Equality, Diversity and Inclusivity (EDI) Sandpit: views on research paradigms and the future of academia

In this report, we summarize the outcome of a consultation session held in January 2024 appraising adopted attitudes within scientific research. This Equality, Diversity & Inclusion (EDI) Sandpit was a collaboration between interdisciplinary researchers from the ECMage (Extracellular Matrix [ECM] ageing across the life course interdisciplinary research network) and BLAST (Building Links in Ageing Science & Translation) networks, both part of the UK Ageing Networks, and the lifETIME (Engineered Tissues for Discovery, Industry and Medicine) Centre for Doctoral Training. Statements representing previously prevalent patterns of thinking that could influence research practice were put to delegate teams to discuss in relation to social and cultural behaviors that have been adopted over the years. Discussions focused on five themes across two main categories, aiming to identify and understand areas where change is needed, as well as to offer suggestions on how best to concentrate efforts to make the most impact

Uncovering the secrets of the Sun’s magnetic field

Humans have admired the Sun for as long as they have existed because life simply would not be possible without it. Today, we know that the Sun is not just a blazing ball of light but an extremely complex space laboratory in our cosmic neighborhood. In this article, you will read about the mystery of the Sun—how it acts as a gigantic magnet through a process called the solar dynamo. We will also describe the methods scientists use to understand this mystery

Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple P. falciparum isolates. However, making functional sense of genomic data relies on the ability to infer binding phenotype from var gene sequence. For P. falciparum rosetting, the binding of infected erythrocytes to uninfected erythrocytes, the analysis of var gene/PfEMP1 sequences encoding the phenotype is limited, with only eight rosette-mediating PfEMP1 variants described to date. These known rosetting PfEMP1 variants fall into two types, characterised by N-terminal domains known as “domain cassette” 11 (DC11) and DC16. Here we test the hypothesis that DC11 and DC16 are the only PfEMP1 types in the P. falciparum genome that mediate rosetting, by examining a set of thirteen recent culture-adapted Kenyan parasite lines. We first analysed the var gene/PfEMP1 repertoires of the Kenyan lines and identified an average of three DC11 or DC16 PfEMP1 variants per genotype. In vitro rosette selection of the parasite lines yielded four with a high rosette frequency, and analysis of their var gene transcription, infected erythrocyte PfEMP1 surface expression, rosette disruption and erythrocyte binding function identified four novel rosette-mediating PfEMP1 variants. Two of these were of the predicted DC11 type (one showing the dual rosetting/IgM-Fc-binding phenotype), whereas two contained DC15 (DBLα1.2-CIDRα1.5b) a PfEMP1 type not previously associated with rosetting. We also showed that a Thai parasite line expressing a DC8-like PfEMP1 binds to erythrocytes to form rosettes. Hence, these data expand current knowledge of rosetting mechanisms and emphasize that the PfEMP1 types mediating rosetting are more diverse than previously recognised

Arithmetic geometry of character varieties with regular monodromy

We count points on a family of smooth character varieties with regular semisimple and regular unipotent monodromies. We show that these varieties are polynomial count and obtain an explicit expression for their E-polynomials using complex representation theory of finite reductive groups. As an application, we give an example of a cohomologically rigid representation which is not physically rigid

Polarised Logics of Pedagogy: Crises, Contexts and Classrooms in the Global South

This novel book demonstrates the polarised logics that exist between exploring cultural, structural, political, and historical contexts as a primary focus for pedagogical research versus an interventionist agenda that isolates pedagogy and its components from their environments. Combining theoretical discussions with empirical evidence and case studies, the book provides a synthesising approach to both research and educational planning, recognising pedagogy as an open system while acknowledging that not all teaching methods are equal when it comes to enhancing learning. Considering the so-called learning crisis and learning poverty in the context of Sustainable Development Goal 4 in the wake of the COVID-19 pandemic, this book is also sensitive to concerns about the mental health and wellbeing of young people and the sustainability of the planet. Ultimately providing a timely, informed, and balanced discussion of these issues, this book will appeal to researchers, scholars, and post-graduate and doctoral students working in pedagogical research or international and comparative education, and anyone interested in the relationship between education and international development

