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UK Longitudinal Linkage Collaboration (UK LLC): the national Trusted Research Environment for longitudinal research
No full textIntroduction The UK Longitudinal Linkage Collaboration (UK LLC) is the national Trusted Research Environment (TRE) for the UK's longitudinal research community, supporting the UK's unparalleled collection of Longitudinal Population Studies (LPS). Initially set up as a COVID-19 research resource, UK LLC is now a generic database for any research for the public good. Objectives UK LLC supports longitudinal research by providing record linkage and TRE services.Methods The UK LLC partnership provides a secure analytics environment, a trusted third-party linkage processor and a comprehensive governance framework to minimise risks to participant confidentiality. UK LLC is ISO 27001 certified and accredited by the UK Statistics Authority as a processor under the Digital Economy Act. The active involvement by members of UK LLC's public involvement programme ensures UK LLC is acceptable to LPS participants and the wider public. All UK LPS are eligible for inclusion. Researchers can apply to access the TRE via an approach that fulfils the needs of the LPS, the linked data owners and includes a review by public contributors. Results Twenty-two LPS have so far joined UK LLC. Where permissions allow, participants are linked to their National Health Service (NHS) England, NHS Wales and place-based records, with work ongoing to link to NHS Scotland and non-health administrative records, including Department for Work and Pensions and His Majesty's (HM) Revenue and Customs. UK LLC Explore allows potential researchers to discover the breadth of data available in the TRE. All applications are listed on UK LLC's publicly accessible Data Access Register. Conclusions UK LLC enables researchers to interrogate pooled LPS participant data that are systematically linked to diverse records. UK LLC remains open to additional LPS joining the partnership and will increase the breadth of data to support the longitudinal research community and attract increasing numbers of researchers across multiple disciplines, government departments and industry.</p
Sir William Whitla and the Apocalypse. The Gary Love Lecture 2023
No full textSir William Whitla, former Professor or Materia Medica at Queen’s University, Belfast was a towering figure in Ulster medicine. A physician, scholar, and philanthropist, his legacy is significant. However, few are aware that, in addition to a number of extremely successful medical texts, he also published a book on biblical prophecy based on an earlier work by Sir Isaac Newton exploring of the prophecy of Daniel and the Apocalypse of St John
Single-pulse Gy-scale irradiation of biological cells at 10<sup>13</sup> Gy s<sup>−1</sup> average dose-rates from a laser-wakefield accelerator
No full textObjective. We report on the first experimental characterisation of a laser-wakefield accelerator able to deliver, in a single pulse, doses in excess of 1 Gy on timescales of the order of a hundred femtoseconds, reaching unprecedented average dose-rates of up to 1013 Gy s−1. Approach. The irradiator is demonstrated to deliver doses tuneable up to 2.2 Gy in a cm2 area and with a high degree of longitudinal and transverse uniformity in a single irradiation. Main results. Proof-of-principle irradiation of patient-derived glioblastoma stem-like cells and human skin fibroblast cells show indications of a differential cellular response, when compared to reference irradiations at conventional dose-rates. These include a statistically significant increase in relative biological effectiveness ( 1.40 ± 0.08 at 50% survival for both cell lines) and a significant reduction of the relative radioresistance of tumour cells. Data analysis provides preliminary indications that these effects might not be fully explained by induced oxygen depletion in the cells but may be instead linked to a higher complexity of the damages triggered by the ultra-high density of ionising tracks of femtosecond-scale radiation pulses. Significance. These results demonstrate an integrated platform for systematic radiobiological studies at unprecedented beam durations and dose-rates, a unique infrastructure for translational research in radiobiology at the femtosecond scale.</p
Religious revival and the challenge of evangelical primitivism: opposition to the brethren and lay preachers in Ulster after the 1859 Revival
No full textDeveloping virtual reality environments for trauma focused cognitive behavioural therapy in clinical routine settings: an open-label case- series study
No full textThis open-label case-series study examined the feasibility of implementing VR Photoscan, a cost-effective Virtual Reality intervention, within a community-based mental health care setting in Northern Ireland. By integrating VR Photoscan into trauma-focused Cognitive Behavioural Therapy, the study explored its acceptability among clients and therapists, and identified practical considerations for future implementation.Using a mixed-methods approach, five Post-Traumatic Stress Disorder diagnosed clients received Trauma Focused -Cognitive Behavioural Therapy, supplemented with VR Photoscan. Symptom changes were assessed using the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) and the Clinical Outcomes in Routine Evaluation-10 (CORE-10). Additionally, semi-structured interviews were conducted with three consenting clients and the participating clinical team, comprised of a service manager, four psychological therapists, and a software company manager, to explore experiences and perspectives of using the VR Photoscan intervention within therapy sessions.Results indicated a reduction in Post-Traumatic Stress Disorder symptoms and psychological distress in most clients, suggesting VR Photoscan can be feasibly integrated into trauma focused therapy for PTSD. While some clinical staff were initially hesitant, they later recognised the value of VR in providing immersive, controlled environments that supported core therapeutic processes. This study offers preliminary evidence for the acceptability and practical integration of VR Photoscan within routine mental health care. Collaboration among therapists, clients, and developers was identified as a key factor in successful implementation. Given the small sample size, and lack of a control group, future research is needed to examine the comparative effectiveness of VR-assisted versus standard PTSD treatment, evaluate strategies for implementation across clinical settings, and explore conditions under which broader adoption may be feasible.<br/
Assessment of frailty in patients with heart failure: a new Heart Failure Frailty Score developed by Delphi consensus
