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Multi-omics analyses reveal the pathogenic role of terminal ileum-derived IgA+β7+ cells in IgA nephropathy.
No full textINTRODUCTION: Galactose-deficient IgA1 (Gd-IgA1) plays a key role in IgA nephropathy (IgAN), but the location of the plasma cells responsible for its production remain unknown. METHODS: To locate Gd-IgA1-producing cells, we profiled intestinal and circulating immune cells from three independent cohorts totaling 99 IgAN cases and 121 healthy controls. The IgA phenotypes-including total IgA, Gd-IgA1, IgA-IgG complexes, secretory IgA, and polymeric IgA levels were measured in paired ileocecal and blood samples. Bulk RNA sequencing, cell deconvolution, and spatial profiling of biopsies identified Gd-IgA1-producing cells in ileocecal samples and blood. Functional studies employed anti-integrin α4β7 monoclonal antibodies in vitro and in a humanized IgAN mouse model. RESULTS: We found significantly elevated levels of ileocecal IgA enriched for polymeric and Gd-IgA1 O-glycoforms in patients with IgAN. In parallel, terminal ileal rather than ascending colon IgA+ B cells were increased. Most of these cells expressed Gd-IgA1 and displayed dysregulation of enzymes involved in O-glycosylation. Furthermore, circulating IgA+ B cells in IgAN exhibited gene expression signatures more closely resembling that of terminal ileum-derived IgA+ B cells, rather than those from ascending colon or tonsil. Integrin β7 was identified as a biomarker for cells of terminal ileal origin, and there was an increase in IgA+β7+ plasmablasts/plasma cells, correlating with disease severity. In a mouse model of IgAN, anti-α4β7 monoclonal antibody reduced β7+ cells and Gd-IgA1 levels in vitro and induced attrition of Peyer's patches, decreased circulating β7+ plasmablasts/plasma cells, and prevented mesangial IgA deposition. CONCLUSIONS: Our study highlights the importance of dysregulated B cell responses in the terminal ileum in IgAN and suggests the α4β7-MAdCAM-1 axis as a potential therapeutic target.</p
The role of spending money on in-game content in the prediction of anxiety and depression among Saudi gamers: validation of the spending money on in-game content scale
No full textThe greatest gaming profit is generated from the purchase of in-game content. This study investigated the role of spending money on in-game content in predicting anxiety and depression, after controlling for age, gender and personality traits. Saudi gamers completed the Spending Money on in-Game Content (SMOIGC) Scale, Ten-Item Personality Inventory and Hospital Anxiety and Depression Scale. Two samples were collected for this study using an online survey. Sample 1 (N = 210; Mean age = 23.99 ± 4.97; 75.14% males) was used to determine the factor structure of the SMOIGC scale and its role in predicting mental health outcomes. The results of exploratory factor analysis (EFA) indicated a three-factor solution, namely withdrawal, potential consequences, and loss of self-control. The regression analysis results indicated that the potential consequence significantly predicted anxiety and depression, even after controlling for demographic variables and personality traits. Sample 2 (N = 210; Mean age = 21.83 ± 4.12; 50.47% males) was utilized to validate the factor structure of the SMOIGC Scale. The results of the confirmatory factor analysis (CFA) validated the three-factor solution identified in the EFA. In both studies, the SMOIGC scale demonstrated high reliability, with Cronbach’s alpha ranging from 0.79 to 0.90. These results suggest the importance of potential consequences in understanding the mental health of gamers. The results also support the reliability and validity of the SMOIGC scale for research purposes in the gaming context.</p
PHYSICALLY-GUIDED OPTICAL INVERSION ENABLE NON-CONTACT SIDE-CHANNEL ATTACK ON ISOLATED SCREENS
No full textNo description supplied</p
Voices of Poor Entrepreneurs: An Ethnographic Study on the Lived Experience of Necessity-based Entrepreneurs in Bangladesh through Bourdieu's Theory of Practice
No full text"Entrepreneurship for the Poor" is not a new phenomenon but a rejuvenated perspective to explore entrepreneurship in the context of poverty. Policymakers and entrepreneurial scholars increasingly turn their attention to entrepreneurship to eradicate poverty. Recent development led us to a vital question: How can one expect to develop policies that will eradicate poverty through supporting entrepreneurship in the context of poverty with first understanding the' everydayness' of entrepreneurship? This thesis provides unique insight into the 'everydayness' of the poorest entrepreneurs.Through the lens of Bourdieu's habitus-based theory of practice, this study explored the nexus between agent and structure to understand the formation of entrepreneurial practices within a deprived community. To fully grasp how the poorest people practice entrepreneurship in real time, an ethnographic study was carried out for four months in three different rural markets within a deprived rural community in Bangladesh. The observation as' observer as participant' approach was employed to witness 'everydayness'. Also, 'semi-structured' interviews were used to rationalise and strengthen a more in-depth