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

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

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

Three Years of Δ14CO2 Observations from Maize Leaves in the Netherlands and Western Europe

Atmospheric Δ14CO2 measurements are useful to investigate the regional signals of anthropogenic CO2 emissions, despite the currently scarce observational network for Δ14CO2. Plant samples are an easily attainable alternative, which have been shown to work well as a qualitative measure of the atmospheric Δ14CO2 signals integrated over the time a plant has grown. Here, we present the 14C analysis results for 89 individual maize (Zea mays) plant samples from 51 different locations that were gathered in the Netherlands in the years 2010 to 2012, and from western Germany and France in 2012. We describe our sampling strategy and results, and include a comparison to a model simulation of the Δ14CO2 that would be accumulated in each plant over a growing season. Our model simulates the Δ14CO2 signatures in good agreement with observed plant samples, resulting in a root-mean-square deviation (RMSD) of 3.30‰. This value is comparable to the measurement uncertainty, but still relatively large (20–50%) compared to the total signal. It is also comparable to the spread in Δ14CO2 values found across multiple plants from a single site, and to the spread found when averaging across larger regions. We nevertheless find that both measurements and model capture the large-scale (>100 km) regional Δ14CO2 gradients, with significant observation-model correlations in all three countries in which we collected samples. The modeled plant results suggest that the largest gradients found in the Netherlands and Germany are associated with emissions from energy production and road traffic, while in France, the 14CO2 enrichment from nuclear sources dominates in many samples. Overall, the required model-based interpretation of plant samples adds additional uncertainty to the already relatively large measurement uncertainty in Δ14CO2, and we suggest that future fossil fuel monitoring efforts should prioritize other strategies such as direct atmospheric sampling of CO2 and Δ14CO2

Strategic verbal rehearsal in adolescents with mild intellectual disabilities: A multi-centre European study

Background: There is a long-held view that verbal short-term memory problems of individuals with intellectual disabilities (ID) might be due to a deficit in verbal rehearsal. However, the evidence is inconclusive and word length effects as indicator of rehearsal have been criticised. Aim & Method: The aim of this multi-site European study was to investigate verbal rehearsal in adolescents with mild ID (n=90) and a comparison group of typically developing children matched individually for mental age (MA, n=90). The investigation involved: (1) a word length experiment with non-verbal recall using pointing and (2) ‘self-paced’ inspection times to infer whether verbal strategies were utilised when memorising a set of pictorial items. Results: The word length effect on recall did not interact with group, suggesting that adolescents with ID and MA comparisons used similar verbal strategies, possibly phonological recoding of picture names. The inspection time data suggested that high span individuals in both groups used verbal labelling or single item rehearsal on more demanding lists, as long named items had longer inspection times. Conclusions: The findings suggest that verbal strategy use is not specifically impaired in adolescents with mild ID and is mental age appropriate, supporting a developmental perspective

European Guideline Robin Sequence An Initiative from the European Reference Network for Rare Craniofacial Anomalies and Ear, Nose and Throat Disorders (ERN-CRANIO)

A European guideline on Robin Sequence was developed within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose, and throat disorders. The guideline provides an overview of optimal care provisions for patients with Robin Sequence and recommendations for the improvement of care.</p

Modelling potential production of macroalgae farms in UK and Dutch coastal waters

There is increasing interest in macroalgae farming in European waters for a range of applications, including food, chemical extraction for biofuel production. This study uses a 3-D numerical model of hydrodynamics and biogeochemistry to investigate potential production and environmental effects of macroalgae farming in UK and Dutch coastal waters. The model included four experimental farms in different coastal settings in Strangford Lough (Northern Ireland), in Sound of Kerrera and Lynn of Lorne (north-west Scotland) and in the Rhine plume (the Netherlands), as well as a hypothetical large-scale farm off the UK north Norfolk coast. The model could not detect significant changes in biogeochemistry and plankton dynamics at any of the farm sites averaged over the farming season. The results showed a range of macroalgae growth behaviours in response to simulated environmental conditions. These were then compared with in situ observations where available, showing good correspondence for some farms and less good correspondence for others. At the most basic level, macroalgae production depended on prevailing nutrient concentrations and light conditions, with higher levels of both resulting in higher macroalgae production. It is shown that under non-elevated and interannually varying winter nutrient conditions, farming success was modulated by the timings of the onset of increasing nutrient concentrations in autumn and nutrient drawdown in spring. Macroalgae carbohydrate content also depended on nutrient concentrations, with higher nutrient concentrations leading to lower carbohydrate content at harvest. This will reduce the energy density of the crop and thus affect its suitability for conversion into biofuel. For the hypothetical large-scale macroalgae farm off the UK north Norfolk coast, the model suggested high, stable farm yields of macroalgae from year to year with substantial carbohydrate content and limited environmental effects

