Exploring older people’s end-of-life care preferences over time: A scoping review

\ua9 The Author(s) 2025. Background: Understanding the evolution of end-of-life preferences over time is important for dynamic, person-centred palliative care. This is particularly relevant for older people whose preferences can be incompletely expressed and subject to change. Aim: To summarise the nature of the current evidence about how and why the end-of-life preferences of older people change over time. Design: A scoping review was performed, using a predefined protocol and following the JBI manual for evidence synthesis. Data Sources: Final searches of Medline, Embase, PsycINFO and Web of Science were carried out in October 2023. Reference lists were also reviewed. Eligibility criteria included studies recruiting people over the age of 60 that explored how or why end-of-life preferences developed over time. Results: Screening identified 52 articles, reporting on 40 studies. A majority were longitudinal studies collecting quantitative data about treatment preferences. Other preference categories included euthanasia, balancing quality and length of life, goals of care, preferred place of death, decision-making and spiritual preferences. Studies explored a variety of factors that may influence preference change or stability. There was a lack of research with ethnic minority groups and people aged over 80. Conclusions: Existing research has focused on preferences about specific therapies, at the expense of understanding what matters most to older people. Synthesis of the available evidence about why preferences change will guide reviews of patients’ advance care plans. To inform dynamic, person-centred end-of-life care we need studies prospectively exploring how older people construct a broader range of preferences, and negotiate these over time

FreqTS: Frequency-Aware Token Selection for Accelerating Diffusion Models

Copyright \ua9 2025, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved.In this paper, we propose FreqTS, a novel Frequency-Aware Token Selection approach for accelerating diffusion models without requiring retraining. Diffusion models have gained significant attention in the field of image synthesis due to their impressive generative capabilities. However, these models often suffer from high computational costs, primarily due to the sequential denoising process and large model size. Additionally, diffusion models tend to prioritize low-frequency features, leading to sub-optimal quantitative results. To address these challenges, FreqTS introduces an amplitude-based sorting method that separates Token features in the frequency domain of diffusion models into high-frequency and low-frequency subsets. It then utilizes fast Token Selection to reduce the presence of low-frequency features, effectively reducing the computational overhead. Moreover, FreqTS incorporates a Bayesian hyper-parameter search to dynamically assign different selection strategies for various denoising processes. Extensive experiments conducted on Stable Diffusion series models, PixArt-Alpha, LCM, and other models demonstrate that FreqTS achieves a minimum acceleration of 2.3 7 without the need for retraining. Furthermore, FreqTS showcases its versatility by being applicable to different sampling techniques and compatible with other dimension-specific acceleration algorithms

Validating the Iowa Test of Consonant Perception in a large cohort of cochlear implant users

\ua9 2025 Author(s). The Iowa Test of Consonant Perception (ITCP) was designed to test word-initial phoneme perception by uniformly sampling frequently used phonemes as well as balancing feature overlap of response competitors. However, the task has only been validated in normal hearing listeners. In this study, a large cohort of cochlear implant users completed the ITCP and two commonly used clinical measures of speech recognition [AzBio sentences and consonant-nucleus-consonant (CNC) words]. At two different signal-to-noise ratios, the ITCP showed strong convergent validity with other speech recognition tasks and good test-retest reliability. The ITCP is a useful tool for both clinicians and experimental researchers

COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients

\ua9 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death. Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations. Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT. Predicted 1-year CRC diagnosis were calculated, and externally validated, using Cox proportional hazards modelling with selected multiple fractional polynomial transformations for age, faecal haemoglobin concentration (f-Hb) value, mean corpuscular volume (MCV), platelet count and sex. Results: At a CRC risk threshold of 0.6% (equivalent to f-Hb = 10 μg Hb/g (μg/g)) overall performance of the validated model across age strata using Harrell\u27s C index was ≥ 0.91% (overall C-statistic 93%, 95% CI 92%–95%) with acceptable calibration. Using this model yields similar numbers of detected and missed cancers, but requires ~20% fewer investigations than a f-Hb ≥ 10 μg/g strategy. For approximately 100,000 people per year with symptoms of suspected CRC, we predict it might save > 4500 colonoscopies with no evidence that more cancers would be missed if we used our model compared to using FIT f-Hb ≥ 10 μg/g. Conclusions: Including age, sex, MCV, platelets and f-Hb in a survival analysis model to predict the risk of CRC yields greater diagnostic utility than a simple binary cut off f-Hb ≥ 10 μg/g

Impact and cost-effectiveness of scaling up HCV testing and treatment strategies for achieving HCV elimination among people who inject drugs in England: a mathematical modelling study