Competing over the ‘left behind’: the effect of independent local lists on the electoral performance of populist parties

Rising dissatisfaction with established politics has driven widespread partisan dealignment, weakening mainstream parties and fuelling the ascent of populist challengers. Yet alongside populist parties, another group has gained traction across Europe: independent local lists (ILLs). These locally organised groups also present themselves as alternatives to party politics and may channel anti-establishment sentiment. This paper investigates how the rise of ILLs affects the performance of populist parties – particulary in so-called ‘left behind’ places – and how this elationship varies across populist parties of different ideological types. The analysis draws on an original dataset of local elections in 670 municipalities over four electoral rounds in the Czech Republic, a country in which both populist parties and ILLs have recently emerged and now play prominent roles. Fixed-effects panel models show that the presence of ILLs significantly impedes the electoral performance of populist parties, including in economically deprived contexts. These findings shed new light on the conditions under which local political actors are able to constrain the development of populist parties, offering broader insights into strategic responses to voter grievances and the rising demand for anti-establishment politics

Unaccompanied children in England and the United Kingdom

Unaccompanied Asylum-Seeking children in England and the UK are known as UASC and are children who have fled from unstable and dangerous environments. They have endured perilous journeys to the UK, and a high number of these children suffer from physical and mental health issues. They face many barriers to settlement and integration into society in the UK. This article is contextualised within the framework of the rights of the child and the rights of the unaccompanied child and explores a number of key themes: the reasons why children flee and the journey to the UK, arrival procedures, initial assessment and health checks, education of the unaccompanied children, the importance of religion and religious identity and unaccompanied children who become missing children. This last theme is a matter of great concern as these children are very vulnerable and are often victims of exploitation, re-trafficking and child slavery

Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation

Background: Inflammation is a key driver of atherosclerosis, yet the mechanisms sustaining inflammation in human plaques remain poorly understood. This study uses a network-based approach to identify immune gene programs involved in the transition from low- to high-risk (rupture-prone) human atherosclerotic plaques. Methods: Expression data from human carotid artery plaques, both stable (low-risk, n = 16) and unstable (high-risk, n = 27), were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Bayesian network inference, operated on the eigengene values from the WGCNA, further extended the WGCNA analysis, and similarity to the signature of T cell subsets was validated in single-cell RNA sequencing data of human plaques, and a loss-of-function study in a mouse model of atherosclerosis. In silico drug repurposing was performed to identify potential therapeutic targets. Results: Our analysis revealed a distinct gene module with a prominent T cell signature, particularly in unstable plaques. Key regulatory factors, RUNX3, IRF7 and in particular PRDM1, were significantly downregulated in plaque T cells from symptomatic versus asymptomatic patients, indicating a protective role. Additionally, as PRDM1 is downstream of IRF7, we opted for PRDM1 as a key target. T cell-specific Prdm1 deficiency in Western-type diet fed Ldlr knockout mice featured accelerated plaque progression. Finally, as PRDM1 targeting drugs are not yet available, we performed in silico drug repurposing, identifying EGFR inhibitors as promising therapeutic candidates. Conclusions: This study highlights a PRDM1-regulated T cell network that distinguishes high-risk from low-risk plaques and demonstrates the regulatory role of T cell PRDM1 in controlling atherosclerosis, positioning this pathway as a promising therapeutic target

Resistance exercise therapy after COVID-19 infection: a randomized, controlled trial

