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Mobility and strength training with and without protein supplements for pre-frail/frail older people with low protein intake: maximising mobility and strength training (MMoST) feasibility randomised controlled trial
Full text linkObjectives: The first objective was to establish the feasibility of conducting a definitive trial to evaluate the effectiveness of mobility and strength training with or without protein supplements for pre-frail/frail older people with low protein intake. The second objective was to finalise outcome measures for a definitive trial. Design: Multicentre feasibility randomised controlled trial. Setting and participants: Four National Health Service (NHS) community trust physiotherapy departments. We recruited via clinical caseloads, an existing cohort study and community advertising. Participants were adults aged ≥60 years, frail or pre-frail, reporting walking difficulties or slow walking and low protein intake (<1 g protein/kg of body weight (kgBW)/day). The recruitment target was 50 participants. Interventions: All participants undertook two times a week mobility and strength training supported by a physiotherapist for 24 weeks. Half of the participants were randomised (1:1) to receive 24 weeks of daily protein supplements to increase protein intake up to 1.6 g/kgBW/day. Primary feasibility objectives: Feasibility outcomes assessed recruitment, intervention fidelity, adherence, tolerance and study retention. Secondary objectives: We assessed clinical data collection at baseline and 5–8 month follow-up including the short physical performance battery (SPPB), 6 min walk test (6MWT) and participant-reported outcomes. Outcome assessors were blinded. Statistical methods: All participants were analysed in the groups as randomised provided they were not withdrawn from the study before their treatment started and contributed outcome data (modified intention to treat). Our primary feasibility and secondary outcome measures were summarised using descriptive statistics such as mean and SD, median and IQR or counts with percentages. Secondary objectives were exploratory, and mean between group differences at follow-up were estimated for each continuous outcome using linear regression models adjusted for baseline outcome score and frailty status, and presented with associated 95% CIs. Results: Initially, recruitment focused on existing caseloads, but patients were more unwell and disabled than anticipated and ineligible. No participants were recruited from the cohort. A community recruitment strategy was implemented. We screened 952 older adults and 20 participants were randomised. We ran out of time to reach our target. We achieved good intervention fidelity for both interventions. The median number of exercise sessions completed was 10.5/16 (IQR 7–13). Six participants received supplements which they tolerated well and took regularly. 14 participants (70%) attended follow-up assessments with no difference in retention between arms. The median age of participants was 76 years (IQR 68.5–80.0) and 15/20 (75%) were frail. All clinical outcomes showed a trend towards larger improvements in the exercise and protein arm, but these were not statistically significant. For example, SPPB scores (mean difference 0.93, 95% CI (−2.70 to 4.56)) and 6MWT (mean difference 41.92 m, 95% CI (−39.05 to 122.89)) were both higher in the exercise and protein arm compared to control. Conclusion: The study was not feasible based on the original protocol. Recruitment was the biggest challenge. We established a more efficient route to recruitment (community advertising) which requires further refinement. Clinical outcomes consistently favoured the exercise and protein group, which should be interpreted cautiously but suggest this question is worthy of further investigation. Trial registration number: ISRCTN30405954
Promises under pressure: the modest predictive power of polygenic risk scores
No full textComment on a controversial topic in genomics and a response to: Roberts, E., Flaum, N. & Evans, D.G. Clinical implementation of polygenic risk scores. Eur J Hum Genet (2025). https://doi.org/10.1038/s41431-025-01931-9
Habitat suitability model for identifying human-wildlife interface and implications for wildlife trade of Sunda pangolin in Borneo
