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The political economy of the original “Thucydides’ Trap”: a conflict economics perspective on the Peloponnesian war
Full text linkThe Peloponnesian War, 431-404, between democratic Athens and oligarchic Sparta was a long, destructive war ending with the total surrender of Athens. Scholars of Thucydides, the ancient historian of the conflict, have dwelt on two different explanations of the causes of the War. First, the “Thucydides’ Trap”, which argues that Sparta’s fear of the growing power of Athens rendered peace arrangements non-credible and made war inevitable. Second, the unwise leadership, which blames key political leaders for their erroneous judgments in the affairs of the state. Using the perspective of the economics of conflict the present study questions both views. It argues that the non-credibility of peace is at best an incomplete explanation of the conflict, and the unwise leadership hypothesis requires a systematic account of the factors affecting leaders to choose war. Noting that the clash between Sparta and Athens had started earlier, in 460, the study shows that its causes related to calculations of material and non-material benefits from victory, perceptions of the probability of military success, problems of domestic political accountability, and the valuation of the future. Importantly, it also shows that the role of these factors differed significantly at the different phases of the extended conflict
Type 1 Diabetes Risk Variants Reduce Beta Cell Function
Full text linkIntroduction: The variants rs10517086 and rs1534422 are predictive of type 1 diabetes mellitus (T1DM) development and poor residual β cell function within the first year of diagnosis. However, the mechanism by which risk is conferred is unknown. We explored the impact of both variants on β cell function in vitro and assessed their relationship with C-peptide in people with T1DM and type 2 diabetes mellitus (T2DM). Methods: Using CRISPR/Cas9, the variants were introduced into a β cell line (BRIN-BD11) and a T cell line (Jurkat cells) from which the conditioned media was applied to otherwise healthy β cells to model the inflammatory environment associated with these variants. Results: Both variants significantly reduced glucose-stimulated insulin secretion, increased production of pro-inflammatory cytokines and reduced expression of several β cell markers and transcription factors (KCNJ11, KCNQ1, SCL2A2, GCK, NKX6.1, Pdx1 NGN3). However, HNF1A was significantly upregulated in the presence of both variants. We subsequently silenced HNF1A in variant expressing BRIN-BD11 cells using siRNA and found that gene expression profiles were normalised. Induction of each variant significantly increased expression of the lncRNAs they encode, which was normalised upon HNF1A silencing. Analysis of the DARE (Diabetes Alliance for Research in England) study revealed an association of rs10517086_A genotype with C-peptide in 153 individuals with T1DM, but not in 417 people with T2DM. Conclusions: These data suggest that rs1534422 and rs10517086 exert multiple insults on the β cell through excessive upregulation of HNF1A and induction of pro-inflammatory cytokines, and highlight their utility as prognostic markers of β cell function
Modelling Task Durations Towards Automated, Big Data, Process Mining
Full text linkBusiness processes are generally time‐sensitive, impacting factors such as customer expectations, cost efficiencies, compliance requirements, supply chain constraints, and timely decision‐making. Time analysis is therefore crucial for customer understanding and process congestion minimisation. Existing process mining methods mainly employ basic statistics, process discovery and data mining techniques. These approaches often lack a structured model or profile to characterise the data related to the duration of individual process tasks. Consequently, it can be difficult to comprehensively understand critical observations such as trends, peaks, and valleys of task durations. This paper proposes a parsimonious generic representation of task duration data that addresses these limitations. A mixture model comprising gamma, uniform and exponential distributions is proposed that allows for peaked components corresponding to durations terminating near a particular value (the peak) with, in addition, flatter components for durations terminating more randomly between the peaks. The modelling is validated using examples from patient billing and the telecom industry. In each scenario, the corresponding fitted models offer a good representation of the underlying process tasks. The model can therefore be used to improve knowledge of these tasks in terms of the mixture components and what they might represent, such as the root causes of task termination. The paper also considers information criteria more appropriate for large data sets where very small effects can appear “significant” using techniques developed for smaller data sets
The effectiveness and risks of Treating people with Idiopathic Pulmonary fibrosis with the Addition of Lansoprazole (TIPAL): study protocol for a randomised placebo-controlled multicentre clinical trial
