International Migration, Integration and Social Cohesion online publications
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Molecular profiling of intestinal cancers:Towards clinical implementation
Full text linkGastrointestinal (GI) cancers are molecularly heterogeneous, resulting in pronounced intertumoral differences in disease progression and treatment response. The diversity of GI malignancies complicates estimation of prognosis and optimal timing and selection of treatment regimens for individual patients. In recent years, it has become clear that gene expression (transcriptomic) profiling of GI tumors reflects key elements of tumor heterogeneity, and as such, is capable of stratifying patients based on molecular tumor properties. Often, these molecular tumor subgroups contain prognostic and predictive value. The Consensus Molecular Subtypes (CMSs) of colorectal cancer (CRC) are an example of such a taxonomy. Although biologically highly informative, clinical usage of transcriptomic taxonomies remains challenging, due to unclear clinical consequence, high costs, the required expertise and technical limitations. As an illustration, tumor classification on low-quality RNA-data from formalin-fixed paraffin-embedded (FFPE) tissue samples, which are widely used in the clinic, remains complicated.In this thesis, we set out to further explore and expand the clinical potential of transcriptomic subtyping of GI malignancies. We did so by optimally making use of the available literature regarding transcriptomic tumor stratification and clinical management, by performing in-depth molecular characterization of GI malignancies, and by studying large retrospective cohorts of patients. First, we focused on CRC, which is a commonly occurring and well-studied example of a GI malignancy with clinically relevant transcriptomic subgroups (the CMSs), and used this cancer type as a source of inspiration for studies on small intestinal adenocarcinomas (SIAs), a rare cancer type for which molecular profiling efforts are scarce
Risk model-based al location of prophylact ic implantable cardioverter defibril lators:Scenarios from patient and societal perspectives
Full text linkImplantable cardioverter defibrillators (ICDs) are widely used for the prevention of sudden cardiac death (SCD) in patients with reduced left ventricular function. Within the current guidelines only a minority of recipients benefit from ICD implantation. At the same time, all recipients face risks ICD-related complications and inappropriate shocks including.This thesis investigates how patient selection for prophylactic ICD implantation can be improved. It leverages data from the Dutch Outcome in ICD Therapy (DO-IT) Registry, a nationwide cohort study evaluating outcomes in patients receiving ICDs for primary prevention. Using these data, risk prediction models were developed and validated to identify patient subgroups most likely to benefit. These models integrate modern treatment outcomes and routine clinical data, enabling clinicians to stratify patients and identify those for whom ICD implantation could be postponed or avoided.Additionally, the study highlights substantial variability in cost-effectiveness across patient groups. Scenario analyses demonstrate that targeted allocation of ICDs, based on the proposed risk models, can reduce complications, inappropriate shocks, and healthcare expenditures, while improving both clinical outcomes and societal value.This thesis emphasizes the importance of shared decision-making and proposes refined risk stratification strategies to optimize ICD allocation. It underscores the need to incorporate both clinical and economic considerations into medical decision-making, aiming to enhance patient outcomes while ensuring the efficient use of healthcare resources
The affects of imperial collecting:The case of the German anthropologist Wilhelm Joest (1852-1897)
Full text linkThis dissertation proposes a radical rethinking of the study of imperial ethnographic collecting, moving from a preoccupation with the self-proclaimed “grand vision” of the collector towards the often less visible affective dimensions. Empire was an affective structure that functioned by shaping the desires of colonisers and colonised alike, and I argue that collecting was inevitably part of its many affective interactions. I base my argument on a microhistorical case study centred around the personal archive of the German anthropologist and collector Wilhelm Joest (1852–1897). In this way, I show how he created his imperial identity through the objects he collected, and how he used this self-fashioning to deflect and disavow the troubled affects that informed his actual collecting. I intimately engage with these emotions, ranging from longing to guilt to sexual desire, and demonstrate how each of these affective constellations shaped the collecting process. I emphasise the close connection between feeling and collecting in empire and highlight the importance of collecting as a strategy for regulating and rerouting affect. This dissertation offers a framework for interrogating the affective history of collecting in order to open up new avenues for meaningful decolonial transformation within and beyond the ethnographic museum
News in perspective:What is news to news users in the digital age?
