Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Background Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma

The Psy-Security-Curriculum ensemble: British Values curriculum policy in English schools

Framed as being in response to terrorist attacks and concerns about religious bias in some English schools, ‘British Values’ (BV) curriculum policy forms part of the British Government’s Counter-Terrorism and Security Act, 2015. This includes a Duty on teachers in England to actively promote British Values to deter students from radicalisation. This paper, first, traces the history of Britishness in the curriculum to reveal a prevalence of nationalistic, colonial values. Next, an ensemble of recent policies and speeches focusing on British Values is analysed, using a psycho-political approach informed by anti-colonial scholarship. Finally, we interrogate two key critiques of the British Values curriculum discourse: the universality of British Values globally, and concerns over the securitisation of education. Findings indicate that the constitution of white British supremacist subjectivities operate through curriculum as a defence mechanism against perceived threats to white privilege, by normalising a racialised state-controlled social order. The focus is on ‘British’ values, but the analytic framework and findings have wider global significance

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

BACKGROUND: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. METHODS: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). RESULTS: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. CONCLUSIONS: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation

The diagnostic strength of the 24-h pad test for self-reported symptoms of urinary incontinence in pregnancy and after childbirth

The clinical impact of incontinence in pregnancy and after childbirth is growing because some studies report the efficacy of physiotherapy in pregnancy and because obstetric choices are supposed to have significant impact on post-reproductive urinary function (Goldberg et al. in Am J Obstet Gynecol 188:1447–1450, 2003). Thus, the need for objective measurement of urinary incontinence in pregnancy is growing. Data on pad testing in pregnancy are lacking. We assessed the clinical relevance of the 24-h pad test during pregnancy and after childbirth, compared with data on self-reported symptoms of urinary incontinence and visual analogue score. According to the receiver operating characteristic curve, the diagnostic value of pad testing for measuring (severity of) self-reported incontinence during pregnancy is not of clinical relevance. However, for the purposes of research, pad tests, combined with subjective/qualitative considerations, play a critical role in allowing comparisons across studies, quantifying the amount of urine loss and establishing a measure of severity

Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence

<p>Abstract</p> <p>Background</p> <p>Flexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing.</p> <p>Methods</p> <p>The data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive.</p> <p>Results</p> <p>Dose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: <it>P </it>= 0.249; oxybutynin: <it>P </it>= 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (<it>P </it>< 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (<it>P </it>< 0.001). Adverse events were increased in the dose adjusted subgroups.</p> <p>Conclusions</p> <p>Flexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin.</p> <p>Trial registration (parent study)</p> <p>The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.</p

Precision Electroweak Tests of the Standard Model

The present status of precision electroweak data is reviewed. These data include measurements of e+e- -> f+fbar, taken at the Z resonance at LEP, which are used to determine the mass and width of the Z boson. In addition, measurements have also been made of the forward-backward asymmetries for leptons and heavy quarks, and also the final state polarisation of the tau-lepton. At SLAC, where the electron beam was polarised, measurements were made of the left-right polarised asymmetry, A_LR, and the left-right forward-backward asymmetries for b and c quarks. The mass, MW, and width, GW, of the W boson have been measured at the Tevatron and at LEP, and the mass of the top quark, Mt, has been measured at the Tevatron. These data, plus other electroweak data, are used in global electroweak fits in which various Standard Model parameters are determined. A comparison is made between the results of the direct measurements of MW and Mt with the indirect results coming from electroweak radiative corrections. Using all precision electroweak data fits are also made to determine limits on the mass of the Higgs boson. The influence on these limits of specific measurements, particularly those which are somewhat inconsistent with the Standard Model, is explored. The data are also analysed in terms of the quasi model-independent epsilon variables. Finally, the impact on the electroweak fits of the improvements in the determination of the W-boson and top-quark masses, expected from the Tevatron Run 2, is examined.Comment: 80 pages, 36 Figures, Late

Technological Revolution, Sustainability and Development in Africa: Overview, Emerging Issues and Challenges

The paper examines the silent technological revolution in sub‐Saharan Africa focusing on emerging issues and challenges. In view of the centrality of technology diffusion in fostering local innovations and economic development in developing countries, it is surprising that our understanding of the challenges and opportunities in scaling‐up technologies remains limited. This paper capitalises on the ongoing silent technological revolution in sub‐Saharan Africa to present an overview of how new technologies have been adopted and utilised to achieve sustainability. The study identified a host of factors such as weak regulatory enforcement systems, lack of financial credit availability, and limited banking services, which have created conditions for technological innovations such as mobile phone‐based banking, mPedigree, “cardiopad,” and M‐PEPEA to emerge. The public policy implications and directions for future research are identified and examined

Spelling dyslexia:a defict of the visual word form

A patient with spelling dyslexia read both words and text accurately but slowly and laboriously letter by letter. Her performance on a test of lexical decision was slow. She had great difficulty in detecting a 'rogue' letter attached to the beginning or end of a word--for example, ksong--or in parsing two unspaced words, such as applepeach. By contrast she was immune to the effects of interpolating extraneous coloured letters in a word, a manipulation that affects normal readers. Therefore it is argued that this patient had damage to an early stage in the reading process, to the visual word form itself