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Plasma complement system markers and their association with cardiometabolic risk factors: an ethnic comparison of White European and Black African men
No full textPopulations of Black African (BA) ancestry are disproportionately affected by cardiometabolic diseases, possibly due to dysregulation of the complement system. This study aimed to determine 1) relationships between fasting complement markers and cardiometabolic risk in BA and White European (WE) men, and 2) whether postprandial complement response differs by ethnicity. Eighty-eight BA and 97 WE men (age=44.4 [42.0-47.6] years, BMI=29.2±4.5 kg/m2) were assessed for fasting plasma complement markers and cardiometabolic risk factors. A second cohort ( n=20 men, 10 BA) (age=31.0±1.1 years, BMI=27.1 [26.0-28.6] kg/m2) men underwent a moderate-to-high-fat feeding protocol to measure postprandial plasma complement, serum insulin, plasma glucose, TAG and non-esterified fatty acids. C4 and Factor D were lower, and iC3b was higher, in BA compared with WE men. C3 and C4 were strongly associated with all adiposity markers in both ethnicities, but the WE cohort showed stronger associations between C3 and subcutaneous adipose tissue, C5 and WC, and iC3b and visceral adipose tissue compared with BA. C3 was associated with all cardiometabolic risk factors in both ethnicities. Associations between C5 and cholesterol, C4 and TAG, and TCC and (both total and LDL)-cholesterol were only observed in the WE cohort. There was a trend towards ethnic differences in postprandial Factor D ( P=0.097) and iC3b ( P=0.085). The weaker associations between the complement system markers with adiposity and lipid profiles in BA compared with WE men suggest ethnic differences in the determinants of complement production and activation, whereby adipose tissue may play a less important role in BA men.</p
Reduced-energy diet in women with gestational diabetes: the dietary intervention in gestational diabetes DiGest randomized clinical trial
No full textReduced-energy diets promote weight loss and improve long-term outcomes in type 2 diabetes but are untested in gestational diabetes. We aimed to identify if weight loss in pregnancy improves perinatal outcomes in gestational diabetes. We performed a multicentre parallel, randomized, controlled, double-blind trial of energy restriction in women with singleton pregnancies, gestational diabetes and body mass index ≥25 kg m− 2. Participants were randomized to receive a standard-energy control diet (2,000 kcal d−1) or reduced-energy intervention diet (1,200 kcal d−1) from enrollment (29 weeks) until delivery, provided as weekly diet boxes (40% carbohydrate, 35% fat, 25% protein). The randomization was performed in a 1:1 ratio, stratified by center and blinded to the participants and study team. Primary outcomes were maternal weight change from enrollment to 36 weeks and offspring birth weight. In total, 425 participants were randomized to the control (n = 211) or intervention (n = 214). Outcome data were available for 388 of 425 (90.1%) participants at 36 weeks and 382 of 425 (89.8%) at delivery. There was no evidence of a difference in maternal weight change to 36 weeks between groups (intervention effect −0.20 (95% confidence interval −1.01, 0.61); P > 0.1) and offspring standardized birth weight (intervention effect 0.005 (−0.19, 0.20); P > 0.1). A reduced-energy diet was safe in pregnancy. ISRCTN registration no. 65152174.</p
Risk Communication about Antimicrobial Resistance: A Content Analysis of Metaphor Use in Global Public Discourse
No full textAntimicrobial resistance (AMR) poses an existential threat to humanity, yetpublic awareness remains low. An underexplored tool for AMR riskcommunication is metaphor. By inviting a comparison between abstract andfamiliar concepts, metaphors can make complex health information moreaccessible. However, metaphor use in the context of AMR has been haphazardand remains poorly understood. We address this issue by providing an integrativecontent analysis of metaphor use in global, English-language, public AMRdiscourse. Four types of public sources were searched: (1) websites of 71 non-profit organisations, (2) national AMR action plans from 84 countries, (3) 819international newspaper articles and (4) 2,616 social media posts. Across allsources, 2,149 metaphors excerpts were extracted. Qualitative content analysisidentified 41 distinct metaphor themes, but 75% of metaphors fell into one of fourthemes: “War against resistance, infections and microbes,” “Heroes and villains ofresistance,” “Post-antibiotic apocalypse and looming crisis of AMR,” and “Silent,creeping threat of AMR.” All key themes are inapt or theoretically problematic bypainting a misleading picture of a finite struggle between good and evil, whichdoes not match the ecological reality of a continuously evolving challenge.Furthermore, most existing metaphors are highly conventional and emotive. Theyaim to raise general awareness about AMR without conferring specificknowledge. Our findings call for an urgent re-framing. Media, policy makers andhealth officials should choose theoretically informed, apt and novel explanatorymetaphors that are specific to the context of AMR and challenge publicmisunderstandings with the potential to prompt behaviour change.</p
