224092 research outputs found
Sort by
Activation of bacterial programmed cell death by phage inhibitors of host immunity
No full textBacterial and archaeal viruses are replete with diverse uncharacterized accessory genes (AGs), which likely interface with host processes. However, large-scale discovery of virus AG functions remains challenging. Here, we developed an integrated computational and experimental discovery platform to identify viral AGs and assign functions. We show that multiple AGs activate unexpected programmed cell death (PCD) activity of distinct restriction-modification (R-M) systems. We describe an exapted type I R-M decoy that kills the host upon sensing several different anti-defense AGs and a self-guarded type III R-M system that restricts phages but also induces PCD when bound by anti-R-M proteins. Other phage counter-defense genes additionally activate non-R-M-based abortive infection systems encoded by prophages. This defense strategy creates a conundrum: lose AGs and be exposed to immunity or keep AGs and trigger PCD. Strategies employed by viruses to avoid this double bind could be an important factor in virus evolution that remains to be explored.</p
Adversarial defence without adversarial defence: instance-level principal component removal for robust language models
No full textPre-trained language models (PLMs) have driven substantial progress in natural language processing but remain vulnerable to adversarial attacks, raising concerns about their robustness in real-world applications. Previous studies have sought to mitigate the impact of adversarial attacks by introducing adversarial perturbations into the training process, either implicitly or explicitly. While both strategies enhance robustness, they often incur high computational costs. In this work, we propose a simple yet effective add-on module that enhances the adversarial robustness of PLMs by removing instance-level principal components, without relying on conventional adversarial defences or perturbing the original training data. Our approach transforms the embedding space to approximate Gaussian properties, thereby reducing its susceptibility to adversarial perturbations while preserving semantic relationships. This transformation aligns embedding distributions in a way that minimises the impact of adversarial noise on decision boundaries, enhancing robustness without requiring adversarial examples or costly training-time augmentation. Evaluations on eight benchmark datasets show that our approach improves adversarial robustness while maintaining comparable before attack accuracy to baselines, achieving a balanced trade-off between robustness and generalisation
Global funding for surgical research between 2016 and 2020: content analysis of public and philanthropic investments
No full textBackground: surgery is an intrinsic component of healthcare, estimated to be involved in the treatment of 28-32% of the global burden of disease. Research is crucial to improving the quality of surgical care and thus patient outcomes. The aim of this study was to analyse global patterns of public and philanthropic investment in surgical research.Methods: publicly available databases of human surgical research funding awards between 2016 and 2020 were searched. Awards were categorized by surgical specialty, cross-cutting research theme, and phase of research.Results: a total of 8042 awards were identified, with a total investment of 0.7 billion annually), contrasting with 2.46 billion (70.7%)), clinical trials received 0.30 billion (8.6%). By cross-cutting research theme, the largest investment was into intraoperative research (0.76 billion (21.9%)), preoperative/neoadjuvant studies (0.04 billion (1.2%)). Global surgery was the least well-funded area of research ($0.03 billion (0.8%)).Conclusion: surgical research remains underfunded in comparison with other specialties, with most investment directed towards preclinical research, not directly involving patients. Only a small proportion was invested in clinical trials, public health, and global surgery. These findings limit the impact of surgical research on improving population health and contrast starkly with the ubiquity of surgical treatments in the management of the global burden of disease. Urgent prioritization of surgical research and evaluation of priorities in research investment are required, to reflect surgery's pivotal role in global healthcare.</p
Fintech and the emerging ecosystems: exploring centralised and decentralised financial technologies
No full textFinancial technologies, commonly referred to as Fintech, are revolutionizing and reorganizing the financial sector. This digital transformation profoundly impacts society and influences our everyday lives in numerous ways, as financial services intersect with various other services we utilize.This book offers contributions from leading researchers in the field, providing a comprehensive understanding of this multifaceted transformation. It encompasses emerging financial technologies such as cryptoassets, including Bitcoin and Non-Fungible Tokens (NFTs), Decentralized Finance (DeFi), Central Bank Digital Currencies (CBDCs), and the growing significance of Artificial Intelligence (AI) and Generative AI.While the primary audience comprises researchers and academics, practitioners and students can also glean practical insights from its contents
The impact of prehabilitation on patient outcomes in oesophagogastric cancer surgery: combined data from four prospective clinical trials performed across the UK and Ireland
No full textBackground: prehabilitation is increasingly being used in patients undergoing multimodality treatment for oesophagogastric cancer (OGC). Most studies to date have been small, single-centre trials. This collaborative study sought to assess the overall impact of prehabilitation on patient outcomes following OGC surgery.Methods: data came from four prospective prehabilitation trials conducted in the UK or Ireland in patients undergoing multimodality treatment for OGC. The studies included three randomised and one non-randomised clinical trial, each comparing a prehabilitation intervention group to controls. The prehabilitation interventions included aerobic training delivered by exercise physiologists alongside dietetic input throughout the treatment pathway. The primary outcome was survival (all-cause and disease-specific mortality). Secondary outcomes were differences in complications, cardio-respiratory fitness (changes in VO 2 peak and anaerobic threshold (AT)), chemotherapy completion rates, hospital length of stay, changes in body mass index, tumour regression and complication rates of anastomotic leak and pneumonia. Cox and logistic regression analysis provided hazard ratios (HR) and odds ratios (OR), respectively, with 95% confidence intervals (CI), adjusted for confounders.Results: among 165 patients included, 88 patients were in the prehabilitation group and 77 patients were in the control group. All-cause and