A feasibility, randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis (BREEZE-IPF): study protocol

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that causes breathlessness and cough that worsen over time, limiting daily activities and negatively impacting quality of life. Although treatments are now available that slow the rate of lung function decline, trials of these treatments have failed to show improvement in symptoms or quality of life. There is an immediate unmet need for evidenced-based interventions that improve patients' symptom burden and make a difference to everyday living. This study aims to assess the feasibility of conducting a definitive randomised controlled trial of a holistic, complex breathlessness intervention in people with IPF. Methods and analysis The trial is a two-centre, randomised controlled feasibility trial of a complex breathlessness intervention compared with usual care in patients with IPF. 50 participants will be recruited from secondary care IPF clinics and randomised 1:1 to either start the intervention within 1 week of randomisation (fast-track group) or to receive usual care for 8 weeks before receiving the intervention (wait-list group). Participants will remain in the study for a total of 16 weeks. Outcome measures will be feasibility outcomes, including recruitment, retention, acceptability and fidelity of the intervention. Clinical outcomes will be measured to inform outcome selection and sample size calculation for a definitive trial. Ethics and dissemination Yorkshire and The Humber – Bradford Leeds Research Ethics Committee approved the study protocol (REC 18/YH/0147). Results of the main trial and all secondary end-points will be submitted for publication in a peer-reviewed journal

Measurements of a low temperature mechanical dissipation peak in a single layer of Ta2O5 doped with TiO2

Thermal noise arising from mechanical dissipation in oxide coatings is a major limitation to many precision measurement systems, including optical frequency standards, high resolution optical spectroscopy and interferometric gravity wave detectors. Presented here are measurements of dissipation as a function of temperature between 7 K and 290 K in ion-beam sputtered Ta2O5 doped with TiO2, showing a loss peak at 20 K. Analysis of the peak provides the first evidence of the source of dissipation in doped Ta2O5 coatings, leading to possibilities for the reduction of thermal noise effects

Thermoelastic dissipation in inhomogeneous media: loss measurements and displacement noise in coated test masses for interferometric gravitational wave detectors

The displacement noise in the test mass mirrors of interferometric gravitational wave detectors is proportional to their elastic dissipation at the observation frequencies. In this paper, we analyze one fundamental source of dissipation in thin coatings, thermoelastic damping associated with the dissimilar thermal and elastic properties of the film and the substrate. We obtain expressions for the thermoelastic dissipation factor necessary to interpret resonant loss measurements, and for the spectral density of displacement noise imposed on a Gaussian beam reflected from the face of a coated mass. The predicted size of these effects is large enough to affect the interpretation of loss measurements, and to influence design choices in advanced gravitational wave detectors.Comment: 42 pages, 7 figures, uses REVTeX

Apparatus for dimensional characterization of fused silica fibers for the suspensions of advanced gravitational wave detectors

Detection of gravitational waves from astrophysical sources remains one of the most challenging problems faced by experimental physicists. A significant limit to the sensitivity of future long-baseline interferometric gravitational wave detectors is thermal displacement noise of the test mass mirrors and their suspensions. Suspension thermal noise results from mechanical dissipation in the fused silica suspension fibers suspending the test mass mirrors and is therefore an important noise source at operating frequencies between ∼10 and 30 Hz. This dissipation occurs due to a combination of thermoelastic damping, surface and bulk losses. Its effects can be reduced by optimizing the thermoelastic and surface loss, and these parameters are a function of the cross sectional dimensions of the fiber along its length. This paper presents a new apparatus capable of high resolution measurements of the cross sectional dimensions of suspension fibers of both rectangular and circular cross section, suitable for use in advanced detector mirror suspensions

Minimal speed of fronts of reaction-convection-diffusion equations

We study the minimal speed of propagating fronts of convection reaction diffusion equations of the form $u_t + \mu \phi(u) u_x = u_{xx} +f(u)$ for positive reaction terms with $f'(0 >0$. The function $\phi(u)$ is continuous and vanishes at $u=0$. A variational principle for the minimal speed of the waves is constructed from which upper and lower bounds are obtained. This permits the a priori assesment of the effect of the convective term on the minimal speed of the traveling fronts. If the convective term is not strong enough, it produces no effect on the minimal speed of the fronts. We show that if $f''(u)/\sqrt{f'(0)} + \mu \phi'(u) < 0$, then the minimal speed is given by the linear value $2 \sqrt{f'(0)}$, and the convective term has no effect on the minimal speed. The results are illustrated by applying them to the exactly solvable case $u_t + \mu u u_x = u_{xx} + u (1 -u)$. Results are also given for the density dependent diffusion case $u_t + \mu \phi(u) u_x = (D(u)u_x)_x +f(u)$.Comment: revised, new results adde

