Publications

The health burden of asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics. Currently available inhaled bronchodilators and anti-inflammatory drugs are effective in most asthmatics, but this palliative therapy requires long-term daily administration. Despite considerable efforts by the pharmaceutical industry, it has been difficult to develop novel therapeutic agents; the leukotriene antagonists and synthesis inhibitors being the only new class of asthma treatments to have been licensed in the last 30 years. It is clearly important to understand more about the underlying mechanisms of asthma and about how current drugs work before rational improvements in therapy can be expected. There are numerous therapies in clinical development that combat the inflammation found in asthma, specifically targeting eosinophils, IgE, adhesion molecules, cytokines and chemokines, inflammatory mediators and cell signalling. In particular, there is the obvious need for new therapy for severe asthma that is poorly controlled by high doses of corticosteroids, as well as agents to counter acute emergency asthma. A long-term goal is to develop disease-modifying immunotherapy, that could be introduced in childhood to alter the natural history of asthma. Thanks to the extensive efforts of the pharmaceutical industry, in the near future we can expect the introduction of a range of novel therapies for asthma.

In the quantitative assessment of coronary arterial dimensions from coronary cineangiograms, the contrast catheter is usually used as a scaling device, requiring the definition of the catheter contours by semi‐ or fully automated contour detection procedures. The image quality of the x‐ray radiated catheter is dependent on the catheter material, concentration of the contrast agent in the catheter, and kilovoltage of the x‐ray source. The effects of these variables on the image quality and accuracy of the size‐measurement of the filmed catheters were studied for four different catheter materials: woven dacron (wd), polyvinylchloride (pv), polyurethane (pu), and nylon. The following parameters were studied: measured size, image contrast, and average brightness gradient along the edges of the displayed catheters. The average differences of the angiographically measured size with the true size for the wd, pv, pu, and nylon catheters were +0.2, ‐ 3.2, ‐ 3.5, and + 9.8%, respectively. The image contrast at various fillings of the catheters was roughly identical for the wd, pv, and pu catheters, and significantly lower for the nylon catheter. Image gradient was highest for the wd catheter, followed by the pv and pu catheters, and lowest for the nylon catheter. From these data it may be concluded that the woven dacron catheter is most suitable for quantitative coronary angiographic studies. The polyvinylchloride and polyurethane catheters perform about equally well but slightly less than the woven dacron catheter. The nylon catheter should not be used for such quantitative studies.

Air pollution and cigarette smoke are recognized health risks. A method was developed for the measurement of the deposition fraction (DF) of polydisperse particulate matter (PM) in human airways. Ten normal volunteers [three females, age range 18–67 years, mean age (SD) 43.9 (14)] made single breath exhalations after inhalation to total lung capacity. The exhaled breath was diverted to a multichannel laser diffraction chamber where the particulate profiler measured 0.3–1.0-µm particles. DF was inversely related to expiration flow-rate, 0.69 (0.02) at 4 l min−1 and 0.5 (0.01) at 13 l min−1, respectively (p<0.05), and was influenced by the inhalation flow-rate [0.70 (0.02) at 3 l min−1 and 0.59 (0.02) at 13 l min−1, respectively (p<0.05)], while no differences were found between nasal and oral inhalation (0.68 (0.05) versus 0.67 (0.06), p>0.05). Higher breath holding times were associated with elevated DF [0.74 (0.02) at 20 s, and 0.62 (0.05) without breath holding (p<0.01)]. When the expiratory flow was controlled and the breath hold time standardized, DF was reproducible (CV = 4.85%). PM can be measured in the exhaled breath and its DF can be quantified using a portable device. These methods may be useful in studies investigating the health effects of air pollution and tobacco smoke.

