Cold-formed steel members are frequently used in conjunction with wood-based panels for the construction of lightweight and economical structural systems, designed with the steel members considered as the sole load bearing components. However, recent research has shown that composite action can be mobilised within these systems, leading to substantial improvements in terms of performance, both at serviceability and ultimate limit states, with all the components of the system being exploited to the greatest possible extent. Under the assumption of a composite scenario, amelioration of the characteristics of the shear interface could lead to further performance benefits. Hence, the aim of the research presented herein is the establishment of a bespoke connection for this type of system, capable of reducing the slip between the components. A series of push-out tests were conducted to assess the performance of innovative connectors, specifically designed for the examined systems. Substantial increases in the shear modulus of the connection have been achieved compared to the one corresponding to the fastening arrangement currently used in practice, leading to up to 30% increase of the flexural stiffness of the system.
Plasma noradrenaline, adrenaline, and cyclic 3959 AMP (cAMP) were measured in seven asthmatic patients with known exercise-induced bronchospasm and six matched non-atopic control subjects during a standard treadmill exercise test and then during matched isocapnic hyperventilation. Normal subjects showed a 5.5 fold rise in noradrenaline and a 3.2 fold rise in adrenaline during exercise compared with a 2.1 fold rise in noradrenaline and no significant rise in adrenaline in asthmatics who all developed bronchoconstriction after exercise (mean fall in peak flow rate 28.4 +/- 5.8%). Plasma cAMP rose 1.4 fold in controls but showed no significant rise in asthmatics. This reduced sympatho-adrenal response to exercise in asthmatics is difficult to explain. The failure of circulating catecholamines to rise and stimulate beta adrenoceptors on the mast cell may facilitate the release of bronchoconstrictor mediators. Matched hyperventilation produced bronchospasm in asthmatics (mean fall in peak flow rate 29.0 +/- 4.4%) but no change in catecholamines in either group suggesting that circulating catecholamines have no direct role in exercise-induced bronchospasm but may play a permissive role via the mast cell.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
1. Venous plasma histamine was measured by a specific and sensitive radioenzymatic assay in seven male extrinsic asthmatic and six age-matched non-atopic non-asthmatic male subjects during exercise and voluntary isocapnic hyperventilation. 2. There was no change in peak expiratory flow in normal subjects with exercise or hyperventilation, but asthmatic subjects showed a 29.4 +/- SEM 5.8% fall after exercise and a 29.0 +/- 5.4% fall after matched hyperventilation. 3. Plasma histamine was significantly higher (P less than 0.05) in asthmatic (6.2 +/- 0.95 nmol/l) than that in normal subjects (3.4 +/- 0.61 mol/l) and showed a significant (P less than 0.01) rise (to 14.4 +/- 1.83 nmol/l) during exercise in asthmatic, but not in normal subjects. This suggests that discharge of mast-cell mediators may occur during exercise in asthmatic subjects who develop exercise-induced asthma. 4. With hyperventilation there was no change in plasma histamine in either asthmatic or normal subjects, but this does not exclude the possibility that mediators may be released locally in the airways.
Background/Introduction Optimal dual antiplatelet therapy (DAPT) in patients with complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) has not been fully investigated. Purpose To evaluate the efficacy and safety of 1-month DAPT followed by 23-month ticagrelor monotherapy in patients who underwent complex PCI. Methods The Global Leaders trial recruited 15,991 patients treated by default with a biolimus A9-eluting stent, and randomised in a 1:1 ratio either to the experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) or to the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy). Complex PCI includes at least one of the following characteristics; left main and/or multivessel PCI, long stenting (defined as total stent length≥46mm), and bifurcation treatment with two stents. The present sub-analysis of the trial evaluated at two years the primary endpoint (composite of all-cause death and new Q-wave myocardial infarction [MI] centrally adjudicated with the Minnesota code). In addition, the patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, and any revascularization) and the net adverse clinical events (NACE) (composite of POCE and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) were also evaluated at two years. Results Of 15,450 patients included in the present analysis, 5,188 (26.7%) patients underwent complex PCI. The experimental strategy, when compared with the reference one, had a significantly lower risk of the primary endpoint (3.56% vs. 5.33%, HR: 0.66; 95% CI: 0.51–0.86; p-value= 0.002; p-value for interaction= 0.019) in patients with complex PCI. Similarly, the experimental treatment was associated with a significantly reduced risk of POCE (14.41% vs. 16.88%, HR: 0.84; 95% CI: 0.74–0.97; p=0.016, p-value for interaction= 0.099) and NACE (15.77% vs. 18.37%, HR: 0.85; 95% CI: 0.74–0.97; p=0.014; p-value for interaction= 0.096). The reduction in ischemic events was predominantly observed in patients with 2 or more characteristics of complex PCI (Figure). In contrast, there was no significant difference in the risk of BARC type 3 or 5 bleeding between the two regimens (2.40% vs. 2.38%, HR: 1.01; 95% CI: 0.71–1.44; p-value=0.956; p-value for interaction= 0.935). Central illustration Conclusion Together with other well-established clinical risk factors, the extent and complexity of stenting should be taken into account in tailoring antiplatelet regimens for secondary prevention. The 1-month DAPT followed by 23-month ticagrelor monotherapy reduced the ischemic events without increasing the risk of bleeding in patients who underwent complex PCI, when compared with the conventional DAPT. Acknowledgement/Funding The Global Leaders trial was supported by the resource from AstraZeneca, Biosensors, and The Medicines Company.
Calcium has a central role coupling stimulus to cellular activities such as secretion and contraction. Because calcium is critical for airway smooth muscle contraction, degranulation of mast cells and secretion of mucus, there has been great interest and hope in the use of calcium channel blockers in the treatment of asthma. We here discuss the effects of calcium channel blockers and also review clinical studies of these drugs in asthma, focusing on recent findings. There have been several recent reviews on this topic (1,2) and it is now possible to evaluate the role of these drugs in the management of asthma.
