Publications

Residual stress is one of the most important initial imperfections for the buckling behavior of steel compression members. An experimental investigation was carried out to quantify the longitudinal residual stress in welded T-section of domestic Q460 high strength steel. The residual stress of 8 specimens with various dimensions was measured by using the splitting method. Based on the experimental data, the magnitude and distribution of both compressive and tensile residual stresses in the entire section were obtained. It was found that the magnitude of tensile residual stresses near the weld was hardly correlated with the sectional dimension, but the magnitude of compressive residual stress in the flange was inversely proportional to the plate thickness and the width-thickness ratio. Moreover, there was no interaction between the flange and web since the total residual stress was close to zero within each plate. According to those conclusions, the distribution model was proposed and compared well with the experimental results. The new model can be used to describe the residual stress in Q460 HSS welded T-section accurately and reliably.

Exposure to biomass fuel smoke is as an important risk factor for COPD (BS-COPD), but it is not known whether this phenotype is different from tobacco-smoke induced COPD (TS-COPD) with reference to lung physiological changes. Aim: To compare lung function profiles between subjects with BS-COPD and TS-COPD. Methods: 17 BS-COPD (mean 43 yrs exposure) and 35 TS-COPD (mean 43 smoking pack yrs) subjects underwent pre and post bronchodilator spirometry to measure FEV1, FVC and FEF25-75%, bodyplethysmography to measure residual volume (RV) and total lung capacity (TLC), impulse oscillometry (IOS) to measure R5Hz and R20Hz and single-breath DLCO to measure lung diffusion. Two sample “t” test was used to compare mean (±SD) lung function parameters between the two groups. Results: There were no significant differences in% predicted values for FEV1, FVC, R20Hz, RV and TLC between TS-COPD and BS-COPD (all p values >0.05). However, BS-COPD showed a trend towards greater small airway obstruction indicated by lower FEF25-75% predicted values [BS: 9% (±3%) vs TS: 12% (±5%), p= 0.02], higher R5Hz% predicted values [BS: 272% (±65%) vs TS: 222% (±94%), p= 0.05] and higher R5-20Hz values normalised to total airway resistance [BS: 0.53 (±0.07) vs TS: 0.46 (±0.13) p=0.05], while TS-COPD showed lower% predicted values for DLCO [TS: 53% (±24%) vs BS: 71% (±33%); p=0.03]. Conclusion: BS-COPD shows similar decrements in Spirometric, IOS and body plethysmographic parameters as TS-COPD. However, BS-COPD was associated with greater small airways obstruction, while TS-COPD was associated with lower DLCO values.

The aim of the present study was to examine the effects of chronic infusion of the long‐acting agonist salmeterol on pulmonary β 2 ‐adrenoceptor function in Sprague‐Dawley rats in vivo and to elucidate the molecular basis of any altered state. Systemic administration of rats with salmeterol for 7 days compromised the ability of salmeterol and prostaglandin E 2 (PGE 2 ), given acutely by the intravenous route, to protect against ACh‐induced bronchoconstriction when compared to rats treated identically with vehicle. β 1 ‐ and β 2 ‐adrenoceptor density was significantly reduced in lung membranes harvested from salmeterol‐treated animals, which was associated with impaired salmeterol‐ and PGE 2 ‐induced cyclic AMP accumulation ex vivo . Three variants of G sα that migrated as 42, 44 and 52 kDa peptides on SDS polyacrylamide gels were detected in lung membranes prepared from both groups of rats but the intensity of each isoform was markedly reduced in rats that received salmeterol. The activity of cytosolic, but not membrane‐associated, G‐protein receptor‐coupled kinase was elevated in the lung of salmeterol‐treated rats when compared to vehicle‐treated animals. The ability of salmeterol, administered systemically, to protect the airways of untreated rats against ACh‐induced bronchoconstriction was short‐acting (t off ∼45 min), which contrasts with its long‐acting nature when given to asthmatic subjects by inhalation. These results indicate that chronic treatment of rats with salmeterol results in heterologous desensitization of pulmonary G s ‐coupled receptors. In light of previous data obtained in rats treated chronically with salbutamol, we propose that a primary mechanism responsible for this effect is a reduction in membrane‐associated G sα . The short‐acting nature of salmeterol, when administered systemically, and the reduction in β‐adrenoceptor number may be due to metabolism to a biologically‐active, short‐acting and non‐selective β‐adrenoceptor agonist. British Journal of Pharmacology (2001) 132 , 1261–1270; doi: 10.1038/sj.bjp.0703946

Abstract Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. (Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca; ClinicalTrials.gov number, NCT04416399 ) Research in context Evidence before this study The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed. Added value of this study In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care. Implications of all the available evidence The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.

