Impact of patient support programmes among patients with severe asthma treated with biological therapies: a systematic literature review and indirect treatment comparison.

INTRODUCTION: Effective treatment of severe asthma requires patient adherence to inhaled and biological medications. Previous work has shown that patient support programmes (PSP) can improve adherence in patients with chronic diseases, but the impact of PSPs in patients with severe asthma treated with biologics has not been thoroughly investigated. METHODS: We conducted a systematic literature review to understand the impact of PSPs on treatment adherence, asthma control and health-related quality of life (HRQoL) in patients with severe asthma. Embase, MEDLINE and EconLit databases were searched for studies published from 2003 (the year of the first biological approval for severe asthma) to June 2023 that described PSP participation among patients with severe asthma on biological treatment. Direct pooling of outcomes was not possible due to the heterogeneity across studies, so an indirect treatment comparison (ITC) was performed to determine the effect of PSP participation on treatment discontinuation. The ITC used patient-level data from patients treated with benralizumab either enrolled in a PSP (VOICE study, Connect 360 PSP) or not enrolled in a PSP (Benralizumab Patient Access Programme study) in the UK. FINDINGS: 25 records of 21 studies were selected. Six studies investigated the impact of PSPs on treatment adherence, asthma control or HRQoL. All six studies reported positive outcomes for patients enrolled in PSPs; the benefits of each PSP were closely linked to the services provided. The ITC showed that patients in the Connect 360 PSP group were less likely to discontinue treatment compared with the non-PSP group (OR 0.26, 95% CI 0.11 to 0.57, p<0.001). CONCLUSIONS: PSPs contribute to positive clinical outcomes in patients with severe asthma on biological treatment. Future analyses will benefit from thorough descriptions of PSP services, and study designs that allow direct comparisons of patient outcomes with and without a PSP.

Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

Measurements of ion-electron energy-transfer cross section in high-energy-density plasmas.

We report on measurements of the ion-electron energy-transfer cross section utilizing low-velocity ion stopping in high-energy-density plasmas at the OMEGA laser facility. These measurements utilize a technique that leverages the close relationship between low-velocity ion stopping and ion-electron equilibration. Shock-driven implosions of capsules filled with D^{3}He gas doped with a trace amount of argon are used to generate densities and temperatures in ranges from 1×10^{23} to 2×10^{24} cm^{-3} and from 1.4 to 2.5 keV, respectively. The energy loss of 1-MeV DD tritons and 3.7-MeV D^{3}He alphas that have velocities lower than the average velocity of the thermal electrons is measured. The energy loss of these ions is used to determine the ion-electron energy-transfer cross section, which is found to be in excellent agreement with quantum-mechanical calculations in the first Born approximation. This result provides an experimental constraint on ion-electron energy transfer in high-energy-density plasmas, which impacts the modeling of alpha heating in inertial confinement fusion implosions, magnetic-field advection in stellar atmospheres, and energy balance in supernova shocks.

X-ray-imaging spectrometer (XRIS) for studies of residual kinetic energy and low-mode asymmetries in inertial confinement fusion implosions at OMEGA (invited).

A system of x-ray imaging spectrometer (XRIS) has been implemented at the OMEGA Laser Facility and is capable of spatially and spectrally resolving x-ray self-emission from 5 to 40 keV. The system consists of three independent imagers with nearly orthogonal lines of sight for 3D reconstructions of the x-ray emission region. The distinct advantage of the XRIS system is its large dynamic range, which is enabled by the use of tantalum apertures with radii ranging from 50 µm to 1 mm, magnifications of 4 to 35×, and image plates with any filtration level. In addition, XRIS is capable of recording 1-100's images along a single line of sight, facilitating advanced statistical inference on the detailed structure of the x-ray emitting regions. Properties such as P0 and P2 of an implosion are measured to 1% and 10% precision, respectively. Furthermore, Te can be determined with 5% accuracy.

In situ calibration of charged particle spectrometers on the OMEGA Laser Facility using 241Am and 226Ra sources.

Charged particle spectrometry is a critical diagnostic to study inertial-confinement-fusion plasmas and high energy density plasmas. The OMEGA Laser Facility has two fixed magnetic charged particle spectrometers (CPSs) to measure MeV-ions. In situ calibration of these spectrometers was carried out using 241Am and 226Ra alpha emitters. The alpha emission spectrum from the sources was measured independently using surface-barrier detectors (SBDs). The energy dispersion and broadening of the CPS systems were determined by comparing the CPS measured alpha spectrum to that of the SBD. The calibration method significantly constrains the energy dispersion, which was previously obtained through the measurement of charged particle fusion products. Overall, a small shift of 100 keV was observed between previous and the calibration done in this work.

A knock-on deuteron imager for measurements of fuel and hotspot asymmetry in direct-drive inertial confinement fusion implosions (invited).

A knock-on deuteron imager (KoDI) has been implemented to measure the fuel and hotspot asymmetry of cryogenic inertial confinement fusion implosions on OMEGA. Energetic neutrons produced by D-T fusion elastically scatter ("knock on") deuterons from the fuel layer with a probability that depends on ρR. Deuterons above 10 MeV are produced by near-forward scattering, and imaging them is equivalent to time-integrated neutron imaging of the hotspot. Deuterons below 6 MeV are produced by a combination of side scattering and ranging in the fuel, and encode information about the spatial distribution of the dense fuel. The KoDI instrument consists of a multi-penumbral aperture positioned 10-20 cm from the implosion using a ten-inch manipulator and a detector pack at 350 cm from the implosion to record penumbral images with magnification of up to 35×. Range filters and the intrinsic properties of CR-39 are used to distinguish different charged-particle images by energy along the same line of sight. Image plates fielded behind the CR-39 record a 10 keV x-ray image using the same aperture. A maximum-likelihood reconstruction algorithm has been implemented to infer the source from the projected penumbral images. The effects of scattering and aperture charging on the instrument point-spread function are assessed. Synthetic data are used to validate the reconstruction algorithm and assess an appropriate termination criterion. Significant aperture charging has been observed in the initial experimental dataset, and increases with aperture distance from the implosion, consistent with a simple model of charging by laser-driven EMP.

Experiments on the dynamics and scaling of spontaneous-magnetic-field saturation in laser-produced plasmas.

In laser-produced high-energy-density plasmas, large-scale strong magnetic fields are spontaneously generated by the Biermann battery effects when temperature and density gradients are misaligned. Saturation of the magnetic field takes place when convection and dissipation balance field generation. While theoretical and numerical modeling provide useful insight into the saturation mechanisms, experimental demonstration remains elusive. In this letter, we report an experiment on the saturation dynamics and scaling of Biermann battery magnetic field in the regime where plasma convection dominates. With time-gated charged-particle radiography and time-resolved Thomson scattering, the field structure and evolution as well as corresponding plasma conditions are measured. In these conditions, the spatially resolved magnetic fields are reconstructed, leading to a picture of field saturation with a scaling of B∼1/L_{T} for a convectively dominated plasma, a regime where the temperature gradient scale (L_{T}) exceeds the ion skin depth.

Effect of Strongly Magnetized Electrons and Ions on Heat Flow and Symmetry of Inertial Fusion Implosions.

This Letter presents the first observation on how a strong, 500 kG, externally applied B field increases the mode-two asymmetry in shock-heated inertial fusion implosions. Using a direct-drive implosion with polar illumination and imposed field, we observed that magnetization produces a significant increase in the implosion oblateness (a 2.5× larger P2 amplitude in x-ray self-emission images) compared with reference experiments with identical drive but with no field applied. The implosions produce strongly magnetized electrons (ω_{e}τ_{e}≫1) and ions (ω_{i}τ_{i}>1) that, as shown using simulations, restrict the cross field heat flow necessary for lateral distribution of the laser and shock heating from the implosion pole to the waist, causing the enhanced mode-two shape.

Proton deflectometry with in situ x-ray reference for absolute measurement of electromagnetic fields in high-energy-density plasmas.

We report a technique of proton deflectometry that uses a grid and an in situ reference x-ray grid image for precise measurements of magnetic fields in high-energy-density plasmas. A D3He fusion implosion provides a bright point source of both protons and x-rays, which is split into beamlets by a grid. The protons undergo deflections as they propagate through the plasma region of interest, whereas the x-rays travel along straight lines. The x-ray image, therefore, provides a zero-deflection reference image. The line-integrated magnetic fields are inferred from the shifts of beamlets between the deflected (proton) and reference (x-ray) images. We developed a system for analysis of these data, including automatic algorithms to find beamlet locations and to calculate their deflections from the reference image. The technique is verified in an experiment performed at OMEGA to measure a nonuniform magnetic field in vacuum and then applied to observe the interaction of an expanding plasma plume with the magnetic field.

Extension of charged-particle spectrometer capabilities for diagnosing implosions on OMEGA, Z, and the NIF.

