Evaluating Patient Preferences of Maintenance Therapy for the Treatment of Chronic Obstructive Pulmonary Disease: A Discrete Choice Experiment in the UK, USA and Germany.

Introduction: With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE). Methods: Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs. A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting. It comprised 18 choice sets, selected using a D-efficient experimental design. Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany. Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs). Results: Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis. Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p<0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p<0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p<0.0001). Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important. Preferences were relatively consistent across the three countries. All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers. Conclusion: When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use. Ensuring that patients' preferences are considered may encourage treatment compliance

Numerical prediction of the Flame Describing Function and thermoacoustic limit cycle for a pressurised gas turbine combustor

The forced flame responses in a pressurized gas turbine combustor are predicted using numerical reacting flow simulations. Two incompressible1 large eddy simulation solvers are used, applying two combustion models and two reaction schemes (4-step and 15-step) at two operating pressures (3 and 6 bar). Although the combustor flow field is little affected by these factors, the flame length and heat release rate are found to depend on combustion model, reaction scheme, and combustor pressure. The flame responses to an upstream velocity perturbation are used to construct the flame describing functions (FDFs). The FDFs exhibit smaller dependence on the combustion model and reaction chemistry than the flame shape and mean heat release rate. The FDFs are validated by predicting combustor thermoacoustic stability at 3 and 6 bar and, for the unstable 6 bar case, also by predicting the frequency and oscillation amplitude of the resulting limit cycle oscillation. All of these numerical predictions are in very good agreement with experimental measurements

Functional Stroke Symptoms: A Narrative Review and Conceptual Model

Stroke services have been reconfigured in recent years to facilitate early intervention. Throughout stroke settings, some patients present with functional symptoms that cannot be attributed to a structural cause. Emphasis on fast diagnosis and treatment means that a proportion of patients entering the care pathway present with functional symptoms that mimic stroke or have functional symptoms in addition to vascular stroke. There is limited understanding of mechanisms underlying functional stroke symptoms, how the treatment of such patients should be managed, and no referral pathway or treatment. Predisposing factors vary between individuals, and symptoms are heterogeneous: onset can be acute or insidious, and duration can be short-lived or chronic in the context of new or recurrent illness cognitions and behaviors. This article proposes a conceptual model of functional symptoms identified in stroke services and some hypotheses based on a narrative review of the functional neurological disorder literature. Predisposing factors may include illness experiences, stressors, and chronic autonomic nervous system arousal. Following the onset of distressing symptoms, perpetuating factors may include implicit cognitive processes, classical and operant conditioning, illness beliefs, and behavioral responses, which could form the basis of treatment targets. The proposed model will inform the development of theory-based interventions as well as a functional stroke care pathway

Modelling for robust feedback control of fluid flows

This paper addresses the problem of designing low-order and linear robust feedback controllers that provide a priori guarantees with respect to stability and performance when applied to a fluid flow. This is challenging, since whilst many flows are governed by a set of nonlinear, partial differential–algebraic equations (the Navier–Stokes equations), the majority of established control system design assumes models of much greater simplicity, in that they are: firstly, linear; secondly, described by ordinary differential equations (ODEs); and thirdly, finite-dimensional. With this in mind, we present a set of techniques that enables the disparity between such models and the underlying flow system to be quantified in a fashion that informs the subsequent design of feedback flow controllers, specifically those based on the H∞ loop-shaping approach. Highlights include the application of a model refinement technique as a means of obtaining low-order models with an associated bound that quantifies the closed-loop degradation incurred by using such finite-dimensional approximations of the underlying flow. In addition, we demonstrate how the influence of the nonlinearity of the flow can be attenuated by a linear feedback controller that employs high loop gain over a select frequency range, and offer an explanation for this in terms of Landahl’s theory of sheared turbulence. To illustrate the application of these techniques, an H∞ loop-shaping controller is designed and applied to the problem of reducing perturbation wall shear stress in plane channel flow. Direct numerical simulation (DNS) results demonstrate robust attenuation of the perturbation shear stresses across a wide range of Reynolds numbers with a single linear controller

Decentralised Control Optimisation for a Glass Furnace by SGA’s

In this paper, the potential of standard genetic algorithms (SGAs) are presented to optimise the discrete PID parameters for multivariable glass furnace. Control oriented models of each multivariable glass furnace; glass temperature and excess oxygen are used to optimise the discrete controller with personalised cost function and adjusted boundaries by SGAs, individually. Well optimised discrete PID parameters by control oriented model are applied to realistic multivariable model by decentralised method

Illness-Related Cognition, Distress and Adjustment in Functional Stroke Symptoms, Vascular Stroke, and Chronic Fatigue Syndrome

Background: High rates of psychological distress are reported in functional conditions and vascular stroke, but there is limited understanding of how patients with functional neurological symptoms in stroke settings respond to symptoms. Aims: This study compared patients with functional stroke symptoms to those with vascular stroke and chronic fatigue syndrome (CFS). Methods: A prospective cohort of 56 patients with functional stroke symptoms were age-gender matched to patients with vascular stroke and CFS. Analysis of variance compared groups on cognitive and behavioral responses to symptoms, psychological distress, and functioning. Sensitivity analyses controlled for known confounders. The proportions of clinical anxiety and depression were compared between groups. Results: The functional stroke symptom group had a higher proportion of clinical anxiety cases than the CFS group, and a higher proportion of clinical depression cases than the vascular stroke group. Patients with functional stroke symptoms reported the highest rate of “damage beliefs” and “all-or-nothing” behaviors and greater symptom focusing and resting behavior than patients with vascular stroke. Limitations: Larger cohorts and a longitudinal design would strengthen study findings. Conclusion: Compared to patients with vascular stroke or CFS, patients with functional stroke symptoms show a somewhat distinct profile of illness-related beliefs and behaviors, as well as higher rates of clinical anxiety. Understanding such group differences provides some insights into aetiology and cognitive-behavioral responses. Appropriate support and referral should be available to patients with functional stroke symptoms to address distress and reduce the likelihood of severe impairment

Test-retest reliability of a 16.1 km time trial in trained cyclists using the CompuTrainer ergometer

Laboratory based cycling time trials (TT) are widely used by both researchers and practitioners, as a method of assessing cycling performance in a controlled environment. Assessments of performance often use TT durations or distances between 20 min and one hour and in the UK the 10 mile (16.1 km) TT is the most frequently used race distance for trained cyclists. The 16.1 km TT has received relatively minimal, but increased attention as a performance criterion in the literature. Therefore, the aim of this study was to assess the reliability of 16.1 km TT performance in a large cohort of trained cyclists using the CompuTrainer cycling ergometer. Trained male cyclists (n = 58, mean±SD age 35±7 yr, height 179±6 cm, weight 79.1±9.4 kg, VO2max. 56.6±6.6 ml.kg.min-1, PPO 365±37 W) performed an initial incremental exercise test to determine PPO and VO2max. The participants then performed two 16.1 km TT on a CompuTrainer cycle ergometer separated by 3-7 days. Differences in time, power output and speed were determined using a Wilcoxon signed ranks or paired t-tests. Reproducibility of the TT performance measures was performed using the coefficient of variation (CV), intraclass correlations, and typical error (TE). There were no differences between any of the performance criteria for the whole cohort (Mean difference = 0.06 min, 0.09 km.h-1, 1.5 W, for time, mean speed and power respectively) between TT1 and TT2. All TT performance data were very reproducible (CV range = 1.1-2.7%) and demonstrated trivial or small TE. The slower cyclists demonstrated marginally lower reliability (CV range = 1.3-3.2%) compared to the fastest group (CV range = 0.7-2.0%). The 16.1 km TT on the CompuTrainer represents a very reliable performance criterion for trained cyclists. Interpretation of test-retest performance outcomes should be performed in the context of the TE of each performance indicator

On the oxidation behavior of titanium within coated nickel-based superalloys

Rutile precipitation within alumina scales grown on coated nickel-based superalloy CMSX-4 has been found to occur preferentially at grain boundaries within the scale. Misorientation analysis using Rodrigues–Frank space has revealed clustering of the misorientation between neighboring grains of corundum and rutile about the established 〈0 0 0 1〉_c{1 1 2¯ 0}_c//〈0 1 0〉_r{1 0 1}_r orientation relationship observed in Ti-containing sapphire crystals. The fraction of interfaces found to exist in this configuration is sufficient to explain the nucleation of rutile from a single corundum grain abutting the rutile grain. The diffusive behavior of Ti has been observed to vary considerably within three commercially used coatings, a plain aluminide coating, a plat-aluminide coating and a diffused platinum coating. Titanium diffusion is enhanced by the presence of Pt. However this did not lead to the precipitation of more rutile, which although observed in all three coatings, was present in sufficient quantity to be detected using XRD only within the plain aluminide coated samples.The work was carried out under the financial support provided by Rolls-Royce plc and Engineering and Physical Sciences Research Councils, UK under the Rolls-Royce/ESPRC Strategic Partnership (EP/M005607/1 & EP/H022309/1). This study was also supported by Nanotechnology Platform Project (NIMS Nanofabrication Platform) sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Financial support was also received from the Seventh Framework Programme of the European Commission: ESTEEM2, contract number 312483. Requests for access to the underlying research data should be directed to the corresponding author and will be considered against commercial interests and data protection.This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S1359645415002281

Type Ia Supernovae Are Excellent Standard Candles in the Near-infrared

Abstract We analyze a set of 89 type Ia supernovae (SNe Ia) that have both optical and near-infrared (NIR) photometry to derive distances and construct low-redshift (z ≤ 0.04) Hubble diagrams. We construct mean light curve (LC) templates using a hierarchical Bayesian model. We explore both Gaussian process (GP) and template methods for fitting the LCs and estimating distances, while including peculiar-velocity and photometric uncertainties. For the 56 SNe Ia with both optical and NIR observations near maximum light, the GP method yields a NIR-only Hubble-diagram with a root mean square (rms) of mag when referenced to the NIR maxima. For each NIR band, a comparable GP method rms is obtained when referencing to NIR-max or B-max. Using NIR LC templates referenced to B-max yields a larger rms value of mag. Fitting the corresponding optical data using standard LC fitters that use LC shape and color corrections yields larger rms values of 0.179 ± 0.018 mag with SALT2 and mag with SNooPy. Applying our GP method to subsets of SNe Ia NIR LCs at NIR maximum light, even without corrections for LC shape, color, or host-galaxy dust reddening, provides smaller rms in the inferred distances, at the ∼2.3–4.1σ level, than standard optical methods that correct for those effects. Our ongoing RAISIN program on the Hubble Space Telescope will exploit this promising infrared approach to limit systematic errors when measuring the expansion history of the universe in order to constrain dark energy.</jats:p