Causes of evolutionary divergence in prostate cancer

Data Availability: Components of the PPCG data set can be accessed through different portals in accordance with the required level of data protection for each data type. The main data constituents, and respective modes of access, are listed in detail in the companion manuscript by GM Jakobsdottir [ref. 19].A preprint version of the article is available at arXiv:2503.13189v1 [q-bio.GN], https://arxiv.org/abs/2503.13189 . It has not been certified by peer review. Submission history: From: Emre Esenturk [v1] Mon, 17 Mar 2025 14:00:02 UTC (818 KB).Code Availability: Codes are available to reviewers. Open-source repository will be made available at the time of publication.Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the causes of this divergence remain unclear. While causal inference could elucidate the factors involved, conventional methods are unsuitable due to the possibility of unobserved confounders and ambiguity in the direction of causality. Here, we propose a method that circumvents these issues and apply it to genomic data from 829 prostate cancer patients. We identify several genetic alterations that drive divergence as well as others that prevent this transition, locking tumours into one trajectory. Further analysis reveals that these genetic alterations may cause each other, implying a positive-feedback loop that accelerates divergence. Our findings provide insights into how cancer subtypes emerge and offer a foundation for genomic surveillance strategies aimed at monitoring the progression of prostate cancer.Centro Nacional de Investigaciones Oncológicas (CNIO), which is funded by the Instituto de Salud Carlos III and recognized by the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) as a ‘Severo Ochoa’ Centre of Excellence (ref. CEX2019000891-S). Both A.F.-S. and G.M. also received support from Spanish Ministry of Science and Innovation grants PID2019-111356RA-I00 and PID2023-151298OB-I00 (MCIN/AEI/ 10.13039/501100011033). Additionally, A.F.-S. was awarded a fellowship from La Caixa Foundation (ID 100010434; LCF/BQ/DR21/11880009). V.J.G. acknowledges infrastructure backing from the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). V.M.H. received support from the Petre Foundation via the University of Sydney Foundation (Australia). H.H.H. is supported by project grants from the Canadian Institutes of Health Research (CIHR) (142246, 152863, 152864, 159567 and 438793). This work was also funded by NHMRC project grants 1104010 (C.M.H., N.M.C.) and 1047581 (C.M.H., N.M.C.), as well as through a federal grant from the Australian Department of Health and Ageing awarded to the Epworth Cancer Centre, Epworth Hospital (N.M.C., C.M.H.). We acknowledge further financial support from Australian Prostate Cancer Research and the University of Melbourne, Australia. M.L. received funding from National Cancer Institute grants P50CA211024, P01CA265768, R01 CA259200, from the U.S.A. Department of Defense (DoD) grants PC160357 and PC200390, as well as from the Prostate Cancer Foundation (22CHAL05). Additional support for SAPCS analytical costs came from the U.S. National Institute of Health (NIH) National Cancer Institute (NCI) Award R01CA285772-01 and a U.S. Prostate Cancer Foundation (PCF) Challenge Award (2023CHAL4150). Genomic sequencing and investigation of Southern African Prostate Cancer Study (SAPCS) data received funding from the U.S. Congressionally Directed Medical Research Programs (CDMRP) Prostate Cancer Research Program (PCRP), which included an Idea Development Award (PC200390, TARGET Africa) and HEROIC Consortium Awards (PC210168 and PC230673, HEROIC PCaPH Africa1K). R.M. and A.T.P. are supported by The Lorenzo and Pamela Galli Medical Research Trust, and A.T.P. also holds an Investigator Grant (2026643) from the National Health and Medical Research Council (NHMRC). B.P. is the recipient of a Victorian Health and Medical Research Fellowship awarded by the Victoria State Government, Australia. K.D.S. is funded by The Novo Nordisk Foundation (grant nos. NNF20OC0059410, NNF21OC0071712), The Danish Cancer Society (grant no. R352-A20573), and Independent Research Fund Denmark (grant no. 9039-00084B). J.R. acknowledges support from a CIHR Project Grant (grant no. PJT-162410) and an Investigator Award from the Ontario Institute for Cancer Research (OICR), which is itself funded by the Government of Ontario. Work at the University of Konstanz was supported by the university and an Exploration Grant from the Boehringer Ingelheim Foundation to A.J.G. J.W. received grants from the Danish Cancer Society (#R147-A9843, #R374-A22518), the Danish Council for Independent Research (#8020-00282, #3101-00177A), the Novo Nordisk Foundation (#NNF200C0060141), and Sygeforsikringen Danmark (#2022-0198). A.L. is supported by Cancer Research UK (C57899/A25812), The John Fell Fund (0012782), the Health Technology Assessment (NIHR 131233), and the John Black Charitable Foundation (TRANSLATE Triallinked biobank). Y-J.L. receives funding from Orchid, Prostate Cancer Research UK & Movember (MA-CT20-011, RIA22-ST2-006) and Cancer Research UK (C16420/A18066). A full list of funding organizations for the Pan Prostate Cancer Group is provided in a companion manuscript [ref. 19: to be published as supplementary material in due course]