understanding of the context where entrepreneurial practices unfold. To explore and understand their world, I have interviewed traders, including water gipsies amulet sellers, and followed their entrepreneurial 'everydayness'.This study made a valuable contribution to Bourdieu's habitus-based theory of practice. Specifically, it challenged the entrenched structural nature of habitus. The study specifically explores how entrepreneurs in poverty continuously shape their habitus by creating new dispositions through their past and present experiences. Each trader contributed to their collective efforts to manipulate the system, which resulted in changes in poverty structures to become more successful entrepreneurs. Furthermore, this research challenges existing understandings of the nature of entrepreneurship in poverty by demonstrating how traders exhibited traits such as innovativeness, risk-taking capacity, alertness, creativity, and resilience through the process of becoming.</p
Figural Stone Sculpture & Image Perception in Pre-Viking England (c. 600–850)
No full textFollowing the arrival of Christian missionaries in Kent (597), figural images became central to the religious life of Anglo-Saxon England. According to Bede (d. 735), the early stages of the conversion process were supported by the use of religious depictions, as the missionaries sent by Gregory the Great carried an image of Christ in procession (HE). By the time he was writing, Bede could contemplate religious images in his own monasteries at Wearmouth and Jarrow (Northumbria), which had been set up to illustrate the content of Scriptures to less knowledgeable audiences (HA). Bede firmly believed in the use of religious images for didactic purposes, and explicitly stated it in his commentary on De Templo. These passages are well known to scholarship, but not much has been done to investigate the perception of religious images besides Bede, and beyond the evidence of written sources. This topic has been explored in the five chapters of this thesis through the analysis of Anglo-Latin texts and Anglo-Saxon figural stone sculpture, covering a period from c. 600 to 850, that is, after the conversion to Christianity and prior to the rise of Wessex, and when the so-called ‘iconoclast debate’ was taking place on the Continent (c. 730-850). Anglo-Latin texts provide useful information especially for the period c. 700-750; Anglo-Saxon figural sculpture dominates the later part of the period, where there is less written evidence, with the earliest carvings being dated c. 750. Figural stone sculpture provides the best evidence to understand the use and perception of figural images in England (c. 750-850), as it survives in large quantity and has rarely been displaced from its original location. This corpus also bears a wide range of iconographies and styles that usefully illustrate how viewers interacted with religious images, while also providing novel evidence on the history of pre-Viking England (c. pre- 850). Despite the popularity of this medium, however, figural stone sculpture hardly featured in Anglo-Latin sources (Chapter 1), and new methodologies had to be tested (Chapters 2-3) before considering the evidence of stone carving (Chapters 4-5). Terminological analysis of Latin sources proved particularly useful in this regard, offering an alternative approach to the topic. The discussion of Latin vocabulary was also relevant to the discussion of Anglo- Saxon figural sculpture (Chapters 4-5), as it inadvertently raised questions also over the stylistic descriptors and labels that we often employ to describe this material (Chapter 5). This thesis therefore resulted into a study of image perception in pre-Viking England, but also a revaluation of our perception (and preconceptions) of Anglo-Saxon figural sculpture. Stylistic analysis was central to this reassessment, and also highlighted new evidence on the religious and political history of early medieval England.</p
Causes, characteristics and improvement strategies for delayed interventions during paediatric deterioration: A mixed methods systematic review
No full textBackgroundChildren are susceptible to deterioration due to compensatory mechanisms. Timely recognition and intervention are strongly associated with improved clinical outcomes, whereas delays elevate mortality risk. Failure to rescue (FtR), the inability to prevent death following deterioration, represents a critical safety concern, yet contributory factors and contextual characteristics remain inadequately synthesised.AimIdentify and evaluate causes, characteristics and improvement strategies associated with delayed intervention during paediatric clinical deterioration in hospitalised children.MethodsA mixed-methods systematic review of five databases was conducted including studies on hospitalised children (0–18 years) reporting outcomes related to FtR (e.g. mortality), published after 2000. Rigour was ensured through PROSPERO registration (CRD420250651864) and appraisal checklists. Data were analysed using a convergent segregated approach.ResultsFifty-two studies included 820,000 hospitalised children and 4.4 million clinical events were synthesised. Qualitative and quantitative findings resulted in three themes: recognition, escalation