Wire arc additive manufacturing (WAAM), a metal 3D printing technique, is attracting increasing attention from the construction industry due to its high efficiency, cost-effectiveness and flexibility in build scales. Test data on the mechanical properties of WAAM stainless steel in fire conditions are however limited. To address this gap, an experimental study into the elevated temperature material properties of WAAM ER316LSi austenitic stainless steel has been conducted. A total of 30 tensile coupons, consisting of 20 as-built coupons and 10 machined coupons, were tested at both room temperature and elevated temperatures. Steady-state tensile testing of the WAAM coupons was conducted in the elevated temperature range of 100 °C to 900 °C with intervals of 100 °C. 3D laser scanning was applied to obtain the geometric properties of the as-built coupons. The elevated temperature mechanical properties and the corresponding reduction factors were derived from the tensile test results. Finally, the elevated temperature material model in EN 1993-1-2, originally developed for conventionally produced stainless steel, was shown to be also applicable to WAAM stainless steel. • Elevated and room temperature tensile tests on 30 WAAM stainless steel coupons. • Use of 3D laser scanning for determining the specimen geometries. • Effect of surface undulations inherent to WAAM on examined material properties. • Development of reduction factors for key mechanical properties. • Proposal of elevated temperature constitutive model for WAAM stainless steel.

Objectives The goal of this study was to investigate sex-based differences in long-term clinical and angiographic outcomes after coronary revascularization with drug-eluting stents (DES). Background The impact of sex on clinical and angiographic outcomes following revascularization with DES is not well established. Methods Individual patient data from 3 all-comers randomized DES trials (SIRTAX, LEADERS, RESOLUTE All-Comers) were pooled. Of 5,011 patients, 4,885 (97.5%) completed 2-year follow-up (1,164 women, 3,721 men). Protocol-mandated angiographic follow-up was available for 1,561 lesions (351 among women, 1,210 among men). The primary endpoint was the composite of cardiac death and myocardial infarction (MI) at 2 years. Results At baseline, women, as compared with men, were older, more frequently had diabetes, obesity, and hypertension, less frequently had smoking habits, previous MI, and previous surgical revascularization, and had a smaller reference diameter of the target vessel as well as a lower SYNTAX score. After adjustment for baseline differences, women and men had a similar risk of cardiac death or MI (odds ratio [OR]: 1.13, 95% confidence interval [CI]: 0.82 to 1.56, p = 0.44), cardiac death (OR: 1.04, 95% CI: 0.61 to 1.80, p = 0.87), and MI (OR: 1.07, 95% CI: 0.75 to 1.53, p = 0.71) at 2 years. Similarly, risks of target lesion revascularization (OR: 1.09, 95% CI: 0.77 to 1.54, p = 0.62), target vessel revascularization (OR: 0.88, 95% CI: 0.63 to 1.22, p = 0.43), and definite or probable stent thrombosis (OR: 0.73, 95% CI: 0.38 to 1.38, p = 0.33) were comparable for women and men. Follow-up angiography showed no differences in terms of in-stent late loss (0.18 ± 0.54 mm vs. 0.20 ± 0.99 mm, p = 0.76) and in-segment binary restenosis (8.5% vs. 8.5%, p = 0.76). Conclusions The unrestricted use of DES is associated with similar long-term safety and efficacy among women and men with coronary artery disease. (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization [SIRTAX]; NCT00297661, LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS]; NCT00389220, RESOLUTE-III All-comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE All-Comers]; NCT00617084)

Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow.OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross-sectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination.CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

"The collapse performance of steel frames generally depends on their ability to resist local damage, however, this ability depends on the behaviour of beam-to-column connections that have not yet to be identified in a methodical and reliable manner. Thus, it is critical to develop a simplified joint model, which could predict the structural collapse resistance to prevent progressive collapse. In this study, component models with different stiffness connections, namely the double web angle (DWA) connection, top-seat with double web angle connection (TSDWA) and welded flange-bolted web connection (WUF) were constructed based on the component method by simplifying its geometry and dividing into a number of basic springs. The proposed component-based connections models with detailed components were implemented within the finite element programme ANSYS, and the models were validated against previously experimental tests. The analysis results show that the component models can accurately reflect the load response and post-fracture path of the substructures with a cost-effective solution, which indicated that the component method has great theoretical significance and applicable value in progressive collapse analysis, and provided a simple and effective tool for the engineers to calculate the progressive collapse resistance."

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