Legitimate realism? On Tucker's Global Discord

Paul Tucker’s Global Discord offers two principal claims. The first predicts a global order of alliances among nations who share some common values, forming a pattern of concentric circles. The second suggests that domestic and international legitimacy in such an order can be normatively understood in terms of David Hume’s theory of conventions and Bernard Williams’s theory of legitimacy. How far can this Hume-Williams programme be justified? Hume’s theory can be questioned by noting that legitimate governmental systems typically need to transcend local conventions. Williams’s theory relies on theorising government in a partial way as involving a public forum. By contrast, a modified contractarian theory, based on mutual advantage among parties with roughly equal power enables us to distinguish whether appeals to culturally specific values are made in good faith, as well as providing the intellectual basis for the virtue of political courage

Predicting risk of psychosis in primary care: a qualitative study

Background P Risk is a new tool which aims to help GPs identify people at risk of developing psychosis using electronic health record data of nonpsychotic symptom consultations, medications and sociodemographic factors. Aim To explore clinicians' and patients' views of the acceptability and usefulness of using P Risk in primary care. Design and setting Semi-structured interviews with GPs, Early Intervention (EI) team clinicians and patients from Bristol and London area. Method Three topic guides were developed to ensure consistency across interviews. Interviews were transcribed verbatim and analysed thematically. Results A total of 10 GPs, 6 EI clinicians, and 13 patients were interviewed. Most clinicians and patients welcomed the development of P Risk as a tool for improving the identification of people at risk of psychosis. However, some clinicians raised concerns about the quality of clinician coding in primary care medical records, availability of effective treatments, limited capacity of EI teams to work with people at risk, increased workload for GPs, and the negative impact on patients from being told about their risk of psychosis. For patients, identification of people at risk only made sense if there was treatment available. Interviewees said that clinicians should explain to patients what psychosis is, what it means to be at risk, which factors drive the risk, and how to address them. Conclusion Whilst most clinicians and patients welcomed the development of P Risk, there needs to be a clear pathway for assessing and offering treatment to those identified as being at risk

Compositional Segmentation of Cardiac Images Leveraging Metadata

Cardiac image segmentation is essential for automated cardiac function assessment and monitoring of changes in cardiac structures over time. Inspired by coarse-to-fine approaches in image analysis, we propose a novel multitask compositional segmentation approach that can simultaneously localize the heart in a cardiac image and perform part-based segmentation of different regions of interest. We demonstrate that this compositional approach achieves better results than direct segmentation of the anatomies. Further, we propose a novel Cross-Modal Feature Integration (CMFI) module to leverage the meta-data related to cardiac imaging collected during image acquisition. We perform experiments on two different modalities, MRI and ultrasound, using public datasets, Multi-Disease, Multi-View, and Multi-Centre (M &Ms-2) and Multi-structure Ultrasound Segmentation (CAMUS) data, to showcase the efficiency of the proposed compositional segmentation method and Cross-Modal Feature Integration module incorporating metadata within the proposed compositional segmentation network. The source code is available: https://github.com/kabbas570/CompSeg-MetaData

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial. / / Methods: FIREFLY-1 investigated the efficacy (arm 1, n = 77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG). In this post hoc analysis, anti-tumor activity and VA were analyzed in arm 1 patients with OPG. Anti-tumor activity was independently assessed per Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG), Response Assessment in Pediatric Neuro-Oncology-LGG (RAPNO), and RANO-LGG criteria. The data cutoff was June 5, 2023. / / Results: Forty-two of 77 patients had OPGs; 35 of 42 had ≥2 VA assessments. The overall response rate in the OPG subgroup according to RANO-HGG, RAPNO, and RANO-LGG criteria were 64%, 50%, and 55%, with clinical benefit rates of 95%, 88%, and 90%, respectively. VA per patient was preserved for 80% of patients; 31% demonstrated improved VA; VA per eye was preserved in 87%, with 27% improving. The safety profile in the arm 1 OPG subgroup was similar to the overall FIREFLY-1 safety analysis set. / / Conclusions: Tovorafenib demonstrated anti-tumor activity in relapsed/refractory BRAF-altered OPG across radiological assessment criteria and was generally well tolerated. Importantly, vision remained stable or improved in most patients

The National Health Service-Galleri multi-cancer screening trial: explanation and justification of unique and important design issues

Despite there being a plethora of multi-cancer early-detection tests, NHS-Galleri (ISRCTN91431511) is the only randomized controlled trial (RCT) of a multi-cancer liquid biopsy in a screening setting thus far. The NHS-Galleri trial has generated much debate, and it has been criticized in the medical press. Some of these criticisms stem from differing opinions over the choice of primary endpoint, others from poor reporting in statements to journalists from those not directly involved in the trial. Some of the debate is positive, and relates to the speed of enrolment, and the equity in participation, which have shown what is possible in large population-based RCTs. Here we explain our reasoning for undertaking the trial and designing it in the way we did. We focus on the reason to consider multi-cancer screening and why we felt that the results from non-randomized clinical studies of GRAIL's Galleri test justified a large RCT. We also consider the very slow progress in adopting effective cancer screening historically and in reducing cancer mortality through early detection. There is a need to plan now for future research and implementation depending on the results of the trial. NHS-Galleri is the first double-blind cancer screening RCT. It also, unusually, uses late-stage cancer incidence (rather than cancer mortality) as its primary outcome