Toward physical realizations of thermodynamic resource theories

Conventional statistical mechanics describes large systems and averages over many particles or over many trials. But work, heat, and entropy impact the small scales that experimentalists can increasingly control, e.g., in single-molecule experiments. The statistical mechanics of small scales has been quantified with two toolkits developed in quantum information theory: resource theories and one-shot information theory. The field has boomed recently, but the theorems amassed have hardly impacted experiments. Can thermodynamic resource theories be realized experimentally? Via what steps can we shift the theory toward physical realizations? Should we care? I present eleven opportunities in physically realizing thermodynamic resource theories.Comment: Publication information added. Cosmetic change

Silica suspension and coating developments for Advanced LIGO

The proposed upgrade to the LIGO detectors to form the Advanced LIGO detector system is intended to incorporate a low thermal noise monolithic fused silica final stage test mass suspension based on developments of the GEO 600 suspension design. This will include fused silica suspension elements jointed to fused silica test mass substrates, to which dielectric mirror coatings are applied. The silica fibres used for GEO 600 were pulled using a Hydrogen-Oxygen flame system. This successful system has some limitations, however, that needed to be overcome for the more demanding suspensions required for Advanced LIGO. To this end a fibre pulling machine based on a CO2 laser as the heating element is being developed in Glasgow with funding from EGO and PPARC. At the moment a significant limitation for proposed detectors like Advanced LIGO is expected to come from the thermal noise of the mirror coatings. An investigation on mechanical losses of silica/tantala coatings was carried out by several labs involved with Advanced LIGO R&D. Doping the tantala coating layer with titania was found to reduce the coating mechanical dissipation. A review of the results is given here

Evaluating Tidal Marsh Sustainability in the Face of Sea-Level Rise: A Hybrid Modeling Approach Applied to San Francisco Bay

Tidal marshes will be threatened by increasing rates of sea-level rise (SLR) over the next century. Managers seek guidance on whether existing and restored marshes will be resilient under a range of potential future conditions, and on prioritizing marsh restoration and conservation activities.Building upon established models, we developed a hybrid approach that involves a mechanistic treatment of marsh accretion dynamics and incorporates spatial variation at a scale relevant for conservation and restoration decision-making. We applied this model to San Francisco Bay, using best-available elevation data and estimates of sediment supply and organic matter accumulation developed for 15 Bay subregions. Accretion models were run over 100 years for 70 combinations of starting elevation, mineral sediment, organic matter, and SLR assumptions. Results were applied spatially to evaluate eight Bay-wide climate change scenarios.Model results indicated that under a high rate of SLR (1.65 m/century), short-term restoration of diked subtidal baylands to mid marsh elevations (-0.2 m MHHW) could be achieved over the next century with sediment concentrations greater than 200 mg/L. However, suspended sediment concentrations greater than 300 mg/L would be required for 100-year mid marsh sustainability (i.e., no elevation loss). Organic matter accumulation had minimal impacts on this threshold. Bay-wide projections of marsh habitat area varied substantially, depending primarily on SLR and sediment assumptions. Across all scenarios, however, the model projected a shift in the mix of intertidal habitats, with a loss of high marsh and gains in low marsh and mudflats.Results suggest a bleak prognosis for long-term natural tidal marsh sustainability under a high-SLR scenario. To minimize marsh loss, we recommend conserving adjacent uplands for marsh migration, redistributing dredged sediment to raise elevations, and concentrating restoration efforts in sediment-rich areas. To assist land managers, we developed a web-based decision support tool (www.prbo.org/sfbayslr)

Entropy production for mechanically or chemically driven biomolecules

Entropy production along a single stochastic trajectory of a biomolecule is discussed for two different sources of non-equilibrium. For a molecule manipulated mechanically by an AFM or an optical tweezer, entropy production (or annihilation) occurs in the molecular conformation proper or in the surrounding medium. Within a Langevin dynamics, a unique identification of these two contributions is possible. The total entropy change obeys an integral fluctuation theorem and a class of further exact relations, which we prove for arbitrarily coupled slow degrees of freedom including hydrodynamic interactions. These theoretical results can therefore also be applied to driven colloidal systems. For transitions between different internal conformations of a biomolecule involving unbalanced chemical reactions, we provide a thermodynamically consistent formulation and identify again the two sources of entropy production, which obey similar exact relations. We clarify the particular role degenerate states have in such a description