and response, with qualitative findings presenting insight into barriers associated with each stage (including unclear escalation pathways and training gaps). Whilst quantitative findings reported prevalence of delayed recognition, escalation and response with pervasive organisational factors contributing to delays (e.g. staffing). Younger children and children with medical complexity (CMC) were at increased risk, and global majority populations were disproportionately affected. Integrated synthesis showed delays stem from individual, organisational, and systemic factors, while experienced nurses play a critical role in timely intervention.ConclusionIndividual, organisational and systemic factors contribute to delayed intervention. CMC and global majority populations were disproportionately affected. Findings highlight critical points of delay. Reporting participant characteristics (e.g. ethnicity, medical complexity) is essential to understand their impact upon deterioration pathways.Implications for clinical practiceNurses are pivotal in recognising and responding to deterioration, and should recognise high-risk groups. Awareness should translate into advocacy for early intervention.</p
Multi-modal assessment of cerebral haemodynamics and neurovascular coupling in ischaemic stroke
No full textBackground: Stroke impairs dynamic cerebral autoregulation (dCA) and neurovascular coupling (NVC). Diminished dCA and NVC associate with inhibited functional outcomes post-stroke. Cerebral haemodynamics assessments are presently expensive, invasive and impractical. Utilisation of macrovascular transcranial Doppler ultrasonography (TCD) and microvascular near-infrared spectroscopy (NIRS) are gaining traction. Multimodal cerebral haemodynamics assessments are attracting popularity but are still in infancy and largely restricted to healthy cohorts. Therefore, employing both techniques complimentarily in stroke survivors remains unexplored, possibly yielding clinical benefit.Aims/Objectives: This thesis presents a novel integrated analysis method to investigate cerebral haemodynamics in acute ischaemic stroke (AIS) and test feasibility in stroke survivors. Additionally, it assessed resting and task-activated differences in cerebral haemodynamics (dCA and NVC) between stroke survivors and healthy controls.Methods: Systematic review identified metrics to optimise TCD-based NVC assessments. Findings were combined with existing literature and informed thesis primary data collection methods: an integrated TCD and NIRS cerebral haemodynamics technique. Clinical feasibility investigations used this technique in stroke survivors and healthy controls, and a novel integrated analysis method was developed to interpret results. Technique feasibility was investigated alongside NVC impacts.Results: NVC assessments would benefit from corresponding vessel insonation, precise positioning and cognitive stimuli, and implementing previously validated protocols where possible/appropriate. Significant differences were identified between macrovascular and microvascular dCA, and arm-movement and dot-counting tasks appeared optimal for inducing NVC responses. Protocol acceptability was high and deemed to feasible in healthy and stroke.Conclusion: This thesis presents novel integrated investigation of stroke survivor cerebral haemodynamics and accompanying integrated analysis to understand and contextualise results. NIRS provides limited complementary information to TCD in this instance, but the technique itself is feasible and warrants further investigation. Future studies may include larger sample sizes and clinical conditions to validate results presented here and compare other metrics including age and recovery stage.</p
Navigating Competition And Collaboration: A Labour Process Study Of Nhs Workforce Experiences With Integrated Care Systems
No full textThis thesis explores the challenging (indeed, paradoxical) experiences of workers in Northern England as the NHS transitions from Clinical Commissioning Groups (CCGs) to Integrated Care Systems (ICS) in the region. While ICS is officially enshrined as a joint, logical, and fair reform agenda at national level, the heritage of NPM ideology can still be seen in the NHS’s marketisation, performance monitoring, and managerial dominance practices, which affect the relationships of power in local working practices, professional stances, and health system properties. By using Labour Process Theory (LPT) as its main analytical framework, the thesis investigates how NHS staff, clinicians and senior managers manage the contradictions between managerial rationality and professional values, metric-driven governance and relational care, and the competitive and collaborative logics of institutions.The research involves a series of semi-structured interviews and adopts a qualitative, interpretivist approach, in which the employee voice is analysed through the lenses of three overarching themes: Control Dynamics, Collaborative Shift, and Transition Experiences. The findings demonstrate that, although ICS brings new aspirations for integrated care, cross-functional cooperation, and patient-centred practices, such ambitions often conflict with enduring NPM ideology structures, short-term funding, audit culture, and