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Digital platforms as drivers of high-tech entrepreneurship?:Dynamics, challenges, and opportunities in the game industry
No full textDigital platforms lower barriers to entrepreneurship by providing access to technologies, distribution, and global markets. Limited extant research has examined whether platform participation enables ventures to scale sustainably, and under what conditions platforms enable high-tech industry development in smaller or peripheral regions. This thesis analyzes these questions through the Dutch game industry. Empirically, the research combines a longitudinal dataset on Dutch game developers that tracks firm activity over time, survival, and collaboration patterns, along with interviews with entrepreneurs, publishers, policymakers, and industry experts. The findings show that platforms broaden entry and enable early experimentation, but they do not remove the structural constraints that shape long-term outcomes. As platform markets mature, competition intensifies and advantages accrue to game developers that build capabilities and internationally connected networks that ensure visibility in saturated markets. Despite expectations of disintermediation, intermediaries remain pivotal: commercialization expertise, market access, and global reach have remained largely concentrated in established publishers, sustaining cross-border dependencies and reinforcing spatial inequality. The thesis further finds that generative AI is adopted unevenly and incrementally, with adoption strategies shaped by firm size, resources, and concerns about quality and ethics. These findings suggest that platform participation modestly democratizes entry but is insufficient to produce self-sustaining high-tech industries without the development of complementary assets and capabilities at the firm-level, supportive institutions, and globally connected intermediaries within the territory.<br/
Digital platforms as drivers of high-tech entrepreneurship?:Dynamics, challenges, and opportunities in the game industry
No full textDigital platforms lower barriers to entrepreneurship by providing access to technologies, distribution, and global markets. Limited extant research has examined whether platform participation enables ventures to scale sustainably, and under what conditions platforms enable high-tech industry development in smaller or peripheral regions. This thesis analyzes these questions through the Dutch game industry. Empirically, the research combines a longitudinal dataset on Dutch game developers that tracks firm activity over time, survival, and collaboration patterns, along with interviews with entrepreneurs, publishers, policymakers, and industry experts. The findings show that platforms broaden entry and enable early experimentation, but they do not remove the structural constraints that shape long-term outcomes. As platform markets mature, competition intensifies and advantages accrue to game developers that build capabilities and internationally connected networks that ensure visibility in saturated markets. Despite expectations of disintermediation, intermediaries remain pivotal: commercialization expertise, market access, and global reach have remained largely concentrated in established publishers, sustaining cross-border dependencies and reinforcing spatial inequality. The thesis further finds that generative AI is adopted unevenly and incrementally, with adoption strategies shaped by firm size, resources, and concerns about quality and ethics. These findings suggest that platform participation modestly democratizes entry but is insufficient to produce self-sustaining high-tech industries without the development of complementary assets and capabilities at the firm-level, supportive institutions, and globally connected intermediaries within the territory.<br/
Music in perioperative care and delirium prevention
No full textNon pharmacological interventions such as deprescribing and perioperative music are becoming increasingly relevant in healthcare. Deprescribing helps reduce medication burden and related risks in older adults with multimorbidity, while perioperative music has demonstrated benefits including reduced anxiety, pain, sleep problems, and opioid use. However, the reporting quality of studies on these interventions is often insufficient. Using the TiDieR checklist, this thesis found gaps in methodological reporting for both deprescribing and music trials.To better understand how music can reduce anxiety, a large dataset of 36,000 tracks was analysed. Music used for coping with anxiety showed distinct characteristics—lower BPM, loudness, energy, and valence—compared to general listening patterns, with genres like lullabies, pop, and hip hop being most common. A systematic review further confirmed that perioperative music significantly reduces pain, stress, anxiety and improves patient satisfaction. A multicentre randomised controlled trial investigating elderly hip fracture patients (MCHOPIN trial) showed mixed but promising results: while the intention to treat analysis did not show a significant reduction in delirium, modified analyses did, alongside fewer postoperative complications and high patient satisfaction.Economic evaluations revealed that perioperative music is likely cost effective for preventing postoperative delirium in elderly hip fracture patients, with comparable healthcare costs between intervention and control groups. In neurosurgical patients, however, the evidence was less conclusive, with no significant differences in delirium. Overall, perioperative music remains an attractive, low risk, and inexpensive intervention with multiple demonstrated benefits. In line with current Dutch guidelines, the thesis recommends considering perioperative music for surgical patients.<br/