Reconceptualising social (in)justice for research in rural South African schools: the roles of space, place and collective response

Many theories of social justice overlook the importance of space and place. In analysing education in the rural Global South, they do not capture the complexity and situatedness of issues such as cultural and linguistic hierarchies in language of instruction, and rural flight and individual life trajectories. We propose a new theoretical framework for understanding (in)justice, developed through a project to improve children’s literacy and wellbeing through community engagement in primary schools in rural South Africa. We argue that combining structural, agential and spatial perspectives, and incorporating the indigenous theory of ‘flocking’, will help us better hear and understand the distinctive experiences of rural children and adults, and support their agency in addressing the injustices and opportunities they face

Key challenges and recommendations for defining organelle membrane contact sites

Intracellular membrane contact sites (MCSs) between organelles have crucial roles in cellular signalling and homeostasis. These sites, which are often disrupted in pathological conditions, enable the exchange of ions, lipids and metabolites between membrane-bound compartments, helping cells adapt to varying physiological conditions. Specific tether proteins and complexes stabilize these interactions and mediate responses to different intracellular or extracellular stimuli. The study of MCSs has progressed in recent years, owing to the development of new methods such as genetically encoded reporter constructs, advanced imaging techniques, including super-resolution microscopy and electron tomography, and proteomic approaches based on mass spectrometry. These tools have enabled unprecedented visualization and quantification of organelle interactions, as well as identification of the molecular players involved. This Expert Recommendation aims to define and map the ‘organelle contactome’, describing key proteins involved in contact site formation and the roles of MCSs in cellular function. We also explore contact site dynamics and detail advantages and disadvantages of the methodologies for studying them. Importantly, we consolidate open questions in contact site research and discuss challenges and limitations of the current experimental approaches

‘Resurrection’ of a flood action group through co-learning

This paper examines the ‘resurrection’ of a flood action group following a decade of inactivity, through a ‘co-learning’ lens. Flood action groups play a crucial role in UK flood risk management, yet many struggle to maintain activity, particularly without sustained external funding. This is, in fact, a common challenge in community-based DRR worldwide. While DRR research often prioritises high-impact/low-frequency hazards, ‘small-scale disasters’ are increasingly recognised as equally significant. Selforganisation is often essential for sustainable DRR in resource-constrained contexts. The paper develops a preliminary co-learning framework to analyse the flood action group's revival. While ‘co-learning’ and ‘co-creation’ are widely used in DRR research, the conceptual interrogation of the terms remains underdeveloped. After clarifying the relationship between these concepts, the paper identifies five key characteristics of colearning from the existing literature in the field of education as follows: solidarity, equal power balance, reciprocal learning, new knowledge creation, collective action for social change. These are then applied as a tentative framework in analysing the case. The paper concludes by reflecting on the framework’s limitations but also exploring its potential to advance co-learning research in DRR

The association between racism and psychosis: An umbrella review

Elevated rates of psychosis are consistently identified in people from racialised backgrounds, with growing evidence from the systematic review literature that suggests a role for racial/ethnic discrimination. We synthesised current systematic review evidence on the association between racial/ethnic discrimination and psychosis. We conducted an umbrella review, systematically searching Medline, Embase, PsycINFO, ProQuest Central and Google Scholar (up to 19 July 2024) for systematic reviews and meta-analyses published in peer-reviewed journals exploring the effect of racial/ethnic discrimination on psychosis. 2898 citations were de-duplicated and screened, included reviews were assessed for risk of bias using AMSTAR-2 and extracted data analysed narratively following a pre-registered protocol (CRD42023400656). Seven reviews (reporting 23 primary studies representing 40,300 participants) met inclusion criteria, five of which explicitly reported on the association between racial/ethnic discrimination and psychosis. All observed evidence of a positive relationship between the two, including meta-analyses for psychotic symptoms (adjusted OR=1.77, 95%CI 1.26, 2.49) and psychotic experiences (pooled OR=1.94, 95%CI 1.42, 2.67). We observed more robust evidence for psychotic outcomes in non-clinical populations. Despite this, results were driven by cross-sectional studies (87%) and were hindered by high heterogeneity and low (n = 2) or critically low (n = 5) AMSTAR-2 review quality scores. The available systematic review evidence supports a role for racial/ethnic discrimination in developing psychosis, but high-quality studies are needed to determine the temporal and mechanistic causal pathways through which this occurs. The current findings add to knowledge on the widespread presence and deleterious impacts of racism on health and inform potential public health interventions that reduce exposure to, and the impact of, racial/ethnic discrimination

Underwater Robotic Simulators Review for Autonomous System Development

The increasing complexity of underwater robotic systems has led to a surge in simulation platforms designed to support perception, planning, and control tasks in marine environments. However, selecting the most appropriate under-water robotic simulator (URS) remains a challenge due to wide variations in fidelity, extensibility, and task suitability. This paper presents a comprehensive review and comparative analysis of five state-of-the-art, ROS-compatible, open-source URSs: Stonefish, DAVE, HoloOcean, MARUS, and UNav-Sim. Each simulator is evaluated across multiple criteria including sensor fidelity, environmental realism, sim-to-real capabilities, and research impact. We evaluate them across architectural design, sensor and physics modeling, task capabilities, and research impact. Additionally, we discuss ongoing challenges in sim-to-real transfer and highlight the need for standardization and benchmarking in the field. Our findings aim to guide practitioners in selecting effective simulation environments and inform future development of more robust and transferable URSs