53417 research outputs found
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Discerning the causes of local deviations in genetic variation: the effect of low-recombination regions
No full textMultiple sclerosis and autoimmunity: learnings from post-streptococcal autoimmunity.
No full textGroup A streptococcus (GAS) or Streptococcus pyogenes, which typically causes a purulent pharyngitis, is the established cause of acute rheumatic fever (ARF) and several other autoimmune diseases. Primary prevention, achieved by treating acute pharyngitis with antibiotics, prevents ARF. After an initial attack of ARF, secondary prevention, using long-term prophylactic antibiotics, prevents further attacks and chronic end-organ damage or chronic rheumatic heart disease. Infection with the Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS). EBV-associated infectious mononucleosis (IM) is a significant risk factor for developing MS. Reasoning by analogy, similar to the role of GAS in ARF, we hypothesise that treating IM with effective antivirals will prevent or at least reduce the incidence of MS. Similarly, once MS is established, the chronic administration of effective EBV antivirals will prevent further MS attacks and prevent end-organ damage or disability in people with MS. Treating IM and preventing EBV latent-lytic cycling in patients with MS needs to be explored as strategies to prevent and treat MS, respectively
Informational complexity as a neural marker of cognitive reserve.
No full textIn Alzheimer's disease (AD), a mismatch between neurological damage and cognitive functioning often is attributed to individual differences in cognitive reserve. Understanding the neural mechanisms of cognitive reserve, which may differ across individuals, could help to assess the therapeutic effectiveness of interventions in AD. Here, 38 elderly participants performed a sustained attention task during high-density EEG while alert and drowsy. We defined cognitive reserve operationally as the ability to maintain task performance under drowsiness, with less impairment indicating higher reserve. Investigating performance variations during the active management of neural challenges offers a novel approach to studying cognitive reserve, capturing dynamics that mirror everyday cognitive demand. We relate performance under neural strain to various measures, including informational complexity using the Lempel-Ziv (LZsum) algorithm. We found a significant interaction between arousal and performance: LZsum values increased in high performers when drowsy but decreased in low performers. This effect was most pronounced in the frontal and central areas. These findings suggest LZsum reflects a compensatory mechanism and has potential as a neural marker of cognitive reserve. Additional structural MRI and network analyses revealed performance-related associations in entorhinal cortex, supramarginal gyrus, and frontoparietal networks, suggesting broader neural correlates of compensatory capacity
Improving outcomes in adult patients who self-harm-evaluating a brief psychological intervention in emergency departments (ASSURED): protocol of a randomised controlled clinical trial.
Get PDFBACKGROUND: Patients with self-harm and suicidal ideation are increasingly presenting in emergency departments (ED) in the UK. Self-harm is the strongest risk factor for suicide. Currently, there are no evidence-based interventions for self-harm offered in the context of general hospitals in the UK. This trial, funded by the National Institute for Health and Care Excellence (NIHR), aims to assess the clinical and cost-effectiveness of the ASSURED intervention. The ASSURED intervention includes up to five rapid follow-up contacts, comprising a narrative interview and enhanced safety planning session and three solution-focused sessions. The trial is sponsored by Devon Partnership NHS Trust and City St George's, University of London. METHODS: ASSURED is a multicentre, two-arm, parallel-group, individually randomised, controlled trial comparing the ASSURED intervention with usual care. The primary outcome is whether study participants re-attend ED and are referred to liaison psychiatry within 18 months from the date of randomisation. Secondary outcomes include suicidality, self-reported self-harm, psychological wellbeing, social outcomes, experiences of attending the ED, and suicide. The study will also evaluate the cost-effectiveness of the intervention. The aim of this study was to recruit and randomise 620 patients across 14 acute hospital sites in London, Devon, Somerset, and the Midlands. Participants are invited to complete research assessments at baseline and 3, 9, and 18 months. The first participant was enrolled in the study in August 2022, and the recruitment target was met in December 2024. DISCUSSION: This will be the first UK trial to test the effectiveness and cost-effectiveness of a rapid intervention for patients presenting to EDs with self-harm and suicidal ideation and has the potential to improve outcomes for these patients. TRIAL REGISTRATION: ISRCTN 13472559. Registered on 18 of November 2021
Patients With Pituitary Neuroendocrine Tumours Requiring Neurosurgery -Who Is Referring Them?