Full text linkThe rise of new technologies has profoundly reshaped the news landscape, characterized by three intertwined elements: genre-blending news content, multifaceted digital platforms, and the prevalence of algorithmic recommendations. As news consumption evolves in this new landscape, users’ perception of news has naturally shifted. Historically, the question “What is news?” was defined by institutional journalism. But what is news to news users in the digital age? This dissertation explores users’ news perception through three empirical chapters, focusing on content, platforms, and algorithms. The first study measures news content on a spectrum along abstract dimensions, based on genre cues recognizable to news users. The second study investigates how varying definitions of news shape users’ news repertoires on digital platforms. The final study examines how genre cues contribute to user perception, particularly in the context of algorithmic news recommendations. Using innovative data collection methods, such as data donation and online field experiments, alongside advanced computational techniques, this dissertation offers both theoretical and methodological insights. By emphasizing the relevance of a user-centric focus in news research, it sheds light on how users navigate the new news landscape and broadly contributes to a more informed and democratic society
Precision medicine in critically ill patients:Exploring ARDS and sepsis subphenotypes
No full textThis thesis is dedicated to advancing the understanding of sepsis and acute respiratory distress syndrome (ARDS) subphenotypes in critically ill patients, with the overarching goal of addressing key challenges that hinder their clinical implementation. This work aims to clarify the biological and clinical variability within sepsis and ARDS populations. Through this comprehensive exploration, it aspires to bring the science of phenotyping one step closer to the bedside in critical care medicine. In this thesis the role of plasma protein biomarkers in identifying biological heterogeneity among COVID-19 patients is investigated. While previous studies assumed significant heterogeneity in COVID-19, analysis of hospitalized patients found limited support for distinct subphenotypes. Further investigation into treatment heterogeneity in severe COVID-19 revealed that vilobelimab, a C5a inhibitor, showed a survival benefit only in patients classified under a predefined sepsis δ-subtype, underscoring the potential of predictive enrichment strategies. In sepsis, multiple subtyping methods were examined, revealing limited overlap between classifications based on clinical, biomarker, and transcriptomic data. However, biomarker-based subtypes appeared to bridge clinical and molecular classifications. The dynamic nature of subphenotypes was further explored, showing frequent transitions over time, with shifts to less inflammatory states associated with improved outcomes. At ICU discharge, an inflammatory profile was linked to higher long-term mortality. Finally, distinct mortality predictors were identified, suggesting modifiable risk factors in Hyperinflammatory patients and emphasizing the need for tailored therapeutic approaches
Dynamics of the alveolar host response and pulmonary infections in ARDS
Full text linkThis thesis explores alveolar host-immune responses, viral kinetics, and secondary pulmonary infections in acute respiratory distress syndrome (ARDS), with a focus on COVID-19-related ARDS. It investigates persistent inflammation, alveolar subphenotypes, fibroproliferation, and their impact on outcomes.The thesis demonstrates that COVID-19 ARDS is characterized by a hyperinflammatory alveolar state with increased inflammatory biomarkers associated with higher mortality and distinct inflammatory profiles in the alveolar and systemic compartments. Two distinct alveolar inflammatory subphenotypes were identified, revealing poor agreement between alveolar and systemic subphenotypes. A fibroproliferative response, marked by increased NT-PCP-III, correlated with short-term outcomes but showed weak association with long-term lung function.The thesis also examines viral dynamics, showing that alveolar SARS-CoV-2 viral loads decrease in a biphasic pattern, with high early viral loads associated with worse outcomes. Pulmonary viral reactivations, particularly HSV, were common in ARDS, and associated with increased inflammation and mortality. Antiviral treatment was found to reduce inflammation.These findings emphasize the role of alveolar inflammation and viral reactivations in ARDS pathophysiology. They support the need for precision medicine strategies targeting these processes to improve patient outcomes. Future research should expand beyond COVID-19-related ARDS to include broader populations at risk for persistent inflammation and viral reactivation
New Insights from Old Programs:The Structure of The First ALGOL 60 System
Full text linkIt is a commonplace that computer programming is hard, especially when one aims at creating a program that is correct. What kind of methods should be used to reach that goal is the subject of heated debates. Our thesis is a contribution to these discussions: To understand what computer programming is, and how it should be done, we propose to study how it is actually done – that is, to induce elements of method from factual observation. Our thesis takes the form of a detailed analysis, based on a careful reconstruction, of a particular well-crafted computer program: the first ALGOL 60 system, designed and implemented at the Mathematical Center (now CWI) by E. W. Dijkstra and J. A. Zonneveld, with the assistance of S. J. Christen and M. J. H. Römgens, on an Electrologica X1 computer. It is divided into three main chapters. Chapter I presents the two elements of the problem the Mathematical Center team was facing, namely the ALGOL 60 language and the X1 computer. Chapter II discusses the principles of its solution, explains the implementation choices made by the Mathematical Center team, and compares them to other possible choices. Chapter III presents the details of the Mathematical Center ALGOL 60 system, on an ISO C version of that system, reverse engineered from its X1 assembler source. This program is about 3000 lines long, and is composed of 173 subroutines working on 57 global variables. Finally, our conclusion, in the form of 17 theses and 4 hypotheses, indicates some lessons, in particular on computer programming methods, that we believe can be drawn from the analysis of that particular computer program
