6,963 publications from this institution
Abstract Wire arc additive manufacturing (WAAM) is a method of metal additive manufacturing (AM) that can be used to fabricate optimised large‐scale structural elements of complex form in a cost‐effective manner, opening up opportunities to unleash the true potential of structural optimisation. To demonstrate this potential, two optimised steel cantilever trusses were fabricated by means of WAAM and tested to investigate their structural performance. The tested specimens comprised members of tubular cross‐section of varying diameter and thickness. The geometric features of the tested specimens were determined using 3D laser scanning, while digital image correlation was employed to monitor the displacement and strain fields during testing. Full details of the experimental programme are provided; the obtained results are analysed and comparisons against equivalent conventional reference designs are made. The results of complementary numerical simulations, undertaken to gain further insight into particular features of the structural response of the examined specimens, are also presented. The structural efficiency of all optimised trusses, as measured by the capacity‐to‐mass ratio, was found to be at least 80% higher than that of the corresponding reference designs, underlining the benefits in terms of structural efficiency that can be achieved by the combination of WAAM with advanced optimisation methods.
In 2003–2004, drug-eluting stents (DES) were approved by regulatory bodies in the European Union and United States. Pivotal studies in the preceding year had demonstrated a major treatment effect (60% to 80%) on angiographic restenosis irrespective of the type of lesion or clinical syndrome. Interventional cardiologists worldwide swiftly embraced this new modality of treatment, with market penetration of 30% to 90%. This disruptive technology—without evidence base— has already had a major impact on our approach to coronary revascularization. Patients traditionally referred for surgery are now revascularized percutaneously. But in 2008–2009, results of major trials comparing percutaneous coronary intervention with coronary artery bypass grafting (SYNTAX, FREEDOM, COMBAT, CARDIA) in patients with 3VD and/or LMS may confirm the value of DES in “surgical” patients, and the beginning of the end of a surgical era might be on the horizon. On the other hand, worrisome information about late stent thrombosis is currently emerging. The drugs used are potent cytostatic or cytotoxic agents with long-term detrimental effects on endothelialization. Large investigator-driven registries with long follow-up suggest an unabated rate of late stent thrombosis even after 3 years. New pharmacological strategies (nonpolymeric reservoir, dual-drug elution, use of antithrombotic and antiinflammatory agents) and new absorbable metallic or nonmetallic platforms are currently being tested. The primary goal is no longer “oncologic” inhibition of neointimal hyperplasia but the restitution of a healthy and functionally active endothelial lining (eg, by capturing progenitor endothelial cells), capable—in conjunction with prohealing drugs (eg, NO donors)—of modulating the healing process without the use of permanent metallic stents. From this viewpoint, we are just at the end of the pioneering phase of the first generation of DES…and the end of the beginning.
Figures; MATLAB input files and numerical results from analytical models generated in MATLAB in conjunction with the numerical continuation toolbox MATCONT; finite element input files for ABAQUS and corresponding results. Paper accepted by Proceedings of the Royal Society A.
The current coronary bioresorbable scaffolds (BRSs) are composed of either an aliphatic polymer or bioresorbable metal alloy. Numerous different polymers are available, each with different chemical compositions, mechanical properties, and subsequent bioresorption times. The purpose of this chapter is to facilitate the understanding of mechanical features of the materials used for bioresorbable scaffolds.
Journal Article Molecular Biology of Receptors Get access PJ BARNES PJ BARNES Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton HospitalLondon SW3 6LY Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 83, Issue 2, May 1992, Pages 339–353, https://doi.org/10.1093/oxfordjournals.qjmed.a068673 Published: 01 May 1992 Article history Accepted: 07 March 1992 Published: 01 May 1992
To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.
Chronic obstructive pulmonary disease (COPD) is associated with glucocorticosteroid insensitive inflammation. Neutrophils from COPD patients migrate more in response to CXCL1 than cells from control subjects. Roflumilast, a PDE4 inhibitor recently approved for COPD in the EU, reduces neutrophil numbers in sputum from COPD patients. The mechanism of this anti-inflammatory effect is not clear, but may be due to inhibition of neutrophil migration. Thus this study investigated the effects of roflumilast N-oxide (RNO), the active metabolite of roflumilast, on neutrophil migration in comparison with another PDE4 inhibitor, rolipram. Neutrophils were isolated from whole blood samples from healthy subjects and COPD patients. Chemotaxis was measured using 48-well Boyden chambers and [Ca 2+ ] i by fluorimetry. Both RNO and rolipram completely inhibited migration of neutrophils from healthy subjects towards CXCL1 (3nM) with EC 50 values of 0.18±0.13 nM and 2.8±0.51 nM, n=4, respectively. A similar response was seen with neutrophils obtained from patients with COPD (EC 50 RNO: 0.74±0.89 nM; rolipram 42±45.9 nM, n=3). Having established that cell migration was attenuated by PDE4 inhibitors, the effects of these compounds on CXCL1 stimulated [Ca 2+ ] i was investigated. RNO (1μM) inhibited the peak of [Ca 2+ ] i and area under the curve (AUC) by 83.0±2.6% and 90.3±2.1%, n=6. Rolipram (1μM) also inhibited these responses by 80.7±3.2% and 86.3±2.1%, n=6. These data indicate that oral PDE4 inhibitors may have added anti-inflammatory effects by reducing CXCL1 stimulated neutrophil migration into the lung via regulation of [Ca 2+ ] i and this could contribute to the anti-inflammatory effects of roflumilast in the treatment of COPD.
