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The impact of polygenic risks on neurotransmitter‐related grey matter atrophy in Alzheimer’s disease
Get PDFPoster presentation at AAIC 2024, Philadelphia, PA, USA, 28 July - 1 August 2024.Background:
Tau protein tangles have been recently shown to accumulate in multiple brainstem nuclei in pre-cortical Alzheimer’s disease (AD) stages. The impact of neurotransmission alterations on brain atrophy and their genetic correlates in AD remain unexplored. Therefore, the aims of this study were: 1) to investigate associations between grey matter (GM) loss across the AD continuum and the distribution of multiple neurotransmitter receptors/transporters; 2) to investigate the impact of polygenic risk scores for AD (PRSs) on such associations.
Method:
T1-weighted MRI scans, genetic and clinical data were selected for 800 ADNI participants (age = 74.1±7.6; M = 55.3%) including 203 cognitively unimpaired older adults (CU), 442 with mild cognitive impairment (MCI) and 155 with AD. GM atrophy was investigated in MCI and AD groups, compared with CU. JuSpace was used to calculate correlations between GM atrophy and the distribution of several neurotransmitters. Two PRSs, with (AD-PRS) and without APOE (AD-PRSnoAPOE) were calculated using a Bayesian approach and investigated as predictors of the strength of correlation between GM volume (GMV) and neurotransmitters in general linear models.
Result:
GM atrophy was primarily in medio-temporal areas in MCI, while was widespread in AD participants. In both groups, atrophy was negatively associated with serotoninergic and dopaminergic receptors/transporters. In the whole sample, AD-PRS and AD-PRSnoAPOE were negatively associated with the strength of correlation between GMV and 2 serotonin receptors (5-HT1a and 5-HT4). AD-PRS was also associated with GMV-FDOPA (negatively) and with GMV-5-HT1b (positively) correlation coefficients. In amyloid positive participants, AD-PRS was associated with GMV-5-HT1b (b = 0.012, p < 0.001) and AD-PRSnoAPOE with GMV-5-HT4 (b = -0.013, p < 0.001) correlation strength only.
Conclusion:
GM loss due to AD may be particularly affected by the alterations in inhibitory serotoninergic and in presynaptic dopaminergic activity, that are known to affect acetylcholine function and memory decline. Such alterations appear to be driven by polygenic risk for AD, with potential specific effects dependent on APOE genotype and amyloid status. Investigating further the impact of AD-PRS on various neurotransmitter-related neural alterations may help clarifying neuropathological changes in pre-clinical AD and support early detection of people at risk of dementia
Polygenic risk for schizophrenia predicts dopamine‐related grey matter volume alterations in people with Alzheimer’s disease and psychotic symptoms
Get PDFPoster presentation at AAIC 2024, Philadelphia, PA, USA, 28 July - 1 August 2024.Background:
Psychotic symptoms may manifest in Alzheimer’s disease (AD), especially in advanced disease stages and in patients with higher polygenic risk scores for schizophrenia (SCZ-PRS). Such genetic risk seems also to influence grey matter volume (GMV) alterations in patients with psychosis. Since multiple neurotransmitter systems, namely dopamine (DA) and serotonin (5-HT), have been implicated in psychosis, the aim of this study was to investigate whether a SCZ-PRS may explain variance in the association between GMV and the cerebral distribution of DA and 5-HT.
Method:
Eight-hundred ADNI participants with genetic data were selected for this study: 203 cognitively unimpaired (CU) and 597 people with AD. Patient were divided into psychotic (PT-PS, n = 121) and non-psychotic (PT-NP, n = 476) based on available NPI-Q data. A SCZ-PRS was calculated for each participant using a Bayesian approach. T1-weighted MRI scans were pre-processed with SMP12 and JuSpace to extract Fisher’s z-transformed individual correlation coefficients between GMV and PET atlases for DA and 5-HT receptors/transporters. General linear models were used to test the association between the SCZ-PRS and GMV-neurotransmitter correlation coefficients (p < 0.05). Analyses were replicated in a sub-sample of amyloid-positive participants.
Result:
The SCZ-PRS was negatively associated with correlations coefficients between GMV and the D2 dopaminergic receptor (D2r) in the whole sample (β = -0.016, p = 0.023) and in the PT-PS group (β = -0.037, p = 0.030). However, the latter association was significant only when analyses were restricted to amyloid-positive participants (Figure 1). In the PT-NP group, the SCZ-PRS was negatively associated with correlations coefficients between GMV and two 5-HT receptors (5-HT1b: β = -0.014, p = 0.027; 5-HT2a: β = -0.013, p = 0.038). No between-group differences in SCZ-PRSs were found.
