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Background The antibacterial, anti-inflammatory and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-moderate disease are lacking. We assessed whether azithromycin is effective in reducing hospitalisation in patients with mild-moderate COVID-19. Methods This open-label, randomised superiority clinical trial at 19 centres in the United Kingdom enrolled adults, ≥18 years, presenting to hospitals with clinically-diagnosed highly-probable or confirmed COVID-19 infection, with

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1–2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.

Background: Pleural infection (PI) is a common and complex disease which can be life threatening for immunocompromised and elderly populations. Prior antibiotic use and special bacterial nutritional requirements hamper the accuracy of bacterial identification using current clinical culture-based techniques. Consequently, PI microbiology remains unclear. Next generation sequencing (NGS) has the potential to improve identification of the total bacterial population of a complex sample. Aim: To discover and characterise the microbial patterns of PI using NGS and bioinformatics techniques. Methods: Pleural fluid samples from the “Pleural Infection Longitudinal Outcome Study” (PILOT, ISRCTN50236700, n=243) underwent bacterial DNA extraction followed by 16S rRNA NGS using Illumina MiSeq. Data were analysed with DADA2 and Phyloseq R packages. Results: Analysis showed diverse microbiological patterns for PI as 391 different pathogens were identified up to the genus level. 131 (54%) samples had one pathogen with relative abundance over 50% and 89 (36%) samples had at least three pathogens with relative abundance over 10%, suggesting a polymicrobial infection. Streptococcus pneumoniae was detected in 40 (16%) and Staphylococcus aureus in 20 (8%) samples. Discussion: We established a methodology to extract bacterial DNA from patients with PI and used it as a template to apply NGS. 16S rRNA gene NGS provides a robust method to investigate the bacteriological patterns in pleural fluid of patients with PI. Funding: National Institute for Health Research, Oxford Biomedical Research Centre

Background Haemophilus influenzae is emerging as the commonest pathogenic microorganism isolated from severe asthmatic airways; it is associated with sputum neutrophilia and may confer steroid resistance. Previous metagenomics studies in asthma were limited by lack of consistent clinical phenotyping and inadequate sequencing depth for species-level bacterial identification. We hypothesise that chronic bacterial infection constitutes a ‘treatable trait’ in non-eosinophilic severe asthma but its prevalence, clinical phenotype and reliable biomarkers need to be defined. Non-typeable Haemophilus influenzae strains (NTHi) can persist within the epithelium and cause episodic airways infections. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes which protect against pulmonary bacterial infection, and respond to NTHi in the presence of professional antigen presenting cells (APCs) via MR1, a molecule expressed ubiquitously in many cell types including epithelial cells. It is not known whether NTHi-infected epithelial cells directly activate MAIT cells. Aims (1) Identify and characterise the sub-phenotype of severe asthmatics with chronic bacterial airways infection using modern molecular microbiological techniques (2) Determine whether MAIT cells directly respond to intra-epithelial infection with NTHi Methods Analysis of induced sputum samples from stable well-phenotyped severe asthmatics using culture, MALDI-TOF, RT-qPCR and metagenomic sequencing of total DNA extracts using the MiSeq platform. In vitro co-culture of MAIT cells with NTHi-infected bronchial epithelial cell lines (BEAS2B) or primary human airway epithelial cells. MAIT cell activation measured using intracellular cytokine staining. Results In a cohort of patients with severe asthma (n=23) H. influenzae was commonly cultured and subsequently identified as the dominant bacterial species by metagenomic sequencing (n=8, Median% Total bacterial reads=87.8%). Clinically significant infection was confirmed using a validated H. influenzae plasmid-based RT-qPCR assay. H. influenzae culture positive patients had sputum neutrophilia and lower FeNO. NTHi induces modest MAIT cell production of IFN-gamma which is partly MR1 dependent. Conclusions H. influenzae is a clinically-relevant pathogen in severe asthma that can be identified reliably using molecular microbiological methods. Ongoing analysis of a larger patient cohort will allow full characterisation of this clinical phenotype. MAIT cells are able to recognise airway epithelial cells infected with viable intracellular NTHi in the absence of APCs.

Wireless communication is highly susceptible to security outbreaks with shear advancement in signal processing technology followed by immense deployment of high-speed mobile communication networks. Pitfalls in current architecture of IEEE 802.16 or Worldwide Interoperability for Microwave Access (WiMAX) have been put forth in recent literature, based on analytical reasoning and design methodologies. With identification of these vulnerabilities, some solutions have also been proposed for their rectification; however, the experimental assessment of these solutions has not been carried out in appropriate manners to justify the satisfaction of constraints. In this paper, we present a generic methodology to simulate and analyze the authentication protocols in WiMAX based on obtained results. We focus on the 1st and 2nd version of Privacy & Key Management (PKM) Protocols, which are implemented in the WiMAX architecture at present and compare their performance characteristics with another proposed solution ISNAP; which claims to eradicate most of the existing threats with introducing minimum overheads. The performance evaluation of these protocols has been carried out by simulating the behavior of BS and SS nodes in real-time wireless network using Linux based hosts. This work intends to establish the formal basis to justify the claims put forth in the specification of ISNAP against PKM v1 & v2.

Security is amongst one of the major issues in Broadband Wireless Access (BWA) Networks. After the launch of the IEEE 802.16 standard (WiMAX), a number of security issues were reported in several articles. Ever since the beginning, work has been in progress for the neutralization of these identified threats. In this paper, the analysis of the authentication protocols implemented in WiMAX has been presented along with the description of the threats posed to them. The paper also describes security sub-layer and limitations of the existing architecture. An approach has also been presented for the prevention of these threats like the avoidance of replay; suppress replay and man-in-the-middle attacks. The proposed approach enhances the network security and strengthens it by resynchronization of the Subscriber Station with the Base Station.