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Associations between use of aspirin and MRI-derived liver fat and fibroinflammation
No full textBackground: The effects of aspirin on hepatic steatosis and fibroinflammation are unclear. The study aimed to examine the association between aspirin use and liver MRI-derived liver fat and corrected T1 (cT1).
Methods: We used UK Biobank imaging cohort data. Aspirin use was self-reported at baseline and imaging assessment, and the main exposures were aspirin use at imaging assessment and longitudinal aspirin use patterns (never users, initiators, discontinuers, vs. persistent users). Outcomes were MRI-derived liver fat (%) and cT1 (ms). Multivariable adjustment analyses and inverse probability of treatment weighting (IPTW) analyses were performed, accounting for demographic, lifestyle and clinical factors.
Results: We included 36413 participants (mean age 64.6 years, 51.4% female). Aspirin use at imaging assessment was associated with lower liver fat (-0.35 (95% CI: -0.51, -
33 0.20)) and slightly higher cT1 (5.13 (95% CI: 3.23, 7.03)). Analyses on longitudinal aspirin use pattern showed that compared to never users, initiators and persistent users showed lower liver fat (-0.48 (-0.69, -0.28) and (-0.24 (-0.45, -0.02)) and higher cT1 (2.94 (0.38, 5.49) and 8.31 (5.65, 10.97)). IPTW analyses showed consistent results. Conclusion: In this large population-based cohort, aspirin use was linked to reduced liver fat, but a small, clinically insignificant (i.e. <80ms) increase in cT1. These findings suggest aspirin may mitigate steatosis through metabolic pathways but does not necessarily rapidly reverse fibroinflammatory injury
Durability of cementitious binders with blast furnace slag in deep sea conditions: analysis of microstructure and phase transformation
No full textPortland cement-blast furnace slag (PC-BFS) cement-based materials exhibit good durability in shallow marine environments but their performance in the deep-sea is poorly understood. This study investigates the degradation of PC-BFS cement pastes after one-year exposure in a deep-sea field site under high hydraulic pressure (3515 m depth) and low temperature (2 °C) conditions. The results show that the main degradation mechanisms involve ettringite formation and Ca leaching, driven by low-temperature seawater ingress under pressure. SEM-EDS and XRD analyses revealed distinct microstructural changes such as Mg and Al enrichment and sulfate/chloride incorporation in BFS rims. Fluorescence imaging confirmed complete seawater infiltration, facilitating BFS dissolution and reprecipitation cycles. The findings highlight the vulnerability of PC-BFS systems to ettringite-induced damage due to their high alumina and low sulfate balance. These insights inform strategies to optimise cementitious materials for deep-sea applications under extreme environments
Incident response planning using a lightweight large language model with reduced hallucination
No full textTimely and effective incident response is key to managing the growing frequency of cyberattacks. However, identifying the right response actions for complex systems is a major technical challenge. A promising approach to mitigate this challenge is to use the security knowledge embedded in large language models (LLMs) to assist security operators during incident handling. Recent research has demonstrated the potential of this approach, but current methods are mainly based on prompt engineering of frontier LLMs, which is costly and prone
to hallucinations. We address these limitations by presenting a novel way to use an LLM for incident response planning with reduced hallucination. Our method includes three steps: fine-tuning, information retrieval, and lookahead planning. We prove that our method generates response plans with a bounded probability of hallucination and that this probability can be made arbitrarily small at the expense of increased planning time under certain assumptions. Moreover, we show that our method is lightweight and can run on commodity hardware. We evaluate our method on logs from incidents reported in the literature. The experimental results show that our method a) achieves up to 22% shorter recovery times than frontier LLMs and b) generalizes to a broad range of incident types and response actions
School performance of preterm infants after intraventricular hemorrhage
No full textImportance Intraventricular hemorrhage (IVH) is a significant complication of preterm birth, affecting approximately 20% of preterm infants. Despite its prevalence, the effect of IVH beyond the impact of prematurity alone has been scarcely studied beyond early childhood, posing an important knowledge gap.
