Health status in the TORCH study of COPD: treatment efficacy and other determinants of change

BACKGROUND: Little is known about factors that determine health status decline in clinical trials of COPD. OBJECTIVES: To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo. METHODS: St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months. MEASUREMENTS AND MAIN RESULTS: Data from 4951 patients in 28 countries were available. SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains. SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001). There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women. Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1. The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change. CONCLUSIONS: In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors. Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation

The INSCHOOL project: showcasing participatory qualitative methods derived from patient and public involvement and engagement (PPIE) work with young people with long-term health conditions

Background Evidence suggests resources and services benefit from being developed in collaboration with the young people they aim to support. Despite this, patient and public involvement and engagement (PPIE) with young people is often tokenistic, limited in engagement and not developmentally tailored to young people. Our paper aims to build knowledge and practice for meaningfully engaging with young people in research design, analysis and as research participants. Methods We report the participatory processes from the INSCHOOL project, examining long-term health conditions and schooling among 11–18 year olds. Young people were consulted at the inception of the project through a hospital- based youth forum. This began a partnership where young people co-designed study documents, informed the recruitment process, developed creative approaches to data collection, participated in pilot interviews, co-analysed the qualitative data and co-presented results. Results PPIE advisors, participants and researchers all benefitted from consistent involvement of young people throughout the project. Long-term engagement allowed advisors and researchers to build rapport and facilitated openness in sharing perspectives. PPIE advisors valued being able to shape the initial aims and language of the research questions, and contribute to every subsequent stage of the project. Advisors co-designed flexible data collection methods for the qualitative project that provided participants with choices in how they took part (interviews, focus groups, written tasks). Further choice was offered through co-designed preparation activities where participants completed one of four creative activities prior to the interview. Participants were therefore able to have control over how they participated and how they described their school experiences. Through participatory analysis meetings advisors used their first-hand experiences to inform the creation of themes and the language used to describe these themes. PPIE in every stage of the process helped researchers to keep the results grounded in young people’s experience and challenge their assumptions as adults

Characterising the Transfer of Biomarkers within the Phobos-Mars System

Procedural and analytical developments required for impact and heat investigation into the detection of biomarkers transported from Mars to Phobos

First e-VLBI observations of GRS 1915+105

We present results from the first successful open call e-VLBI science run, observing the X-ray binary GRS 1915+105. e-VLBI science allows the rapid production of VLBI radio maps, within hours of an observation rather than weeks, facilitating a decision for follow-up observations. A total of 6 telescopes observing at 5 GHz across the European VLBI Network (EVN) were correlated in real time at the Joint Institute for VLBI in Europe (JIVE). Constant data rates of 128 Mbps were transferred from each telescope, giving 4 TB of raw sampled data over the 12 hours of the whole experiment. Throughout this, GRS 1915+105 was observed for a total of 5.5 hours, producing 2.8 GB of visibilities of correlated data. A weak flare occurred during our observations, and we detected a slightly resolved component of 2.7 x 1.2 milliarcsecond with a position angle of 140 (+/-2) degrees. The peak brightness was 10.2 mJy per beam, with a total integrated radio flux of 11.1 mJy.Comment: Accepted for publication in MNRAS 4 pages, 3 figure

Design of a speed meter interferometer proof-of-principle experiment

The second generation of large scale interferometric gravitational wave detectors will be limited by quantum noise over a wide frequency range in their detection band. Further sensitivity improvements for future upgrades or new detectors beyond the second generation motivate the development of measurement schemes to mitigate the impact of quantum noise in these instruments. Two strands of development are being pursued to reach this goal, focusing both on modifications of the well-established Michelson detector configuration and development of different detector topologies. In this paper, we present the design of the world's first Sagnac speed meter interferometer which is currently being constructed at the University of Glasgow. With this proof-of-principle experiment we aim to demonstrate the theoretically predicted lower quantum noise in a Sagnac interferometer compared to an equivalent Michelson interferometer, to qualify Sagnac speed meters for further research towards an implementation in a future generation large scale gravitational wave detector, such as the planned Einstein Telescope observatory.Comment: Revised version: 16 pages, 6 figure

Application of a stochastic weather generator to assess climate change impacts in a semi-arid climate: The Upper Indus Basin

Assessing local climate change impacts requires downscaling from Global Climate Model simulations. Here, a stochastic rainfall model (RainSim) combined with a rainfall conditioned weather generator (CRU WG) have been successfully applied in a semi-arid mountain climate, for part of the Upper Indus Basin (UIB), for point stations at a daily time-step to explore climate change impacts. Validation of the simulated time-series against observations (1961–1990) demonstrated the models’ skill in reproducing climatological means of core variables with monthly RMSE of <2.0 mm for precipitation and ⩽0.4 °C for mean temperature and daily temperature range. This level of performance is impressive given complexity of climate processes operating in this mountainous context at the boundary between monsoonal and mid-latitude (westerly) weather systems. Of equal importance the model captures well the observed interannual variability as quantified by the first and last decile of 30-year climatic periods. Differences between a control (1961–1990) and future (2071–2100) regional climate model (RCM) time-slice experiment were then used to provide change factors which could be applied within the rainfall and weather models to produce perturbed ‘future’ weather time-series. These project year-round increases in precipitation (maximum seasonal mean change:+27%, annual mean change: +18%) with increased intensity in the wettest months (February, March, April) and year-round increases in mean temperature (annual mean +4.8 °C). Climatic constraints on the productivity of natural resource-dependent systems were also assessed using relevant indices from the European Climate Assessment (ECA) and indicate potential future risk to water resources and local agriculture. However, the uniformity of projected temperature increases is in stark contrast to recent seasonally asymmetrical trends in observations, so an alternative scenario of extrapolated trends was also explored. We conclude that interannual variability in climate will continue to have the dominant impact on water resources management whichever trajectory is followed. This demonstrates the need for sophisticated downscaling methods which can evaluate changes in variability and sequencing of events to explore climate change impacts in this region

Demonstration of a switchable damping system to allow low-noise operation of high-Q low-mass suspension systems

Low mass suspension systems with high-Q pendulum stages are used to enable quantum radiation pressure noise limited experiments. Utilising multiple pendulum stages with vertical blade springs and materials with high quality factors provides attenuation of seismic and thermal noise, however damping of these high-Q pendulum systems in multiple degrees of freedom is essential for practical implementation. Viscous damping such as eddy-current damping can be employed but introduces displacement noise from force noise due to thermal fluctuations in the damping system. In this paper we demonstrate a passive damping system with adjustable damping strength as a solution for this problem that can be used for low mass suspension systems without adding additional displacement noise in science mode. We show a reduction of the damping factor by a factor of 8 on a test suspension and provide a general optimisation for this system.Comment: 5 pages, 5 figure