143174 research outputs found
Sort by
Fatigue crack growth curves for material selection, design and service-life studies of carbon-fibre reinforced-plastic composites: effect of test temperature and R-ratio
No full textThe growth of cracks between plies, i.e. delaminations, in continuous fibre polymer matrix composites under cyclic-fatigue loading in operational aircraft structures has always been a very important factor, which has the potential to significantly decrease the service life of such structures. Whilst current designs are based on a ‘no growth’ design philosophy, delamination growth can nevertheless arise in operational aircraft and compromise structural integrity.
Therefore, the present paper addresses the problem of fatigue crack growth in composite structures, with special relevance to composite airframes. An immediate challenge facing the composites community is to extend the ‘no-growth’ design philosophy to allow for the nucleation and growth of small, naturally-occurring delaminations in composite structures. The main aim of the present paper is, therefore, to investigate the robustness of the Hartman-Schijve methodology to meet this challenge when the effects of test temperature, together with the R-ratio, on the fatigue behaviour are considered
Exact solutions for steadily translating deep water waves carrying hollow vortices
No full textThis paper reports analytical solutions for steadily travelling two-dimensional water waves on deep water, without gravity or surface tension, carrying a cotravelling periodic row of hollow vortices. The solutions are hollow-vortex regularisations of the exact solutions of Crowdy & Roenby (Fluid Dyn. Res., vol. 46, 2014, 031424) for the analogous waves carrying a submerged point-vortex row, the free-surface shapes of which coincide with those for pure capillary waves and, like those, exhibit steady pinchoff at a critical wave amplitude. The same pinchoff phenomenon is shown to occur for the hollow-vortex regularisations. The new wave solutions are likely to provide a useful basis for perturbative, asymptotic or numerical studies when additional effects such as gravity, capillarity or compressibility are incorporated
Systems vaccinology analysis of saRNA immunisation identifies an acute innate immune signature correlated with adaptive immunity.
No full textSelf-amplifying RNA (saRNA) vaccines are a next-generation RNA vaccine platform with great potential. Systems vaccinology provides a potent tool to interrogate vaccine-induced responses in volunteers and to dissect the mechanisms by which vaccines elicit a protective immune response or cause reactogenicity. In the current study, we performed transcriptomic analysis on blood samples collected from volunteers vaccinated as part of a phase I study of an saRNA vaccine expressing SARS-CoV-2 spike antigen. We observed significant gene overexpression following vaccination, both at the prime and boost vaccinations. Over-expressed genes were predominantly associated with type I interferon signalling pathways and associated with innate immune cell recruitment. This
transcriptomic signature was reflected by an increase in cytokines in the plasma at the same timepoint and a significant increase in monocytes in the blood, both of which correlated with the antibody response to the vaccine. When individuals were segregated by the degree of reactogenicity, we also detected differences in gene expression related to immune responses. Overall, this shows that saRNA induces a potent, acute inflammatory response with similarities to other RNA vaccines, it will be important to further dissect the role of the over-expressed genes in immunogenicity and reactogenicity
The role of copd and inhaled corticosteroids in major adverse cardiovascular events in cardiovascular-kidney-metabolic populations
No full textBackground: Cardiovascular-kidney-metabolic (CKM) disease and chronic obstructive pulmonary disease (COPD) are associated with major adverse cardiovascular events (MACE). Whether COPD further increases MACE risk within CKM populations, and whether this potential risk is modifiable through inhaled corticosteroids (ICS), is unknown. Within CKM populations, we investigated the relationship between (1) COPD and subsequent MACE, and (2) amongst concurrent CKM-COPD populations, we investigated the relationship between ICS and subsequent MACE.
Methods: We used Clinical Practice Research Datalink (CPRD) Aurum, Hospital Episode Statistics and Office of National Statistics data, between January 1st, 2010, and March 29th, 2021. We created five discrete cohorts: chronic kidney disease (CKD), type-II diabetes mellitus (T2DM), obesity, MACE history, and older adults (aged ≥65-years-old [“Age65+”]). CKD, T2DM, obesity, and Age65+ cohorts were MACE-naïve at the time of inclusion. Aim(1) exposures were a)COPD, b)incident COPD, and c)being at risk of COPD without diagnosis (defined as age ≥40-years-old, smoking history, no evidence of asthma, and frequent respiratory infections requiring antibiotics). Aim(2) exposure was ICS prescription (control group: long-acting bronchodilators). The outcome was MACE (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, or cardiovascular-specific mortality). We implemented Cox Proportional Hazards models.
Results: COPD was associated with MACE amongst all cohorts, but was comparatively weak in the MACE history cohort(cohort total; adjusted hazard ratio [95% confidence interval]): CKD(N=573,626; 1.29[1.26,1.32]), T2DM(N=649,506; 1.30[1.26,1.35], obesity(N=225,273; 1.41[1.34,1.48]), MACE history(N=507,889; 1.04[1.02,1.06]), and Age65+(N=592,123, 1.59[1.52,1.66]). Incident COPD was associated with subsequent MACE in CKD only (1.28[1.13,1.45]). Being at risk of COPD was associated with subsequent MACE in CKD (1.18[1.07,1.30]), MACE history (1.16[1.08,1.25]), and Age65+(1.28[1.13,1.46]). ICS prescription was not associated with subsequent MACE in any concurrent CKM-COPD cohort.