disease-specific mortality were not improved by prehabilitation (HR 0.67 95% CI 0.21–2.12 and HR 0.82 95% CI 0.42–1.57, respectively). The prehabilitation group experienced fewer major complications (20% vs. 36%, p = 0.034; adjusted OR of 0.54; 95%CI 0.26–1.13). There was a mitigated decline in VO 2 peak following neo-adjuvant therapy (delta prehabilitation −1.07 mL/kg/min vs. control −2.74 mL/kg/min; p = 0.035) and chemotherapy completion rates were significantly higher following prehabilitation (90% vs. 73%; p = 0.016). Hospital length of stay (10 vs. 12 days, p = 0.402) and neoadjuvant chemotherapy response (Mandard 1–3 41% vs. 35%; p = 0.494) favoured prehabilitation, albeit not statistically significantly. Conclusion: despite some limitations in terms of heterogeneity of study methodology, this study suggests a number of meaningful clinical benefits from prehabilitation before surgery for OGC patients. Current initiatives to agree on national standards for delivering prehabilitation and the results of ongoing trials will help to further refine this important intervention and expand the evidence base to support the widespread adoption and implementation of prehabilitation programs.</p
Workshop 1 report: regulatory regimes: national and comparative regulation of public transport
No full textThis workshop was based on 10 resource papers, the experience of 11 countries from a range of income and market maturity levels and the lived experience of 18 participants. It considered four research questions. The first relates to the main trends in competition and ownership in Land Passenger Transport in the 21st Century to date. The second examines the differences between more mature and less mature markets and industries. The third assesses whether recent trends can be explained by reworkings of the regulatory cycle. The fourth considers the extent models of the regulatory cycle can take into account new forms of collaboration, particularly between the private and the public sector. Having reviewed the evidence, some emerging concepts are identified, along with policy and research recommendations. Implications for future Thredbo conferences are considered
Novel insight into the mechanisms of neurotoxicity induced by type I and type II pyrethroids via disrupting the gut-brain axis in lizards
No full textType I and type II pyrethroids are widely used and frequently detected in agricultural environments. The neurotoxic effects and underlying mechanisms of pyrethroids in native animal populations, including lizards as common farmland inhabitants, remain unclear. This study exposed male lizards (Eremias argus) to type I bifenthrin (BF) and type II fluvalinate (FA) pyrethroids for 28 days, resulting in abnormal behaviors. Targeted analyses indicated that neurotransmitters, including dopamine, GABA, acetylcholine, and choline in lizard plasma, were significantly decreased with alterations in the cholinergic synapse, dopaminergic synapse, and cAMP signaling pathway in the brain after BF and FA treatment. Nervous system-related genes such as CACNA1A, CACNA1B, and CACNA1C were significantly down-regulated and highly correlated with arachidonic acid metabolism pathway-related metabolites in lizard gut. A notable decrease in metabolites within the arachidonic acid metabolism pathway and alterations in the gut microbiome were indicative for anti-inflammatory responses and neurotoxic effects. Interestingly, increased type I BF bioaccumulation in lizard intestines induced a higher abundance of Akkermansia, which resulted in reduced inflammation in the gut and lower neurotoxic effects compared to the low-dose BF exposure group. This study reveals contrasting dose-responses between pyrethroid types and suggests gut-brain axis-regulated neurotoxicity in lizards.</p
Exceptionally low genomic diversity in the underutilised legume Kersting's groundnut
No full textIdentifying crops with novel and climate resilience traits is imperative to ensure food security. Without a basic understanding of the genomes and genomic diversity of these crops they will remain underutilised or could even become lost. Kersting's groundnut [Macrotyloma geocarpum (Harms) Maréchal & Baudet] is one such crop, regarded as a useful, drought tolerant and sometimes valuable legume. Here, we present the assembly and annotation of the genome of Kersting's groundnut and an analysis of genomic diversity across a diversity panel. Accessions are grouped by geography and seed coat colour, one of the key traits used to describe the accessions. Four candidate genes involved in pathways relating to pigments or flavonoids are revealed. One of the important findings is that Kersting's groundnut retains very low diversity, about 85-95% less than two other legumes, suggesting a pressing need to conserve the existing diversity of Kersting's groundnut.</p
Understanding perceived tranquility in urban Woonerf streets: case studies in two Dutch cities' into the community
No full textBackground: in an increasingly urbanised world, the demand for tranquil spaces is growing. Woonerf streets in the Netherlands exemplify a human-centred urban design, where pedestrian and vehicular movement coexist seamlessly, facilitated by a restricted speed limit of 15 km/h. While previous studies have relied on predictive models to assess tranquillity based on noise exposure and greenery levels (e.g., the Green View Index), urban environments involve diverse sound sources, each influencing human perception differently.Methods: this study integrates objective sound measurements with subjective tranquillity assessments, considering eight perceptual attributes to capture the complexity of urban soundscapes. Data were collected from 61 Woonerf streets in Groningen and Leeuwarden, incorporating audio recordings, visual analysis, and resident questionnaires to evaluate the relationship between noise levels, environmental characteristics, and perceived tranquillity.Results: findings indicate that Woonerf streets are generally perceived as pleasant and uneventful, aligning with their intended function as quiet, community-friendly spaces. Streets with more greenery and cultural elements had higher perceived tranquillity, even when objective noise levels remained similar to less visually enriched streets. However, results reveal a discrepancy between predicted and subjective tranquillity, highlighting the limitations of conventional models in accurately reflecting human experience.Conclusions: these findings have significant implications for urban planning and policy. The results suggest that objective noise and environmental indices alone are insufficient to capture tranquillity as perceived by residents. Instead, a more holistic approach is needed-one that incorporates human sensory perception, urban design elements and socio-environmental factors to create more effective tranquillity assessment frameworks.<br/
Data sources:
Access Repository Dashboard
Do you manage e-Prints Soton? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!