Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (β2-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analysers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.
Nitric oxide can be detected in the exhaled air of animals and normal human subjects, is increased in patients with asthma and bronchiectasis, and may be modulated by inhaled corticosteroids. Nitric oxide may provide a noninvasive means of monitoring inflammation in the respiratory tract and the measurement of exhaled nitric oxide has attracted increasing interest. However, interpretation of exhaled nitric oxide measurements may be difficult and there is a wide variation in the reported levels of nitric oxide in exhaled air, suggesting that technical factors are important.
An analytical model that describes a thin-walled I-section column under pure compression based on variational principles is presented. The Rayleigh–Ritz method is combined with continuous displacement functions to formulate the total potential energy that is minimized. A system of differential and integral equilibrium equations is formulated for the structural component for which numerical continuation reveals progressive cellular buckling (or snaking) arising from the nonlinear interaction between the weakly stable overall mode and the strongly stable local buckling mode. The resulting behaviour is highly unstable and is postulated to be highly sensitive to initial geometric imperfections.
Objectives This study examined the clinical outcomes at 5 years in RAVEL (A Randomized Comparison of a Sirolimus-Eluting Stent With a Standard Stent for Coronary Revascularization), the first controlled trial of drug-eluting stents. Background The 6-month rate of angiographic coronary restenosis has been markedly lowered by sirolimus-eluting stents (SES). The long-term performance of drug-eluting stents, however, is under close scrutiny. Methods The trial included 238 patients (mean age 60.7 ± 10.4 years, 76% men) with a single, de novo native coronary artery lesion, randomly assigned to treatment with SES versus bare-metal stents (BMS). Rates of major adverse cardiac events (MACE), defined as all-cause mortality, myocardial infarction, and percutaneous or surgical revascularization up to 5 years of follow-up, and rates of stent thrombosis were compared between the 2 treatment groups. Results Complete datasets were available in 92.5% of patients treated with SES and 89.1% of patients assigned to BMS. The 1-, 3-, and 5-year rates of survival free from target lesion revascularization (TLR) were, respectively, 99.2%, 93.8%, and 89.7% in the SES group versus 75.9%, 75.0%, and 74.0% in the control group (p < 0.001; log-rank). Rates of all MACE at 5 years were 25.8% in patients treated with SES versus 35.2% in patients assigned to BMS (p = 0.03; log-rank). Rates of stent thrombosis, per protocol or by the Academic Research Consortium definitions, were similar in both groups. Conclusions The 5-year rate of TLR associated with SES was significantly lower than that with BMS. There was no apparent adverse effect associated with the use of SES, although the trial was not powered to examine uncommon complications.
The mechanical behaviour and design of fixed-ended unequal-leg angle section steel members subjected to axial compression are studied herein. The mechanical response of unequal-leg angle section columns is first described, with a particular emphasis on the relationship between torsional and local buckling, alongside the important transition from equal-leg to unequal-leg angle behaviour. Existing experimental data on unequal-leg angle section steel columns are then employed to validate numerical models developed within the commercial finite element package ABAQUS. A comprehensive parametric study is subsequently conducted that encompasses a broad spectrum of geometric configurations and global slenderness values. The mechanical behaviour and ultimate resistance of fixed-ended unequal-leg angle section columns are shown to be dependent on not only the global slenderness, but also on the ratio of the elastic torsional-flexural to minor-axis flexural buckling loads. The existing experimental data alongside the numerical parametric study results are employed to evaluate the resistance predictions given by the current Eurocode 3 design provisions, revealing an excessive level of conservatism. Finally, a new design approach for fixed-ended unequal-leg angle section steel columns, suitable for incorporation into future revisions of Eurocode 3, is proposed that significantly improves the accuracy and consistency of the resistance predictions. A reliability analysis of the proposed design approach is conducted in accordance with the procedure within EN 1990, resulting in a recommended partial safety factor γ M1 = 1 . 0 . • Description of critical and post-buckling behaviour of unequal-leg angle section steel columns. • Developed finite element models validated against existing experimental results and employed for a comprehensive parametric study. • High level of conservatism observed in the ultimate resistance predictions following current Eurocode design provisions. • Development of new design approach using generated numerical and collected experimental results. • Assessment and verification of reliability of the new design approach with EN 1990 procedure.
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