\ua9 2024 The AuthorsBackground: England aims to reach the World Health Organization (WHO) elimination target of decreasing HCV incidence among people who inject drugs (PWID) to <2 per 100 person-years (/100pyrs) by 2030. We assessed what testing and treatment strategies will achieve this target and whether they are cost-effective. Methods: A dynamic deterministic HCV transmission model among PWID was developed for four England regions, utilising data on the scale-up of HCV treatment among PWID in prisons, drug treatment centres (DTC, where opioid agonist therapy is provided), and any other setting (e.g., primary care). The model projected whether the elimination target will be reached with existing testing and treatment initiatives (‘status quo’ model, SQ), or whether improvements are needed from 2024. Cost data was collated through practitioners\u27 interviews and published literature. The mean incremental cost-effectiveness ratio (ICER per quality adjusted life year (QALY) saved, 50-year time horizon; 3.5% discount rate) of SQ (assumes counterfactual of no treatment scale-up post-2015) and improved model (counterfactual: SQ model) was compared to a willingness-to-pay threshold of \ua320,000/QALY saved. Findings: The SQ model projects HCV incidence will decrease by 79.7–98.6% (range of medians) over 2015–2030 to 0.2–2.2/100pyrs, with an ICER of \ua3308–1609/QALY saved across the regions. There is >80% probability of achieving the incidence target in three regions, and 40% probability in the other region. If annual testing in DTC increases to 80% (from 27%) or 75% of people get tested during their prison stay (from 55%) from 2024 in the lower impact region, then their probability increases to >65%, with both strategies being highly cost-effective. Interpretation: Many England regions could reach the WHO HCV elimination target by 2030 under existing testing and treatment pathways. Scaling up of testing in DTC or prisons will help achieve this target and is highly cost-effective. Funding: NIHR

Deep phenotyping of T regulatory cells in psoriatic arthritis highlights targetable mechanisms of disease

\ua9 2024 The Authors. Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely psoriatic arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs. Here, we propose that checkpoint receptors can identify functional Tregs in PsA. Using unbiased BD Rhapsody single-cell analysis, we have analyzed the expression pattern of checkpoint receptors in Tregs and found that PsA Tregs are enriched in the expression of CTLA4, TIGIT, PD-1, and GITR while TIM3 was downregulated. Furthermore, PD-1+ Tregs in PsA had an increased type 1 phenotype and expressed the protease asparaginyl endopeptidase. By harnessing the PD-1 signaling pathway and inhibiting asparaginyl endopeptidase, PsA Treg function was significantly enhanced in in vitro suppressor assays. Next, we interrogated the cell interaction pathways of Tregs in PsA and found a diminished crosstalk with circulating osteoclast precursors through the CD244–CD48 coreceptor pathways. Therapeutically, PsA Treg function could be enhanced by modulating PD-1 and osteoclast interactions. Our study suggests that unconventional immune cell crosstalk with Tregs is severely diminished in PsA

Biallelic variants in <em>RYR1</em> and <em>STAC3</em> are predominant causes of King-Denborough Syndrome in an African cohort

\ua9 The Author(s) 2025. King-Denborough Syndrome (KDS) is a congenital myopathy (CM) characterised by myopathy, dysmorphic features and susceptibility to malignant hyperthermia. The objective of this study was to investigate the genotype-phenotype correlation in Black African patients presenting with CM, specifically those with KDS-like phenotypes, who remained undiagnosed for over 25 years. A cohort of 67 Black African patients with CM was studied, of whom 44 were clinically evaluated and diagnosed with KDS. Whole-exome sequencing (WES) was performed as part of an international genomics study (ICGNMD) to identify potential pathogenic mutations. Genomic assessments focused on identifying relevant genes, including RYR1 and STAC3, and establishing genotype-phenotype correlations. The study identified RYR1 and STAC3 mutations as the predominant genetic causes of KDS in this cohort, with mutations in both genes exhibiting autosomal recessive inheritance. While RYR1 has previously been linked to autosomal dominant mutations, STAC3, which was formerly associated exclusively with Native American Myopathy/Bailey-Bloch Myopathy, congenital hypotonia, and susceptibility to malignant hyperthermia, is now newly associated with CM-KDS in this study. This establishes the first genotype-phenotype correlation for 44 Black African individuals with KDS. This study marks a significant milestone in research on understudied African populations with CM, emphasising the lengthy diagnostic journey these patients endured. The findings highlight the pressing need for improved access to genomic medicine in underserved regions and underscore the importance of expanding research and diagnostic capabilities in Africa. This work contributes to the advancement of genetic medicine in underrepresented populations, facilitating better diagnostic and therapeutic outcomes

Amyloid-beta metabolism in age-related neurocardiovascular diseases

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. Epidemiological evidence suggests the presence of common risk factors for the development and prognosis of both cardio- and cerebrovascular diseases, including stroke, Alzheimer\u27s disease, vascular dementia, heart, and peripheral vascular diseases. Accumulation of harmful blood signals may induce organotypic endothelial dysfunction affecting blood-brain barrier function and vascular health in age-related diseases. Genetic-, age-, lifestyle- or cardiovascular therapy-associated imbalance of amyloid-beta (Aβ) peptide metabolism in the brain and periphery may be the missing link between age-related neurocardiovascular diseases. Genetic polymorphisms of genes related to Aβ metabolism, lifestyle modifications, drugs used in clinical practice, and Aβ-specific treatments may modulate Aβ levels, affecting brain, vascular, and cardiac diseases. This narrative review elaborates on the effects of interventions on Aβ metabolism in the brain, cerebrospinal fluid, blood, and peripheral heart or vascular tissues. Implications for clinical applicability, gaps in knowledge, and future perspectives of Aβ as the link among age-related neurocardiovascular diseases are also discussed