Conclusions: COPD was an independent risk factor for MACE in CKM populations. ICS did not attenuate MACE amongst CKM-COPD groups. Incident COPD was associated with MACE in CKD, and being at risk of COPD was associated with MACE in CKD, MACE history, and Age65+ cohorts
Ethnic differences in the burden of cardiovascular disease risk factors among adult residents of London: the TOGETHER study
No full textBackground: Cardiovascular disease (CVD) remains the leading cause of premature death in England, with ethnic minority populations disproportionately affected, largely due to differences in socioeconomic factors, exposure and/or susceptibility to CVD risk factors. Midlife risk assessment does not fully account for observed variation in CVD incidence and mortality. Early and precise quantification of risk factor burden across diverse populations is therefore essential to inform targeted prevention strategies. This study assessed the prevalence of CVD risk factors in apparently healthy individuals residing in London.
Methods: This cross-sectional study included CVD-free individuals aged 30–90 years residing in London and registered with general practices using the Egton Medical Information Systems (EMIS) electronic health record system. Unadjusted, crude estimates of traditional CVD risk factors were assessed across participants of different ethnicities who underwent a CVD risk assessment between 2009-2020.
Results: Among 607,327 registered individuals, 83,414 were included (52.0% women, median age 45 [IQR:36-48] years). Ethnic distribution was: White (43.6%), Asian (30.1%), Black (9.7%), Chinese/Other (4.0%), Mixed (2.1%). Overall, 7.8% were current smokers, 31.5% had obesity [universally defined as body mass index (BMI)≥30.0 kg/m2], 48.5% had elevated blood pressure (BP≥140/90 mmHg), 44.9% had hypercholesterolemia (≥5.0 mmol/l), 28.2% had elevated triglycerides (TG)≥1.7 mmol/l and 25.9% had low high-density lipoprotein cholesterol (HDL-C<1.0/1.3 mmol/l for males/females, respectively). Smoking prevalence was highest among White individuals (9.7%). Obesity prevalence varied across groups, with higher proportions in Black participants (42.3%) and lower in Asian individuals (26.1%). Elevated BP was recorded more frequently in Mixed (54.9%) and Black (53.0%) participants and less frequently in those classified as Chinese/Other (42.7%). Total cholesterol ≥5.0 mmol/L was more commonly documented in Mixed (56.8%) and White (49.8%) participants. Higher proportions of Asian individuals had elevated TG (30.9%) and low HDL-C (31.6%), while corresponding proportions were lower among Black participants (14.4% and 19.5%, respectively).
Conclusions: This large-scale analysis of a diverse population suggests variation in CVD risk factor burden among relatively young individuals without CVD. While not implying causality, these findings reflect inequalities between ethnic groups and support an appraisal of early, tailored, and equitable public health policies to improve CVD risk management across diverse populations
Real-time roadworks detection and high definition (HD) map updates for autonomous vehicles
No full textThe increasing prevalence of roadworks poses significant challenges to maintaining accurate and up-to-date high-definition (HD) maps, crucial for autonomous vehicle (AV) safety and efficiency. Current methods for updating HD maps are expensive, time-consuming, and not responsive to real-time changes. This paper proposes a real-time, low-cost pipeline for updating HD maps with roadworks information using a monocular camera and a Contrastive Language–Image Pre-Training-based Vision Language Model (VLM), achieving robust few-shot sign recognition with minimal annotated data. The workflow is designed for low-cost, real-time deployment using only monocular camera input, and supports rapid, incremental HD map updates directly in OpenDRIVE format. Extensive experiments demonstrate that our system outperforms conventional baselines (e.g., fine-tuned You Only Look Once (YOLO) v11) not only in data-scarce settings but also across challenging environmental conditions. The recognition model is trained on a diverse dataset of 3752 real and virtual images, enhanced through data augmentation techniques. The model achieves a 97.12% recognition rate on a test dataset of 752 images and a root mean square error (RMSE) of less than 1.2 m for positional accuracy, processing single image inputs in 1.54 s. By leveraging the OpenDRIVE format, this approach ensures seamless data exchange between different HD map systems, facilitating real-time updates that accurately reflect current road conditions. The methodology demonstrates significant benefits in terms of responsiveness, cost and time efficiency, enhanced safety, and flexibility. Trials on the United Kingdom motorways validate the pipeline's effectiveness, offering a robust solution to dynamic road conditions and enabling safer, more efficient AV navigation
A global analysis of pollen-based reconstructions of land climate changes during Dansgaard–Oeschger events
No full textDansgaard–Oeschger (D–O) warming events are comparable in magnitude and rate to the anticipated 21st century warming. As such, they provide a good target for evaluation of the ability of state-of-the-art climate models to simulate rapid climate changes. Despite the wealth of qualitative information about climate changes during the D-O events, there has been no attempt to date to make quantitative reconstructions globally. Here we use frequency-corrected Tolerance-weighted Weighted Averaging Partial Least Squares regression (fxTWA-PLS) to reconstruct mean temperature of the coldest month, mean temperature of the warmest month, and a plant-available moisture index across multiple D-O events between 50 and 30 ka based on available pollen records across the globe. The reconstruction of plant-available moisture is corrected for the impact of changing atmospheric CO2 concentrations on plant water use efficiency. These reconstructions show that the largest warming occurred in northern extratropics, especially Eurasia, while western North America and the southern extratropics were characterised by cooling. The change in winter temperature was significantly larger than the change in summer temperature in the northern extratropics and the tropics, indicating that the D-O warming events were characterised by reduced seasonality, but there was no significant difference between the summer and winter temperature changes in the southern extratropics. The antiphasing between northern and southern extratropical changes, and the west-east pattern of cooling and warming in North America were generally consistent across the eight D-O events examined, although coherency is greatest during the strongest events.
There was no globally consistent pattern between changes in moisture and changes in temperature. These reconstructions can be used to evaluate the spatial patterns of changes in temperature and moisture in the transient simulations of the D-O events planned as part of the Palaeoclimate Modelling Intercomparison Project
A radio-genomics biomarker for precision epidermal growth factor receptor mutation targeting therapy in non-small cell lung cancer
No full textNewer-generation tyrosine kinase inhibitors (TKIs) have shown increasing efficacy in cancers driven by specific mutations, with epidermal growth factor receptor (EGFR) alterations remaining the most common actionable targets in non-small cell lung cancer (NSCLC). Treatment decisions are currently guided by tissue sampling and genetic testing, which are limited by procedural risks, patient tolerance, tumour heterogeneity and mutation evolution. Because co-mutations involving EGFR and other targetable genes can diminish treatment response, identifying exclusive EGFR mutation, defined by the absence of other actionable alterations, represents a clinically favourable scenario for first-line EGFR-TKI therapy. We developed a CT-based radiomics signature, EGFR-RPV, to predict exclusive EGFR mutational status using NSCLC patients (n=304) from a multi-centre cohort with paired imaging and genomics data, and validated performance in an independent testing set (n=51), alongside transcriptomics enrichment analysis. EGFR-RPV predicted exclusive EGFR mutation with accuracies of 0.77 (95% CI 0.66–0.88) and 0.71 (95% CI 0.54–0.89) in internal and external testing, respectively, and stratified patient prognosis (hazard ratio 2.15, 95% CI 1.50–3.08).
FAM190A and CBMO1 were enriched in exclusive EGFR-positive cases, consistent with their roles in cell division regulation and vitamin A biosynthesis, respectively. EGFR-RPV thus offers a non-invasive approach to identify exclusive EGFR mutations, with a potential role in guiding first-line EGFR-TKI use
SE Journals in 2036: Looking back at the future we need to have
No full textIn 2025, SE publishing faces an existential crisis of scalability. As our communities swell globally and integrate fast-moving methodologies like LLMs, traditional peer-review practices are collapsing under the strain. The "bureaucratic anomaly" of monolithic review has become mathematically unsustainable, creating a stochastic
"lottery" that punishes novelty and exhausts researchers.
This paper, written from the perspective of 2036, documents potential solutions. Here, the editors of ASE, EMSE, IST, JSS, TOSEM and TSE dream a collective dream of a brighter future. In summary first we stopped fighting (The Journal Alliance). Then we fixed the process (The Lottery / Unbundling / Fixing the Benchmark Graveyard). And then we fixed the culture (Cathedrals/Bazaars)
Slip over liquid-infused gratings in the singular limit of a nearly inviscid lubricant
No full textWe consider shear-driven longitudinal flow of an exterior fluid over a periodic array of rectangular grooves filled with an immiscible interior fluid (the “lubricant”), the grooves being formed by infinitely thin ridges protruding from a flat substrate. The ratio λ of the effective slip length to the semi-period is a function of the ratio µ of the interior to exterior viscosities and the ratio h of the grooves depth to the semi-period. We focus on the limit µ 1, which is singular for that geometry. We find that the viscous resistance to the imposed shear is dominated by a boundary layer of exponentially small extent about the ridge tips, resulting in the effective slip length scaling
as µ −1/2 — not µ −1 as implied by intuitive arguments overlooking the tip contributions (and by proposed approximations in the literature). Analyzing that exponential region in conjunction with an integral force balance, we find the simple asymptotic approximation λ ≈ µ
−1/2; using conformal mappings, we also calculate the leading-order correction to that result, which introduces
a dependence upon h. The ensuing asymptotic expansion breaks down for h = O(µ ¹/²), upon transitioning to a lubrication geometry. We accordingly conduct a companion asymptotic analysis in the distinguished limit of small µ and fixed H = h/µ1/2, which gives λ ≈ µ−1/2H/(1 + H) as well as a closed-form leading-order correction to that approximation; the intuitive µ −1 scaling is accordingly only relevant to the regime H 1 corresponding to extremely shallow grooves. We demonstrate excellent agreement between our predictions and numerical solutions constructed using a boundary-integral formulation