Objective To investigate the association of IVH with national school performance throughout childhood to adolescence.
Design, Setting, and Participants This population-based cohort study included all very preterm infants (<32 weeks’ gestation) and full-term infants (≥37 weeks’ gestation) born in New South Wales, Australia, between January 1, 2007, and December 31, 2013. Cohorts were very preterm children with low-grade (grades 1-2) or high-grade (grades 3-4) IVH, very preterm controls without IVH, and full-term controls. Analyses were conducted from January 30 to September 18, 2024.
Exposure IVH grade 1 to 4.
Main Outcomes and Measures The primary outcome was overall performance on standardized national school assessments at age 8 to 9, 10 to 11, and 12 to 13 years, including adjusted mean differences (AMDs) in z scores between children with IVH and very preterm controls. Secondary outcomes were domain-specific performance in reading, writing, spelling, grammar, and numeracy and whether children met the national minimum standards overall and for each domain. Academic trajectories were also compared by group.
Results This study included 408 189 children: 557 with low-grade IVH, 85 with high-grade IVH, 2557 very preterm controls without IVH, and 404 990 full-term controls. Children with low-grade IVH performed similarly to preterm controls at age 8 to 9 years (AMD in overall academic z score, −0.06; 95% CI, −0.14 to 0.03), 10 to 11 years (AMD, −0.09; 95% CI, −0.21 to 0.03), and 12 to 13 years (AMD, −0.04; 95% CI, −0.24 to 0.16). Children with grade 2 IVH (n = 145), however, performed significantly worse than very preterm controls at age 8 to 9 years (AMD, −0.20; 95% CI, −0.36 to −0.04). Children with high-grade IVH performed significantly worse than very preterm controls at age 8 to 9 years (AMD, −0.50; 95% CI, −0.71 to −0.30), 10 to 11 years (AMD, −0.59; 95% CI, −0.85 to −0.34), and 12 to 13 years (AMD, −0.61; 95% CI, −1.05 to −0.17). Numeracy was a consistently weak domain for children with high-grade IVH throughout school age (eg, at age 8 to 9 years, AMD in the numeracy z score compared with very preterm controls was −0.49 [95% CI, −0.70 to −0.28]). Differences in academic trajectories between groups remained fixed with increasing age; however, all groups showed improvement over time (eg, adjusted β for very preterm children, 32.3 [95% CI, 31.2-33.5]; children with low-grade IVH, 31.5 [95% CI, 29.0-34.0]; high-grade IVH, 30.2 [95% CI, 24.1-36.4]).
Conclusions and Relevance In this cohort study, the association of low-grade IVH with worse school performance appeared limited to children with grade 2 IVH. Children with high-grade IVH consistently showed poorer academic performance into adolescence than their peers born very preterm without IVH. Nevertheless, very preterm children, regardless of IVH grade, demonstrated academic progress over time, underscoring the need for ongoing educational support to help them to realize their full potential
Optimised and 3D printed steel garden bridge: from design to experimental verification
No full textWire-arc directed energy deposition (DED-Arc), or wire arc additive manufacturing (WAAM), enables large-scale, intricate metallic components to be created in an automated manner, with great promise in construction. This paper presents the design, manufacture and experimental verification of a 4 m-span, East Asian garden bridge-inspired and structurally optimised DED-Arc steel pedestrian bridge. The bridge consists of optimised DED-Arc steel tubular components as the main load-carrying structure, and wooden boards on top as the decking. The structural performance of the bridge was examined through non-destructive testing of the fully assembled bridge up to the design load and destructive testing to failure of a duplicate of the main arch, which confirmed the load-carrying capacity of the bridge and showed generally good correlation with the prior numerical simulations. This study successfully demonstrates the feasibility of integrating DED-Arc with structural optimisation at scale, and its significant role in construction automation and decarbonisation
Humanitarian management of drought needs better water security data