Conclusion:
The SCZ-PRS was differentially associated with GMV alterations linked to either DA, in PT-PS, or 5-HT, in PT-NP, that are both neurotransmitters previously implicated in psychotic symptoms. However, the influence of SCZ-PRS on DA-related GMV loss appears to be primarily relevant to psychotic manifestations in AD. These findings suggest that future innovative pharmacological interventions targeting the DA system may be beneficial to treat psychosis in AD
Do We Have Sufficient Evidence to Derive Innovative Approaches to Assessing Unmet Need, Delivering Education on Bladder and Bowel Continence Health, and Providing a Better Environment for Joint Decision‐Making? ICI‐RS 2024
Get PDFData Availability Statement:
The authors have nothing to report.Acknowledgments:
We are grateful to all contributors to this debate and discussion held at the ICI-RS meeting in Bristol, June 2024.Context:
Improved continence outcomes are reliant on identification of unmet need, education delivery, and shared decision-making. The evidence base on which to derive innovative approaches in these areas was unclear.
Methods:
A debate held at the International Consultation on Incontinence-Research Society meeting, held in Bristol in June 2024, considered ways to improve research requirements to advance these areas.
Results and Conclusion:
Artificial intelligence solutions and digital approaches to healthcare are emerging at pace and offer possibilities to improve these three key areas but this must be driven by person-centered approaches. Care must be taken to avoid increasing inequality through digital exclusion and language barriers. Research questions are highlighted to derive innovation in these three key areas
Optimisation of a converging-diverging nozzle for the wet-to-dry expansion of the siloxane MM
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Data will be made available on request.Wet-to-dry expansion within the nozzle guide vane of an ORC turbine has been proposed as a means to improve the power output of ORC systems for waste-heat recovery (< 250 °C). However, given the rapid fluid acceleration in the stator, the phases can develop significant velocity and temperature disparity due to density difference and finite rate of interphase heat transfer. Since these factors can significantly affect the phase-change process, wet-to-dry nozzle design techniques must account for non-equilibrium effects. The first part of this paper aims to further verify a previously developed quasi-1D inviscid non-equilibrium nozzle design tool by comparing it to non-equilibrium CFD simulations, which, unlike the design model, account for lateral flow variations, viscous and turbulence effects, along with secondary momentum forces. Within the CFD model, the interphase mass, momentum, and energy exchange models have been updated using correlations better tailored to evaporating droplet flows and a corrected drag equation. Moreover, the definition of the vapour mass fraction has been modified, while a simplified droplet breakup model has been used to predict the droplet size. The results from the CFD simulations indicate that the outlet vapour mass fraction is approximately 10 to 15% lower than that predicted by the quasi-1D tool. However, the overall flow behaviour and phase-change pattern were in satisfactory agreement, justifying the use of the design tool for 1D optimisation. As such, the quasi-1D tool is coupled to a gradient-based optimiser to optimise the nozzle pressure profile and enhance evaporation of siloxane MM for expansions with an inlet pressure ranging from 450 to 650 kPa, and inlet vapour quality of 0.3. CFD simulations of the optimised geometries indicate an increase of 3.3 to 5.7% in the outlet vapour mass fraction, which was raised from 84.9, 87.7 and 90.5% to 88.2, 93.4 and 95.7% for 450, 550 and 650 kPa inlet pressures respectively. However, a more abrupt expansion in the optimised nozzles resulted in the development of a shock and led to deterioration in nozzle efficiency compared to the baseline nozzles. Finally, a CFD-based shape optimisation was conducted, which demonstrated that it may be difficult to further enhance the vapourisation rate. However, the optimised geometry did mitigate the effect of the oblique shock that appears in the diverging section of the nozzle, raising the expansion efficiency by around 3%.This project was supported by the Royal Academy of Engineering, United Kingdom under the Research Fellowship scheme (2019–2024). Award number: RF\201819\18\23. The authors would also like to express gratitude towards City, University of London for funding the Ph.D. studentship of Mr Pawel Ogrodniczak
Measuring and mapping authentic assessment with a novel quantitative typology
Get PDFAuthentic assessments are seen as a promising response to many of the challenges currently facing Higher Education. Studies have identified shared characteristics of authentic assessments, but it is also argued that the term is vague and subjective. Drawing on existing frameworks we have established a standardised measure to evaluate authenticity in the axes of product and process allowing graphical representation and mapping across programmes. We have mapped the assessments on two programmes in our institution. We show an appropriate increase of authenticity of assessment year-on-year in one programme and have identified assessments which have been altered to increase their authenticity in the other. Our tool will allow educators to estimate authenticity on their academic programmes, guide discussions and identify areas for improvement. A balanced mix of assessments in a programme ensures both skills development and knowledge requirements are fulfilled, with sustainability of assessment enabling increasingly authentic assessments over time.DUTCH