No abstract is provided for this article.

Abstract Rationale Chronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging, demonstrated by the accumulation of senescent cells in lung tissue. MicroRNA (miR)-34a is induces senescence by suppressing the key anti-aging molecule, sirtuin-1 (SIRT1). Senescent cells spread senescence to neighboring and distant cells, which favors the progression of COPD and its comorbidities. The mechanisms for spreading senescence remain undetermined but may be mediated by the transfer of microRNAs in extracellular vesicles. Objectives To analyze the miRNA content of extracellular vesicles in COPD and explore their effect on cellular senescence of healthy cells Methods EVs were isolated from small airway epithelial cells (SAEC) from healthy donors or COPD patients. Recipient healthy SAEC were cultured with EVs and the expression of miR-34a and markers of cellular senescence, p21 CIP1 and SIRT1, were measured. Main Results EVs from COPD cells induce senescence in healthy recipient cells via the selective transfer of miR-34a. We showed that COPD SAEC produce increased numbers of EVs enriched with miR-34a. EVs are taken up by healthy cells, resulting in reduced expression of the anti-aging molecule sirtuin-1 and increased expression of markers of senescence, such as p21 CIP1 and positive staining for senescence-associated β-galactosidase Conclusions Our findings provide evidence of the mechanism by which EVs spread cellular senescence in human primary cells via miR-34a, rather than via soluble mediators. EVs enriched with miR-34a may spread senescence locally, accounting for disease progression, but also provide a mechanism for distant spread to account for comorbidities and multimorbidity of the elderly.

The aim of this study was to evaluate the relationship between body mass index (BMI) and outcomes in patients with coronary artery disease undergoing percutaneous revascularisation.In 13 randomised trials, 22,922 patients were stratified (in kg/m2) as underweight (BMI <18.5), normal weight (18.5 ≤BMI <25, used as reference), overweight (25 ≤BMI <30), and obese (Class I [30 ≤BMI <35], Class II [35 ≤BMI <40], or Class III [BMI ≥40]). The primary endpoint was all-cause death at five years. Secondary endpoints were cardiac and non-cardiac death, target (TLR) and non-target lesion revascularisation (NTLR), myocardial infarction (MI), and definite/probable stent thrombosis. Despite adjustment for multiple confounders, overweight and Class I obesity were associated with lower all-cause mortality versus normal weight (HR 0.83, 95% CI: 0.71-0.96, and HR 0.83, 95% CI: 0.69-0.96, respectively); however, non-cardiac death was the major contributor to this effect (HR 0.77, 95% CI: 0.63-0.94 for overweight). Conversely, cardiac mortality was higher in severely obese individuals (HR 1.62, 95% CI: 1.05-2.51 for Class III obesity). Obesity was associated with higher rates of NTLR (HR 1.28, 95% CI: 1.04-1.58 for Class II obesity) but not with TLR, MI and stent thrombosis.Moderately increased BMI is associated with improved survival post PCI, mostly due to lower non-cardiac but not cardiac mortality.

No abstract is provided for this article.

No abstract is provided for this article.

Abstract The primary aim of the present study is to explore the use, advantages and potential of two advanced data acquisition techniques – 3D scanning and digital image correlation (DIC), in the testing of metallic structures. 3D scanning is a novel method for capturing the full outer geometry of an object. It is being increasingly used in experimental studies for the determination of dimensional parameters and the characterisation of local and global imperfections, examples of which are given and discussed. Digital image correlation (DIC) is a rapidly evolving technology for the full‐field measurement of the displacements and strains over a surface. A brief introduction to DIC and its workflow is firstly provided. Example applications of DIC in various scales of experiments, including material tests, structural element tests and full‐scale structural system tests, are subsequently discussed. These new‐generation data acquisition techniques enable structural researchers to gain a deeper insight into the behaviour of metallic structures in experimental research.