Plasmon-Enhanced Photo-Luminescence Emission in Hybrid Metal–Perovskite Nanowires
No full textSemiconductor photonic nanowires are critical components for nanoscale light manipulation in integrated photonic and electronic devices. Optimizing their optical performance requires enhanced photon conversion efficiency, for which a promising solution is to combine semiconductors with noble metals, using the surface plasmon resonance of noble metals to enhance the photon absorption efficiency. Here, we report plasmon-enhanced light emission in a hybrid nanowire device composed of perovskite semiconductor nanowires and silver nanoparticles formed using superfluid helium droplets. A cesium lead halide perovskite-based four-layer structure (CsPbBr3/PMMA/Ag/Si) effectively reduces the metal’s plasmonic losses while ensuring efficient surface plasmon–photon coupling at moderate power. Microphotoluminescence and time-resolved spectroscopy techniques are used to investigate the optical properties and emission dynamics of carriers and excitons within the hybrid device. Our results demonstrate an intensity enhancement factor of 29 compared with pure semiconductor structures at 4 K, along with enhanced carrier recombination dynamics due to plasmonic interactions between silver nanoparticles and perovskite nanowires. This work advances existing approaches for exciting photonic nanowires at low photon densities, with potential applications in optimizing single-photon excitations and emissions for quantum information processing.</p
The GLOB-cAGE Consortium: A Global Cardiovascular Collaborative Network of Older Adults with Cardiovascular Disease
No full textBackground: GLOB-cAGE is a newly established unprecedented consortium that brings together cohorts of older persons with cardiovascular disease worldwide. GLOB-cAGE aims to harmonize non-identifiable data from longitudinal cohorts examining cardiovascular health and cardiovascular disease diagnosis and management in older individuals to perform meta-regression analyses using combined repositories of standardized subject-level data points. Methods and Design: Studies registered into GLOB-cAGE are population-based longitudinal cohort studies or clinical trials, either ongoing or completed, that involve assessing cardiovascular health as a central objective. Cross-sectional studies that significantly contribute to cardiovascular research in older individuals may also be included. The GLOB-cAGE will consist of individuals already diagnosed with cardiovascular disease and primary prevention of individuals at different risks of cardiovascular disease. The studies should have a minimum sample size of 100 participants, and the participants are either adults aged above 65 years or above 40 years with longitudinal follow-up over the next few decades. Enrollment in GLOB-cAGE may involve collaboration on non-identifiable or anonymized raw or processed data for joint analyses. Sites unable to provide raw or processed data due to institutional or other reasons may participate in alternative ways, including performing separate analyses in-house. At the time of writing, there are at least ten participating teams from nine countries and 27 studies enrolled in GLOB-cAGE. Conclusions: The GLOB-cAGE consortium is an international effort to bring together cardiovascular disease research in older persons, focusing on providing greater representation from diverse countries battling population aging. It addresses the evidence gaps from the insufficient enrolment of older individuals in randomized controlled trials and permits investigators to conduct high-quality epidemiological studies.</p
Dissecting the regulatory mechanisms governing the histone 3 lysine 9 methyltransferase Clr4