Traditional methods, consumers’ stereotyping of farmers and the compensatory effects of ethical food cues

Purpose: Attesting to the growing interest in ethical food, scholarship has examined how consumers respond to different cues associated with food ethicality. However, the psychological mechanisms through which ethical food cues shape consumer preferences have been overlooked. Focusing on an underexamined cue (traditional production methods) and drawing from the Stereotype Content Model, this study aims to examine whether a warmth stereotyping of farmers may explain the influence of this cue on consumer preferences. Moreover, the paper also explores how the interaction of cues of localness and traditionality affect consumers’ perceptions of farmers. The paper documents compensatory effects between traditional methods and localness in specific circumstances. Design/methodology/approach: Two online experiments (Study 1, n = 291; Study 2, n = 183) were conducted to test the hypotheses. This paper manipulates farming methods and localness and measure perceptions of warmth and consumer responses to the profile of a fictitious farm. A model of moderated mediation is examined which identifies compensatory effects between traditional farming methods and perceptions of localness. Findings: A warm stereotype of farmers explains the positive effect of traditional farming methods and localness on consumers’ food attitudes and preferences. Furthermore, different ethical cues can have a compensatory effect on consumers’ perceptions of warmth. Specifically, for consumers with strong opposition to long supply chains, the adoption of traditional farming methods compensates for the perceived warmth of geographically distant farmers. Thus, consumers who would usually dislike distant farmers retain a positive impression of them if these farmers can boast traditional farming cues. Furthermore, we find no evidence of an additive effect between traditional farming methods and localness on warmth: the addition of the two cues does not significantly increase perceptions of warmth. Research limitations/implications: The study demonstrates that the social perception of farmers plays a key role in food preferences and the perception of ethical cues in food consumption. Moreover, it shows how different cues may influence perceptions of warmth depending on consumers’ involvement. Practical implications: For the promotion of ethical food systems, farmers could increase favourable consumer attitudes by foregrounding the ethical cues of localness and traditional farming methods. Originality/value: The results extend our understanding of the mechanisms underpinning preferences for ethical food and explicate how multiple ethical cues influence ethical food consumption

Introduction to the Research Handbook on the International Court of Justice

This Research Handbook presents an in-depth examination of the International Court of Justice (ICJ) and its jurisprudence. Contributing authors dissect the global governance functions of the ICJ and its impact on national legal orders worldwide.This project was funded by the CaPE Project, Marie Skłodowska-Curie Actions, grant agreement number 708228, Horizon 2020

Towards reducing teacher burden in Performance-Based assessments using aivaluate: an emotionally intelligent LLM-Augmented pedagogical AI conversational agent

