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XCALibre.jl: A Julia XPU unstructured finite volume Computational Fluid Dynamics library
No full textUnderstanding the behaviour of fluid flow, such as air over a wing, oil lubrication in gas turbines,or cooling air flow in a combustor or turbine is crucial in many engineering applications, fromdesigning aircraft and automotive components to optimising energy systems. ComputationalFluid Dynamics (CFD) enables engineers to model real-world processes, optimise designs,and predict performance for a wide range of scenarios, and it has become a vital part of themodern engineering design process for creating efficient, safe, and sustainable designs. Asengineers seek to develop and optimise new designs, particularly in fields where there is adrive to push the current state-of-the-art or physical limits of existing design solutions, often,new CFD methodologies or physical models are required. Therefore, extendable and flexibleCFD frameworks are needed, for example, to allow seamless integration with machine learningmodels. In this paper, the features of the first release of the Julia package XCALibre.jl arepresented. Designed with extensibility in mind, XCALibre.jl is aiming to facilitate the rapidprototyping of new fluid models and to easily integrate with Julia’s powerful ecosystem, enablingaccess to optimisation libraries and machine learning frameworks to enhance its functionalityand expand its application potential, whilst offering multi-threaded performance on CPUs andGPU acceleration.</p
Getting to GRIPS with MR-Egger: Modelling directional pleiotropy independently of allele coding.
No full textMendelian Randomisation Egger regression (MR-Egger) is a popular method for causal inference using single-nucleotide polymorphisms (SNPs) as instrumental variables. It allows all SNPs to have direct pleiotropic effects on the outcome, provided that those effects are independent of the effects on the exposure, known as the InSIDE assumption. However, the results of MR-Egger, and the InSIDE assumption itself, are sensitive to which allele is coded as the effect allele for each SNP. A pragmatic convention is to code the alleles with positive effects on the exposure, which has some advantages in interpretation but some statistical limitations. Here we show that if the InSIDE assumption holds under all-positive coding of the exposure effects, it cannot hold under all-positive coding of the pleiotropic effects, and argue that this undermines the soundness of MR-Egger. We propose a modification that has the Genotype Recoding Invariance Property (GRIP), achieving the main aim of MR-Egger without the difficulties of allele coding. Our approach, MR-GRIP, is valid under a "Variance Independent of Covariance Explained" assumption (VICE), which amounts to an inverse relationship between exposure effects and pleiotropic effects. Examples and simulations suggest that MR-GRIP can reconcile differences between MR-Egger and alternative methods.</p
VVV-WIT-13: An eruptive young star with cool molecular features
No full textContext.
Outburst phenomena are observed at different stages of stellar evolution, due to the enhancement of the mass accretion rate on protostars or even stellar merger events. In the case of a young stellar object (YSO), the episodic mass accretion event plays an important role in the pre-main-sequence stellar mass assembly. Here we investigate an infrared eruptive source (RA = 16:53:44.38; Dec = − 43:28:19.47), identified from the decade-long VISTA Variables in the Vía Láctea survey (VVV). We named this target after a group of variable sources discovered by VVV, as VVV-WIT-13, where WIT stands for ‘What is this?’, due to its unique photometric variation behaviour and the mysterious origin of the outburst. This target exhibited an outburst with a 5.7 mag amplitude in the
K
s
-band, remained on its brightness plateau for 3.5 years, and then rapidly faded to its pre-eruptive brightness afterwards.
Aims.
Our aim is to reveal the variable nature and outburst origin of VVV-WIT-13 by presenting our follow-up photometric and spectroscopic observations along with theoretical models.
Methods.
We gathered photometric time series in both near- and mid-infrared wavelengths. We obtained near-infrared spectra during the outburst and decaying stages on XSHOOTER/VLT and FIRE/Magellan, and then fitted the detected molecular absorption features using models from ExoMol. We applied 2D numerical simulations to re-create the observables of the eruptive phenomenon.
Results.
We observe deep AlO absorption bands in the infrared spectra of VVV-WIT-13, during the outburst stage, along with other more common absorption bands (e.g. CO). Our best-fit model suggests a 600 K temperature of the AlO absorption band. In the decaying stage, the AlO bands disappeared, whilst broad blue-shifted H
2
lines arose, a common indicator of stellar wind and outflow. The observational evidence suggests that the CO and TiO features originate from an outflow or a wind environment.
Conclusions.
