Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8-30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates.

Morbidity and mortality following cardiac valve surgery is high. Immunity is an important contributor to outcome. This study examines the relationship of staphylococcal and endotoxin antibody levels to outcome following cardiac surgery.

To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient's room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently wearing a mask (either surgical or particulate respirator type N95) while caring for a SARS patient was protective for the nurses, and consistent use of the N95 mask was more protective than not wearing a mask. Risk was reduced by consistent use of a surgical mask, but not significantly. Risk was lower with consistent use of a N95 mask than with consistent use of a surgical mask. We conclude that activities related to intubation increase SARS risk and use of a mask (particularly a N95 mask) is protective.

The constant exposure of the liver to food and bacterial antigens through the mesenteric circulation requires it to maintain tolerance while preserving the ability to mount an effective immune response against pathogens. We investigated the contribution of the liver's tolerogenic nature on the establishment of chronic viral infections.

Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive pVDC signature was constructed from 124 U.S. EPA ToxCast high-throughput screening (HTS) assays and used to rank 1060 chemicals for their potential to disrupt vascular development. Thirty-seven compounds were selected for targeted testing in transgenic Tg(kdrl:EGFP) and Tg(fli1:EGFP) zebrafish embryos to identify chemicals that impair developmental angiogenesis. We hypothesized that zebrafish angiogenesis toxicity data would correlate with human cell-based and cell-free in vitro HTS ToxCast data. Univariate statistical associations used to filter HTS data based on correlations with zebrafish angiogenic inhibition in vivo revealed 132 total significant associations, 33 of which were already captured in the pVDC signature, and 689 non-significant assay associations. Correlated assays were enriched in cytokine and extracellular matrix pathways. Taken together, the findings indicate the utility of zebrafish assays to evaluate an HTS-based predictive toxicity signature and also provide an experimental basis for expansion of the pVDC signature with novel HTS assays.

Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein (GP) antibodies suggest that Fc-dependent activation of effector cells, including natural killer (NK) cells, could play a role in vaccination against Ebola virus disease.

The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) was requested to evaluate the genotoxic potential of flavouring substances from subgroup 2.2 of FGE.19 in the Flavouring Group Evaluation 208 Revision 2 (FGE.208Rev2). In FGE.208Rev1, the CEF Panel evaluated genotoxicity studies on p-mentha-1,8-dien-7-al [FL-no: 05.117], the representative substance for FGE.19 subgroup 2.2. The Comet assay performed in liver showed a positive result, and therefore, the Panel concluded that p-mentha-1,8-dien-7-al [FL-no: 05.117] is genotoxic in vivo and that, accordingly, there is a safety concern for its use as flavouring substance. Since p-mentha-1,8-dien-7-al [FL-no: 05.117] is representative for the nine remaining substances of subgroup 2.2 (p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], myrtenal [FL-no: 05.106], 2,6,6-trimethyl-1-cyclohexen-1-carboxaldehyde [FL-no: 05.121], myrtenyl formate [FL-no: 09.272], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278], myrtenyl acetate [FL-no: 09.302], myrtenyl-2-methylbutyrate [FL-no: 09.899] and myrtenyl-3-methylbutyrate [FL-no: 09.900]), the Panel concluded in the previous revision of FGE.208 (FGE.208Rev1) that there is a potential safety concern for these substances. Subsequently, the industry has submitted genotoxicity studies on five substances of FGE.19 subgroup 2.2: p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], myrtenal [FL-no: 05.106], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278] and myrtenyl acetate [FL-no: 09.302], which are evaluated in the present revision of FGE.208 (FGE.208Rev2). The Panel concluded that the concern for genotoxicity could be ruled out for p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278] and myrtenyl acetate [FL-no: 09.302], which will be evaluated through the Procedure. Genotoxicity data on myrtenal [FL-no: 05.106] were considered equivocal, therefore, it cannot be evaluated through the Procedure, presently. p-Mentha-1,8-dien-7-al [FL-no: 05.117] and four substances not supported by industry (2,6,6-trimethyl-1-cyclohexen-1-carboxaldehyde [FL-no: 05.121], myrtenyl formate [FL-no: 09.272], myrtenyl-2-methylbutyrate [FL-no: 09.899] and myrtenyl-3-methylbutyrate [FL-no: 09.900]) have been deleted from the Union List.