Angel-headed hipsters:Psychedelic militancy in nineteen-eighties North America
Full text linkThe psychedelic dimension of religious experience occupies a marginal position in the scholarship of American culture. For the last seven decades, scholars have viewed the psychedelicist church movement as, variously, an excuse for taking illegal drugs, an inauthentic mode of religious fellowship, and a purely oppositional “counter-culture.” More recent scholarship challenges these interpretations by emphasizing the legitimacy of the experiences occasioned by psychedelics.Psychedelicism in the 1980s took shape as the “zine scene,” a vast information network composed of approximately ten thousand self-publishers. The convergence of underground networks that coalesced into this expansive literary microcosm can be traced back to the SubGenius Church. This fellowship of psychedelicist hipsters organized its members into an epistolary network. This intra-church postal exchange was the seed out of which the zine scene bloomed. However, the SubGenius Church would not retain its position at the fore of the zine scene indefinitely. A mass defection ensued after the SubGenius leadership brokered deals with major media corporations. The subsequent commercialization of the Church provoked long-time SubGeniuses to relocate to Factsheet Five, a newly created fanzine directory. It was here that the zine scene developed into a major cultural phenomenon.Through an examination of the hipster militants of the zine scene, this dissertation re-centers psychedelicist fellowships in 1980s hip culture. It is only by recognizing the interplay between the hipsters of the psychedelicist church movement, and hip capitalism, that the role of esotericism in American culture can be understood
Genders as genres:Understanding dynamic categories
Full text linkWhat does it mean to be of a particular gender? I answer this question with an account of genders as dynamic categories, exploring the analogy between what genders are (e.g., men or women) and what genres are (e.g., Novels, Ballads, or Hip-Hop). For instance, due to its relation to other and earlier pieces, we recognize, e.g., a particular song as Hip-Hop. However, the piece will also develop that genre further. Likewise, e.g., the category of men emerges, persists and transforms through a specific sort of response of individuals to earlier supposed men, which emerges in social interactions.Drawing on critical and (trans-)feminist theory, phenomenologist, enactivist, and systems theoretical approaches, I show that gender categories themselves develop in a dynamic between three elements: (1) at any given time, there is an enactment class of individuals ambiguously belonging to the category in question; (2) these individuals are, in an embodied and intersubjective way, enacted as practical reinterpretations of earlier members of that category; (3) this unfolds in a matrix of hermeneutic and material relations, which loop with both the class and the enaction.Thereby, that an individual is gendered, emerges between two levels of enaction, that of bodily people and that of the dynamic between them. As what an individual is gendered in enaction, however, is constituted by relations within and beyond that situation. This responsive realization gives rise to feedbacking histories of acts, people, relations, and enactment classes, thus explaining how gender can be both solid and open to change
Microbial alchemy in ulcerative colitis:Crafting the recipe for fecal microbiota transplantation
No full textThis thesis explores the therapeutic potential of fecal microbiota transplantation (FMT) in ulcerative colitis (UC), an inflammatory bowel disease with rising incidence. It is structured into three parts.Part 1 addresses the scientific rationale and methodology behind FMT. It demonstrates that higher bacterial alpha-diversity in both donors and recipients is associated with improved clinical response. It also shows that anoxic processing of donor feces preserves obligate anaerobes better than standard anaerobic methods, potentially enhancing treatment efficacy. Part 2 focuses on the practical application of FMT in UC. It presents the protocol of the TURN2 trial, a randomized controlled study integrating donor selection based on microbiota profiles and anaerobic stool processing. It also provides insights into the challenges and costs of donor screening at Amsterdam UMC, underscoring the need to develop donor-independent microbiota-based therapies.Part 3 investigates microbial interactions beyond bacteria. It shows that the protozoa Blastocystis spp. and Dientamoeba fragilis are more prevalent in healthy individuals than UC patients, and their presence correlates with higher bacterial diversity and lower yeast overgrowth. These findings question the routine exclusion of these organisms in donor screening and highlight the need to better understand their ecological role in the gut.Together, the studies in this thesis aim to advance FMT towards a more effective, evidence-based, and ecologically informed treatment strategy for UC