Fashioning the pregnant body : wearing pregnant bodies

Drawing on qualitative research including in-depth interviewing and extensive participant observation this thesis maps a particular story of production and consumption of maternity wear in England at the turn of the twenty-first century. Arguing that these processes are not mutually exclusive but rather intricately interwoven, I analyse both the ways in which maternity wear is produced for and by high street and small independent retail and also personal accounts of its consumption. Having described the broad context for its problematic material production, 1 go on to analyse the cultural production of maternity wear in key retail spaces of representation. I argue that whilst the strategic and spatial marginality of maternity wear on the high street for example can be seen to be the result of less than favourable production issues that put tremendous pressure on margins and profitability, cultural discourses of the pregnant body and motherhood also structure the nature of provision and representation. These discourses which become imbued not only in the retail spaces themselves but also the clothing sold within them, it is further argued, are also significant in structuring women’s embodied consumption experiences during pregnancy. Such inherent links between production and consumption, economics and culture can be seen to be significant at the level of personal experience as I describe through my analysis of women’s embodied experience. However I also identify wider implications for the maternity wear market as a whole since the ways in which women consume clothing during pregnancy, indeed dress and wear their pregnant bodies, has important consequences for its sustainability and future growth. The contribution of this thesis however goes beyond identifying the need for an expanded focus towards cultural economies in order to fully understand the workings of a market and indeed consumption processes themselves. I also identify the need for embodied theory to be at the heart of studies into fashion and dress. Consumption of clothing during pregnancy as it is understood here is about far more than the acquisition (and indeed flows) of material goods. Rather the process is explicitly embodied. My analysis takes a progressively in-depth look at the embodied nature of clothing consumption during pregnancy and argues that constant corporeo-sartorial negotiation is at the heart of women’s experiences. The material cultural significance of clothing and bodies (for example as is mapped out in retail spaces of representation) are not merely academic nuances to be identified for discussion, they have material consequences for the ways in which pregnant bodies are dressed and indeed lived

“POOL: A Social History of Segregation Exhibition” Exploring Social Justice Through the Lens of Water Safety Awareness and Art-based Education

Art exhibitions, with a focus on water safety and drowning prevention, are rarely seen as a medium to address social justice and public health, or water safety awareness and drowning prevention efforts in communities. Globally, data have shown drowning is considered a “neglected public health threat” (World Health Organization, 2021, CDC, 2023). Additionally, reports have shown that across the globe there are demographic groups of people impacted by drowning, historical traumas, and social determinants, also impacting some communities that are at greater risk (WHO 2021, CDC, 2023). Although there are national and international efforts to address the importance of water safety, drowning prevention, and its disproportionate impact on historically marginalized, Black, Indigenous People of Color (BIPOC), and culturally and linguistically diverse (CLD) groups, alternative mediums, such as exhibitions of art, which can portray narratives of groups of people and their relationships with water, should be explored to counter stigma, and correct the narratives of BIPOC’s communal relationships to water, in an effort combat drowning disparities. As readers, you are encouraged to participate in this ongoing research and enter the “POOL” http://poolphl.com/, and explore “A Social History of Segregation” and Learn http://poolphl.com/learn.html (POOL-ongoing, 2021)

Antibody correlates of protection against Delta infection after vaccination: A nested case-control within the UK-based SIREN study

Objectives: To investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations.// Methods: We performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection.// Results: In total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p = 0.02) and Omicron nAbT (p = 0.002). At seven days before infection, controls had higher anti-S levels (p 40 were associated with reduced odds of Delta infection (89%, [69–96%]; p 100 (p = 0.009) and >400 (p = 0.007).// Conclusions: We have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase

The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause a fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. To identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play key roles in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine-N7 methyltransferase nsp14, and the nsp16 2′-O-methyltransferase with its activating cofactor, nsp10. We performed an in vitro high-throughput screen for inhibitors of nsp14 using a custom compound library of over 5000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified four compounds as potential inhibitors of nsp14, all of which also showed antiviral capacity in a cell-based model of SARS-CoV-2 infection. Three of the four compounds also exhibited synergistic effects on viral replication with remdesivir

Co-Designing an Air Quality Web App with School Pupils and Staff : The SAMHE Web App

This methods paper describes a new UK-wide citizen science project, the Schools’ Air Quality Monitoring for Health and Education (SAMHE) project, which is exploring indoor air quality (IAQ) in schools. Central to the project is a Web App, where school teachers and pupils can see air quality and environmental data from their classroom, learn about the significance of the data that their monitor collects, enter important contextual information to support data analysis by researchers, and are supported to do their own experiments related to air quality. School use of the SAMHE Web App is essential to the project’s aims to 1) improve understanding of air quality in schools; 2) empower teachers and pupils to make informed decisions about management of their classroom environment, including ventilation; and 3) support the UK’s next generation to think differently about air quality. Therefore, it is critical that the SAMHE Web App was co-designed with schools, to maximise its acceptability within schools, and to ensure that teachers and pupils engage with it. This paper describes the co-design process used within SAMHE, how co-design has helped shape the web app (including overall theme, visualisation of data, and supporting materials), and some lessons learned from the process that will be useful for future software development and citizen science projects with schools

CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination ("vaccine breakthrough") have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination : a nested case-control within the SIREN study

Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283).Objectives To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. Trial registration number ISRCTN11041050Publisher PDFPeer reviewe

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice