Human Cysteine Cathepsins Are Not Reliable Markers of Infection by Pseudomonas aeruginosa in Cystic Fibrosis

Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+) and P. aeruginosa-negative (6 Ps−) samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (∼2-fold) in the Ps+ and Ps− groups (p<0.001), which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens). Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps− samples, despite the possible release of the ∼31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection

Towards good practice guidelines for the contour method of residual stress measurement

Accurate measurement of residual stress in metallic components using the contour method relies on the achievement of a good quality cut, on the appropriate measurement of the deformed cut surface and on the robust analysis of the measured data. There is currently no published standard or code of practice for the contour method. As a first step towards such a standard, this study draws on research investigations addressing the three main steps in the method: how best to cut the specimens; how to measure the deformation contour of the cut surface; and how to analyse the data. Good practice guidance is provided throughout the text accompanied by more detailed observations and advice tabulated in Appendi

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Family buying behavior: A communication perspective

This dissertation is a deep qualitative examination of intrafamily action during episodes of vacation planning and purchase. It serves as a metatheoretical counterpoint to the positivistic paradigm which dominates the literature. Employing the theory, Co-ordinated Management of Meaning, as theoretical framework, it seeks to reveal the social-constructed reality of intra-family meaning and action. Three cases are reported. Though demographically similar, these families co-construct accounts of vacation planning process and action which are widely divergent. The results indicate that vacation-planning and purchase is a contextually varied phenomenon which is analytically accessible through a rules perspective. Coherent intra-family meaning and action is identified by reference to context markers such as cultural pattern, family narrative, autobiography, biography, relationship, episode and age. Many different constitutive and regulative rules are reported. New light is cast on the varied local meanings of influence, vacation and consensus. Regulative rules are found to be a useful analytic device for examining intrafamily process. Families co-constructed dissimilar accounts of how they dealt with conflict in vacation purchase planning. These accounts rotate around systemic constructions of consensus, compromise and control. The findings call into question the universality of the knowledge claims of the dominant paradigm, whose concepts, constructs and claims do not capture the contextually varied processes expressed in intra-family action

Hosted CRM: literature review and research questions

"January 2006"--Cover.Cover title.Includes bibliographical references: leaf 19-20.Also available online at http://www.mgsm.edu.auiii, 20 leave

Sales force automation: what do we know?

Cover title."September 2005".Also available in an electronic version at MGSM home page: http://www.mgsm.edu.au[28] leave

ROI on CRM: a customer-journey approach

20 page(s

Modelling business-to-business relationship quality

"January 2003".Cover title.Bibliography: p. 15-18.Also available online at MGSM website: http://www.mgsm.edu.au18