Dundee and Angus College

Patient reported outcomes are important measures in clinical trials. We assessed two bronchiectasis disease specific quality of life questionnaires in patients with bronchiectasis due to PCD. The Bronchiectasis Health Questionnaire is a ten question disease-specific tool with a total score ranging from 0-100 with 100 being best quality of life. The QoL-B has 37 items in 8 domains. Questionnaires were administered in 86 people with PCD from 11 centres in 9 European countries as part of the EMBARC-BRIDGE study Average patient age was 44yrs (+/-16yrs), 31 male (36%), FEV1%pred (66% +/- 24). Average BHQ score was 60.9, range from 42.91-83.83. Average QoLB-Respiratory score was 63 (11.1-88.9). BHQ Total score and Qol-B Resp showed good correlation with disease severity (BSI score r= -0.41; 95%CI -0.64 to -0.26, r=-0.34 95%CI -0.60-0.02) and breathlessness (MRC dyspnoea score r= -0.61; 95%CI -0.74 to -0.44, r=-0.55 95%CI -0.73 to -0.31), but not sputum volume or lung function p>0.05. There was good correlation between BHQ and all QoL-B domains (Physical r=0.61, Role 0.60, Vitality 0.80, Emotion, 0.54, Social 0.44, Treatment Burden 0.50, Health 0.70 and Respiration 0.73, all p<0.001). Patients with worse BHQ and QoLB-Resp scores had more annual exacerbations [no exacerbations (BHQ 65.8 CI 61.7-70.2, QolB 68.5 CI 59.4-77.8) vs 1-2 (61.35 56.4-66.4; 54.2 CI 45.4-63.0) vs 3+ (56.1, CI 53.1-59.9 ; 54.5. CI 42.2 – 66.7)]. MCID was calculated using 0.5stdev of the mean as 5.1 points for BHQ and 9.7 for QoLB-Resp. QOL-B and BHQ scores correlate with disease severity and clinical outcomes in adults with PCD.

<bold>Background</bold> Neutrophil elastase (NE) is activated by CatC, and increased airway NE activity is linked to poor outcomes in people with bronchiectasis (BE). We report the effects of the CatC inhibitor BI 1291583 on NE activity in people with BE in the AIRLEAF^® study. <bold>Methods</bold> AIRLEAF^® enrolled 322 adults with BE, examining once-daily BI 1291583 administration (1/2.5/5 mg doses) vs placebo up to 48 weeks. Participants had a history of pulmonary exacerbations (PExs) requiring antibiotic treatment in the year prior to screening (≥2 PExs or 1 PEx with St. George’s Respiratory Questionnaire [SGRQ] Symptoms score >40). Free sputum NE activity was measured at baseline and over time, using a fluorescent substrate-based enzymatic activity assay. Descriptive statistics for absolute NE activity over time were calculated; change from baseline in sputum NE activity and corresponding NE inhibition were estimated using a mixed model with repeated measures. <bold>Results</bold> At baseline, mean sputum NE activity was similar across all treatment groups, with no differences in participants who had ≥2 PExs or 1 PEx with SGRQ Symptoms score >40. Higher baseline NE activity (p<0.01) was observed in those positive for <italic>P. aeruginosa</italic> and those from East Asia. At Weeks 12 and 24, placebo-corrected-mean-adjusted NE inhibition was 24.1% and 44.9%, 78.4% and 78.9%, and 80.2% and 90.8% in the BI 1291583 1 mg, 2.5 mg, and 5 mg groups, respectively. <bold>Conclusions</bold> Dose-dependent NE inhibition was seen with BI 1291583. However, the 2.5 mg dose achieved the greatest clinical efficacy in AIRLEAF^®;¹ several mechanisms may be responsible for this. ¹Chalmers JD, <italic>et al.</italic> Eur Respir J 2025;65:2401551

Abstract Diffraction and refraction of nonlinear shallow water waves due to uneven bathymetry is studied numerically in two and three dimensions. The numerical tank consists of a wavemaker at the upwave side of the domain, the submerged obstacles in the middle of the domain, and a numerical wave absorber on the downwave of the domain. The numerical wavemaker is capable of generating solitary and cnoidal waves as solutions of the Green-Naghdi (GN) equations. The nonlinear wave refraction and diffraction is studied by use of the Level I GN equations. The system of equations are solved numerically in time domain by use of a second-order finite difference approach, and in a boundary-fitted coordinate system. Various forms of three-dimensional bathymetry with large slopes, including flat and curved ramps from deep to shallow regions are considered. Results include solitary and cnoidal wave surface elevation and particle velocities and are compared with the existing solutions where possible. Overall very good agreement is observed. Discussion is provided on the nonlinearity and dispersion effects on the wave diffraction and refraction, as well as on the performance of the GN equations in solving these problems.

Abstract Water current interaction with a hydrokinetic energy converter is studied by use of computational fluid dynamics. Mass of water turbine (MOWT) consists of several thin paddles attached to a conveyor, that are allowed to rotate around the hull. As the incoming current passes under the current energy converter, the paddles move to the direction of the water flow. The motion of the paddles is converted to electricity through the power take-off system of the device. In this study, a two-dimensional computational current tank is generated and the current-structure interaction of a simple geometry is studied. Good agreement between the computed forces and existing data for the same geometry are observed. The velocity and the pressure fields around the MOWT are determined and discussion is provided on the velocity and pressure distribution around the body. Moreover, the forces on individual paddles of the MOWT are computed and compared with the empirical relations. It is found that the current-induced force on the leading paddle is substantially different from that on the downstream paddles due to the change of the flow field. For efficient energy production from this device, optimization is necessary to find a suitable configuration. To obtain an optimum design of the MOWT, the effect of the configuration of the paddles is investigated by considering several combinations and assessing the current-induced loads on the paddles.

Introduction: Elastin degradation is a common pathological feature of bronchiectasis (BE) and cardiovascular (CV) disease. Our previous study has shown that elevated levels of serum desmosine (sDES), a degradation product from elastin, is strongly associated with an increased risk of severe exacerbation, but its long-term implication to CV outcomes is unknown. Aim: To investigate whether the levels of sDES are associated with long-term CV mortality in BE. Methods: Patients with BE (n=433, age 67 (58-74) years, FEV1(pred) 71.9 (50.0-91.0), female 60.7%, idiopathic bronchiectasis 45%, bronchiectasis severity Index (BSI) score 6 (4-10)) were included. sDES levels were measured using a stable isotope dilution LC-MS/MS method. Results: A total of 88 deaths (26 respiratory, 39 CV, 23 others) were recorded during the follow-up period of 6.7 years. Patients were divided into four quantiles based on serum desmosine levels. We found that elevated sDES levels were associated with all-cause mortality (HR 1.86 (1.46-2.37) per SD, p Conclusion: sDES is an independent predictor of long-term CV risk in BE.

Evaluation of accessibility within a tabletop context is much more complicated than it is within a video game environment. There is a considerable amount of variation in game systems, game mechanisms, and interaction regimes. Games may be entirely verbal, or completely non-verbal. They might be real-time or turn based, or based on simultaneous actions. They can be competitive or co-operative, or shift from one to the other during a single game session. They might involve visual pattern recognition or force players to memorise game state without visual cues. They may involve touch, or smell. They might involve social deduction or betrayal. They can encompass all sensory faculties, in differing degrees. Almost all games have accessibility considerations that should be taken into account, but there is currently no comprehensive tool by which this can be done that encompasses the rich variety of tabletop gaming interaction metaphors. In this paper, the authors discuss the heuristic lens that is used by the Meeple Centred Design tabletop accessibility project. This is a tool that has been applied to one hundred and sixteen games to date, and the full results of these have been published for analysis and consideration within the wider tabletop gaming community.

Dexter Dias William Heinemann, 2017 , HB, 848 pp, £25.00, 978-1785150166 Dias has looked at the ‘ten types of human’ in his quest to understand the human mind. He believes it must have evolved in the same way the human body evolved and adapted, and in this first part he deals with what he calls the …

Ubiquity Press is an open access publisher of peer-reviewed academic journals, books and data. We operate a highly cost-efficient model that makes quality open access publishing affordable for everyone. Ubiquity has joined forces with De Gruyter. Read the announcement.

Pyrochlore minerals are common accessory phases in the syenite and nepheline syenite rocks of the Motzfeldt alkaline center, Gardar Province, South Greenland, and are of important economic interest due to their exceptional ability to host various high field strength elements. In this study pyrochlore from two distinct intrusive units within the Motzfeldt Center have been studied. The largely homogeneous syenite and nepheline syenite rocks of the Flinks Dal formation host oscillatory and sector-zoned pyrochlore, which have experienced minor alteration in the presence of high-temperature, dominantly juvenile magmatic fluids. Alteration is characterized by variable decrease in the Na, Ca, and F contents and addition of Sr and K, accompanied by introduction of A and Y site vacancies. Pyrochlore from the more heterogeneous and intensely altered syenite rocks of the Motzfeldt So Formation are pervasively altered through interaction with lower temperature evolved hydrothermal fluids. During this phase of alteration cations are preferentially leached from the A and Y sites, accompanied by progressively increasing hydration. In both formations the proportion of B -site cations remains unaltered regardless of the degree of alteration. The alteration encoded in the pyrochlores of the Motzfeldt Center records the different hydrothermal conditions the two formations experienced during the subsolidus, showing how evolution of fluids within one intrusive unit can vary both spatially and temporally.

The objectives of the study were to describe the experience of patients immediately prior to a diagnosis of Hughes syndrome (HS) or antiphospholipid syndrome and post-diagnosis. A questionnaire survey was carried out set in the Hughes Syndrome Foundation, St. Thomas' Hospital, London, 2006. Participants were all patients who are members of the Hughes Syndrome Foundation. The main outcome measures were responses to a questionnaire relating to the experiences of people with a diagnosis of HS, such as number of hospitalisations, number of consultants seen, number of miscarriages, etc. A total of 157 patients completed the questionnaire, giving a response rate of 60.4%. Most (85%) were women and mean age was 46 years (SD 12). The median time to diagnosis was 3 years. The median number of consultants seen was 2 (max 19) with a median time in hospital pre-diagnosis of 10 days. The most common initial diagnoses were migraines, multiple sclerosis and systemic lupus erythematosus. Among women, 46% had had a miscarriage. Two thirds of respondents thought a blood test would have led to an earlier diagnosis. Comments from patients indicated a lack of awareness among specialists and general practitioners. The survey demonstrated a long time lag for diagnosis of Hughes syndrome, with increased costs to the NHS and emotional and financial cost to the patient. Greater awareness of this condition would benefit patients and the NHS.