No full textThe histone methyltransferase Clr4 is essential for heterochromatin formation in Schizosaccharomyces pombe, catalysing the methylation of histone H3 at lysine 9 (H3K9). Recent studies have shown that the ubiquitination of histone H3 at lysine 14 (H3K14Ub) stimulates Clr4’s catalytic activity, while phosphorylation of its autoregulatory loop (ARL) modulates activity during meiosis. This thesis focuses on exploring the structural dynamics and regulatory mechanisms of Clr4 using NMR spectroscopy, with a focus on how post-translational modifications influence its function. I optimised recombinant expression of the C-terminal catalytic domain of Clr4 (Clr4-SET) using a Golden Gate cloning system to screen purification and solubility tags. While this did not markedly improve solubility, it provided a useful tool for future applications. A key achievement was the synthesis at milligram-scale, of site-specific H3K14Ub conjugates using halogen ketone-mediated cross-linking. Additionally, I successfully expressed and purified isotopically labelled Clr4-SET and obtained 2D and 3D NMR spectra—making this work the first detailed NMR study of Clr4. Titration experiments revealed significant chemical shift perturbations upon H3K14Ub binding and CDK1-mediated phosphorylation, indicating conformational changes linked to activation. These findings provide a foundation for future structural studies aimed at understanding Clr4’s regulatory mechanisms and their broader implications for chromatin regulation in S. pombe.</p
Factors impacting uptake of cardiac rehabilitation in people with chronic heart failure: targets for interventions
No full textIntroduction: Participation in exercise-based cardiac rehabilitation (ExCR) can improve quality of life and reduced hospital readmission, but uptake is low in people with chronic heart failure (CHF). This may be impacted by frailty and other comorbidities.Aim: Explore the impact of frailty and other patient related factors on acceptance of referral to CR service following an admission to hospital with an episode of acute decompensated CHF (ADHF) in order to identify targets for behaviour change interventions.Methods:1. Systematic review exploring the benefits of physical activity interventions in people with long term cardiac conditions and frailty.2. Audits addressing the eligibility and access of inpatients with ADHF to referral to CR service.3. Observational study investigating the relationship between frailty and referral to CR service.4. Qualitative interviews, focus group and survey identifying targets for interventions to increase acceptance of referral to CR service by people with CHF.Results: Frailty impacts eligibility for ExCR but probably not acceptance rate for referral to a programme, if eligible. Exercise based interventions can improve physical function in people with CHF and frailty. Most eligible inpatients are offered referral to ExCR by the heart failure nursing service (HFNS). Qualitative data showed people with de novo CHF have different reasons (need for information, hope for recovery) for engagement with ExCR compared with those with established CHF (learning to live with limitations).Conclusion Work should focus on co-designing interventions with stakeholders including those newly diagnosed and people with established CHF, as they may need different approaches. The HFNS may be an effective way of providing novel face to face interventions at different point in the patient journey. Those patients currently ineligible for ExCR, may need adapted programmes or novel interventions.</p
BREATHE: the development and assessment of a breathing-based intervention for hypertension management
No full textHypertension is the leading preventable risk factor for cardiovascular disease, stroke and premature death (Zhou et al., 2021a), affecting 1.2 billion people worldwide (Zhou et al., 2021b). Hypertension is typically managed with medication, but optimal blood pressure management can be affected by factors such as stress, psychological wellbeing and multiple drug intolerances. The ESC/ESH 2018 (Williams et al., 2018) guidelines recommended a holistic approach to hypertension, including lifestyle modifications and medication. The updated ESH guidelines (Mancia et al., 2023) incorporated the impact of anxiety and stress on hypertension. Health psychology represents an approach that can inform and support the holistic management of hypertension. Specifically, the use of behavioural and self-management interventions to mediate the effect of psychological wellbeing on hypertension.This PhD was born out of the unique arrangement of an integrated specialist health psychology clinic within a hypertension outpatient clinic. To improve access and implementation of health psychology in hypertension management, this PhD sought to develop an intervention informed by health psychology, yet suitable for wide scale roll out in the National Health Service (NHS). A review of existing literature and a health psychology clinic demonstrated that breathing practice and biofeedback were well-suited interventions for patients with hypertension.Consequently, the PhD developed an intervention that integrated breathing practice and biofeedback into hypertension management: BREATHE (Biofeedback REactivity and Awareness To HEalth). The intervention was directly informed by feedback from patients with hypertension and NHS stakeholders. This ensured that BREATHE reflected patient preferences, whilst remaining feasible and suitable for NHS implementation. BREATHE was assessed in an ongoing feasibility study to inform continued development.This PhD demonstrated how health psychology can support the holistic management of hypertension, specifically the effect of psychological wellbeing. The development of BREATHE will continue beyond the scope of this PhD, in the ongoing feasibility study, grant applications for larger studies, and ultimately, NHS implementation.</p