Data Availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Background: Performance-based assessments (PBAs), such as viva voce exams and oral presentations, offer comprehensive evaluations of student knowledge and skills but place substantial burdens on teachers. The integration of emotionally intelligent, LLM-augmented AI conversational agents presents a potential solution to alleviate teacher burden while maintaining the integrity and effectiveness of PBAs. This study investigates the use of AIvaluate, a pedagogical AI conversational agent designed to support teachers during oral PBAs by offering emotionally intelligent insights and streamlining the assessment process. A counterbalanced mixed-methods study design was employed with 35 teachers and students participating in both traditional face-to-face and AIvaluate-supported assessments. Data was collected through teacher-assigned grades, System Usability Scale (SUS) questionnaires, and qualitative open-response surveys. Quantitative and qualitative analyses were conducted to compare grading outcomes, system usability, and teacher preferences between the two assessment formats. Teachers issued significantly higher grades to students in AIvaluate-supported assessments (p = 0.033), attributed to more structured, consistent questioning and emotional state reporting. The overall SUS score for AIvaluate indicated “acceptable” usability, surpassing the face-to-face format. Thematic analysis revealed key strengths of AIvaluate, including automated question prompts, real-time emotional insights, and the convenience of remote operation. However, teachers noted limitations, such as occasional technical issues and the lack of a personal connection compared to traditional face-to-face interactions. AIvaluate demonstrates the potential to reduce teacher burden in PBAs while maintaining usability and assessment quality. Its emotionally intelligent features and automated functionalities enhance the assessment process, offering a scalable, technology-driven solution for modern education. While AIvaluate shows promise in reducing teacher burden during PBAs, technical limitations, emotional disconnection, and variability in assessment impact emphasise the need for further investigation before large-scale adoption. Future research should explore building further functionality to address the diverse needs of teachers, while focusing on addressing technical limitations and assessing long-term impacts on teacher satisfaction and student outcomes.No funding was obtained for this study

The Impact of Regulatory Changes on Rating Shopping and Rating Catering Behavior in the European Securitization Market

JEL classification: G21; G28.Data Availability: The dataset used is available from the corresponding author on request.A version of the article was developed as the Working Paper Series no. 2290, available online at: https://www.ecb.europa.eu/pub/pdf/scpwps/ecb.wp2920~f44cdd68b2.en.pdf . © European Central Bank, 2024. All rights reserved. Any reproduction, publication and reprint in the form of a different publication, whether printed or produced electronically, in whole or in part, is permitted only with the explicit written authorisation of the ECB or the authors. This paper can be downloaded without charge from https://www.ecb.europa.eu, from the Social Science Research Network electronic library ( https://ssrn.com/ ) or from RePEc: Research Papers in Economics. Information on all of the papers published in the ECB Working Paper Series can be found on the ECB’s website ( https://www.ecb.europa.eu/pub/research/working-papers/html/index.en.html ). PDF ISBN 978-92-899-6400-5 ISSN 1725-2806 doi:10.2866/23087 QB-AR-24-037-EN-N.We examine whether rating shopping and rating catering behaviors two mechanisms associated with credit rating inflation remained prevalent in the European securitization market following the Global Financial Crisis (GFC) and the subsequent introduction of regulatory reforms targeting credit rating agencies (CRAs). Using a dataset of 12,469 asset-backed security (ABS) tranches issued between 1998 and 2018, we analyze the information content of yield spreads at issuance and compare patterns across pre- and post-reform periods. Our findings suggest that rating catering is no longer reflected in pricing after the reforms, while indicators of rating shopping persist, particularly among tranches with fewer published ratings. We also find continued signs of investor over-reliance on ratings, especially for high-quality ABS. These results are consistent with a shift in investor perceptions and market practices post-GFC, although the extent to which this shift reflects regulatory changes versus broader crisis-related adjustments remains open to interpretation.The authors did not receive support from any organization for the submitted work