Full text linkIntroduction Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease frequently complicated by gastro-oesophageal reflux disease. Although several observational studies and a pilot study have investigated the role of proton pump inhibitors (PPIs) in IPF, their efficacy is unknown and there is much debate in international IPF guidelines on their use. We aim to undertake an adequately powered double-blind placebo-controlled randomised multicentre clinical trial to assess the change in forced vital capacity (FVC), cough and other important patient-reported outcomes, following 12-month therapy with PPIs in people with IPF. Methods and analysis A total of 298 patients with IPF diagnosed by a multidisciplinary team according to international guidelines who are not receiving PPIs will be enrolled. Patients are randomised equally to receive two capsules of lansoprazole or two placebo capsules, two times per day for 12 months. The primary outcome for the trial is change in FVC, measured at home, between the first week and last week of the study period. Secondary assessments include cough frequency (in a subgroup) measured using the VitaloJAK cough monitor, the King's Brief Interstitial Lung Disease questionnaire, the Raghu Scale for Pulmonary Fibrosis, Medical Research Council dyspnoea score, EQ-5D-5L, Leicester Cough Questionnaire, modified DeMeester reflux symptoms questionnaire and opportunistically captured routine lung function measurements. High-resolution CT scoring will be undertaken in a subgroup. The trial is designed to determine whether treating people with IPF with lansoprazole will reduce the reduction in FVC over a year. The COVID-19 pandemic required the study to be undertaken as a remote trial. Ethics and dissemination This study received ethical approval from the East of England Cambridgeshire and Hertfordshire Research Ethics Committee (reference 20/EE/0043; integrated research application system number 269050). Trial results will be published in a peer-reviewed journal upon completion.</p
Experiences of Social Disconnection in a Bereaved Community Sample from Ontario, Canada
Full text linkLower perceived social support is a known risk factor for problematic grief reactions, but specific facets such as social disconnection may play a critical role in shaping grief responses. This study utilized the Oxford-Grief Social Disconnection Scale (OG-SD) to examine the demographic, loss-related, and psychological correlates of its three core dimensions, as identified in previous research: Negative Interpretation of Others’ Reactions to Grief Expression, Altered Social Self, and Safety in Solitude. Participants were a non-probability sample of N = 1171 bereaved adults living in Ontario, Canada. Confirmatory factor analysis (CFA) was used to confirm the three dimensions of grief-related social disconnection identified in previous research. Correlation and one-way ANOVA tests explored demographic and loss-related correlates of these dimensions, while associations with symptoms of Prolonged Grief Disorder (PGD), depression, and anxiety were assessed through correlational analyses. CFA results confirmed that the OG-SD was best reflected by a correlated three-factor model comprising Negative Interpretation of Others’ Reactions to Grief Expression, Altered Social Self, and Safety in Solitude latent variables. Distinct associations between the core dimensions of social disconnection and loss-related variables were identified, and significant associations between all three dimensions and scores on measures of PGD, depression, and anxiety were also observed. Findings from this study not only provide additional support for the validity and reliability of the OG-SD in a general population sample of Canadian adults, for the first time, but also identify demographic, loss-related, and psychological factors associated with social disconnection
Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation
Full text linkSARS-CoV-2 has claimed more than 7 million lives worldwide and has been associated with prolonged inflammation, immune dysregulation and persistence of symptoms following severe infection. Understanding the T cell mediated immune response and factors impacting development and continuity of SARS-CoV-2 specific memory T cells is pivotal for developing better therapeutic and monitoring strategies for those most at risk from COVID-19. Here we present a comprehensive analysis of memory T cells in a convalescent cohort (n=20), three months post Omicron infection. Utilising flow cytometry to investigate CD4 +CD45RO + and CD8 +CD45RO + memory T cell IL-2 expression following Omicron (B.1.1.529/BA.1) peptide pool stimulation, alongside T cell receptor repertoire profiling and RNA-Seq analysis, we have identified several immunological features associated with hospitalised status. We observed that while there was no significant difference in median CD4 +CD45RO + IL-2 + and CD8 + CD45RO + IL-2 + memory T cell count between subgroups, the hospitalised subgroup expressed significantly more IL-2 per cell following Omicron peptide pool exposure in the CD8 +CD45RO + population (p <0.03) and trended towards significance in CD4 +CD45RO + cells (p <0.06). T cell receptor repertoire analysis found that the non-hospitalised subgroup had a much higher number of circulating clonotypes, targeting a wider range of predominantly MHC-I epitopes across the SARS-CoV-2 genome. Several immunodominant epitopes, conserved between both subgroups, were observed, however hospitalised individuals were less likely to express putative HLA alleles responsible for pMHC presentation which may impact TCR affinity. We observed a bias towards shorter CDR3 segments in TCRβ repertoire analysis within the hospitalised subgroup, alongside lower rates of repertoire overlap in CDR3 sequences compared to the non-hospitalised subgroup. We found a significant proportion of TCRs targeted epitopes along the SARS-CoV-2 genome including non-structural proteins, responsible for viral replication and immune evasion. These findings highlight how the continuity of T cell based protective immunity is impacted by both the viral replication cycle of SARS-CoV-2 upon intracellular and innate immune responses, and HLA-type upon TCR affinity and clonotype formation. Our novel Epitope Target Analysis Pipeline (Epi-TAP) could prove beneficial in development of new therapeutic strategies through rapid identification of shared immunodominant epitopes across non-hospitalised and hospitalised subgroups.</p
Federated Learning Framework for Real-Time Activity and Context Monitoring Using Edge Devices
Full text linkWith the increasing need for effective elderly care solutions, this paper presents a novel federated learning-based system that uses smartphones as edge devices to monitor and enhance elderly care in real-time. In this system, elderly individuals carry smartphones equipped with Inertial Measurement Unit (IMU) sensors, including an accelerometer for activity recognition, a barometer for altitude detection, and a combination of the accelerometer, gyrometer, and magnetometer for location tracking. The smartphones continuously collect real-time data as the elderly individuals go about their daily routines. These data are processed locally on each device to train personalized models for activity recognition and contextual monitoring. The locally trained models are then sent to a federated server, where the FedAvg algorithm is used to aggregate model parameters, creating an improved global model. This aggregated model is subsequently distributed back to the smartphones, enhancing their activity recognition capabilities. In addition to model updates, information on the users’ location, altitude, and context is sent to the server to enable the continuous monitoring and tracking of the elderly. By integrating activity recognition with location and altitude data, the system provides a comprehensive framework for tracking and supporting the well-being of elderly individuals across diverse environments. This approach offers a scalable and efficient solution for elderly care, contributing to enhanced safety and overall quality of life
“We’re all in this together”: patient and public involvement and engagement in developing a new psychosocial intervention for adults with an intellectual disability who display aggressive challenging behaviour
Full text linkBackground: Although there is consensus regarding the added value of adults with an intellectual disability and family carers as Patient and Public Involvement and Engagement (PPIE) members in research studies, there is limited reporting on the practice and impact of their involvement. Methods: PPIE input was integral to the application process and subsequent research activities in the NIHR-funded PETAL (PErsonalised Treatment packages for Adults With Learning disabilities) programme. We also conducted semi-structured interviews with five researchers/PPIE facilitators and four family carers, and a focus group with three adults with an intellectual disability who are members of the programme advisory groups. The GRIPP2 checklist guided the reporting of PPIE activities. Results: Thematic analysis identified four overarching themes: (a) Motivation for being a PPIE member, (b) Added value of PPIE input into research (c) Logistics and practicalities of PPIE activities, and (d) Insights and reflections. Family carers highlighted the benefit of giving a voice to adults with an intellectual disability in PPIE activities within research. Both PPIE groups were positive about being able to share their thoughts and feelings with the PETAL research team and making valued contributions to research activities. All stakeholders highlighted the importance of accessible meeting formats to facilitate PPIE activities. They also reflected on how meaningful collaboration could enhance research in the field of intellectual disability. Researchers raised the need for greater diversity within PPIE groups. Conclusions: Future work should aim to further develop PPIE processes and identify strategies to maximise the diversity and inclusion of adults with an intellectual disability and family carers in research advisory groups
Hydrogen safety for systems at ambient and cryogenic temperature: A comparative study of hazards and consequence modelling
Full text linkTransport and storage of hydrogen as a liquid (LH2) is being widely investigated as a solution for scaling up the supply infrastructure and addressing the growth of hydrogen demand worldwide. While there is a relatively well-established knowledge and understanding of hazards and associated risks for gaseous hydrogen at ambient temperature, several knowledge gaps are yet open regarding the behaviour in incident scenarios of cryogenic hydrogen, including LH2. This paper aims at presenting the models and tools that can be used to close relevant knowledge gaps for hydrogen safety engineering of LH2 systems and infrastructure. Analytical studies and computational fluid dynamics (CFD) modelling are used complementarily to assess relevant incident scenarios and compare the consequences and hazard distances for hydrogen systems at ambient and cryogenic temperature. The research encompasses the main phenomena characterising an incident scenario: release and dispersion, ignition, and combustion. Experimental tests on cryogenic hydrogen systems are used for the validation of correlations and numerical models. It is observed that engineering tools originally developed for hydrogen at ambient temperature are yet applicable to the cryogenic temperature field. For a same storage pressure and nozzle diameter, the decrease of hydrogen temperature from ambient to cryogenic 80 K may lead to longer hazard distances associated to unignited and ignited hydrogen releases. The potential for ignition by spark discharge or spontaneous ignition mechanism is seen to decrease with the decrease of hydrogen temperature. CFD modelling is used to give insights into the pressure dynamics created by LH2 vessels rupture in a fire using experimental data from literature.</p