No full textAimsThe Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF.Methods and resultsThe HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their opinions on specific questions prepared by the Steering Committee. The experts were invited to vote and share their views anonymously, using a 5-point Likert scale over iterative rounds. An 80% threshold was set for agreement or disagreement for each statement. Twenty-two variables from four domains (clinical, functional, psycho-cognitive and social) have been selected for inclusion in the HFFS after the third round of the Delphi process. A shorter version (S-HFFS), including 10 variables, has also been developed for daily clinical use.ConclusionsThe HFFS is a new multidimensional tool for the identification of frailty in patients with HF. It should also enables healthcare providers to identify potential ‘red flags’ for frailty in order to develop personalized care plans. The next step will be to validate the new score in patients with HF.<br/
Implantable and injectable drug delivery systems for pain management
No full textIntroductionPain is a widespread global health issue, significantly affecting quality of life and contributing to disability. It is estimated that between 20% and 30% of the global population suffer from some form of non-cancer chronic pain. Around 80% of surgical patients report postoperative acute pain, with less than 50% achieving adequate pain control. Despite these statistics, the management of pain still remains a significant challenge for clinicians, with many patients experiencing poorly controlled pain or adverse effects related to analgesic medication.Areas CoveredThis literature review outlines current pain management strategies, focusing on non-oral postoperative pain therapies, including injectable drug delivery systems (such as in situ forming implants, micro- and nano-based formulations) and implantable drug delivery systems. Emphasis is placed on solid implantable devices designed for sustained drug delivery, which can offer more efficient localized drug delivery at the pain site.Expert OpinionWhile pharmacological treatments, including oral opioids and nonsteroidal anti-inflammatory drugs, are commonly used, implantable controlled release systems are emerging as more effective alternatives. These systems provide localized pain relief with reduced systemic exposure, minimizing side effects, opioid use, and the risk of addiction, offering a promising solution for improved postoperative pain management.<br/
UAV individual identification via distilled RF fingerprints-based LLM in ISAC networks
No full textUnmanned aerial vehicle (UAV) individual (ID) identification is a critical security surveillance strategy in low-altitude integrated sensing and communication (ISAC) networks. In this paper, we propose a novel dynamic knowledge distillation (KD)-enabled wireless radio frequency fingerprint large language model (RFF-LLM) framework for UAV ID identification. First, we propose an RFF-LLM framework based on the modified GPT-2 model to improve the identification accuracy in complex outdoor environments. Then, considering the parameter overhead of the RFF-LLM, we design a dynamic KD strategy to compress the model. Specifically, the proximal policy optimization (PPO) algorithm is employed to dynamically adjust the distillation temperature, overcoming the local optimum dilemma inherent in static KD. As a next step, the knowledge of the RFF-LLM is adequately transferred to the lightweight Lite-HRNet model. Finally, our experiments are conducted based on the self-built drone RFF dataset of Release one, namely DRFF-R1, by collecting the I/Q signals of 20 commercial UAVs in channel 149. The experiment results show that the proposed framework achieves 98.38% ID identification accuracy with merely 0.15 million parameters and 2.74 ms response time, which outperforms the benchmarks.<br/
Cultural models within general practice/family medicine training: a scoping review protocol
No full textIntroduction Cultural competency, cultural safety, cultural humility and transcultural care have developed as frameworks to better equip medical professionals towards a more culturally appropriate healthcare system. The aim of this scoping review is to map the use of these cultural models within general practice/general practitioner (GP) training. We have elected to use the term ‘GP’ to encompass all trainee doctors within general practice/family medicine.Methods and analysis This scoping review will be conducted in accordance with the Scoping Review Methods Manual by the Joanna Briggs Institute and the Arksey and O’Malley framework for scoping studies and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Searches were conducted in EMBASE, MEDLINE and Web of Science Core Collection, with the support of a subject librarian. Published literature on cultural competence, cultural safety, cultural humility and transcultural care related to GP training will be included. There will be no restriction placed on language. References will be managed on EndNote, and titles and abstracts will be screened against the inclusion criteria by two independent reviewers. Potentially relevant sources will be retrieved in full and their citation imported into Rayyan. Data will be extracted on the year, type of study, country or countries of affiliated authors, characteristics of participants, research design and setting, cultural model being examined, definitions used, attitudes, outcome and application of the model, and purpose of the study. We aim to use basic qualitative content analysis for data extracted to map the landscape of the published literature around cultural competence, cultural humility, cultural safety and transcultural care.Ethics and dissemination Ethics approval was not required for this Scoping Review protocol. Findings will be disseminated through conference presentations and publication in a scientific journal.<br/
Exploring protein aggregation in biological products: from mechanistic understanding to practical solutions
No full textProteins are vital for the regulation of several cellular functions, including the synthesis of structural components. The change in environmental conditions will impact conformational stability and result in aggregation. Protein aggregation involves different states of proteins, like nonnative, unfolded, and native states, which make them complex processes. The proper understanding of protein aggregation pathways involving the role of thermodynamically unfavoured lag phase, soluble protofibrils triggered polymerization through an exponential phase, and depleted free monomers owing to the saturation phase resulted in the leveling off of the polymerization process. The aggregated therapeutic proteins can induce deleterious immune responses in patients, and control of the aggregation is essential for better therapeutic protein stability and targeting with the help of stable protein structures and function. Protein–protein interactions (PPIs) are important for protein stability, aggregation rate, and solubility, while advanced computational and biophysical methods have been developed to characterize therapeutic protein aggregation better. Hence, an effective strategy for controlling, monitoring, and reproducing protein aggregation propensities of the polypeptide chains is required. An in-depth understanding of protein aggregation mechanisms, characterization, and combat strategies will counter the issues of protein aggregation. It will also reduce the cost of the product, time constraints, stable & effective product availability, and potential immunogenicity