Leveraging implementation science to advance non-pharmacological dementia research
No full textDementia research has produced a wide range of non-pharmacological innovations and interventions that may be used to promote healthy ageing for people with dementia and their caregivers. However, there are complex real-world challenges that limit the adoption and use of this research in real, contributing to an “implementation gap”. Research often remains within the academic community, unable to reach the intended end-users in practice settings. The field of implementation science provides systematic approaches to study and address the broad and complex factors that may influence successful research adoption. This dissertation leveraged the field of implementation science to design and guide a systematic scoping review, qualitative interview studies, and multiple case studies to examine the dissemination and implementation of non-pharmacological dementia research. Results from the systematic scoping review determined that successful dementia research adoption is influenced by complex organizational, social, financial, and political factors present in the implementation environment. These results also signaled a gap in knowledge surrounding the roles, responsibilities, and activities of stakeholders in the implementation context. Interviews and multiple case studies were conducted to elucidate the various strategies used by dementia researchers and public and private research funders to address unique challenges in dementia research. Results highlighted the importance of approaching implementation challenges with a comprehensive “research ecosystem” approach. This dissertation contributed practical insights, revealing the resources, infrastructure, and competencies essential to dementia research implementation. Findings also determined key capacity-building areas to direct future research investment and accelerate the translation of non-pharmacological dementia interventions into practice.<br/
A battle on two fronts:Pancreatic cancer during the Covid-19 pandemic
No full textPart I of this thesis focused on improving outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) and those undergoing pancreatic surgery.Chapter II introduced the Multi-Omics DEep Learning Prognosis correlated subtyping model (MODEL-P), designed to identify PDAC subtypes associated with survival outcomes. MODEL-P predicted prognosis more accurately than existing methods, such as the tumor marker Ca19.9, and may guide personalized treatment based on prognosis-related subtypes.Chapter III presented a nationwide retrospective study which investigated the value of extending mortality reporting after pancreatic surgery from the traditional 30-day period to 90 days. This study found that 90-day mortality more reliably captured complication-related deaths compared to the 30-day standard, which missed 30% of complication-related deaths. The findings suggested that adopting a 90-day mortality reporting timeframe would improve the accuracy and reliability of surgical audits and clinical trials.Chapters IV-VI examined postoperative complications, particularly pancreatic fistula (POPF), in relation to preoperative therapies. Chapter IV showed that preoperative chemoradiotherapy reduced the risk of POPF in patients undergoing pancreatoduodenectomy. Chapter V confirmed, through a systematic review and meta-analysis, that preoperative chemoradiotherapy was associated with a lower rate of grade B/C POPF compared to immediate surgery. Chapter VI, presented the FIBROPANC trial, in which high-dose stereotactic body radiotherapy (SBRT) was investigated in high-risk patients. While SBRT increased pancreatic tissue firmness, it did not reduce the POPF rate, suggesting that other interventions may be needed.Part II of this thesis focused on the challenges faced by PDAC patients during the coronavirus disease 2019 (COVID-19) pandemic. Chapter VIII assessed the immunogenicity and safety of COVID-19 vaccines in PDAC patients. The study found that PDAC patients had similar antibody responses to healthy controls after both priming and booster vaccinations. Chapter IX explored the immune transcriptome in postmortem lung biopsies, and found that mast cells contributed to the pathophysiology of COVID-19 pneumonitis. Chapter X identified immune changes in COVID-19 patients with pulmonary arterial thrombosis, suggesting that targeting IL-1 and IL-6 may reduce the risk of thrombosis in these patients.Chapter XI evaluated the antiviral effects of Rintatolimod in pancreatic cancer cells. The study found that Rintatolimod activated innate immune pathways and increased the expression of cytokines and angiogenesis-related genes. Chapter XII assessed infection control measures in a professional sports team, showing that regular testing and preventive protocols may prevent COVID-19 outbreaks. Finally, Chapter XIII discussed the risks of preventive SARS-CoV-2 testing, and underscored that early detection could lead to improper isolation periods for asymptomatic carriers.<br/
Multiple team membership:Embracing Influences and experiences
No full textMultiple team membership (MTM)—defined as working on more than one team at a time—is ingrained in organizational functioning worldwide. It is a practice that represents the daily reality of many employees, as organizations increasingly adopt work across multiple concurrent teams to accomplish complex tasks, achieve faster results, and leverage employees’ resources as efficiently as possible. Nevertheless, scholarly interest in MTM has gained momentum only recently, raising questions about the applicability of much of our existing knowledge derived from single-team contexts. Understanding MTM is important due to this evident disconnect between research and practice, as well as the vast opportunities MTM offers for shaping workplaces through employees’ far-reaching networks of teams. This dissertation directs attention to MTM’s influences and experiences in three chapters (i.e., chapters 2 to 4), studying them using different theoretical perspectives and methods. In chapter 2, I conducted an integrative review of the multiteaming literature to understand MTM’s influence on effectiveness outcomes. As a result of this critical evaluation of extant work, I delineated and elaborated on three sources of variance to explain the inconsistency in findings: 1) what is being studied—the aspects and nature of multiteaming; 2) how MTM is thought to affect effectiveness—the processes through which multiteaming transforms into (in)effectiveness; and 3) who are the multiteamers—the characteristics of multiteamers. In chapter 3, I studied how team MTM alters team communication and information processes. Using adaptive structuration theory as a lens, I designed a study to understand when teams organize their work more asynchronously for their members’ MTM and what are the subsequent implications of team asynchronicity on team outcomes like creativity. By showing that team asynchronicity is a common and costly remedy for MTM, I thus provided initial evidence regarding scholars’ advice on using technologies asynchronously for team MTM, directed focus to the duality of MTM and technology use that is common in practice, and shifted attention to studying team virtuality from a malleable lens. In chapter 4, I delved into knowledge workers’ accounts of MTM to uncover their rationales and approaches for multiteaming. In an inductive qualitative study, I found distinct context-based, task-based, and person-based workers’ rationales to justify MTM, and specified workers’ MTM approaches, which entailed prioritizing efforts, arranging participation across teams, and resorting to suboptimal work practices.The emergent model presented workers that adopted a person-based rationale placed greater emphasis and importance on arranging their MTM participation.Together, my work contributes to the scholarly discussion on multiteaming by (a) consolidating research insights in the literature around the relationship between MTM and effectiveness outcomes (chapter 2), (b) examining the team-level influence of MTM on underlying team communication and information processes (chapter 3), and (c) identifying the MTM rationales and approaches of knowledge workers and their intersections (chapter 4).<br/
Simple models for a complex mechanism:TFIIH & transcription stress in cells and C. elegans
Full text linkSafeguarding the structural and functional integrity of the genome is vital for sustaining life, , yet this is a constant challenge due to persistent DNA damage from both internal metabolic processes and external environmental factors. Failures in the pathways that ensure DNA repair and replication fidelity can lead to severe outcomes, including developmental and neurological disorders, cancer, and accelerated aging. To manage this, cells rely on the DNA damage response (DDR), a complex network that detects DNA damage, signals its presence, and coordinates appropriate repair mechanisms. Among these, nucleotide excision repair (NER) is critical for recognizing and removing bulky, helix-distorting lesions, particularly those caused by ultraviolet (UV) radiation.This thesis focuses in three research parts on the mechanisms that govern NER and the consequences of its dysfunction. It combines genetic, proteomic, cellular, and imaging-based methods using in vitro models and the model organism Caenorhabditis elegans. The first part presents novel experimental tools for studying NER. The second part centers on the TFIIH subunit TTDA (GTF-2H5). And the third part explores the molecular basis of various NER-related disorders, including xeroderma pigmentosum (XP), Cockayne syndrome (CS), XP-CS, and UV-sensitive syndrome (UVsS).<br/
