oxygen measurement value was 34.1 (±19.6) mm Hg. Wound closure of >75% was observed in 14/20 (70.0%) patients. There was a 91.3% (±14.9%) wound area reduction by 3 months (P = .001) and mean time for 100% closure was 77.6 ± 32.5 days. Mean pain scores reduced from 2.4 (±1.8) at baseline to .5 (±1.0) at 3 months (P = .008). All patients were very satisfied using the ambulatory device. Use of TOT in chronic diabetic foot wounds stimulates a healing state, underpinning the concept that oxygen plays a central role in wound healing. Our results are more compelling if you consider they started with relatively large-sized DFUs and majority of patients were frail with underlying peripheral artery disease. (NCT03863054).

Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea.

This study aimed to explore the effect of mandibular advancement splints (MAS) on upper airway anatomy during wakefulness in obstructive sleep apnoea (OSA). Patients commencing treatment for OSA with MAS were recruited. Response to treatment was defined by a >or=50% reduction in the apnoea/hypopnoea index. Nasopharyngoscopy was performed in the supine position. Nasopharyngoscopy was performed in 18 responders and 17 nonresponders. Mandibular advancement caused an increase in the calibre of the velopharynx (mean+/- sem +40+/-10%), with relatively minor changes occurring in the oropharynx and hypopharynx. An increase in cross-sectional area of the velopharynx with mandibular advancement occurred to a greater extent in responders than nonresponders (+56+/-16% versus +22+/-13%; p<0.05). Upper airway collapse during the Müller manoeuvre, relative to the baseline cross-sectional area, was greater in nonresponders than responders in the velopharynx (-94+/-4% versus -69+/-9%; p<0.01) and oropharynx (-37+/-6% versus -16+/-3%; p<0.01). When the Müller manoeuvre was performed with mandibular advancement, airway collapse was greater in nonresponders than responders in the velopharynx (-80+/-11% versus +9+/-37%; p<0.001), oropharynx (-36+/-6% versus -20+/-5%; p<0.05) and hypopharynx (-64+/-6% versus -42+/-6%; p<0.05). These results indicate that velopharyngeal calibre is modified by MAS treatment and this may be useful for predicting treatment response.

Plasmons in strongly coupled shock-compressed matter.

We present the first measurements of the plasmon dispersion and damping in laser shock-compressed solid matter. Petawatt laser produced K-α radiation scatters on boron targets compressed by a 10 ns-long 400 J laser pulse. In the vicinity of the Fermi momentum, the scattering spectra show dispersionless, collisionally damped plasmons, indicating a strongly coupled electron liquid. These observations agree with calculations that include the Born-Mermin approximation to account for electron-ion collisional damping and local field corrections reflecting electron-electron correlations.