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Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study
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Data will be shared according to the GENFI data sharing agreement, after review by the GENFI data access committee with final approval granted by the GENFI steering committee.Supplementary data are available online at: https://academic.oup.com/braincomms/article/6/4/fcae185/7693659?login=true#supplementary-data .Appendix I: Coinvestigators of GENFI Consortium is available online at: https://academic.oup.com/braincomms/article/6/4/fcae185/7693659?login=true#479111702 .The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (β = −1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (β = −0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia.J.C.v.S. was supported by the Dioraphte Foundation grant 09-02-03-00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and Bluefield Project. F.M. received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease. R.S.-V. is supported by Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2) and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). D.G. received support from the European Joint Programme-Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. C.G. received funding from the European Joint Programme-Neurodegenerative Disease Research-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, Swedish Frontotemporal Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council. M.M. has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. J.B.R. has received funding from the Welcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). E.F. has received funding from a Canadian Institute of Health Research grant #327387. R.V. has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. J.L. received funding for this work by the Deutsche Forschungsgemeinschaft German Research Foundation under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198). M.O. has received funding from the Germany’s Federal Ministry of Education and Research (BMBF). J.D.R. is supported by the Bluefield Project and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and a Miriam Marks Brain Research UK Senior Fellowship. D.A. received funding from the Fondation Recherche Alzheimer and the Swiss National Science Foundation (project CRSK-3_196354/1). M.B. is supported by a fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). M.D. was supported by the ERC Consolidator Grant LIGHTUP (project #772953). Several authors of this publication (J.C.v.S., M.S., R.V., A.d.M., M.O., R.V. and J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND)—project ID no. 739510. This work was also supported by the European Joint Programme—Neurodegenerative Disease Research GENFI-PROX grant (2019-02248 to J.D.R., M.O., B.B., C.G., J.C.v.S. and M.S.) and by the Clinician Scientist programme ‘PRECISE.net’ funded by the Else Kröner-Fresenius-Stiftung (to C.W., D.M. and M.S.). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission
Thalamus involvement in genetic frontotemporal dementia assessed using structural and diffusion MRI: a GENFI study
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Anonymized data may be shared upon reasonable request from a qualified academic investigator for the purpose of replication of procedures and results detailed in this article.Supplementary data are available online at: https://academic.oup.com/braincomms/article/7/6/fcaf420/8301026#supplementary-data .Thalamic subregions are commonly, but variably, affected by different forms of frontotemporal dementia. We aimed to better characterize thalamic subregional involvement in genetic frontotemporal dementia with a recently published thalamus segmentation tool that utilizes structural and diffusion MRI, offering additional assessment of mean diffusivity and a more fine-grained analysis of the pulvinar specifically compared to previous studies. Using this tool, we performed thalamus segmentations in MRI scans from C9orf72, GRN and MAPT mutation carriers and mutation non-carriers with suitable 3-Tesla MRI cross-sectional data from the GENetic Frontotemporal dementia Initiative. Mutation carriers were divided according to their genetic group and Clinical Dementia Rating® Dementia Staging Instrument plus National Alzheimer’s Coordinating Center Behaviour and Language Domains global score (0 or 0.5: presymptomatic/prodromal stage, 1 or higher: symptomatic stage). Following stringent quality control and harmonization across sites and scanners, we compared volumes and mean diffusivity values of thalamic subregions in C9orf72 (47 presymptomatic, 10 symptomatic), GRN (57 presymptomatic, 11 symptomatic) and MAPT (31 presymptomatic, 12 symptomatic) mutation carriers to those in 109 mutation non-carriers with analyses of covariance including age and sex (and total intracranial volume for volumetric comparisons) as covariates. Presymptomatic C9orf72 expansion carriers showed smaller volumes (3–8% difference from non-carriers) and higher mean diffusivity (2–5% difference from non-carriers) for several thalamic subregions, including all pulvinar subdivisions. We found subtly larger volumes of the ventral anterior subregion and the non-medial pulvinar (3% difference from non-carriers for both) in presymptomatic GRN mutation carriers, and of the anteroventral subregion (5% difference from non-carriers) in presymptomatic MAPT mutation carriers. Symptomatic mutation carriers in all three genetic groups showed significantly smaller volumes and widespread higher mean diffusivity of thalamic subregions compared with non-carriers, which were overall most prominent in subregions involved in associative and limbic functions (the midline, medial pulvinar, anteroventral, mediodorsal, laterodorsal and lateral posterior subregions). Notably smaller volume (12–23% difference from non-carriers) and higher mean diffusivity (16–23% difference from non-carriers) of the most medial part of the medial pulvinar was a shared feature across the three genetic groups at the symptomatic stage. Overall, our study confirms that thalamic subregions are affected in genetic frontotemporal dementia and identifies prominent involvement of the most medial part of the medial pulvinar as a potential unifying feature in the variable pattern of thalamic subregional involvement across the main genetic groups.This work was primarily funded by Alzheimer’s Research UK (ARUK-IRG2019A003). S.S. and D.C.A. are also supported by the Wellcome Trust (221915). D.C.A. and H.F.J.T. are also supported by the UK Medical Research Council (MR/W031566/1, EP/Y028856/1) and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). M.B. acknowledges the support of NVIDIA Corporation with the donation of the Titan V GPU used for part of the analyses in this research. J.E.I. is also supported by the National Institute of Health (1RF1MH123195, 1R01AG070988, 1UM1MH130981, 1RF1AG080371, 1R21NS138995). J.B.R. has received funding from the Wellcome Trust (103838; 220258) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the UK Medical Research Council (MC_UU_00030/14; MR/T033371/1) and the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR203312: BRC-1215-20014), and the Holt Fellowship. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. D.M.C. is supported by the UK Dementia Research Institute which receives its funding from Dementia Research Institute Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK, Alzheimer’s Association (SG-666374-UK BIRTH COHORT) and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. J.C.V.S., L.C.J. and H.S. are supported by the Dioraphte Foundation grant 09-02-03-00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), ZonMw Onderzoeksprogramma Dementie (YOD-INCLUDED, project number 10510032120002), Alzheimer Nederland and the Bluefield Project. R.S.-V. is supported by Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2) and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). C.G. received funding from EU Joint Programme-Neurodegenerative Disease Research-Prefrontals Vetenskapsrådet Dnr 529-2014-7504, Vetenskapsrådet 2019-0224, Vetenskapsrådet 2015-02926, Vetenskapsrådet 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation, Dementia Foundation and Region Stockholm ALF-project. D.G. received support from the EU Joint Programme-Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. R.V. has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. J.L. received funding for this work from the Deutsche Forschungsgemeinschaft German Research Foundation under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198). M.O. has received funding from Germany’s Federal Ministry of Education and Research (BMBF). E.F. has received funding from a Canadian Institute of Health Research grant #327387. M.M. has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. F.M. is supported by the Tau Consortium and has received funding from the Carlos III Health Institute (PI19/01637). J.D.R. is supported by the Bluefield Project and the National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, and has received funding from a UK Medical Research Council Clinician Scientist Fellowship (MR/M008525/1) and a Miriam Marks Brain Research UK Senior Fellowship. Several authors of this publication (J.C.V.S., M.S., R.V., A.d.M., M.O., R.V. and J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND)—Project ID No 739510. This work was also supported by the EU Joint Programme-Neurodegenerative Disease Research GENFI-PROX grant [2019-02248; to J.D.R., M.O., B.B., C.G., J.C.V.S. and M.S.]
Timeless: Wings ascend forever
Get PDFThis thesis was submitted for the award of Master of Philosophy and was awarded by Brunel University LondonThis thesis includes chapters one to nine of a novel and a critical reflective essay. My novel
Timeless: Wings Ascend Forever is a neo-Victorian Gothic Fantasy inspired by R. L. Stevenson's
The Strange Case of Dr Jekyll and Mr Hyde (1886). The novel examines the double identities
of the protagonists James and Seraph and explores the moral ambiguity of the characters in
a Victorian setting. Through an analysis of the novel as a significant addition to the neo-
Victorian gothic and fantasy genres, this critical thesis underscores the importance of
reassessing the gothic motif of doubling in both contemporary and forthcoming literary
works. The reflective essay focuses on both the novel and Jekyll and Hyde in the context of
gothic reflections between the Victorian past and the contemporary present. It examines how
double identities interact and how these identities are represented in late-Victorian and neo-
Victorian gothic works. This thesis critically reflects on the novel in relation to its key gothic
intertexts.
The first chapter of the reflective essay explores the types of genres and narrative
structures that my novel encounters and the purpose of using the themes and tropes of said
genres in relation to the representation of double identities. The second chapter is a
comparative study that analyses the novel alongside Jekyll and Hyde in terms of the texts’
representations of double identities, reflecting on questions of moral ambiguity and
degeneration. This chapter also reflects on my writing choices and demonstrates the
relationship between double identities in contemporary (textual and filmic) reworkings of
Victorian gothic fiction and fantasy fiction. This thesis explores the limitations of the gothic
double and the implications of double identities in relation to attempts to differentiate
between reality and fantasy, considering questions of historical accuracy, myths, and fantastical elements that are central to the construction of my novel and its intertextual
relationship with Jekyll and Hyde
The influence of AI chatbot quality on user proactive engagement: Integrating cognitive absorption, motivational, decision, and trust perspectives
No full textThis thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonAs artificial intelligence continues to reshape service experiences, chatbots are no longer viewed as simple support tools, but as frontline representatives of brand experience. While many organisations have adopted AI chatbots to streamline operations, far less is understood about how users psychologically engage with these systems, particularly in high-contact, emotionally sensitive industries like hospitality. This study addresses that gap by developing and validating a comprehensive framework to explain how the perceived quality of AI chatbot systems influences user proactive engagement. The research is situated in the UK hospitality sector, where the pressure for seamless, reliable, and emotionally responsive service is especially high.