We find that VVV-WIT-13 is an eruptive young star with instability occurring in the accretion disk. One favoured theoretical explanation of this event is a disrupted gas clump at a distance of 3 au from the source. If confirmed, this would be the first such event observed in real time.</p
Concurrent genomic assessment of circulating tumour cells and ctDNA to guide therapy in metastatic breast cancer
No full textBACKGROUND: Molecular analysis of actionable driver mutations and somatic copy number alterations (sCNAs) in circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) is increasingly being used to guide personalised medicine in patients with cancer. In previous CTC studies, high numbers of CTCs were needed for successful recovery of individual CTCs for molecular analysis at a time when patients typically have very short survival, limiting clinical applicability. Here, by performing longitudinal analyses of ctDNA and CTCs across a broad range of CTC counts, we hypothesized that CTCs could reveal synergistic and additional genomic information to ctDNA at points when therapeutic interventions could be considered in the follow up of patients with metastatic breast cancer (MBC). METHODS: Eight patients underwent serial blood sampling. CTCs were captured via CellSearch-DEPArray from 7.5 mL (CellSave tubes), while 15 mL (EDTA tubes) was used for cfDNA extraction. A total of 58 cfDNA samples and 192 CTCs from the 8 patients were compared by shallow whole genome sequencing sWGS and targeted next generation sequencing using custom designed mutation panels (cfDNA; dual barcoding Ion AmpliSeq HD technology (556 hotspots across 24 genes) and CTCs; SingleSeq-compatible AmpliSeq technology across 539 of the 556 (97%) hotspots). RESULTS: The majority of patient samples showed complementary genomic information in CTCs and ctDNA from the same blood sample. However, genome changes were detected in CTCs from some blood samples that were ctDNA negative despite progression providing actionable information at times when ctDNA analysis was not informative. Across the CTCs and ctDNA, common regions of loss included chromosome 13q14 containing the RB1 gene, detected in 3 of 4 patients receiving CDK4/6 inhibitors and amplification of 17q12 containing the ERBB2 gene in 2 of the 7 patients with HER2 negative metastatic disease, suggesting evolution to HER2 positive disease. CONCLUSIONS: Our study shows that CTCs provide key information that would have been missed by ctDNA monitoring alone and extends CTC and cfDNA genomic profiling to patients with a broad range of CTC counts for blood-based monitoring of HER2 status and other clinically actionable targets for informing treatment decisions in metastatic disease.</p
Impact of β-defensin 103 (DEFB103) copy number variation on bull sperm parameters and post-insemination uterine gene expression.
No full textPregnancy rates for elite bulls used in artificial insemination (AI) can vary significantly and therefore the identification of molecular markers for fertility and targets to improve bull selection is important. β-defensin peptides have diverse regulatory roles in sperm function across multiple species but the role of copy number variation (CNV) on fertility parameters has not been previously evaluated. In this study, Holstein-Friesian bulls were screened based on reliable field fertility data to identify two groups (High and Low fertility (HF and LF, respectively)) of n = 10 bulls/group which were genotyped for β-defensin 103 (DEFB103) gene CNV by droplet digital PCR. Overall, low DEFB103 copy number (CN) was associated with increased sperm motility across all bulls (n = 20, p </p
Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists: A State-of-the-Art Narrative Review
No full textGlucagon-like peptide-1 receptor agonists (GLP-1RAs)-along with the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA tirzepatide-are widely acknowledged for their efficacy in managing both type 2 diabetes mellitus and obesity, with expanding indications in cardiometabolic risk reduction. While their glycemic, weight-lowering, and cardiovascular benefits are well established through randomized trials and meta-analyses, concerns remain regarding their safety and tolerability across diverse populations and clinical settings. Gastrointestinal (GI) adverse events-particularly nausea, vomiting, diarrhea, and constipation-are the most common side effects, generally emerging during dose escalation and resolving over time. However, accumulating evidence has identified additional GI complications, including cholelithiasis, cholecystitis, gastroparesis, and bowel obstruction, which may warrant caution in susceptible individuals. Injection-site reactions and worsening of pre-existing diabetic retinopathy are also relevant clinical concerns. Although rare, associations with nonarteritic anterior ischemic optic neuropathy, pancreatitis, medullary thyroid carcinoma, and acute kidney injury (AKI) have been reported, primarily through pharmacovigilance and case-based evidence. Importantly, large-scale randomized trials, meta-analyses, and observational studies suggest that GLP-1RAs do not significantly increase AKI risk and may even confer renal benefits in high-risk populations. There is no confirmed elevated risk of suicidality, but surveillance remains warranted. Safety data in special populations-such as pregnant or lactating women, pediatric patients, and those with advanced renal or hepatic impairment-remain limited and require further study. This state-of-the-art narrative review synthesizes current evidence from clinical trials, pharmacovigilance databases, and real-world cohorts to provide a comprehensive evaluation of the safety and tolerability of GLP-1RAs and tirzepatide. We present clinical strategies for adverse event mitigation, monitoring recommendations, contraindications, and practical considerations for treatment discontinuation or switching. Although these agents offer transformative therapeutic potential, their optimal use requires individualized care, careful patient selection, and ongoing safety surveillance. Future research should prioritize long-term safety in underrepresented populations and strategies to mitigate lean mass loss during therapy.</p
Oura megale n. gen. n. sp., a large early Cambrian deuteropod with a delta-shaped tailpiece
No full textWe describe Oura megale n. gen. n. sp., a large (ca. 14 cm long) euarthropod from the lower Cambrian Chengjiang Konservat-Lagerstätte of Yunnan Province, China. It possesses stalked, compound eyes and a possible raptorial frontal appendage (synapomorphies and symplesiomorphies of lower stem-and upper stem-group euarthropods, respectively), but in combination with deuteropodan synapomorphies (e.g., a multi-segmented head). Micro-X-ray fluorescence shows a thorax that consists of 10 comparatively long and five comparatively short segments. The terminal segment articulates with a large, delta-shaped tailpiece that may have conferred high positional manoeuvrability in the water column. The phylogenetic position of O. megale n. gen. n. sp. in the euarthropod stem may add support to the homology of raptorial frontal appendages between lower stem-group euarthropods and deuteropods.</p
A unique, far-travelled graptolite-bearing erratic pebble from the Lowestoft Till (Quaternary: Anglian Stage) of North Lopham, Norfolk
No full textAn erratic chert pebble discovered on an exposure of the Lowestoft Till (Anglian Stage, Pleistocene) of North Lopham, Norfolk, UK, contains graptolites preserved three-dimensionally in silica in a mode not known in the UK. The graptolites are
Monograptus parapriodon
,
Monograptus priodon
,
Monoclimacis linnarssoni
and an undetermined retiolitid that indicate an
Oktavites spiralis
Biozone (mid-late Telychian, Late Llandovery, Silurian) age. The graptolites are associated with organic-walled microfossils, some containing internal bodies. The combination of lithology, preservation and low thermal maturity seem to exclude a British origin. The closest comparison is with Silurian chert pebbles in Miocene and Pleistocene gravels in central Germany, thought to be derived from bedrock in the Frankenwald region of Thuringia. A conjectured natural transport vector for this pebble involves drainage along the proto-Rhine system flowing into early/mid Pleistocene North Sea deltaic/marine deposits, with subsequent glacial transport to Norfolk. The possibility of an anthropogenic vector is also considered, but dismissed.</p
Machine learning-based classification of adavu speed in Bharatanatyam dancers using 1D force platform data
No full textThis study explores Bharatanatyam (BN) using modern technology and machine learning. Twelve BN dancers participated, and their performances were analyzed using a force platform to capture real-time data during adavu movements at different tempos. The study focused on the Vertical Ground Reaction Force (VGRF) and Center of Pressure (COP) time series. The data was fed into various supervised machine-learning algorithms optimized for performance. The ensemble bagging classifier achieved the highest accuracy of 72% and a recall score of 79%, outperforming other classifiers in precision. Hybrid feature sets combining VGRF and COP data were also evaluated, but VGRF alone was more effective in predicting adavu speed. Feature selection techniques, such as ANOVA, identified 11 critical features from the VGRF signal, improving the SVM classifier’s accuracy to 73%. Overall, the study emphasizes the importance of VGRF signals in predicting adavu speed, achieving an accuracy of 74.42% compared to COP data across different machine-learning models. This research demonstrates the innovative application of machine learning in analyzing Bharatanatyam dance, offering new insights and precision in understanding complex dance movements.</p
Children’s voices in disaster recovery: Lessons from the 2023 Turkey-Syria earthquake
No full textDisasters have a devastating impact on populations, with children being one of the most at-risk groups. Although their vulnerability in disasters is widely recognised, children's own voices are still largely missing from disaster recovery research and planning. This study aims to address that gap by listening directly to the experiences and perspectives of children aged 11 to 14 in Nurdağı, Gaziantep, one of the hardest-hit areas in Türkiye, on disaster relief and recovery. Using a qualitative, child-centred approach, grounded in a socio-ecological, rights-based framework, we conducted interviews with 58 children, alongside 47 additional interviews with parents, teachers, and first responders, to understand how young people coped with life after the earthquake, what challenges they faced, and what they believe would support recovery. The findings show that children struggled with difficult living conditions, trauma, disrupted education, and changing social relationships, but they also demonstrated remarkable insight, emotional intelligence, and a desire to be involved in rebuilding their communities. Many children questioned the fairness of aid distribution and called for more attention to mental health and safer schools. Rather than portraying children as passive victims, the study highlights their capacity to reflect, adapt, and contribute. It calls for more inclusive, responsive recovery strategies that treat children as active participants in disaster planning and post-disaster rebuilding. The study offers actionable recommendations for policymakers, educators, and humanitarian practitioners to better integrate children's perspectives into long-term recovery planning and resilience-building initiatives.</p