Authentieke opdrachten worden gezien als een veelbelovende oplossing voor veel van de uitdagingen waar het hoger onderwijs momenteel voor staat. Studies hebben gedeelde kenmerken van authentieke opdrachten geïdentificeerd, maar het is ook vastgesteld dat de term vaag en subjectief is. Op basis van bestaande theorien hebben we een gestandaardiseerde maatstaf opgesteld om authenticiteit te evalueren in de gebieden van product en proces, waardoor we een grafische weergave kunnen geven op studie programme niveau. We hebben de beoordelingen in twee programma's binnen onze instelling in kaart gebracht. We zien een toename van de authenticiteit van opdrachten van jaar tot jaar in de programma’s en hebben opdrachten geïdentificeerd die zijn aangepast om hun authenticiteit te vergroten. Onze tool stelt docenten in staat om de authenticiteit van hun academische programma's in te schatten, discussies te sturen en verbeterpunten te identificeren. Een gebalanceerde mix van opdrachten in een programma zorgt ervoor dat zowel de ontwikkeling van vaardigheden als de kennisvereisten worden vervuld
Modelling visibility and surface deformation in particle-fluid flow fields generated by helicopter rotors
Get PDFThe article archived on this institutional repository is a preprint available at: arXiv:2412.16438v1 [physics.flu-dyn], https://arxiv.org/abs/2412.16438v1 . It has not been certified by peer review.As a helicopter descends towards a bed of sand, a high velocity particle laden cloud can form around the helicopter body, a phenomenon known as "brownout", and a consequence of which can potentially be a significant deterioration in visibility for the helicopter pilot. Here we consider a recently developed physically based rational mathematical model for the generation of wind-driven particle flow fields from otherwise static particle beds, one application of which is the scenario considered here. We introduce a directional opacity measure, defined for each observation angle from the helicopter cockpit, and show how visibility may vary in the model as certain parameters are varied. In particular, we demonstrate a counterintuitive result suggesting that, with specific yet potentially realistic parameter choices, pilot visibility may be improved in some viewing directions if the helicopter were hovering at a lower altitude. We also calculate the associated deformation of the upper surface of the particle bed, and show how certain surface deformation features may be sensitive to variation of key parameters...
Causation processes and innovation strategy in small- and medium-sized firms in emerging countries: The moderating role of founder-CEOs' human capital
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The data that has been used is confidential.In the dynamic and resource-constrained environment of emerging countries, small- and medium-sized enterprises (SMEs) face unique challenges in pursuing innovation strategy. This study addresses a critical gap in understanding how founder-CEOs' causation processes interact with human capital to shape SMEs' innovation strategy. While previous research has separately explored the impact of causation processes on innovation and the influence of founder-CEOs' managerial experience, these streams remain disconnected. Drawing on human capital theory, we investigate how adopting causation processes affects innovation strategy in emerging country SMEs, focusing on the moderating role of founder-CEOs' human capital. Our primary analysis utilises two waves of multi-informant survey data from 103 Indian SMEs. Results reveal that founder-CEOs' specific human capital moderates the relationship between causation processes and innovation strategy. This moderating effect strengthens with rich marketing experience but weakens with extensive technological experience. We supplement our findings with qualitative insights from interviews with 14 Indian and 19 Chinese SME founder-CEOs. This additional analysis provides further context and validates the applicability of our results. Our research contributes to a nuanced understanding of SME innovation dynamics in emerging countries and offers valuable implications for both theory and practice in fostering innovation-driven growth in this vital economic context.Key project of National Science Foundation of China (Grant No. 72032008), and National Social Sciences Foundation of China
AI-Enabled Healthcare and Enhanced Computational Resource Management With Digital Twins Into Task Offloading Strategies