Accounting for the start of life:Shifting practices, costs, and value in an IVF clinic
No full textRising healthcare costs are a major societal concern. Yet, little is known about how costs or shortages impact medical practice, or how accounting systems can improve decision-making as care is increasingly personalized to individual patients. This dissertation investigates the co-creation and implementation of a cost management system in a fertility clinic as part of a value-based healthcare (VBHC) strategy, focusing on how clinicians use and shape accounting. It explores (1) how cost concerns impact daily medical decisions, (2) how cost variation can be traced and managed, and (3) how enabling cost information improves workforce wellbeing across medical domains and contexts. Using a predominantly interventionist research design and a practice-theoretical lens, the research combines ethnographic and quantitative methods across eight studies to develop and evaluate a tailored system—time-driven activity-based costing with process mining (TDABC-PM). Drawing on a decade of fertility care data (4190 pregnancy trajectories, 18 445 treatments), it shows how care pathway re-design (three care delivery changes) significantly reduced costs (€322–€4,089 per patient, about €1.3m nationally) and improved time-to-pregnancy. A national survey across medical domains further reveals how enabling cost information improves psychological wellbeing and motivation in the workforce.The research introduces the concept of teleological indeterminacy to examine how manager’s and clinician’s engagement with accounting practices impacts their situational judgments of what resource use is appropriate for specific patients. It advances understanding of how cost management systems—when designed with and for users—can improve care value, financial sustainability, and workforce wellbeing. It offers practical and theoretical contributions to tackling cost containment and workforce issues simultaneously.<br/
Vascular models to study migraine:From human isolated blood vessels to vessel-on-chip
Full text linkIn this thesis, the vascular effects of CGRP and novel pharmacological treatment of migraine targeting CGRP (receptors) are investigated. CGRP is a neuropeptide that is involved in migraine pathophysiology, but is also a potent vasodilator that can offer cardiovascular protective effects. Here, human isolated coronary arteries and human isolated middle meningeal arteries are used for functional pharmacological studies. In addition, a vessel-on-chip model is developed to be able to study patient-specific vascular responses. CGRP was shown to induce relaxation of human coronary arteries via Gβγ subunits, in contrast to the cAMP-dependent mechanisms that were hypothesized previously. In addition, sex differences were observed for CGRP-induced relaxation of human middle meningeal arteries and differential expression of receptor subunits was observed between human coronary arteries and human middle meningeal arteries. In addition, some of the CGRP receptor antagonist show different behavior in these two vascular beds, when considering potency and Schild analysis. Moreover, an additional effect was observed when combining CGRP receptor inhibition using the monoclonal antibody erenumab and the small molecule CGRP receptor antagonists and CGRP receptor antagonists were shown to worsen outcomes of cerebral ischemic stroke in mice.The thesis offers new insights in CGRP (receptor) blockade, intracellular signaling pathways, sex differences and receptor expression in the human vasculature. In addition, it describes the development of a novel vessel-on-chip model that can be used to study patient-specific blood vessel responses in the future.<br/
Digital health in cardiovascular disease:The current status of remote monitoring in heart failure and the potential future development
No full textThe thesis explores the role of digital health technologies in managing heart failure (HF) and out-of-hospital cardiac arrest (OHCA). It evaluates the effectiveness of remote monitoring (RM) in HF care, focusing on its potential to reduce mortality and hospitalizations, while addressing the need for greater standardization and personalized approaches.Wearable technologies for HF monitoring are examined, with an emphasis on their promise and the challenges in achieving broad clinical implementation. The integration of AI with these technologies is discussed as a pathway for more personalized and responsive care.The thesis also investigates the use of wrist-based photoplethysmography (PPG) for OHCA detection, presenting promising results from clinical studies. It highlights how AI algorithms can enhance early intervention and improve survival rates.<br/