Get PDFOBJECTIVE: Patients living with pituitary neuroendocrine tumours (PitNETs) present with a spectrum of clinical manifestations and often follow a circuitous route to diagnosis, resulting in diagnostic delays. The objective of this study is to identify and report the various sources of referrals for patients who underwent pituitary resection for PitNETs in a tertiary referral centre for pituitary disease. DESIGN: Retrospective population-based cohort study. PATIENTS: Patients undergoing a first surgery for management of PitNET in Northern Ireland between 01/01/2000-19/07/2019. MEASUREMENTS: Demographics, referral sources, incidentaloma rates, apoplexy rates, symptoms, age at diagnosis and diagnostic delay according to referral source. RESULTS: Data were retrospectively analysed for 520 patients in whom the referral source leading to diagnosis was known. Fifty-seven percent of patients were male. Median age at diagnosis was 54 years (range 18-85). Patients were referred from 29 different sources. The majority of referrals came from general practice (23%), ophthalmology (14%), emergency medicine (9%), optician/optometry (9%) and internists (8%). Twenty-nine patients were referred following radiological discovery of an incidentaloma. Twenty-seven patients were referred with an initial presentation of pituitary apoplexy, with emergency medicine accounting for 70% of these referrals. Visual disturbance and headache were the most frequently documented symptoms. Median diagnostic delay was 2 years (range 0-25 years). CONCLUSIONS: Patients with PitNETs encounter a range of clinical services in their journey to pituitary surgery. Raising awareness of these tumours and educating healthcare professionals across all disciplines could reduce diagnostic delays, thereby minimising the adverse sequelae of delayed diagnosis
From Adoption to Actionability: Investigating Learning Analytics Integration in Learning Design for Higher Education Teaching Practice
No full textWhile learning analytics has gained significant attention in higher education, educators find it a constant challenge to translate learning analytics insights into actionable learning design decisions. This thesis investigates the integration of learning analytics in learning design through a theoretically grounded approach anchored in self-regulated learning, guided by three research questions: RQ-1: What actionable insights can be drawn from the relationship between learning analytics and learning design? RQ-2: What barriers and enablers do educators face when adopting learning analytics in learning design? RQ-3: What is the relationship between learner personality traits and learner engagement across different learning design activities? RQ-1 examined the practicalities required for successful integration through a systematic literature review combining bibliometric and thematic analysis of 85 empirical studies. The critical finding revealed that only 18.8% of studies demonstrated empirical evidence for actioning learning analytics in learning design, exposing widespread low adoption. This established the theoretical foundation through the Learning Analytics integrated Learning Design framework while imposing the investigation of implementation barriers, laying the foundation for RQ-2. RQ-2 investigated what prevents educators from using learning analytics in learning design, building on RQ-1's low adoption rates. A survey of 120 educators across 34 institutions in 8 countries identified factors affecting adoption patterns across educators in Computer Science and Engineering and other disciplines. These findings constructed the organisational onion framework, capturing technical, formal and informal level factors contributing to adoption. This revealed that systematic attention to multiple organisational layers is required; while educator perceptions on motivating factors highlighted the need to understand individual learner differences for effective integration, providing the foundation for RQ-3. RQ-3 addressed the empirical gap for closing the loop of actioning learning analytics, examining learning behaviours among different personalities across learning design activity types. Analysis of 72 learners across 100 activities categorised according to the Open University Learning Design Initiative taxonomy identified four distinct learner archetypes: resource explorers, consistent achievers, collaborative learners and delayed starters. This provides empirical evidence captured through learning analytics, for personalising learning design based on individual learner characteristics. This research makes distinct contributions towards actionability and adoption of learning analytics-informed learning design. Theoretical contributions include a learning analytics integrated learning design framework, organisational onion model for adoption, and learner personality-based learning design guidelines. Empirical contributions comprise adoption rates across faculties, and learner personality-engagement correlations. Practical contributions propose an assessed toolkit with implementation guidelines. Methodological contributions incorporate a mixed-method approach combining bibliometric analysis, survey methodology, and learning analytics data analysis. This research transforms learning analytics and learning design integration into systematic, evidence-based practice in higher education teaching
The Paradox of Non-Human Rights
No full textThis chapter takes inspiration from Costas Douzinas’s work on the paradoxes of human rights to illuminate the contradictory logic that underpins the emerging discourse of non-human rights. It interrogates the ontological and anthropological foundations upon which rights are granted, revealing how efforts to extend rights beyond the human often reproduce rather than displace anthropocentrism. What appears to be a progressive project of ‘decentring’ the human frequently results in a subtle form of ‘recentering,’ as non-human beings—animals, rivers, or machines—are recognized as rights-bearing subjects only insofar as they resemble humans. In this way, the human continues to serve as the moral and legal benchmark for determining worth, assimilating and flattening non-humans' alterity into familiar conceptual frameworks. Situating non-human rights within broader philosophical, economic, scientific, and technological contexts, the chapter exposes a pervasive metaphysical drive to overcome otherness and reaffirm a disembodied, abstract conception of the human as the ultimate standard of value, agency, and existence