Get PDFEfficient management of computational resources and data in the healthcare sector is increasingly challenging, particularly with the advent of advanced healthcare technologies. Effective task offloading mechanisms are crucial for enhancing system performance, patient care, and data security. This study aims to introduce and evaluate a novel framework for task offloading in healthcare environments. The framework seeks to address real-time healthcare demands through dynamic offloading strategies, incorporating digital twins (DT) and social health determinants to personalise and improve healthcare interventions. Employing both partial and binary offloading strategies, multi-protocol communications are supported by the framework, ensuring seamless data exchange. The integration of DT and social health determinants into offloading decisions stands at the core of the methodology, rigorously tested in real-time settings. Iterative testing confirms the framework’s effectiveness, demonstrating a 10% enhancement in energy efficiency and a 20% reduction in network latency with 20 MEC nodes. The inclusion of 30 MEC nodes further reduced latency by 33.4% and power usage by 53.8% for data sizes up to 100 MB, evidencing significant advancements in healthcare technology integration. A significant gap in existing literature is bridged, and a new trajectory for technological innovation in healthcare systems is set by the research. The study underscores the potential of sophisticated offloading techniques to revolutionise healthcare delivery, offering a holistic solution to the challenges of data and computational management in medical contexts.10.13039/501100007914-Brunel University London, Uxbridge, U.K
Micro Software Defined Control (μSDC): Empowering Smart Grids With Enhanced Control and Optimization
Get PDFIt has become a fundamental component of the electrical networking system, both in residential and industrial settings, to adopt advanced power meter architecture. With traditional smart meters, a bi-channel communication network is established between homes and utility companies, providing consumers with information regarding their daily power consumption. Manual meter reading, however, may result in inaccurate meter logging and incorrect billing criteria, which will lead to an increase in overhead costs associated with deploying meter readers and billing power consumption for each site within metropolitan and large urban areas. Moreover, the current smart metering system does not enable consumers to predict their future energy consumption, only providing insights into their current power consumption and accumulative costs. In order to address these issues, we propose a novel intelligent Software-Defined Control (SDC) super cluster with a comprehensive architecture based on SDN routing capabilities, which differs from conventional commercial smart meters. The developed micro cluster is enhanced to run full availability and high performance compared to traditional metering system. Moreover it deploys intelligent capabilities to predict the consumption of power per home, we implemented a polynomial model experimentally. Furthermore, we propose an intelligent Software-Defined Controller Gateway (SDN-GW) to serve as a traffic predictor between distributed metering nodes and the cloud data warehouse, eliminating congestion caused by the large volumes of traffic data generated periodically by the metering nodes. Based on the experimental results, the software-defined control system was estimated to have 97.75% percent accuracy in power prediction, and the traffic flow predictor demonstrated 98.79% percent accuracy in network traffic prediction. Furthermore, the proposed SDN-GW achieved 29.37% power consumption rate compared to standard routing engine
Enhancing offloading with cybersecurity in edge computing for digital twin-driven patient monitoring
Get PDFData Availability Statement: Data is available on request from the authors.In healthcare, the use of digital twin (DT) technology has been recognised as essential for enhancing patient care through real-time remote monitoring. However, concerns regarding risk prediction, task offloading, and data security have been raised due to the integration of the Internet of Things (IoT) in remote healthcare. In this study, a new method was introduced, combines edge computing with sophisticated cybersecurity solutions. A vast amount of environmental and physiological data has been gathered, allowing for thorough understanding of patients. The system included hybrid encryption, threat prediction, Merkle Tree verification, certificate-based authentication, and secure communication. The feasibility of the proposal was evaluated by using an ESP32-Azure IoT Kit and Azure Cloud to evaluate the system's capacity to securely send patient data to healthcare institutions and stakeholders, while simultaneously upholding data confidentiality. The system demonstrated a notable improvement in encryption speed, with 27.18%, represented as the improved efficiency and achieved storage efficiency ratio 0.673. Furthermore, the evidence from the simulations showed that the system's performance was not affected by encryption since encryption times continuously remained within a narrow range. Moreover, proactive alert of probable security risks would be detected from the predictive analytics, hence strong data integrity assurance. The results suggest the proposed system provided a proactive, personalised care approach for cybersecurity-protected DT healthcare (DTH) high-level modelling and simulation, enabled via IoT and cloud computing under improved threat prediction.Brunel University London. Grant Number: K015
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