Beyond FEV1 in COPD: a review of patient-reported outcomes and their measurement

Abstract: Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences. Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being. Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1). However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life. Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient. Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments. We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts. Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials. We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years. Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments. The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials. In turn, this will help us to understand better the patient's experience of the disease

Measurement of Turbulence Power Spectra in Agitated Vessels of Different Size with a Laser-Doppler Velocimeter

We have used the laser-Doppler velocimeter with a new noise reduction technique for measurements in water-filled, turbine-agitated vessels of several sizes, but of the same geometry. Mean velocities, turbulence intensities and turbulence power spectra were obtained in the impeller stream region. With these results we hope, in the future, to put scaling rules for mixing vessels on a sounder basis

Modelling survival and connectivity of Mnemiopsis leidyi in the south-western North Sea and Scheldt estuaries

Three different models were applied to study the reproduction, survival and dispersal of Mnemiopsis leidyi in the Scheldt estuaries and the southern North Sea: a high-resolution particle tracking model with passive particles, a low-resolution particle tracking model with a reproduction model coupled to a biogeochemical model, and a dynamic energy budget (DEB) model. The results of the models, each with its strengths and weaknesses, suggest the following conceptual situation: (i) the estuaries possess enough retention capability to keep an overwintering population, and enough exchange with coastal waters of the North Sea to seed offshore populations; (ii) M. leidyi can survive in the North Sea, and be transported over considerable distances, thus facilitating connectivity between coastal embayments; (iii) under current climatic conditions, M. leidyi may not be able to reproduce in large numbers in coastal and offshore waters of the North Sea, but this may change with global warming; however, this result is subject to substantial uncertainty. Further quantitative observational work is needed on the effects of temperature, salinity and food availability on reproduction and on mortality at different life stages to improve models such as used here

Changes in wave climate over the northwest European shelf seas during the last 12,000 years

Because of the depth attenuation of wave orbital velocity, wave-induced bed shear stress is much more sensitive to changes in total water depth than tidal-induced bed shear stress. The ratio between wave- and tidal-induced bed shear stress in many shelf sea regions has varied considerably over the recent geological past because of combined eustatic changes in sea level and isostatic adjustment. In order to capture the high-frequency nature of wind events, a two-dimensional spectral wave model is here applied at high temporal resolution to time slices from 12 ka BP to present using paleobathymetries of the NW European shelf seas. By contrasting paleowave climates and bed shear stress distributions with present-day conditions, the model results demonstrate that, in regions of the shelf seas that remained wet continuously over the last 12,000 years, annual root-mean-square (rms) and peak wave heights increased from 12 ka BP to present. This increase in wave height was accompanied by a large reduction in the annual rms wave- induced bed shear stress, primarily caused by a reduction in the magnitude of wave orbital velocity penetrating to the bed for increasing relative sea level. In regions of the shelf seas which remained wet over the last 12,000 years, the annual mean ratio of wave- to (M-2) tidal-induced bed shear stress decreased from 1 (at 12 ka BP) to its present-day value of 0.5. Therefore compared to present- day conditions, waves had a more important contribution to large-scale sediment transport processes in the Celtic Sea and the northwestern North Sea at 12 ka BP

The role of Joule heating in the formation of nanogaps by electromigration

We investigate the formation of nanogaps in gold wires due to electromigration. We show that the breaking process will not start until a local temperature of typically 400 K is reached by Joule heating. This value is rather independent of the temperature of the sample environment (4.2-295 K). Furthermore, we demonstrate that the breaking dynamics can be controlled by minimizing the total series resistance of the system. In this way, the local temperature rise just before break down is limited and melting effects are prevented. Hence, electrodes with gaps < 2 nm are easily made, without the need of active feedback. For optimized samples, we observe quantized conductance steps prior the gap formation.Comment: including 7 figure

A heart rate analysis of developmental change in feedback processing and rule shifting from childhood to early adulthood

Over the course of development, the ability to switch between diVerent tasks on the basis of feedback cues increases profoundly, but the role of performance monitoring remains uncl

Optimizing a dynamic fossil fuel CO2 emission model with CTDAS (CarbonTracker Data Assimilation Shell, v1.0) for an urban area using atmospheric observations of CO2, CO, NOx, and SO2

We present a modelling framework for fossil fuel CO2 emissions in an urban environment, which allows constraints from emission inventories to be combined with atmospheric observations of CO2 and its co-emitted species CO, NOx , and SO2. Rather than a static assignment of average emission rates to each unit area of the urban domain, the fossil fuel emissions we use are dynamic: they vary in time and space in relation to data that describe or approximate the activity within a sector, such as traffic density, power demand, 2m temperature (as proxy for heating demand), and sunlight and wind speed (as proxies for renewable energy supply). Through inverse modelling, we optimize the relationships between these activity data and the resulting emissions of all species within the dynamic fossil fuel emission model, based on atmospheric mole fraction observations. The advantage of this novel approach is that the optimized parameters (emission factors and emission ratios, N D 44) in this dynamic emission model (a) vary much less over space and time, (b) allow for a physical interpretation of mean and uncertainty, and (c) have better defined uncertainties and covariance structure. This makes them more suited to extrapolate, optimize, and interpret than the gridded emissions themselves. The merits of this approach are investigated using a pseudo-observation-based ensemble Kalman filter inversion set-up for the Dutch Rijnmond area at 1km-1km resolution. We find that the fossil fuel emission model approximates the gridded emissions well (annual mean differences < 2 %, hourly temporal r2 D 0:21-0.95), while reported errors in the underlying parameters allow a full covariance structure to be created readily. Propagating this error structure into atmospheric mole fractions shows a strong dominance of a few large sectors and a few dominant uncertainties, most notably the emission ratios of the various gases considered. If the prior emission ratios are either sufficiently well-known or well constrained from a dense observation network, we find that including observations of co-emitted species improves our ability to estimate emissions per sector relative to using CO2 mole fractions only. Nevertheless, the total CO2 emissions can be well constrained with CO2 as the only tracer in the inversion. Because some sectors are sampled only sparsely over a day, we find that propagating solutions from day-to-day leads to largest uncertainty reduction and smallest CO2 residuals over the 14 consecutive days considered. Although we can technically estimate the temporal distribution of some emission categories like shipping separate from their total magnitude, the controlling parameters are difficult to distinguish. Overall, we conclude that our new system looks promising for application in verification studies, provided that reliable urban atmospheric transport fields and reasonable a priori emission ratios for CO2 and its co-emitted species can be produced

Controlled formation of metallic nanowires via Au nanoparticle ac trapping

Applying ac voltages, we trapped gold nanoparticles between microfabricated electrodes under well-defined conditions. We demonstrate that the nanoparticles can be controllably fused together to form homogeneous gold nanowires with pre-defined diameters and conductance values. Whereas electromigration is known to form a gap when a dc voltage is applied, this ac technique achieves the opposite, thereby completing the toolkit for the fabrication of nanoscale junctions.Comment: Nanotechnology 18, 235202 (2007