This conceptual article argues for a broader view of the role of events in social systems. When analyzed as social phenomena, events can be seen as social actors that have the potential to both sustain and transform social systems. The maintenance of social systems is often reliant on iterative events, regularly occurring celebrations that tend to confirm social structures. In contrast, pulsar events have the potential to transform social structures. In this sense events can be seen as actors that have important influences on social systems, particularly in linking localized small world networks with the global space of flows. These ideas are explored through the case of Barcelona, which illustrates the interplay between these different types of events in their total portfolio, and how the extension of ritual in the sense of Collins can also contribute to the generation of new relationships and practices in the contemporary network society. Barcelona is examined as an eventful city in which the alternation of continuity through iterative events and change through pulsar events contributes to increasing the network effects of events.
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Background: A venous leg ulcer (VLU) has a significant negative impact on quality of life. Prevention of a VLU is not yet imbedded in clinical practice because risk factors for developing a first VLU are not well known. Objectives: To explore further the progression of chronic venous disease (CVD) into a first VLU from the patient’s perspective. Methods: A qualitative study using semistructured interviews was conducted among male and female patients with a VLU. Patients from primary and secondary care,under and over 50 years of age, and with first and recurrent VLUs were included. The interviews were transcribed and analysed using a narrative approach to a thematic analysis. Transcripts were organized in chronological order and an iterative process was used to code the transcripts. Results: Four key themes and the connections made between them emerged from the 11 narratives on the progression of CVD towards a first VLU: ‘comorbidity’, ‘mobility’, ‘work and lifestyle’ and ‘acknowledgment of CVD’. Comorbidity was linked to reduced mobility and late acknowledgment of CVD. Comorbidity also affected work and lifestyle and vice versa. Work and lifestyle affected mobility and was linked to the acknowledgment of CVD. Conclusions: A reduction in mobility as a result of comorbidity and work and lifestyle occurred before the VLU developed. Patients did not recognize symptoms of CVD and did not acknowledge the chronicity of CVD. Healthcare professionals should be aware of reductions in mobility and the knowledge deficit in patients with CVD.
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Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
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Digital transformation has been recognized for its potential to contribute to sustainability goals. It requires companies to develop their Data Analytic Capability (DAC), defined as their ability to collect, manage and analyze data effectively. Despite the governmental efforts to promote digitalization, there seems to be a knowledge gap on how to proceed, with 37% of Dutch SMEs reporting a lack of knowledge, and 33% reporting a lack of support in developing DAC. Participants in the interviews that we organized preparing this proposal indicated a need for guidance on how to develop DAC within their organization given their unique context (e.g. age and experience of the workforce, presence of legacy systems, high daily workload, lack of knowledge of digitalization). While a lot of attention has been given to the technological aspects of DAC, the people, process, and organizational culture aspects are as important, requiring a comprehensive approach and thus a bundling of knowledge from different expertise. Therefore, the objective of this KIEM proposal is to identify organizational enablers and inhibitors of DAC through a series of interviews and case studies, and use these to formulate a preliminary roadmap to DAC. From a structure perspective, the objective of the KIEM proposal will be to explore and solidify the partnership between Breda University of Applied Sciences (BUas), Avans University of Applied Sciences (Avans), Logistics Community Brabant (LCB), van Berkel Logistics BV, Smink Group BV, and iValueImprovement BV. This partnership will be used to develop the preliminary roadmap and pre-test it using action methodology. The action research protocol and preliminary roadmap thereby developed in this KIEM project will form the basis for a subsequent RAAK proposal.
CRISPR/Cas genome engineering unleashed a scientific revolution, but entails socio-ethical dilemmas as genetic changes might affect evolution and objections exist against genetically modified organisms. CRISPR-mediated epigenetic editing offers an alternative to reprogram gene functioning long-term, without changing the genetic sequence. Although preclinical studies indicate effective gene expression modulation, long-term effects are unpredictable. This limited understanding of epigenetics and transcription dynamics hampers straightforward applications and prevents full exploitation of epigenetic editing in biotechnological and health/medical applications.Epi-Guide-Edit will analyse existing and newly-generated screening data to predict long-term responsiveness to epigenetic editing (cancer cells, plant protoplasts). Robust rules to achieve long-term epigenetic reprogramming will be distilled based on i) responsiveness to various epigenetic effector domains targeting selected genes, ii) (epi)genetic/chromatin composition before/after editing, and iii) transcription dynamics. Sustained reprogramming will be examined in complex systems (2/3D fibroblast/immune/cancer co-cultures; tomato plants), providing insights for improving tumor/immune responses, skin care or crop breeding. The iterative optimisations of Epi-Guide-Edit rules to non-genetically reprogram eventually any gene of interest will enable exploitation of gene regulation in diverse biological models addressing major societal challenges.The optimally balanced consortium of (applied) universities, ethical and industrial experts facilitates timely socioeconomic impact. Specifically, the developed knowledge/tools will be shared with a wide-spectrum of students/teachers ensuring training of next-generation professionals. Epi-Guide-Edit will thus result in widely applicable effective epigenetic editing tools, whilst training next-generation scientists, and guiding public acceptance.