Влияние облучения и отжига на термическую стабильность радиационных дефектов в кремнии

Описан отжиг А-центров, дивакансий, А-центров, модифицированных водородом, в n-Si (P ≈ 10^14 см^-3), в отсутствие и при наличии примеси платины, после облучения протонами с энергией 1,8 МэВ. Показано, что энергия активации отжига радиационных дефектов при взаимодействии с водородно-вакансионными дефектами уменьшается с 1,1 до 0,8 эВ при увеличении концентрации платины в кремнии, так как деформационные поля, создаваемые атомами платины, уменьшают энергию переориентации дефектов. Уточнено энергетическое положение в запрещенной зоне кремния донорного уровня А-центра (ЕV + 0,415 эВ) на основании известных данных о положении А-центра, модифицированного атомом углерода (ЕV + 0,38 эВ) или водорода (ЕV + 0,28 эВ).Описано відпал А-центрів, дивакансій, А-центрів, модифікованих воднем, у n-Si (P ≈ 10^14 см^-3), за відсутності та при наявності домішки платини, після опромінення протонами з енергією 1,8 МеВ. Показано, що енергія активації відпалу радіаційних дефектів при взаємодії з воднево-вакансійними дефектами зменшується від 1,1 до 0,8 еВ зі збільшенням концентрації платини в кремнії, оскільки деформаційні поля, які створюються атомами платини, зменшують енергію переорієнтації дефектів. Уточнено енергетичне положення у забороненій зоні кремнію донорного рівня А-центра (ЕV + 0,415 еВ), виходячи із відомих даних щодо положення А-центра, модифікованого атомом вуглецю (ЕV + 0,38 еВ) або водню (ЕV + 0,28 еВ).The annealing of A-centers, divacancies, A-centers modified by hydrogen was described for n-Si (P ≈ 10^14 cm^-3), with and without platinum dopants, after the irradiation by protons with energy 1.8 MeV. It was shown that the activation energy of annealing for radiation defects under their interaction with hydrogen-vacancy defects is decreased from 1.1 to 0.8 eV with the increasing of platinum concentration in silicon, because the deformation fields, creating by platinum atoms, decrease the energy of the defect re-orientation. In the forbidden zone of silicon the energy state for the donor level of A-center (ЕV + 0.415 eV) was specified based on the data about the position of A-center modified by the carbon atom (ЕV + 0.38 eV) or the hydrogen atom (ЕV + 0.28 eV)

Connectivity of larval stages of sedentary marine communities between hard substrates and offshore structures in the North Sea

Man-made structures including rigs, pipelines, cables, renewable energy devices, and ship wrecks, offer hard substrate in the largely soft-sediment environment of the North Sea. These structures become colonised by sedentary organisms and non-migratory reef fish, and form local ecosystems that attract larger predators including seals, birds, and fish. It is possible that these structures form a system of interconnected reef environments through the planktonic dispersal of the pelagic stages of organisms by ocean currents. Changes to the overall arrangement of hard substrate areas through removal or addition of individual man-made structures will affect the interconnectivity and could impact on the ecosystem. Here, we assessed the connectivity of sectors with oil and gas structures, wind farms, wrecks, and natural hard substrate, using a model that simulates the drift of planktonic stages of seven organisms with sedentary adult stages associated with hard substrate, applied to the period 2001–2010. Connectivity was assessed using a classification system designed to address the function of sectors in the network. Results showed a relatively stable overall spatial distribution of sector function but with distinct variations between species and years. The results are discussed in the context of decommissioning of oil and gas infrastructure in the North Sea

Assessing health status over time:Impact of recall period and anchor question on the minimal clinically important difference of copd health status tools

BACKGROUND: The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant. Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID. This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St. George's Respiratory Questionnaire (SGRQ). METHODS: Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR). CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months. A 15-point Global Rating of Change scale (GRC) was completed at each follow-up. A five-point GRC was used as second anchor at 12 months. Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID. The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency. RESULTS: In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up. Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ). MCID estimates for improvement ranged - 3.1 to - 1.4 for CAT, - 0.6 to - 0.3 for CCQ, and - 10.3 to - 7.6 for SGRQ. Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR. Significantly absolute lower MCID estimates were observed for CAT (difference - 1.4: CI -2.3 to - 0.5) and CCQ (difference - 0.2: CI -0.3 to -0.1) using a five-point GRC. CONCLUSIONS: The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values. However, the design of the anchor question was likely to influence the MCID of CAT and CCQ. TRIAL REGISTRATION: RIMTCORE trial # DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer)