Recent publications
Communication plays a vital role in multi-agent systems, fostering collaboration and coordination. However, in real-world scenarios where communication is bandwidth-limited, existing multi-agent reinforcement learning (MARL) algorithms often provide agents with a binary choice: either transmitting a fixed amount of data or no information at all. This rigid communication strategy hinders the ability to effectively utilize bandwidth. To overcome this challenge, we present the Dynamic Size Message Scheduling (DSMS) method, which introduces finer-grained communication scheduling by considering the actual size of the information being exchanged. Our approach lies in adapting message sizes using Fourier transform-based compression techniques with clipping, enabling agents to tailor their messages to match the allocated bandwidth according to importance weights. This method realizes a balance between information loss and bandwidth utilization. Receiving agents reliably decompress the messages using the inverse Fourier transform. We evaluate DSMS in cooperative tasks where the agent has partial observability. Experimental results demonstrate that DSMS significantly improves performance by optimizing the utilization of bandwidth and effectively balancing information importance.
This paper has two aims. First, we argue that Wittgenstein’s notion of petrification can be used to explain phenomena in advanced mathematics, sometimes better than more popular views on mathematics, such as formalism, even though petrification usually suffers from a diet of examples of a very basic nature (in particular a focus on addition of small numbers). Second, we analyse current disagreements on the absolute undecidability of CH under the notion of petrification and hinge epistemology. We argue that in contemporary set theory the usage of construction techniques for set-theoretic models in which the Continuum Hypothesis holds and those in which it fails have petrified into the normative demand that CH remain undecidable. That is, the continuous and successful practices involving the construction of various set-theoretic models now act as a normative hinge shared among practitioners, i.e., have normative force in the discipline. However, not all hinges are universal, which is why we find disagreements in set theory. We will show that this is a refinement of, and partially conflicts with, the arguments presented by set theorist Joel David Hamkins.
- Bocuzzi Valentina
- Bridoux Jessica
- Pirotte Michelle
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- Marcion Guillaume
CD38 is a multifunctional transmembrane glycoprotein found in multiple tissues and overexpressed in many cancer cells, notably in hematological malignancies such as leukemia and multiple myeloma (MM). Therefore, targeting CD38 remains an attractive strategy for cancer treatment in hematological malignancies as well as in solid tumors. It plays a critical role in the progression of these diseases through its ADP-ribosyl cyclase and cADPR-hydrolase activities. Its importance has led to the development of various anti-CD38 monoclonal antibodies (mAbs), including daratumumab and isatuximab, approved for MM treatment. These mAbs exert their anti-tumor effects through Fc-dependent immune mechanisms and immunomodulation, enhancing T-cell and NK-cell-mediated responses. However, resistance mechanisms arise during the treatment with daratumumab, creating the necessity for new therapies. This review explains current knowledge about the role of CD38 as a target in oncology and aims to delineate the use of single domain antibodies (sdAbs) as innovative theranostic tools in nuclear medicine. For diagnostic purposes, PET radionuclides like ⁶⁸ Ga, ⁶⁴Cu, and SPECT radionuclides like 99mTc and ¹¹¹In, are commonly used. Significant progress has been made in anti-CD38 radioligand therapy (RLT), with anti-CD38 antibodies providing insights into tumor biology and treatment efficacy. In terms of therapy, RLT is a promising approach that offers precise targeting of malignant cells while minimizing exposure to healthy tissue. This involves the use of radionuclides emitting α particles, like ²²⁵Ac, ²¹²Pb or ²¹¹At, and β⁻-particles like ⁹⁰Y, ¹³¹I, or ¹⁷⁷Lu, to exert cytotoxic effects. Derived from Camelidae heavy chain antibodies, sdAbs offer advantages over conventional mAbs such as small size, high stability, specificity, and ability to recognize hidden epitopes. CD38-specific sdAbs, such as sdAb 2F8, characterized by our laboratory, showing excellent tumor targeting and their engineered constructs, such as biparatopic antibodies and chimeric antibodies, represent a new generation of theranostic agents for diagnosis and treatment CD38-expressing malignancies.
Fat accumulation, de novo lipogenesis, and glycolysis are key drivers of hepatocyte reprogramming and the consequent metabolic dysfunction-associated steatotic liver disease (MASLD). Here we report that obesity leads to dysregulated expression of hepatic protein-tyrosine phosphatases (PTPs). PTPRK was found to be increased in steatotic hepatocytes in both humans and mice, and correlates positively with PPARγ-induced lipogenic signaling. High-fat-fed PTPRK knockout male and female mice have lower weight gain and reduced hepatic fat accumulation. Phosphoproteomic analysis in primary hepatocytes and hepatic metabolomics identified fructose-1,6-bisphosphatase 1 and glycolysis as PTPRK targets in metabolic reprogramming. Mechanistically, PTPRK-induced glycolysis enhances PPARγ and lipogenesis in hepatocytes. Silencing PTPRK in liver cancer cell lines reduces colony-forming capacity and high-fat-fed PTPRK knockout mice exposed to a hepatic carcinogen develop smaller tumours. Our study defines the role of PTPRK in the regulation of hepatic glycolysis, lipid metabolism, and tumour development in obesity.
Energy systems design is challenged by uncertainties in energy carrier costs. This study explores hydrogen and conventional energy carrier costs, providing global insights with a focus on Belgium. Over two years, European natural gas prices surged 55-fold, while solid biomass prices varied only 1.8-fold over 13 years. Regression analysis (adjusted R2>0.9) reveals mutual correlations among energy carriers, allowing for cost ranking relative to the natural gas price. The relationship between electricity and natural gas prices underscores financial challenges for heat pumps in Belgium. Hydrogen cost estimations for 2024 are 43.7, 48.8, 16.4, and 17.5 €/GJH2,LHV for green, yellow (grid), grey and blue hydrogen, respectively. Achieving cost parity between blue and grey hydrogen requires a carbon tax of 67.5–123 €/tonCO2. Present approach incorporates uncertainties in energy carrier costs by varying natural gas price scenarios, facilitating prompt identification of cases for in-depth evaluation in future energy systems.
Looking back at the preceding seven chapters, this chapter reflects on specific features of loneliness risk factors and potential consequences and evaluates the effectiveness of loneliness interventions in the European Union. In addition, the chapter highlights the unique features of the EU Loneliness Survey and suggests avenues for future research. Finally, the authors discuss the importance of monitoring loneliness over time and reflect on policy developments in the European Union and globally.
While Chap. 1 introduces the concept of loneliness as a negative feeling associated with perceived deficiencies in the quantity and quality of social relationships, this chapter focuses on how this concept is operationalised and measured in surveys. We start by discussing the literature on the measurement of loneliness, which often relies on the use of psychometric scales. In large-scale surveys the use of a direct question on loneliness, in which the respondents self-report how frequently they feel lonely, is also common. The chapter discusses existing measures of loneliness used by different surveys administered in the European Union, together with their limitations. The chapter then addresses how loneliness is dichotomised in the analysis of survey data, both for scales based on indirect questions and for direct questions, and the potential issues associated with presenting results on loneliness. Finally, the chapter introduces the recent European Union Loneliness Survey (EU Loneliness Survey), the first ad hoc survey on the topic of loneliness covering all European Union member states. It discusses how this survey measures loneliness, and the modules and questions included. A methodological section focuses on survey design and choices related to data collection, highlighting unique features of the survey and discussing its limitations. The chapter concludes with a comparison of overall levels of loneliness according to different measures used in the EU Loneliness Survey across all 27 EU countries.
Loneliness has emerged as a prominent concern in recent years, leading to it being described as the ‘epidemic’ of the twenty-first century. The COVID-19 pandemic, coupled with the distancing measures implemented to curb its spread, further heightened those worries. This introductory chapter explores the growing emphasis on loneliness in both public discourse and the political arena and discusses the underlying reasons for this increased public attention. It then presents the recent joint project of the European Commission and the European Parliament aimed at generating additional scientific insights into the risk factors and consequences of loneliness, as well as the effectiveness of loneliness interventions in the European Union. Lastly, the chapter explains the structure and organisation of this volume.
This chapter analyses the prevalence of loneliness in the European Union along several dimensions, exploring vulnerabilities within specific demographic groups and mitigating or triggering factors such as meaningful social connections and life events. The first part of the chapter investigates which demographic and socio-economic groups are more vulnerable to loneliness. In particular, it considers characteristics such as age, gender, socio-economic status, sexual orientation, disability, migration background and population density of the place of residence. The second part of the chapter is devoted to shedding light on the relationship between loneliness and social connectedness. Regression analysis is used to investigate how the risk of feeling lonely is associated with a rich set of variables related to respondents’ social interactions and relationships. Finally, the chapter looks into life events that might trigger loneliness. Major life transitions, such as retirement or leaving the education system, may bring disruptions to people’s social networks and thus increase the risk of feeling lonely.
The use of repetitive Transcranial Magnetic Stimulation (rTMS) in treating major depressive disorder (MDD) is increasingly being explored in precision medicine. However, there’s a notable lack of understanding of the underlying neurobiological effects, which limits our ability to correlate specific imaging features with treatment efficacy. As one possible neurobiological mechanism, clinical research has already shown that in MDD, lower norepinephrine release in the locus coeruleus (LC) triggers depressive symptoms, and pharmacological approaches that block norepinephrine reuptake boost its levels, easing depression. Surprisingly, the LC has not received a more pronounced focus in contemporary rTMS research. This study investigates the role of the LC in MDD and its response to high-frequency (HF)-rTMS using ¹⁸FDG-PET imaging. We compared LC metabolic connectivity between MDD patients (n = 43) and healthy controls (n = 32). Additionally, we evaluated the predictive value of LC connectivity for HF-rTMS treatment outcomes and examined post-treatment changes in LC metabolic connectivity. Our findings revealed significant differences in LC metabolic connectivity between MDD patients and controls. Baseline LC metabolic connectivity did not predict HF-rTMS treatment outcomes. However, post-treatment analyses showed a significant correlation between improved clinical outcomes and attenuation of LC metabolic connectivity in regions associated with cognitive control and the default mode network. Notably, a reduction in state anxiety moderated this relationship, highlighting the role of anxiety in HF-rTMS efficacy for MDD treatment. Our findings suggest that LC metabolic connectivity, influenced by state anxiety levels, may be crucial in HF-rTMS efficacy, offering further insights for personalized MDD treatment strategies.
Introduction
Delirium, a clinical manifestation of acute encephalopathy, is associated with extended hospitalisation, long-term cognitive dysfunction, increased mortality and high healthcare costs. Despite intensive research, there is still no targeted treatment. Delirium is characterised by electroencephalography (EEG) slowing, increased relative delta power and decreased functional connectivity. Recent studies suggest that transcranial alternating current stimulation (tACS) can entrain EEG activity, strengthen connectivity and improve cognitive functioning. Hence, tACS offers a potential treatment for augmenting EEG activity and reducing the duration of delirium. This study aims to evaluate the feasibility and assess the efficacy of tACS in reducing relative delta power.
Methods and analysis
A randomised, double-blind, sham-controlled trial will be conducted across three medical centres in the Netherlands. The study comprises two phases: a pilot phase (n=30) and a main study phase (n=129). Participants are patients aged 50 years and older who are diagnosed with delirium using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria (DSM-5-TR), that persists despite treatment of underlying causes. During the pilot phase, participants will be randomised (1:1) to receive either standardised (10 Hz) tACS or sham tACS. In the main study phase, participants will be randomised to standardised tACS, sham tACS or personalised tACS, in which tACS settings are tailored to the participant. All participants will undergo daily 30 min of (sham) stimulation for up to 14 days or until delirium resolution or hospital discharge. Sixty-four-channel resting-state EEG will be recorded pre- and post the first tACS session, and following the final tACS session. Daily delirium assessments will be acquired using the Intensive Care Delirium Screening Checklist and Delirium Observation Screening Scale. The pilot phase will assess the percentage of completed tACS sessions and increased care requirements post-tACS. The primary outcome variable is change in relative delta EEG power. Secondary outcomes include (1) delirium duration and severity, (2) quantitative EEG measurements, (3) length of hospital stay, (4) cognitive functioning at 3 months post-tACS and (5) tACS treatment burden. Study recruitment started in April 2024 and is ongoing.
Ethics and dissemination
The study has been approved by the Medical Ethics Committee of the Utrecht University Medical Center and the Institutional Review Boards of all participating centres. Trial results will be disseminated via peer-reviewed publications and conference presentations.
Trial registration number
NCT06285721 .
In the soil environment, microplastics (MPs) commonly coexist with organic pollutants such as nonylphenol (NP), affecting the migration of NP through adsorption/desorption. However, few studies have focused on the interaction between NP and MPs in soil, especially for MPs of different types and ageing characteristics. In this study, non-polar polypropylene (PP) and polar polyamide (PA) MPs were aged either photochemically (144 h) or within soil (60 days), then used to determine the effect of 5 % MPs on the adsorption behaviour of NP (0.1-4.0 mg/L) in soil. Results showed that both ageing processes significantly promoted the conversion of-CH 3 groups to CO and CO on the surface of PPMPs, while PAMPs exhibited amide groups changes and a reduction in average particle size due to ageing. Additionally, both ageing processes promoted the adsorption of NP by soil containing PPMPs, due to an increase in oxygen-containing functional groups and specific surface area. In contrast, the NP adsorption capacity of soil containing PAMPs decreased by 15.4 % following photochemical ageing due to hydrolysis of amide groups, but increased by 21.15 % after soil ageing due to reorganization of amide groups, respectively. The soil-PAMPs systems exhibited a stronger affinity for NP compared to the soil-PPMPs systems, which was primarily attributed to the dominant role of hydrogen bonding. NP was found to be distributed mainly on soil particles in the soil-PPMPs systems, while it tended to be adsorbed by MPs in the soil-PAMPs systems, especially in the soil aged MPs system. This study provides a comprehensive analysis of the complex effects of MPs on coexisting pollutants in soil environments, highlighting the effect of MP characteristics on the adsorption of organic pollutants, which is essential for understanding the transport behaviour of organic pollutants.
Human skin is colonized with skin microbiota that includes commensal bacteria, fungi, arthropods, archaea and viruses. The composition of the microbiota varies at different anatomical locations according to changes in body temperature, pH, humidity/hydration or sebum content. A homeostatic skin microbiota is crucial to maintain epithelial barrier functions, to protect from invading pathogens and to interact with the immune system. Therefore, maintaining homeostasis holds promise to be an achievable goal for microbiome‐directed treatment strategies as well as a prophylactic strategy to prevent the development of skin diseases, as dysbiosis or disruption of homeostatic skin microbiota is associated with skin inflammation. A healthy skin microbiome is likely modulated by genetic as well as environmental and lifestyle factors. In this review, we aim to provide a complete overview of the lifestyle and environmental factors that can contribute to maintaining the skin microbiome healthy. Awareness of these factors could be the basis for a prophylactic strategy to prevent the development of skin diseases or to be used as a therapeutic approach.
In this study, we answer the call for integrating insights from different language-related research areas in international business. We investigate the antecedents and outcomes of mandating English as a common language in the Indian subsidiaries and joint ventures of Cummins, a large US-headquartered industrial, multinational enterprise (MNE). Our Transaction Cost Theory lens shows how the mandated adoption of English significantly improved the Indian subsidiaries’ position in the MNE’s network. Through retrospectively analyzing the experience of the authors in top and middle management roles with Cummins in India and utilizing a range of publicly available information, we also identified the significant role of English in fostering inclusion in India, where the broad societal context of diversity and inclusion is very different from that prevailing in the MNE’s home country.
Marine sediments bury ∼160 Tg of organic carbon (OC) annually and represent an essential component of the global carbon cycle. OC burial is inherently multifactorial; however, in the past decade, the role of iron in regulating OC burial via the formation of organo‐mineral associations, known as “rusty carbon sink,” has been extensively studied. Despite widespread recognition, the origin of the OC preserved within these associations and the effect of the bottom‐water oxygenation on their stability are still debated. Here, we investigate the rusty carbon sink in sediments collected across transects from the head to mouth of three Swedish fjords presenting contrasting bottom‐water oxygenation regimes (the oxic Hake fjord, seasonally hypoxic Gullmar fjord, and anoxic By fjord). We found that the oxygenation regimes, the intensity of benthic iron cycling or the OC origin have little to no influence on the amount of OC bound to Fe (OC – Fe). The lack of correlation with any of the parameters studied, in combination with an increase in the OC – Fe in the fjords with riverine input suggest, at least partially, an allochthonous origin of these organo‐mineral associations. Our results also show that the rusty carbon sink plays a modest role in the OC burial in these fjords (∼6% OC is bound to Fe). While these fjords still represent important OC burial hotspots with an average of ∼35 g C m⁻² buried annually, the OC burial is controlled by other sedimentary processes, such as the high mass accumulation rates found in these fjord systems.
The UN sustainable development goals (SDGs) and the Paris climate target require a holistic transformation towards human well-being within planetary boundaries. However, there are growing debates on how to best pursue these targets. Proposed transformation strategies include market- and technology-driven green-growth, shifting towards a sufficiency-oriented post-growth economy, and a transformation driven primarily by strong government action. Here we quantify three alternative sustainable development pathways (SDPs), Economy-driven Innovation, Resilient Communities, and Managing the Global Commons, that reflect these different societal strategies. We compare the quantifications from two integrated assessment models and two sectoral models of the buildings and materials sectors across a broad set of indicators for sustainable development and climate action. Our global multi-scenario and multi-model analysis shows that all three SDPs enable substantial progress towards the human development goals of the SDGs. They simultaneously limit global warming and prevent further environmental degradation, with the sufficiency-oriented Resilient Communities scenario showing the lowest peak warming and lowest reliance on carbon dioxide removal as well as the largest improvements in biodiversity intactness. The SDPs also alleviate the concerns about the biogeophysical and technological feasibility of narrowly-focused climate change mitigation scenarios. However, the shifts in energy and food consumption patterns assumed in the SDPs, ranging from moderate in Economy-driven Innovation to very ambitious in Resilient Communities, also lead to increased challenges regarding socio-cultural feasibility.
Objective
Chemical, biological, radiological, and nuclear (CBRN) incidents require meticulous preparedness, particularly in the Middle East and North Africa (MENA) region. This study evaluated CBRN response operational flowcharts, tabletop training scenarios methods, and a health sector preparedness assessment tool specific to the MENA region.
Methods
An online Delphi survey engaging international disaster medicine experts was conducted. Content validity indices (CVIs) were used to validate the items. Consensus metrics, including interquartile ranges (IQRs) and Kendall’s W coefficient, were utilized to assess the panelists’ agreement levels. Advanced artificial intelligence computing methods, including sentiment analysis and machine-learning methods (t-distributed stochastic neighbor embedding [t-SNE] and k-means), were used to cluster the consensus data.
Results
Forty experts participated in this study. The item-level CVIs for the CBRN response flowcharts, preparedness assessment tool, and tabletop scenarios were 0.96, 0.85, and 0.84, respectively, indicating strong content validity. Consensus analysis demonstrated an IQR of 0 for most items and a strong Kendall’s W coefficient, indicating a high level of agreement among the panelists. The t-SNE and k-means identified four clusters with greater European response engagement.
Conclusions
This study validated essential CBRN preparedness and response tools using broad expert consensus, demonstrating their applicability across different geographic areas.
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