Chinese Film Spectatorship In The Streaming Era: Viewing Behavior, Technology, And Censorship
No full textTechnology, viewing environment and censorship have the capacity to shape and influence audience behaviour throughout a film screening. This is evident not only in immersive cinematic environments, but also more prominent in highly flexible streaming media viewing environments. This empirical research examines the behavioural patterns of Chinese film spectators in streaming media usage. It also considers the impact of COVID-19 on China’s film industry. The data collection for this study combined questionnaire survey and participant observation, which include 2,016 questionnaires, 6 groups of bullet screen data from 3 films on both Tencent Video and iQIYI, and participant observation data from 16 spectators. A mixed analysis method was adopted, combining both quantitative and qualitative analysis. Based on interpretivism, this study incorporates natural language processing (NLP) technology into film-viewing behaviour research. It focuses on the processing and understanding of textual language when exploring behavioral classification, causes and correlations. Findings indicates that, Chinese government film censorship have restricted the development of streaming media and film industry. Chinese streaming platforms strive to develop functionality and portability, such as bullet screen and multi-device synchronisation, but still need to standardise the film consumption management system. Moreover, new cinema formats and streaming platforms are exploring integration to support the sustainable development of China’s film industry. From the perspective of film spectators, audience demographic characteristics and living environment shape their streaming media viewing behaviour patterns. Multitasking behaviours and active control of viewing represent the main characteristics of the streaming viewing model of Chinese film spectators. Accordingly, Hall’s encoding/decoding and the uses and gratifications theory (UGT) play a crucial role in addressing research questions. Overall, this research provides both theoretical and empirical insights into streaming media development and film spectator behaviour studies. It also contributes to broader disciplines of media and audience research both within China and internationally.</p
Kemalist boundaries and beyond: Discursive constructions of secular identity in 21st-century Turkey
No full textThis thesis explores the discursive construction of secular national identity, both at the level of elite (media) communication and by ordinary citizens in the context of 21st-century Turkey. More specifically, it investigates how journalists of Turkey’s main secular newspaper articulate secular national identity via 222 opinion pieces in a period of lost hegemony. This dataset is paired with 23 semi-structured interviews with non-elite Turkish secularists in order to comprehensibly understand the discourse about Turkish secular identity.By juxtaposing the theoretical frameworks of ethnosymbolism and Critical Discourse Studies (CDS), this research offers a nuanced understanding of how such an identity is both constructed and contested through discourse, shedding light on the intricate interplay between cultural symbols, nationalism, power relations, and collective identities.The datasets are analysed and interpreted using the Discourse-Historical Approach in CDS, identifying the legitimation strategies employed by the journalists. The analysis revealed that the journalists have been affected by an ontological insecurity embedded in the loss of identity and perceived threats to what they hold to be the only valid Turkish identity.Results of the research indicate that the Kemalist secular identity as performed by the Cumhuriyet journalists was not necessarily shared by the secularists interviewed. Instead, it showed that a new secular identity has been emerging, one characterised by a number of ambiguities about what it means to be a Turkish secularist and rendering the borders of Us/Them more porous.Against this background, the research suggests that Kemalism is no longer the only secular identity available to Turks and that historical definitions of, for example, democracy and modernity may no longer be tenable and require new lacunas of meaning. Thus, the study makes a significant contribution to the literature on national identity, in particular by showing the impact of ontological insecurity on identity construction.</p