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Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEVFrom Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEVIn individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

The simulated data set described in this paper was created by an ensemble of nine different crop models: HERMES (HE), Simplace (L5), SiriusQuality (SQ), MONICA (MO), Sirius2014 (S2), FASSET (FA), 4M (4M), SSM (SS), DSSAT-CSM IXIM (IX). Simulations were performed for grain maize (six models) and winter wheat (eight models) under diverse conditions over agriculturally relevant areas in the EU-27 at a 25 x 25 km spatial resolution. Simulations were drawn from combinations of three representative concentration pathways and climate outputs from five general circulation models for time periods 2040-2069 and 2070-2099. Historical climate data was the basis for simulation years 1980-2010 and considered as a baseline. Simulation results from 1980-2010 and 2040-2069 were used to analyze crop responses to changing climatic variables and their diverging sensitivities to these variables. This data paper describes the creation, motivation and format of the simulation results to enable others to use the data set.

Nano- to micrometer-sized surface defects on UV-grade fused silica surfaces are known to be effectively smoothed through the use of high-temperature localized CO 2 laser heating, thereby enhancing optical properties. However, the details of the mass transport and the effect of hydroxyl content on the laser smoothing of defective silica at sub-micron length scales are still not completely understood. In this study, we examine the morphological evolution of sub-micron, dry-etched periodic surface structures on type II and type III SiO 2 substrates under 10.6 μm CO 2 laser irradiation using atomic force microscopy (AFM). In situ thermal imaging was used to map the transient temperature field across the heated region, allowing assessment of the T -dependent mass transport mechanisms under different laser-heating conditions. Computational fluid dynamics simulations correlated well with experimental results, and showed that for large effective capillary numbers ( N c > 2), surface diffusion is negligible and smoothing is dictated by capillary action, despite the relatively small spatial scales studied here. Extracted viscosity values over 1700–2000 K were higher than the predicted bulk values, but were consistent with the surface depletion of OH groups, which was confirmed using confocal Raman microscopy.

Evaporation kinetics of fused silica were measured up to ≈3000K using CO(2) laser heating, while solid-gas phase chemistry of silica was assessed with hydrogen, air, and nitrogen. Enhanced evaporation in hydrogen was attributed to an additional reduction pathway, while oxidizing conditions pushed the reaction backwards. The observed mass transport limitations supported use of a near-equilibrium analysis for interpreting kinetic data. A semi-empirical model of the evaporation kinetics is derived that accounts for heating, gas chemistry and transport properties. The approach described should have application to materials laser processing, and in applications requiring knowledge of thermal decomposition chemistry under extreme temperatures.

The advantage of using mid-infrared (IR) 4.6 {micro}m lasers, versus far-infrared 10.6 {micro}m lasers, for mitigating damage growth on fused silica is investigated. In contrast to fused silica's high absorption at 10.6 {micro}m, silica absorption at 4.6 {micro}m is two orders of magnitude less. The much reduced absorption at 4.6 {micro}m enables deep heat penetration into fused silica when it is heated using the mid-IR laser, which in turn leads to more effective mitigation of damage sites with deep cracks. The advantage of using mid-IR versus far-IR laser for damage growth mitigation under non-evaporative condition is quantified by defining a figure of merit (FOM) that relates the crack healing depth to laser power required. Based on our FOM, we show that for damage cracks up to at least 500 {micro}m in depth, mitigation using a 4.6 {micro}m mid-IR laser is more efficient than mitigation using a 10.6 {micro}m far-IR laser.

Fused-silica microstructural changes associated with localized 10.6 microm CO(2) laser heating are reported. Spatially resolved shifts in the high-frequency asymmetric stretch transverse-optic phonon mode of SiO(2) were measured using confocal Raman microscopy, allowing construction of axial fictive temperature (T(f)) maps for various laser-heating conditions. A Fourier conduction-based finite-element model was employed to compute on-axis temperature-time histories, and, in conjunction with a Tool-Narayanaswamy form for structural relaxation, used to fit T(f)(z) profiles to extract relaxation parameters. Good agreement between the calculated and measured T(f) was found, yielding reasonable values for relaxation time and activation enthalpy in the laser-modified silica.

In situ spatial and temporal surface temperature profiles of CO2 laser-heated silica were obtained using a long wave infrared (LWIR) HgCdTe camera. Solutions to the linear diffusion equation with volumetric and surface heating are shown to describe the temperature evolution for a range of beam powers, over which the peak surface temperature scales linearly with power. These solutions were used with on-axis steady state and transient experimental temperatures to extract thermal diffusivity and conductivity for a variety of materials, including silica, spinel, sapphire, and lithium fluoride. Experimentally-derived thermal properties agreed well with reported values and, for silica, thermal conductivity and diffusivity are shown to be approximately independent of temperature between 300 and 2800K. While for silica our analysis based on a temperature independent thermal conductivity is shown to be accurate, for other materials studied this treatment yields effective thermal properties that represent reasonable approximations for laser heating. Implementation of a single-wavelength radiation measurement in the semi-transparent regime is generally discussed, and estimates of the apparent temperature deviation from the actual outer surface temperature are also presented. The experimental approach and the simple analysis presented yield surface temperature measurements that can be used to validate more complex physical models, help discriminate dominant heat transport mechanisms, and to predict temperature distribution and evolution during laser-based material processing.

Nineteen-ninety-eight was a mixed performance year for the high yield bond market in the United States, with much below average returns and spreads over default-risk-free Treasury Bonds but continued relatively low default rates and losses and another record year of new insurance. Returns and new insurance were excellent through the first seven months of the year but returns reversed and new issues dried up, temporarily, in the wake of August's Russians default and the emerging market turmoil, causing another short-term flight to quality. Returns in 1998 on high yield bonds in the U.S. were slightly above 4.0% for the entire year, about 8.5% lower than historical averages. Return spreads also were much below average (-8.7%).

Our study of ZnSe quantum dots is motivated by the inherent interest in quantum confined systems and by the potential for shorter wavelength laser operation enabled by blue-shifted quantum confined energy levels. The optical and electronic properties of these nanocrystals as a function of the fabrication process were investigated with various optical techniques including photoluminescence (PL) lifetimes, and absorption, PL , and excitation spectroscopy.

We have prepared ZnSe nanocrystals embedded in potassium borosilicate glass matrices in concentrations up to 14 wt%. The optical and electronic properties of these nanocrystals as a function of the fabrication process were investigated with High Resolution Transmission Electron Microscopy (HRTEM) and various optical techniques including absorption, photoluminescence, and excitation spectroscopy, and photoluminescence lifetime measurements. HRTEM confirms the presence of nanocrystals and indicates an average diameter size of 50 Å. The majority of the photoluminescence extends throughout the visible and is highly red-shifted from the absorptionedge, indicating emission from trap states such as Se vacancies. Contributions from the ZnSe nanocrystals as well as the borosilicate glass matrix are also observed. Exponential and biexponential photoluminescence decays are observed with decay times ranging from a few nanoseconds to a few hundred nanoseconds. The significance of these results to the optical and electronic properties of the ZnSe nanocrystals and their relevance as luminescent materials for light emitting applications will be discussed.

Laser-induced growth of optical damage can limit component lifetime and, therefore, increase operating costs of large-aperture fusion-class laser systems. While far-infrared (IR) lasers have been used previously to treat laser damage on fused silica optics and render it benign, little is known about the effectiveness of less-absorbing mid-IR lasers for this purpose. In this study, we quantitatively compare the effectiveness and efficiency of mid-IR (4.6 μm) versus far-IR (10.6 μm) lasers in mitigating damage growth on fused silica surfaces. The nonlinear volumetric heating due to mid-IR laser absorption is analyzed by solving the heat equation numerically, taking into account the temperature-dependent absorption coefficient α(T) at λ=4.6 μm, while far-IR laser heating is well described by a linear analytic approximation to the laser-driven temperature rise. In both cases, the predicted results agree well with surface temperature measurements based on IR radiometry, as well as subsurface fictive temperature measurements based on confocal Raman microscopy. Damage mitigation efficiency is assessed using a figure of merit (FOM) relating the crack healing depth to laser power required, under minimally ablative conditions. Based on our FOM, we show that, for cracks up to at least 500 μm in depth, mitigation with a 4.6 μm mid-IR laser is more efficient than mitigation with a 10.6 μm far-IR laser. This conclusion is corroborated by direct application of each laser system to the mitigation of pulsed laser-induced damage possessing fractures up to 225 μm in depth.

An experimental and analytical approach is described to determine the temperature dependent intrinsic lattice thermal conductivity, k(T), for a broad range of materials. k(T) of silica, sapphire, spinel, and lithium fluoride were derived from surface temperature measurements. Surfaces were heated from room temperature up to 3000 K using a CO2-laser irradiance ≤5 kW/cm2. The solution of the nonlinear heat flow equation was used to extract parameters of k(T)=A×Te, where −1.13≤e≤0 depending on the material. Results generally show good agreement with reported k(T). Below evaporation, the phonon-only k remains the dominant heat transport mechanism during laser heating.

Laser dye DCM in an ethylene glycol solution is a favored medium for converting the argon-ion 488- and 514-nm pump lines to tunable radiation in the 600-730-nm region. However, the dye precipitates from solution, is a powerful mutagen, and the glycol solvent is hygroscopic. Replacement dyes in 3-phenyl-1- propanol or 2-phenoxyethanol, particularly the latter, are proposed.