New designs and a new analysis technique have been developed for an existing compact charged-particle spectrometer on the NIF and OMEGA. The new analysis technique extends the capabilities of this diagnostic to measure arbitrarily shaped ion spectra down to 1 MeV with yields as low as 106. Three different designs are provided optimized for the measurement of DD protons, T3He deuterons, and 3He3He protons. The designs are highly customizable, and a generalized framework is provided for optimizing the design for alternative applications. Additionally, the understanding of the detector's response and uncertainties is greatly expanded upon. A new calibration procedure is also developed to increase the precision of the measurements.

Thermal decoupling of deuterium and tritium during the inertial confinement fusion shock-convergence phase.

A series of thin glass-shell shock-driven DT gas-filled capsule implosions was conducted at the OMEGA laser facility. These experiments generate conditions relevant to the central plasma during the shock-convergence phase of ablatively driven inertial confinement fusion (ICF) implosions. The spectral temperatures inferred from the DTn and DDn spectra are most consistent with a two-ion-temperature plasma, where the initial apparent temperature ratio, T_{T}/T_{D}, is 1.5. This is an experimental confirmation of the long-standing conjecture that plasma shocks couple energy directly proportional to the species mass in multi-ion plasmas. The apparent temperature ratio trend with equilibration time matches expected thermal equilibration described by hydrodynamic theory. This indicates that deuterium and tritium ions have different energy distributions for the time period surrounding shock convergence in ignition-relevant ICF implosions.

An x-ray penumbral imager for measurements of electron-temperature profiles in inertial confinement fusion implosions at OMEGA.

Hot-spot shape and electron temperature (Te) are key performance metrics used to assess the efficiency of converting shell kinetic energy into hot-spot thermal energy in inertial confinement fusion implosions. X-ray penumbral imaging offers a means to diagnose hot-spot shape and Te, where the latter can be used as a surrogate measure of the ion temperature (Ti) in sufficiently equilibrated hot spots. We have implemented a new x-ray penumbral imager on OMEGA. We demonstrate minimal line-of-sight variations in the inferred Te for a set of implosions. Furthermore, we demonstrate spatially resolved Te measurements with an average uncertainty of 10% with 6 µm spatial resolution.

Yield degradation due to laser drive asymmetry in D3He backlit proton radiography experiments at OMEGA.

Mono-energetic proton radiography is a vital diagnostic for numerous high-energy-density-physics, inertial-confinement-fusion, and laboratory-astrophysics experiments at OMEGA. With a large number of campaigns executing hundreds of shots, general trends in D3He backlighter performance are statistically observed. Each experimental configuration uses a different number of beams and drive symmetry, causing the backlighter to perform differently. Here, we analyze the impact of these variables on the overall performance of the D3He backlighter for proton-radiography studies. This study finds that increasing laser drive asymmetry can degrade the performance of the D3He backlighter. The results of this study can be used to help experimental designs that use proton radiography.

Constraining physical models at gigabar pressures.

High-energy-density (HED) experiments in convergent geometry are able to test physical models at pressures beyond hundreds of millions of atmospheres. The measurements from these experiments are generally highly integrated and require unique analysis techniques to procure quantitative information. This work describes a methodology to constrain the physics in convergent HED experiments by adapting the methods common to many other fields of physics. As an example, a mechanical model of an imploding shell is constrained by data from a thin-shelled direct-drive exploding-pusher experiment on the OMEGA laser system using Bayesian inference, resulting in the reconstruction of the shell dynamics and energy transfer during the implosion. The model is tested by analyzing synthetic data from a one-dimensional hydrodynamics code and is sampled using a Markov chain Monte Carlo to generate the posterior distributions of the model parameters. The goal of this work is to demonstrate a general methodology that can be used to draw conclusions from a wide variety of HED experiments.

Energy Flow in Thin Shell Implosions and Explosions.

Energy flow and balance in convergent systems beyond petapascal energy densities controls the fate of late-stage stars and the potential for controlling thermonuclear inertial fusion ignition. Time-resolved x-ray self-emission imaging combined with a Bayesian inference analysis is used to describe the energy flow and the potential information stored in the rebounding spherical shock at 0.22 PPa (2.2 Gbar or billions of atmospheres pressure). This analysis, together with a simple mechanical model, describes the trajectory of the shell and the time history of the pressure at the fuel-shell interface, ablation pressure, and energy partitioning including kinetic energy of the shell and internal energy of the fuel. The techniques used here provide a fully self-consistent uncertainty analysis of integrated implosion data, a thermodynamic-path independent measurement of pressure in the petapascal range, and can be used to deduce the energy flow in a wide variety of implosion systems to petapascal energy densities.