fragmented commissioning. Thus, staff experience adaptation strain, emotional labour, and moral dissonance. The study also illuminates ongoing inequities in funding allocation and service workforce investment across the North of England, with potentially important implications for the ability of ICSs to address structural health disparity.By constructing the ’NPM ideology–ICS Workforce Experience Transition Model’, this thesis provides a framework that connects Labour Process Theory with empirical evidence. The model demonstrates how staff experiences of managerial oversight, surveillance, and collaboration shape morale, resistance, and perceptions of organisational change. It shows that while ICS reforms aim to promote collaboration, their effectiveness is limited if the residual logics of NPM competition, performance pressures, and managerial control remain embedded in practice. The findings highlight a need to foster cultures of trust, supportive leadership, and a stronger moral economy in healthcare, rather than just focusing on redesigning structures. These insights are particularly relevant for policymakers, NHS leaders, and reformers who seek to make collaborative models such as ICS more sustainable and inclusive.</p
Geopolitical risk and international business: a multi-disciplinary review and research agenda
No full textPurposeDespite heightened geopolitical tensions in the current global business environment, a comprehensive understanding of geopolitical risk has remained understudied in international business literature. Accordingly, the purpose of this paper is to synthesize and analyse existing research on the interface of geopolitical risk and international business activities, aiming to identify theoretical/methodological gaps and areas of future research.Design/methodology/approachThrough a systematic literature review method, this study critically evaluates 138 peer-reviewed articles published in a sample of 29 leading journals between 1990 and 2025.FindingsThis review paper provides novel research avenues around three key themes. First, it highlights the complexity and implications of competing geo-economic blocs and multi-polar geo-strategies for multinational enterprises’ (MNEs) activities. Second, it emphasizes the importance of non-market strategies as tools of mitigating geopolitical risk and multi-actor global threats. Third, the paper explores how the extraction and international trade of natural resources turn into seminal factors of growing geopolitical tensions.Practical implicationsThis study suggests a variety of methodological tools to assist IB researchers and policymakers in identifying ways to mitigate emerging risks stemming from shifting geographies and international political conflicts.Originality/valueMoving beyond home-host conflict unit of analysis, this study considers MNEs’ activities in an emerging and dynamic geo-economic context of competing and collaborative geo-economic groups, supply chains and trade corridors. Accordingly, the findings advance both theoretical and practical understandings of international business practices in a fragmented business environment.</p
LADA Diabetes Classification by Combining Genetic and Conventional Risk Factors
No full textLatent Autoimmune Diabetes in Adults (LADA) is the second most prevalent genre of diabetes after Type 2 but rarely recognised as a complex disease within its own right. Amid limited research benchmarks on LADA in the state-of-the-art, this thesis proposes a three-stage analysis for an accurate classification of LADA, with each stage informing benchmarks for the proceeding stage of analysis. Stage one models LADA using conventional variables alongside individual machine learning algorithms, where a classification accuracy of 85.51%, sensitivity of 84.09%, and specificity of 86.93%, alongside a precision of 86.93%, a recall of 84.53% and an F1 score of 85.71% are achieved. Stage two builds an ensemble of machine learning techniques identified in stage one along with building a novel Neural Ensemble Model (NEM) of three efficient deep learning techniques to model LADA classification and informs variable importance using conventional variables. Stage two generated a prediction accuracy of 92.00%, sensitivity of 91.77%, and specificity of 92.23% alongside a precision of 92.23%, recall at 91.79% and an F1 score of 92.02%. Stage three further improves the classification accuracy of LADA by introducing carefully chosen genetic variables below and above Genome Wide Association Studies (GWAS) along with the conventional variables fed as pseudo-random input sequence into the NEM model. Three different subsets including conventional variables alone, conventional and genetic variables below GWAS, and above GWAS are empirically investigated to determine the most reliable identification of case, control, precision, recall and variable importance. The proposed NEM model achieves a greater prediction accuracy when utilising a combination of conventional variables and eleven genetic variables below GWAS levels, with an accuracy of 96.06%, sensitivity of 97.45%, and specificity of 94.68% alongside a precision of 94.68%, recall of 97.38% and an F1 score of 96.01%, ultimately achieving a 97.45% correct identification of a positive LADA cases.</p