Framework for food governance in Bangladesh

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonThis thesis investigates the issue of food adulteration in Bangladesh through the lens of systemic governance, with a focus on its profound socio-economic and public health ramifications. It critically examines how the historical evolution of governance mechanisms, fragmented legal frameworks, overlapping institutional mandates, and ineffective enforcement mechanisms have perpetuated food adulteration. This thesis contends that addressing this problem necessitates a preventive, governance-oriented strategy rather than reactionary enforcement approaches. The strengthening and optimisation of existing regulatory frameworks is key to tackling systemic inefficiencies and reducing consumer vulnerabilities. Additionally, preventive regulation, multi-stakeholder collaboration, and gradual improvements are identified as foundational pillars for meaningful progress. Technological advancements and consumer empowerment are pointed out as important drivers of long-term regulatory effectiveness. In emphasising the interconnected roles of the law, government and society, this thesis integrates socio-legal methodology with doctrinal analysis, historical inquiry, and comparative insights. This desk-based research critiques the deficiencies of Bangladesh’s existing food safety governance structures by drawing on international best practices, particularly those recommended by the Codex Alimentarius and United Nations. It synthesises legal analysis with policy-driven insights by drawing from case law, legislation, academic publications, regulatory reports, media sources, and legal commentaries across various jurisdictions to develop a governance blueprint tailored to Bangladesh’s institutional and socio-economic context. This thesis concludes that reorganising internal governance, forming collaborative partnerships with industry, and actively empowering consumers are the three areas where the government must take the lead to effectuate change. However, regulatory systems must be continuously adjusted and improved, as complete eradication of food adulteration remains an unrealistic goal. A preferable approach could be to adopt modest adjustments through open communication rather than attempting to achieve perfection all at once. The safety of Bangladesh's food supply and the overall health of the population depend on this collaborative and preventative model

Macroeconomic shocks and income inequality: An empirical investigation on the distributional channels of monetary policy and oil price news shocks

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonThis thesis provides a deeper insight into the connection between macroeconomic shocks and income inequality across various economies. Through empirical analysis of the distributional channels of propagation, the study reveals that macroeconomic shocks, such as monetary policy and oil price news, impact the income distribution asymmetrically. This observation is consistent across both economies studied, the US and the UK. Particularly, a contractionary monetary policy shock in the UK is found to produce an increase in inequality through the earnings heterogeneity and income composition channel. While low-income households are mainly left unaffected due to their high exposure to social benefits, high-income households race away because of the higher proportion of capital income components. These asymmetric effects also exist in the US, an economy investigated by looking at the time-varying effects of a contractionary monetary policy shock. In line with previous findings in the UK, the study finds that the same channels are in place. However, by adding another layer of complexity to the model, the study shows that the US income distribution became more responsive to monetary contractions in the more recent periods of the sample. This is mainly rooted in the dominant effects of the capital income components leading to a stronger effect of the income composition channel. Finally, the thesis examines a different macroeconomic shock: oil price news shocks. When including all deciles of the income distribution in the modelling approach the asymmetric effects of these shocks again are detected. The overall picture i.e. capital income components make up a significant part of rich households and hence, are the main drivers for the different reactions of this group, is confirmed

Post-politics and the Anthropocene: towards a post-foundational environmental political theory

The concept of post-politics has played a key role in diagnosing Anthropocene discourse and showing how it has reinforced the managerial, technocratic, and market logics of much environmental politics. From the homogenising and naturalising discourse of humankind as a destructive species to the fetishisation of CO2 in carbon offsetting projects and the strategic mobilisation of emergency narratives: all partake in the depoliticisation of the environmental debate. Yet, the diagnosis has also been criticised for not giving enough leverage to alternative voices and for restricting the scope of what ‘proper’ political action can consist of. In this chapter, I show how a re-engagement with the sophisticated theoretical underpinnings of post-foundational political theory can provide us with the tools to move beyond these controversies. While defending the post-political thesis, I argue that a genuine post-foundational engagement with the Anthropocene should also recognise the altered, much more politicised historical conjuncture in which we live today

Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb in acute and subacute Stroke (RHOMBUS II): results of a feasibility randomised controlled trial

Data availability statement: Data are available upon reasonable request. Data will be made available on the Figshare data repository.Objective: To investigate the safety, feasibility and acceptability of the Neurofenix platform for upper-limb rehabilitation in acute and subacute stroke. Design: A feasibility randomised controlled trial with a parallel process evaluation. Setting: Acute Stroke Unit and participants’ homes (London, UK). Participants: 24 adults (>18 years), acute and subacute poststroke, new unilateral weakness, scoring 9–25 on the Motricity Index (elbow and shoulder), with sufficient cognitive and communicative abilities to participate. Interventions: Participants randomised to the intervention or control group on a 2:1 ratio. The intervention group (n=16) received usual care plus the Neurofenix platform for 7 weeks. The control group (n=8) received usual care only. Outcomes: Safety was assessed through adverse events (AEs), pain, spasticity and fatigue. Feasibility was assessed through training and support requirements and intervention fidelity. Acceptability was assessed through a satisfaction questionnaire. Impairment, activity and participation outcomes were also collected at baseline and 7 weeks to assess their suitability for use in a definitive trial. Randomisation: Computer-generated, allocation sequence concealed by opaque, sealed envelopes. Blinding: Participants and assessors were not blinded; statistician blinded for data processing and analysis. Results: 192 stroke survivors were screened for eligibility, and 24 were recruited and randomised. Intervention group: n=16, mean age 66.5 years; median 9.5 days post stroke. Control group: n=8, mean age 64.6 years; median 17.5 days post stroke. Three participants withdrew before the 7-week assessment, n=21 included in the analysis (intervention group n=15; control group n=6). No significant group differences in fatigue, spasticity, pain scores or total number of AEs. The median (IQR) time to train participants was 98 (64) min over 1–3 sessions. Participants trained with the platform for a median (range) of 11 (1-58) hours, equating to 94 min extra per week. The mean satisfaction score was 34.9 out of 40. Conclusion: The Neurofenix platform is safe, feasible and well accepted as an adjunct to usual care in acute and subacute stroke rehabilitation. There was a wide range of engagement with the platform in a cohort of stroke survivors which was varied in age and level of impairment. Recruitment, training and support were manageable and completion of data was good, indicating that a future randomised controlled trial would be feasible. Trial registration number: ISRCTN11440079.This work was supported by The Stroke Association and MedCity grant number SA MC 21\10001

SharkNet Networks Applications in Smart Manufacturing Using IoT and Machine Learning

Data Availability Statement: The necessary research data have been presented in the article.With the advancement of Industry 4.0, 3D printing has become a critical technology in smart manufacturing; however, challenges remain in the integrated management, quality control, and remote monitoring of multiple 3D printers. This study proposes an intelligent cloud monitoring system based on the SharkNet dynamic network, IoT, and artificial neural networks (ANNs). The system utilizes a SharkNet dynamic network to integrate low-cost sensors for environmental monitoring to enable low-latency data transmission and deploys ANN models on the cloud for print quality prediction and process parameter optimization. Next, we experimentally validated the system using the Taguchi design and ANN-based analysis, focusing on optimizing printing process parameters and improving surface quality. The main results show that the designed system has a communication delay of 40–50 ms and 99.8% transmission reliability under moderate load, and the system reduces the surface roughness prediction error to less than 17.2%. In addition, the ANN model outperforms conventional methods in capturing the nonlinear relationships of the variables, and the system can be based on the model to improve print quality and productivity by enabling real-time parameter adjustments. The system retains a high degree of scalability in terms of real-time monitoring and parallel or complex control of multiple devices, which demonstrates its potential for applications in smart manufacturing.This research was funded by the Graduate Student Innovation Program of Shanxi Province, Grant No. 2023SJ214. It was also partly funded by Brunel University London