The conceptual model integrates two complementary theoretical foundations: Expectancy Violation Theory, which explains how people respond to unexpected experiences in human–machine interactions; and the System and User Characteristics for Cognitive Absorption framework, which explores how technological and psychological factors influence deep engagement with digital systems. Together, these theories guide the model’s development and interpretation.
The study conceptualises AI chatbot quality as a multidimensional construct, encompassing usefulness, ease of use, system quality, and service quality, and explores its influence through five psychological mediators: trust, cognitive absorption, motivation, decision comfort, and decision confidence. A sequential mixed-methods approach was adopted. In the qualitative phase, 14 interviews with hospitality professionals and academic experts helped refine the constructs and ensure contextual fit. The quantitative phase was based on responses from 413 participants who had experience interacting with chatbots in hospitality settings. Partial Least Squares Structural Equation Modelling was used to test the model.
The findings offer both theoretical and practical insight. Trust, shaped by perceptions of competence, benevolence, and integrity, played a central role in translating system quality into user confidence and motivation (Rezaei et al., 2024). Cognitive absorption emerged as essential for sustained engagement, reinforcing the need for chatbots to offer not just functional value but immersive, enjoyable experiences (Sarraf et al., 2024). Motivation proved to be multidimensional, with users driven by hedonic, functional, cognitive, and social incentives (Kautish et al., 2023). Importantly, the study distinguishes between decision confidence and decision comfort. While both relate to user assurance in decision-making, only decision comfort—how emotionally at ease users feel, significantly predicted engagement. This points to the growing importance of emotional intelligence in AI design (Barta et al., 2023; Castelo et al., 2019).
Beyond its empirical contributions, the study offers a practical framework for hospitality organisations aiming to improve their AI service strategies. The results suggest that successful chatbot deployment requires more than technical functionality, it also demands psychological sensitivity. Chatbots that communicate clearly, build trust, and ease decision-making anxiety are more likely to encourage repeat engagement and foster stronger user relationships.
In short, this research reframes AI chatbots not just as automated agents, but as emotionally intelligent touchpoints. By aligning technical performance with psychological experience, organisations can create more human-centred AI interactions that resonate with users and deliver lasting value
Developing a Framework for Using Large Language Models for Viva Assessments in Higher Education
Get PDFThis paper presents a comprehensive framework for evaluating Large Language Models (LLMs) based on educational performance areas and established evaluation metrics. The study bridges the gap between traditional academic assessment criteria and modern AI evaluation techniques, aligning metrics such as coherence, relevance, completeness, and creativity with performance areas like problem definition, methodology, and product outcomes. Drawing insights from experimental results, the framework highlights the top 10 evaluation metrics frequently observed and emphasizes their significance in assessing AI -generated responses. A critical analysis identifies limitations in the initial framework proposed by ChatGPT, leading to refined strategies for more comprehensive evaluation. The refined framework addresses limitations of subjectivity, overlapping criteria, and weighting mechanisms, offering a dynamic evaluation model for both technical and educational contexts. The findings contribute to advancing interdisciplinary evaluation methodologies and offer valuable insights for educators, researchers, and developers in optimizing LLM applications for educational purposes.10.13039/501100000780-European Union: Partially funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Commission-EU. Neither the European Union nor the granting authority can be held responsible for them
The impact of technology: how features, resources and task demands shape digital well-being
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Despite growing awareness that digital technology has both positive and negative implications, the role of specific features in shaping users’ overall well-being remains inadequately understood. We aim to investigate the relationship between technology features, type of task, users’ resources and well-being, to address conflicting empirical evidence in the extant literature.
Design/methodology/approach:
We draw on the Conservation of Resources theory and Involvement theory to analyse user experiences with the digital platforms of a local authority in England. We use an explanatory case-study, nested in a critical realist perspective, and draw on observations, document analysis and interviews with two stakeholder groups.
Findings:
We find that digital well-being is a situated condition shaped by users’ goals, resources and experiences. This explains why the same technology feature – e.g. self-service – supports well-being in low-involvement tasks but not in high-involvement ones. We also show that the hedonic and functional aspects of technology are interdependent in the production of digital well-being and describe how the alignment between resources’ affordances and the users’ specific needs and goals shape well-being.
