'Now I care': a qualitative study of how overweight adolescents managed their weight in the transition to adulthood

Objectives: A qualitative study of recalled experiences of early adolescent overweight/obesity revealed low levels of weight-related concern. This further analysis aimed to explore weight-related concern and weight-loss efforts as participants transitioned into adulthood. Design, participants and methods: Participants were 35 young adults from a population-based cohort study who had body mass index (BMI) >95th centile between ages 11 and 15 and participated in semistructured interviews aged 24. At age 24, they were categorised as: ‘slimmers’ (N=13) who had lower BMI Z-scores at 24 than their adolescent peak and were not obese (BMI<30 kg/m2); ‘relapsers’ (N=8, of whom 2 were morbidly obese (BMI>35 kg/m2) at age 24); ‘stable’ (N=3, of whom 1 morbidly obese); and ‘gainers’ (N=11, of whom 5 morbidly obese). Themes were identified and coded using NVivo qualitative data analysis software, blind to participants’ current weight status. Results: Contrasting with the lack of concern recalled in respect of earlier adolescence, weight-related concerns and/or desire to lose weight generally increased around the time of school leaving and almost all participants described some form of exercise (formal/informal) and dietary weight-control strategies. Among ‘slimmers’, there was some (subtle) evidence of more consistent use of exercise, self-monitoring of diet and exercise and of lifestyle changes becoming habitual and/or part of identity. Few participants had accessed professional support. Diet clubs seemed to have been used most by ‘gainers’, some only recently. Labour-market and housing transitions were strong influences, described as facilitating weight losses by some, but increases by others. For some participants, it appeared that weight loss was simply a by-product of these transitions. Conclusions: In contrast to earlier adolescence, even the heaviest participants tended to show actual weight loss action or preparation for action. The transition to adulthood could thus be a key life stage for interventions

Exploring how parents of children with unilateral hearing loss make habilitation decisions: a qualitative study

Objective This study sought to explore the decision making needs of parents managing the hearing and communication needs of children with unilateral hearing loss. Design An inductive, qualitative method was used. The data were analysed using a constant comparative approach, consistent with Grounded Theory method. Study sample Twenty one families participated in interviews yielding data on twenty two children. Each of these families had at least one child with unilateral hearing loss. The age range of the children varied from four months to sixteen years old. All parents were English speaking and received care from National Health Service Audiology departments across the United Kingdom. Results Parents valued professionals’ opinions, but information provision was inconsistent. As their children mature, parents increasingly valued their child’s input. Parent-child discussions focussed on how different management strategies fit their child’s preferences. Parents were proactive in obtaining professional advice, and integrating this with their own iterative assessment of their child’s performance. Conclusions Decision making is an iterative process. Parents make nuanced decisions which aim to preserve a sense of what is normal for them. Clinicians need to recognise the parental view, including where it may contrast with a medicalised or clinical view

Media, power and representation

This is an Accepted Manuscript of a book chapter published by Routledge in The Routledge Handbook of English Language Studies on 20th June 2018, available online: https://www.routledge.com/The-Routledge-Handbook-of-English-Language-Studies/Seargeant-Hewings-Pihlaja/p/book/9781138913455As the ubiquity and potential influence of the media increase, the language and imagery used to create meaning in this domain are of continued and enhanced interest to English Language researchers. While ‘the media’ or even ‘the English-speaking media’ is not one homogenous entity, the term is used throughout this chapter to refer broadly to a collection of media types such as newspapers, television, radio and so on. Media English can be understood as referring to the ways in which reality is linguistically constructed through these platforms. Additionally, media institutions play a significant role not only in terms of communication but also by way of ‘mediating society to itself’ (Matheson 2005: 1) in that the media helps to construct societal norms and values. Media language is distinctive because media discourses can be ‘fixed’ (i.e. recorded for posterity) as well as being interactive (people can react to subject matter, often using media forms to publically share their response(s), themselves becoming producers of media content). In investigating Media English, scholars analyse overall styles or genres in order to explore and challenge particular choices of language and/or imagery within a given media text

Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV 2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case

Background: Ronapreve demonstrated clinical application in post-exposure prophylaxis, mild/moderate disease and in the treatment of seronegative patients with severe COVID19 prior to the emergence of the Omicron variant in late 2021. Numerous reports have described loss of in vitro neutralisation activity of Ronapreve and other monoclonal antibodies for BA.1 Omicron and subsequent sub-lineages of the Omicron variant. With some exceptions, global policy makers have recommended against the use of existing monoclonal antibodies in COVID19. Gaps in knowledge regarding the mechanism of action of monoclonal antibodies are noted, and further preclinical study will help understand positioning of new monoclonal antibodies under development. Objectives: The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication as a paradigm for a monoclonal antibody combination. The study also sought to confirm absence of in vivo activity against BA.1 Omicron (B.1.1.529) relative to the Delta (B.1.617.2) variant. Methods: Virological efficacy of Ronapreve was assessed in K18-hACE2 mice inoculated with either the SARS-CoV-2 Delta or Omicron variants. Viral replication in tissues was quantified using qRT-PCR to measure sub-genomic viral RNA to the E gene (sgE) as a proxy. A histological examination in combination with staining for viral antigen served to determine viral spread and associated damage. Results: Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post infection, for the Delta variant but not the Omicron variant of SARS-CoV-2 at doses 2-fold higher than those shown to be active against previous variants of the virus. It also appeared to block brain infection which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a mild multifocal granulomatous inflammation in which the virus appeared to be confined. A similar tendency was also observed in Omicron infected, Ronapreve-treated animals. Conclusions: The current study provides evidence of an altered tissue response to the SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data also demonstrate that experimental designs that reflect the treatment use case are achievable in animal models for monoclonal antibodies deployed against susceptible variants. Extreme caution should be taken when interpreting prophylactic experimental designs when assessing plausibility of monoclonal antibodies for treatment use cases

Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection

Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed

Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research

Currently nitazoxanide is being assessed as a candidate therapeutic for SARS-CoV-2. Nitazoxanide is rapidly broken down to its active metabolite tizoxanide upon administration. Unlike many other candidates being investigated, tizoxanide plasma concentrations achieve antiviral levels after administration of the approved dose, although higher doses are expected to be needed to maintain these concentrations across the dosing interval in the majority of patients. Here an LC-MS/MS assay is described that has been validated in accordance with Food and Drug Administration (FDA) guidelines. Fundamental parameters have been evaluated, and these included accuracy, precision and sensitivity. The assay was validated for human plasma, mouse plasma and Dulbecco's Modified Eagles Medium (DMEM) containing varying concentrations of Foetal Bovine Serum (FBS). Matrix effects are a well-documented source of concern for chromatographic analysis, with the potential to impact various stages of the analytical process, including suppression or enhancement of ionisation. Herein a validated LC-MS/MS analytical method is presented capable of quantifying tizoxanide in multiple matrices with minimal impact of matrix effects. The validated assay presented here was linear from 15.6 ng/mL to 1000 ng/mL. The presented assay here has applications in both pre-clinical and clinical research and may be used to facilitate further investigations into the application of nitazoxanide against SARS-CoV-2

Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters.

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed