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

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

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

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

Background: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. Methods/design: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, Econ Lit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. Discussion: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this

Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: Comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion

The potential use of bone progenitors, multipotential stromal cells (MSCs) helping spine fusion is increasing, but convenient MSC sources and effective processing methods are critical factors yet to be optimised. The aim of this study was to test the effect of bone marrow processing on the MSC abundance and to compare the differentiation capabilities of vertebral body-bone marrow (VB-BM) MSCs versus iliac crest-bone marrow (IC-BM) MSCs. We assessed the effect of the red blood cell lysis (ammonium chloride, AC) and density-gradient centrifugation (Lymphoprep™, LMP), on the extracted VB-BM and IC-BM MSC numbers. The MSC abundance (indicated by colony counts and CD45lowCD271high cell numbers), phenotype, proliferation and tri-lineage differentiation of VB-BM MSCs were compared with donor-matched IC-BM MSCs. Importantly, the MSC attachment and osteogenesis were examined when VB-BM and IC-BM samples were loaded on a beta-tricalcium phosphate scaffold. In contrast to LMP, using AC yielded more colonies from IC-BM and VB-BM aspirates (p = 0.0019 & p = 0.0201 respectively). For IC-BM and VB-BM, the colony counts and CD45lowCD271high cell numbers were comparable (p = 0.5186, p = 0.2640 respectively). Furthermore, cultured VB-BM MSCs exhibited the same phenotype, proliferative and adipogenic potential, but a higher osteogenic and chondrogenic capabilities than IC-BM MSCs (p = 0.0010 and p = 0.0005 for calcium and glycosaminoglycan (GAG) levels, respectively). The gene expression data confirmed higher chondrogenesis for VB-BM MSCs than IC-BM MSCs, but osteogenic gene expression levels were comparable. When loaded on Vitoss™, both MSCs showed a similar degree of attachment and survival, but a better osteogenic ability was detected for VB-BM MSCs as measured by alkaline phosphatase activity (p = 0.0386). Collectively, the BM processing using AC had more MSC yield than using LMP. VB-BM MSCs have a comparable phenotype and proliferative capacity, but higher chondrogenesis and osteogenesis with or without using scaffold than donor-matched IC-BM MSCs. Given better accessibility, VB-BM could be an ideal MSC source for spinal bone fusion

Removal processes for tributyltin during municipal wastewater treatment

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Springer.The fate and behaviour of tributyltin (TBT) at two wastewater treatment works was examined. Both sites had two inlet streams, and each utilised high rate biological filters (biofilters) on one the streams, before treatment of the combined flows on trickling filters, with one having additional tertiary processes, installed to remove ammonia and solids. The study was designed to determine if these processes enhanced the removal of TBT. Degradation of TBT was observed in one of the biofilters, possibly as a result of temperature and hydraulic loading. At the treatment works with tertiary processes, the mass flux showed the overall removal of TBT was 68 %, predominantly due to removal with solids in the primary settlement processes. However, overall removal of 95 % was observed in the conventional trickling filter works with 94 % of this due to biodegradation in the trickling filter. The two works both removed TBT, but at different treatment stages and by different processes. Differences in the form (solubility) of TBT in the influent may have attributed to this, although further understanding of factors controlling degradation would allow for a more complete assessment of the potential of biological processes to remove hazardous compounds from wastewaters.United Utilities PL

Nature of the many-body excitations in a quantum wire: Theory and experiment

The natural excitations of an interacting one-dimensional system at low energy are hydrodynamic modes of Luttinger liquid, protected by the Lorentz invariance of the linear dispersion. We show that beyond low energies, where quadratic dispersion reduces the symmetry to Galilean, the main character of the many-body excitations changes into a hierarchy: calculations of dynamic correlation functions for fermions (without spin) show that the spectral weights of the excitations are proportional to powers of $\mathcal{R}^{2}/L^{2}$, where $\mathcal{R}$ is a length-scale related to interactions and $L$ is the system length. Thus only small numbers of excitations carry the principal spectral power in representative regions on the energy-momentum planes. We have analysed the spectral function in detail and have shown that the first-level (strongest) excitations form a mode with parabolic dispersion, like that of a renormalised single particle. The second-level excitations produce a singular power-law line shape to the first-level mode and multiple power-laws at the spectral edge. We have illustrated crossover to Luttinger liquid at low energy by calculating the local density of state through all energy scales: from linear to non-linear, and to above the chemical potential energies. In order to test this model, we have carried out experiments to measure momentum-resolved tunnelling of electrons (fermions with spin) from/to a wire formed within a GaAs heterostructure. We observe well-resolved spin-charge separation at low energy with appreciable interaction strength and only a parabolic dispersion of the first-level mode at higher energies. We find structure resembling the second-level excitations, which dies away rapidly at high momentum in line with the theoretical predictions here.We acknowledge financial support from the UK EPSRC through Grants No. EP/J01690X/1 and No. EP/J016888/1 and from the DFG through SFB/TRR 49. This research was supported in part by the National Science Foundation under Grant No. NSF PHY11-25915.This is the author accepted manuscript. The final version is available from APS via http://dx.doi.org/10.1103/PhysRevB.93.07514