Importance: Long COVID presents an unmet therapeutic need. Objective: To determine the effects of a resistance exercise intervention on exercise capacity in adults after COVID-19 infection. Secondary objectives included assessments of health status. Design: A two-arm randomized, controlled clinical trial including adults with a hospital or community diagnosis of COVID-19 in the preceding 12 months was undertaken during June 2021-April 2024. Setting: Community and secondary care, multicenter. Participants: 233 individuals with Long-COVID were randomized. 117 (50.2%) individuals were assigned to the intervention group, and 116 (49.8%) individuals were assigned to the control group. Shuttle walk tests at baseline and 3-months were completed in 224 and 193 participants, respectively. Intervention: Personalized resistance exercise intervention for 3-months. Control: Treatment-as-usual. Main outcome measures: The primary outcome was the distance achieved (m) in the incremental shuttle walk test undertaken 3-months after randomization. Secondary outcome measures included health-related quality of life (EQ-5D-5L), anxiety and depression (Patient Health Questionnaire) and grip strength. Results: 233 adults (median (interquartile range) 53.6 (43.8, 60.8) years; 146 (62.7%) female, 91 (39.1%) hospitalized with COVID-19) were randomized (n=117 (50.2%) intervention group, n=116 (49.8%) control group). The median (interquartile range) percentage adherence with the exercise intervention was 71.0 (47.8, 96.8), equivalent of performing the exercises on 5 days/week. The mean (SD) distances achieved in the incremental shuttle walk test at baseline and at follow-up were 328 (225) m and 389 (249) m, in 224 and 193 individuals, respectively. The change in incremental shuttle walk test distance at three months compared to baseline was 83 (118) m in the intervention group (n=94) and 47 (95) m in the control group (n=98) (effect estimate (95%) confidence interval 36.5 (6.6, 66.3) m; p=0.017). By three months, compared to the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 (0.01, 0.11); p=0.018), Patient Health Questionnaire category (0.5 (0.2, 0.8); p=0.013) and handgrip strength (2.58 (0.92, 4.24) kg; p=0.002). Conclusions and Relevance: In this randomized clinical trial, a program of resistance exercise for 3 months in adults after COVID-19 infection improved exercise capacity and appeared to improve health-related quality of life, anxiety and depression, and grip strength

Associations of 13C-sucrose breath test dynamics with anthropometry and demographics: a comparison of studies in the United Kingdom and Zambia

Background: The 13C-sucrose breath test (13C-SBT) is a non-invasive diagnostic test that has been used to assess intestinal sucrase-isomaltase activity, which may be altered in gut function disorders such as environmental enteric dysfunction (EED), a syndrome characterized by chronic inflammation and histologic changes in the small intestine and thought to be ubiquitous among people living without access to improved water and sanitation. However, characterizing associations between 13C-SBT breath curves and gut function status requires disaggregating associations with sucrase-isomaltase activity from associations with other aspects of sucrose metabolism. Objective: This analysis aimed to identify anthropometric and demographic patterns in 13C-SBT breath curves. Methods: We investigated the associations between anthropometry (height, weight, body mass index) or demographics (sex, age) and each of three mechanistic pharmacokinetic model parameters estimated from 13C-SBT breath curves, comparing adult populations in UK and Zambia, who have different risk of EED. Results: Zambian participants had higher values of the parameter associated with intestinal sucrase-isomaltase activity and liver metabolism (ρ: 2.4 (UK) vs 3.5 (Zambia), p=0.005) and higher fractions of tracer recovery (κ: 0.69 (UK) vs 0.93 (Zambia), p=<0.001). The rate-limiting parameter, speculated to be associated with pulmonary excretion of plasma bicarbonate as CO2, was lower among Zambian participants (πρ: 0.30 (UK) vs 0.22 (Zambia), p=0.009). We found a similar association between the rate-limiting parameter (πρ) and weight in both cohorts, with higher weight associated with slower tracer recovery. We did not find significant associations between anthropometry and the parameter associated with sucrase-isomaltase activity (ρ), helping to alleviate concerns about potential confounding by anthropometry when using ρ as a model-based 13C-SBT diagnostic of intestinal sucrase-isomaltase activity. Conclusions: The associations we identified between weight and the rate-limiting parameter (πρ) should be further investigated and better understood mechanistically. These anthropometric associations identified for adults should be further confirmed in infants and children