No full textDroughts are a primary driver of humanitarian crises in arid regions, yet early warning systems that index humanitarian financing often omit water security data in favour of food security monitoring. Based on 42 expert interviews assessing management barriers and information needs during the 2020–24 drought in the Horn of Africa, resulting in an estimated 71,100 excess deaths in Somalia alone, we find water security data to be critical in shifting management to proactive mechanisms. Monitoring of water availability (such as water quality and groundwater/surface water levels) and water access (such as water prices and household surveys) is needed to design solutions that proactively mitigate water shortages and their secondary impacts on food security (such as through borehole rehabilitation, alternative water supplies, and cash transfers). Furthermore, if causal relations between water and food insecurity are analysed, the cost–benefit basis for financing water supply interventions can be more completely propositioned, and food insecurity hotspots can be better anticipated
Histone lactylation: a new epigenetic mark in the malaria parasite Plasmodium
No full textEpigenetic processes play important roles in the biology of the malaria parasite Plasmodium falciparum. Here, we characterised a new epigenetic mark, histone lactylation, for the first time in Plasmodium: it was found in two human malaria parasites, P. falciparum and P. knowlesi, and also in vivo in two rodent malaria models, P. yoelii and P. berghei. Histones were increasingly lactylated in response to elevated lactate levels in vitro and in vivo, making this mark uniquely well-placed to act as a metabolic sensor, since severe falciparum malaria characteristically leads to hyperlactataemia in the human host. Mass spectrometry showed that lysines on several parasite histones could be lactylated, as well as many non-histone chromatin proteins. Histone lactylation was less abundant and less inducible in P. knowlesi than P. falciparum, suggesting that P. falciparum may have evolved particular epigenetic responses to this characteristic feature of its pathology. Finally, in the rodent model P. yoelii, hyperlactataemia correlated with parasite transcriptomic programmes that suggested metabolic ‘dormancy’
THU036-YI Integrating spatial lipidomics with imaging mass cytometry: a novel approach for metabolic profiling of liver fibrosis
No full textIn vivo prediction of intervertebral disc strains and segmental kinematics from clinical MRI during lumbar extension
No full textIntroduction: Excessive intervertebral disc (IVD) strains and vertebral body motions are associated with lower back pain (LBP). Quantifying these strains and motions may aid in predicting the success of candidate LBP treatments and enable better prediction of pre-operative instability and post-operative implant failure, but cannot currently be obtained in routine clinical assessment. Thus, the aim of this study was to evaluate the feasibility of utilising clinical measures of spinal alignment, IVD geometry, and disc degeneration to predict in vivo IVD strains and vertebral translations.
Methods: Fifteen participants presenting no LBP were subjected to one unloaded and one supine extension-loaded MRI scan. MRI-based digital volume correlation (DVC) was used to quantify the principal and shear strains of lumbar IVDs and anterior-posterior, cranial-caudal, and total translation of the vertebral bodies (L1-S1). IVD height, anterior-posterior IVD height ratio, segmental lordosis, lumbar lordosis, lumbar height, sacral angle, and Pfirrmann grade were evaluated using the reference MR images. Multivariate linear regression was used to predict level-wise strains and translations.
Results: IVD strains and vertebral translations were successfully predicted from clinical measures of spinal alignment and disc degeneration, but only at the L4-L5 and L5-S1 levels. Specifically, greater minimum principal IVD strains and vertebral anterolisthesis were associated with a reduced anterior-posterior IVD height ratio at L4-L5 (p < 0.01). Greater peak minimum principal strains and
anterolisthesis were associated with taller IVDs in the L5-S1 segment (p < 0.05). In the same segment, increased sacral angle was associated with greater peak minimum principal strains (p < 0.05) but lower anterolisthesis (p < 0.01).
Discussion: This study demonstrates the potential of utilising radiographic variables to predict the biomechanical behaviour at the segmental level, giving rise to future exploration of complex loading patterns in patient cohorts with specific spinal pathologies