Full text linkPangolins are the most trafficked mammals in the world. Sunda pangolins (Manis javanica), in particular, are critically endangered due to their proximity to consumption hotspots, and the scale of the globalized illegal trade network. Data on their ecological drivers can inform targeted strategies to cauterise supply lines. We used data from 1,455 camera-stations deployed between 2008-2024 across a heterogenous mix of landscapes in Sabah, northern Borneo, to model the geomorphological and anthropogenic drivers of Sunda pangolin distribution. Our most parsimonious logistic regression model included six variables: accessibility to human population (ß=0.597, p=0.004), soil cation exchange capacity (ß= -0.665, p=0.003), soil clay content (ß= -0.311, p=0.051), soil nitrogen concentration (ß=0.9862, p=0.0001), soil bulk density (ß=0.43, p=0.143) and topographic position index (ß=-0.61, p=0.005). The model performed well as evaluated using an out-of-sample test dataset (sensitivity =0.89, specificity =0.57 and AUC=0.73). A high proportion (~43%) of rural, human-dominated areas were identified as highly suitable pangolin habitat, but only ~15% of these areas are protected. We further confirmed the overlap in highly suitable pangolin habitat and human-occupied land using an independent citizen science dataset of pangolin detections collected between 2019-2024 (Boyce index=0.75). Our results illustrate that Sunda pangolins often live in high-risk areas but also suggest an opportunity to develop community centered conservation strategies to curb poaching and cauterize supply lines fueling the trade of Sunda pangolins in Southeast Asia
Avoiding routine gastric residual volume measurement in neonatal critical care (the neoGASTRIC trial): study protocol for a multi-centre, unblinded, randomised, controlled trial
Full text linkBackground: Routine measurement of gastric residual volumes involves regularly aspirating the entire stomach contents to assess the volume and colour of the aspirate to inform feeding. This is an established practice in many United Kingdom and Australian neonatal units for preterm infants receiving gastric tube feeds. The rationale is to assess feed tolerance and to predict and potentially prevent necrotising enterocolitis, a serious gut condition. Routine measurement of gastric residual volumes may also be associated with adverse outcomes and harm, including delayed achievement of full enteral feeds and longer neonatal unit stay. Evidence to support the routine measurement of gastric residuals is poor and previous small trials have not been generalisable to United Kingdom or Australian neonatal care.Methods: The aim of the neoGASTRIC trial is to test whether avoiding routine measurement of gastric residual volumes in preterm infants reduces the time taken for an infant to reach full enteral feeds without increasing necrotising enterocolitis. neoGASTRIC is an individually randomised controlled trial in neonatal units in the UK and Australia. A target of 7,040 infants born before 34 weeks’ gestation will be randomly allocated, prior to receiving 24 hours of enteral feeds >15 ml/kg/day, on a 1:1 basis to have no routine gastric residual volumes measured, or to have gastric residual volumes measured routinely. Opt-out consent will be used with parent and staff views explored as part of an embedded process evaluation. The primary superiority outcome is time to reach full milk feeds ≥145 ml/kg/day for three consecutive days. Bell’s stage 2 or 3 necrotising enterocolitis following blinded adjudication will be the key secondary, non-inferiority safety outcome. Other neonatal core outcomes and health care resource use and costs prior to discharge will be evaluated.Discussion: neoGASTRIC will address a research priority that affects more than 20,000 preterm infants in the United Kingdom and Australia annually. Even modest improvements in clinical outcomes and resource use could result in large clinical benefits and savings at a population level.Trial registration: ISRCTN: 16710849, prospectively registered 8 February 2023 https://www.isrctn.com/ISRCTN1671084
Preparing Timepix3 for deployment in low-radioactivity natural settings: an integrated workflow for charged particle detection and imaging
Full text linkThe natural sedimentary environment possesses a mixed field of α-, β-, and γ-radiation emitted from the radioactive decay of radionuclides such as potassium-40 (K-40), uranium-238 (U-238), and thorium-232 (Th-232). These emissions are responsible for dose accumulation in feldspar and quartz mineral grains, forming the basis of luminescence dating. The inhomogeneous spatial distribution of radionuclides in sediments and local energy deposition at the grain level can cause microdosimetric variations, contributing to overdispersion in equivalent dose (D_e) distributions. Understanding and resolving these variations requires a detector that can simultaneously map various types of radiation and their energy deposition at the micron scale. Here we present a workflow for configuring and applying Timepix3 (silicon-based hybrid pixel detector, 14 × 14 mm2 active area, 256 × 256 pixels, 300 μm thickness) for high-sensitivity imaging of α- and β-particles simultaneously in mixed-radiation fields. The workflow includes particle-track reconstruction, charged-particle identification, background suppression, and energy calibration with a mixed α-particle source (Pu-239, Am-241, Cm-244; 5.15–5.80 MeV) in air. A linear energy calibration response was obtained; however, the detector was unable to fully resolve three α-particle peaks. While this appears to be a limitation, it ultimately provides insights into the detector's response under conditions that closely mimic the energy spectra of natural radiation, broad energy distributions, and measurement conditions such as ambient atmospheric pressure