Originality/value:
We address the conflicting evidence regarding the impact of digital technology on well-being, in the extant literature. This will support future researchers to critically analyse under what conditions technology will benefit vs harm individual well-being and society. It also highlights the importance of designing digital platforms that are aligned with the level of user involvement, to create digital solutions that promote user well-being and foster an inclusive society.This project received funding from the Global Lives Research Centre at Brunel University London, UK
Investigation on the AE characteristics and progressive failure behaviors of tunnels by strength reduction method
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The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The fracture features and failure mechanisms of tunnels excavated in shallow and deep rock masses are investigated using a series of three-dimensional heterogeneous models that incorporate cross section, tunnel alignment, faults and tunnel support system. The strength reduction method is embedded in the rock failure process analysis method to achieve the gradual fracture process, macro failure mode and safety factor, and to reproduce the characteristic fracture phenomenon of surrounding rock masses. The mechanical mechanisms and acoustic emission energy of deep rocks at the different stages of the whole formation process of zonal disintegration are further discussed. The results indicate that the zonal disintegration process is triggered by the stress redistribution; cross section influences the stress buildup, stress shadow and stress transfer as well as the failure mode of surrounding rock mass; the dip of faults and tunnel support system can affect zonal disintegration pattern near the tunnel surface along their strikes; the twin-tunnel layout makes zonal disintegration pattern more intricate. These insights advance our understanding of the zonal disintegration in deep engineering.The author(s) declare that financial support was received for the research and/or publication of this article. The present work was financially supported by the Beijing Natural Science Foundation, China (Grant No. 2244099), the China Postdoctoral Science Foundation, China (Grant No. 2023TQ0025) and the Major National Science and Technology Project for Deep Earth: Mobile tailings-waste homogeneous filling and rock pressure coordination control technology, China (Grant No. 2024ZD1003805)
Evaluation of the Parental Engagement Toolkit: final report for the City of London Corporation
Get PDFThis report presents the findings of an evaluation of the ‘Parental Engagement Toolkit: accessible tools for the City Family of schools’ (CoLC, 2024 a & b). The City of London Corporation (CoLC) commissioned The Parenting Circle to devise two toolkits to be used in primary and secondary schools across the City Family of Schools.City of London Corporation
Enhancing creativity with domain-specific design heuristics for digital product innovation
No full textSupplemental material is available online at: https://www.tandfonline.com/doi/full/10.1080/14606925.2025.2496711#supplemental-material-section (MS Word (6 MB)).A key challenge for product designers is the generation of creative ideas that meet the functional and usability requirements of clients and users. This challenge has been further compounded by the opportunities arising from the integration of digital technologies. To enhance creativity in design practice, we proposed a domain-specific DHS, supported by a novel framework, to specifically aid the concept generation phase. Using this framework, DHS10 was developed specifically for digital innovation, based on the analysis of 583 award-winning concept designs in the field of digital innovation. An empirical evaluation study investigated the effectiveness and advantages of this tool. The findings suggest that DHS10 can serve as an effective ideation tool, helping design students generate a higher number of innovative and diverse concepts for digital innovation while reducing design fixation.This work was supported by the Humanities and Social Sciences Research Youth Fund Project of the Ministry of Education of China [No. 23YJCZH094]
Multi-Scale Residual Convolutional Neural Network with Hybrid Attention for Bearing Fault Detection
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The data presented in this paper are available upon request from the corresponding author. The data are not publicly available due to considerations of privacy protection and ethical principles.This paper proposes an advanced deep convolutional neural network model for motor bearing fault detection that was designed to overcome the limitations of traditional models in feature extraction, accuracy, and generalization under complex operating conditions. The model combines multi-scale residuals, hybrid attention mechanisms, and dual global pooling to enhance the performance. Convolutional layers efficiently extract features, while hybrid attention mechanisms strengthen the feature representation. The multi-scale residual network structure captures features at various scales, and fault classification is performed using global average and max pooling. The model was trained with the Adam optimizer and sparse categorical cross-entropy loss by incorporating a learning rate decay mechanism to refine the training process. Experiments on the University of Paderborn bearing dataset across four conditions showed that the model had superior performance, where it achieved a diagnostic accuracy of 99.7%, which surpassed traditional models, like AMCNN, LeNet5, and AlexNet. Comparative experiments on rolling bearing vibration and motor current datasets across four bearing conditions highlighted the model’s effectiveness and broad applicability in motor fault detection. Its robust feature extraction and classification capabilities make it a reliable solution for motor bearing fault diagnosis, with significant potential for real-world applications. This makes it a reliable solution for motor bearing fault diagnosis with significant potential for practical applications.This research was funded by the Jiangsu Graduate Research Fund Innovation Project (grant number KYCX23_3059) and the APC was funded by Changzhou University
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