The COVID-19 pandemic has necessitated many novel responses in healthcare including sport and exercise medicine. The cessation of elite sport almost globally has had significant economic implications and resulted in pressure to resume sport in very controlled conditions. This includes protecting pitch-side medical staff and players from infection. The ongoing prevalence of SARS-CoV-2 and the desire to resume professional sport required urgent best practice guidelines to be developed so that sport could be resumed as safely as possible. This set of best practice recommendations assembles early evidence for managing SARS-CoV-2 and integrates expert opinion to provide a uniform and pragmatic approach to enhance on-field and pitch-side safety for the clinician and player. The nature of SARS-CoV-2 transmission creates new hazards during resuscitation and emergency care and procedures. Recommendations for the use and type of personal protective equipment during on-field or pitch-side emergency medical care is provided based on the clinical scenario and projected risk of viral transmission.

Aggregation of therapeutic bispecific antibodies negatively affects the yield, shelf-life, efficacy and safety of these products. Pairs of stable Chinese hamster ovary (CHO) cell lines produced two difficult-to-express bispecific antibodies with different levels of aggregated product (10-75% aggregate) in a miniaturised bioreactor system. Here, transcriptome analysis was used to interpret the biological causes for the aggregation and to identify strategies to improve product yield and quality. Differential expression- and gene set analysis revealed upregulated proteasomal degradation, unfolded protein response and autophagy processes to be correlated with reduced protein aggregation. Fourteen candidate genes with the potential to reduce aggregation were co-expressed in the stable clones for validation. Of these, HSP90B1, DDIT3, AKT1S1, and ATG16L1, were found to significantly lower aggregation in the stable producers and two (HSP90B1 and DNAJC3) increased titres of the anti-HER2 monoclonal antibody trastuzumab by 50% during transient expression. It is suggested that this approach could be of general use for defining aggregation bottlenecks in CHO cells.

Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine.

Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available.

Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults.

Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS-C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS-C within the first 24 hours of hospital presentation.

The etiology of type 1 diabetes has polygenic and environmental determinants that lead to autoimmune responses against pancreatic β cells and promote β cell death. The autoimmunity is considered silent without metabolic consequences until late preclinical stages,and it remains unknown how early in the disease process the pancreatic β cell is compromised. To address this, we investigated preprandial nonfasting and postprandial blood glucose concentrations and islet autoantibody development in 1,050 children with high genetic risk of type 1 diabetes. Pre- and postprandial blood glucose decreased between 4 and 18 months of age and gradually increased until the final measurements at 3.6 years of age. Determinants of blood glucose trajectories in the first year of life included sex, body mass index, glucose-related genetic risk scores, and the type 1 diabetes-susceptible INS gene. Children who developed islet autoantibodies had early elevations in blood glucose concentrations. A sharp and sustained rise in postprandial blood glucose was observed at around 2 months prior to autoantibody seroconversion, with further increases in postprandial and, subsequently, preprandial values after seroconversion. These findings show heterogeneity in blood glucose control in infancy and early childhood and suggest that islet autoimmunity is concurrent or subsequent to insults on the pancreatic islets.

The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates.

A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the United Kingdom in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence.

To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation.

Nursing has seen a dominance of women within the profession, and today, the presence of men in the role remains less understood and appreciated. Males considering or entering nursing face challenges concerning role misconception, marginalization, and gender bias. With a looming shortage of nurses on the horizon, it is more important now than ever before to find better ways of engaging males into nursing. The aim of the study was to examine the psychological constructs that influence male perceptions of nursing as they seek to navigate the profession, and what aspects influence men to consider nursing as a career. To achieve this, a systematic review and mixed research synthesis (integrated design) was conducted. English language research published between 1999 and 2019 was eligible. The methodological rigor of qualitative articles followed the Critical Appraisal Skills Program, while the Best Evidence Medical Education guided the quantitative review. Among the 24 publications identified, three sub-themes emerged from the overarching theme of the funambulist or tightrope walker. Sub-themes included societal, inner and collective voices that inform men's place in nursing or their decision making about entering the profession. There is a need to re-visit what it means to be a nurse in order to address the gendered stereotypes that impact men entering the nursing profession.

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.