How do children trust STEM And Non-STEM information from robots? The role of children’s theory of artificial mind (ToAM)
Full text linkGiven the integration of robots into educational contexts, understanding how children evaluate information from artificial agents is essential. This dissertation examines how children aged 4 to 6 selectively trust robots when receiving information across STEM (Science, Technology, Engineering, and Mathematics) and non-STEM domains. Building on the Theory of Artificial Mind (ToAM) which is an extension of the Theory of Mind (ToM), the association between ToM/ToAM and selective trust was investigated. Three research questions guided this study: (1) To what extent do children’s selective trust in robots and humans differ? (2) How does the domain of testimony (non-STEM versus STEM) influence children’s selective trust? (3) Do ToAM and ToM relate to children’s selective trust in robot and human informants? The study employed a conflicting informants paradigm wherein 107 Chinese children (M = 5.57 years, SD = 0.58, 44.86% girls) were randomly allocated into two between-subjects conditions: a Nao-accurate condition and a Human-accurate condition. Each child encountered four informant dyads (one human, one robot) who provided conflicting testimony across four domains: one non-STEM domain (object labelling) and three STEM domains (physical science, life science, mathematics). Standardised scales were used to assess children’s ToM and ToAM abilities, with a focus on core components including desire, belief, knowledge, and emotion. Statistical analyses indicated that children consistently preferred accurate informants, irrespective of informant type, particularly in non-STEM domain. However, domain-specific analyses revealed nuanced preferences. Interestingly, within the physical science domain, children demonstrated notable uncertainty; they were inclined to nominate robots despite their inaccuracies yet endorsed information provided by humans and deemed humans as reliable source. Lastly, in the Nao-accurate condition, children’s ToM and ToAM scores both negatively predicted selective trust, suggesting that children with stronger cognitive functions were more cautious about trusting robots. In contrast, no significant relationships emerged in the Human-accurate condition. Collectively, these findings deepen our understanding of how young children evaluate informational reliability in AI-integrated early STEM education and highlight their developing cognitive sophistication
Fully automated plaque quantification with human-level performance and validation in large-scale cardiac CT cohort
Full text linkBackground: Coronary artery disease is the leading cause of morbidity and mortality worldwide, with atherosclerotic plaque burden recognised as a critical biomarker for cardiovascular risk. Although calcium scoring is widely used, it provides only partial information, and its manual nature limits scalability. Large-scale cardiac CT angiography (CCTA) registries linked with long-term outcomes offer a unique opportunity for population-level risk stratification. However, the absence of robust, fully automated tools for comprehensive plaque quantification—including both calcified plaque (CP) and non-calcified plaque (NCP)—continues to impede clinical translation. Purpose: We aimed to develop and validate a fully automated AI pipeline for vessel and lumen segmentation, plaque region identification, and quantification of both CP and NCP. We evaluated its agreement with expert assessment and its correlation with conventional calcium scoring. Methods: We employed an active learning framework to train and refine the vessel and lumen segmentation model, leveraging iterative feedback from clinical experts as illustrated in Figure 1 (a). A total of 1,200 patients from the ORFAN and NHS-Pilot studies were used across all training tasks, with non-overlapping subsets allocated for vessel/lumen segmentation and for quantification of CP and NCP. Plaque region identification and CP/NCP segmentation models were trained to delineate plaque within the anatomical "sandwich" between lumen and vessel walls (See Figure 1(b) for a sample). Model outputs were compared against expert annotations. Validation included assessment of the correlation between AI-derived CP/NCP burden and manual calcium scoring using the correlation coefficient at the patient level. Results: The lumen and vessel segmentation models performed exceptionally well, attaining an overall agreement of 0.95 Dice similarity with expert annotators in an external cohort through model refinement via an active learning process. Initially, the plaque quantification method was compared to clinical annotations of burden in 104 cases, resulting in a Pearson’s correlation of 0.93 for NCP and 0.98 for CP regions. Following this, the method was externally validated in a multicentre cohort of 19463 patients from ORFAN to thoroughly confirm its performance against human-calcium scoring, achieving a Spearman’s correlation coefficient of 0.81 (p-value<0.01) for CP and 0.66 (p-value<0.001) for NCP, as shown in Figure 1 (b). Conclusion: This study demonstrates the feasibility of fully automating the quantification of calcified and non-calcified coronary plaque using artificial intelligence. Manual assessment of plaque burden in large-scale cohorts such as ORFAN is impractical; AI offers a scalable alternative that enables population-level risk stratification. Given the strong association between plaque burden and cardiovascular risk, this work lays the foundation for improved disease prediction and management in large and diverse patient populations
First Associated Neutrino Search for a Failed Supernova Candidate with Super-Kamiokande
Full text linkIn 2024, a failed supernova (SN) candidate, M31-2014-DS1, was reported in the Andromeda galaxy (M31), located at a distance of approximately 770 kpc. In this Letter, we search for neutrinos from this failed SN using data from Super-Kamiokande (SK). Based on the estimated time of black hole formation inferred from optical and infrared observations, we define a search window for neutrino events in the SK data. Using this window, we develop a dedicated analysis method for failed SNe and apply it to M31-2014-DS1, by conducting a cluster search using the timing and energy information of candidate events. No significant neutrino excess is observed within the search region. Consequently, we place an upper limit on the time-integrated electron antineutrino luminosity from M31-2014-DS1 and discuss its implications for various failed SN models and their neutrino emission characteristics. Despite the 18 MeV threshold adopted to suppress backgrounds, the search remains sufficiently sensitive to constrain the Shen-TM1 equation of state, in a more optimistic emission scenario with progenitor stars of 40 M⊙ and relatively high mean electron-antineutrino energies of about 23.2 MeV, yielding a 90% confidence level upper limit of 1.76 × 1053 erg on the time-integrated electron antineutrino luminosity, moderately above the expected value of 1.35 × 1053 erg
Psychiatric disorders associated with increased risk of colorectal cancer in the UK biobank cohort
Full text linkPsychiatric disorders are associated with several cancers. However, data on the association between different types of psychiatric disorders and colorectal cancer (CRC) are scarce. The aim of this study was to determine whether there is an association between psychiatric disorders and CRC using UK Biobank. We excluded participants with a previous diagnosis of cancer (except non-melanoma skin cancer) prior to baseline and conducted a matched cohort study with new-onset psychiatric disorder patients after recruitment as the exposure group and matched non-psychiatric disorder individuals as the reference group. Through UK Biobank, we obtained clinical diagnoses for the psychiatric-disorder patients from their hospital records. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) of CRC risk after diagnosis of a psychiatric disorder. We identified 29,769 individuals with psychiatric disorders. During follow-up (median duration of 5.69 [IQR: 5.43] years), 190 cases of CRC were identified in the psychiatric patients (1.13 per 1000 person-years), compared with 921 cases in the reference individuals (0.53 per 1000 person-years). Individuals with clinically confirmed psychiatric disorders were associated with an elevated hazard of CRC (HR, 1.93 [95% CI, 1.64–2.27]). The risk of CRC in psychiatric patients is higher in those with multiple psychiatric disorders than single (HR 2.53 [95% CI, 1.90–3.37] vs. 1.78 [95%CI, 1.48–2.13], p < 0.05). Our findings suggest: patients with psychiatric disorders were associated with an elevated hazard of CRC. These findings highlight the need for measures to decrease the risk of CRC in individuals with psychiatric disorders, such as monitoring and early intervention
