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Tax reporting by digital platforms under DAC7:A proportionality assessment
Get PDFIn early 2021, the European Union (EU) introduced a standardized tax reporting requirement for digital platforms through a Council Directive known as DAC7. The rules introduced by this Directive require third-party operators of digital platforms to systematically collect, verify, store, and report specific personal and transactional data about platform sellers to the tax authorities of the Member States. This data is then automatically exchanged between EU tax authorities.While DAC7 rules for digital platforms pursue a worthy goal (e.g., combating tax evasion) which, at first glance, would justify a public intrusion into the private sphere of both platform sellers and third-party platform operators, a key question that arises is whether such intrusion does not exceed what is necessary in the public interest. This essentially concerns a matter of ‘means’ and ‘ends’ or, in other words, of proportionality.This book provides a comprehensive and in-depth assessment of the proportionality of DAC7 rules for digital platforms. It examines whether these rules are aligned with the general EU law principle of proportionality from both a policy and legal perspective and, when this is not the case, it identifies potential improvements that could be made to ensure such alignment
The ileal pouch in IBD:Unraveling the complexities
Get PDFApproximately 10% of ulcerative colitis patients undergo a proctocolectomy within ten years of their diagnosis. An ileal pouch-anal anastomosis is the gold standard for restoring bowel continuity. While pouch patients generally experience a good quality of life, both short- and long-term complications are common.The first part of this dissertation focuses on various outcomes and complications of the pouch, including chronic pouchitis, pre-pouch ileitis, Crohn’s-like disease of the pouch (CDP), and solitary pouch ulcers. Establishing the correct diagnosis is challenging due to the lack of clear definitions and overlapping clinical and endoscopic parameters. Patients presenting with pre-pouch ileitis or structural issues such as strictures, fistulas, or a chronic sinus are often diagnosed with CDP, even in the absence of preoperative evidence of Crohn’s disease. Our study found that nearly half of the patients diagnosed with CDP had a fistula or sinus closely associated with the anastomosis, which is indicative of (late) anastomotic leakage. As a result, these patients were incorrectly treated with medication instead of surgery. A MRI one year after surgery or at the initiation of step-up therapy is recommended to rule out postoperative complications.The second part of the dissertation examines the effect of tofacitinib in patients with ulcerative colitis as well as those with chronic pouchitis. In our pilot study on chronic pouchitis patients, 31% achieved clinical remission, and 54% showed a clinical response after eight weeks of treatment with tofacitinib. However, endoscopic and histological scores did not significantly improve. In patients with ulcerative colitis who still had their colon in situ, tofacitinib was also investigated, with 38% showing histo-endoscopic improvement. Gene expression analysis confirmed the effect of tofacitinib on the JAK-STAT signaling pathway, and CLC (Charcot-Leyden Crystal) was identified as a potential biomarker for predicting response to tofacitinib
New insights into anastomotic leakage after rectal cancer resection
Get PDFAnastomotic leakage (AL) is a severe complication after rectal cancer surgery, occurring in 20-25% of cases, resulting in increased morbidity, mortality, extended recovery periods, additional interventions, and significant economic burdens. This dissertation provides new insights into the etiology, long-term outcomes, and economic impacts of AL, presenting innovative strategies for prevention and treatment.The first part investigates the gut microbiome's influence on anastomotic healing. Microbial dysbiosis, characterized by decreased diversity and increased facultative anaerobes like Enterococcus, negatively impacts recovery. Tranexamic acid, an inhibitor of plasminogen activation, effectively reduces collagen breakdown and AL incidence in mouse models without disturbing microbial balance. Additionally, brief dietary prehabilitation using a high-fiber diet enhances microbial diversity and reduces AL rates. Clinical translation through perioperative microbiome analyses within the IMARI study revealed significant microbial shifts postoperatively, including Enterococcus dominance and reduced alpha diversity, providing valuable insights into human perioperative microbiome dynamics.The second part assesses the long-term clinical outcomes of AL. The STOMA-score enables clinicians to better predict stoma risk one year post-leakage based on patient and leakage characteristics. Additionally, various AL treatment strategies are compared, emphasizing reactivation leakages after stoma reversal, an underestimated issue significantly affecting quality of life and surgical complexity.The third part addresses the financial implications of AL. Cost analyses reveal substantial variation internationally and methodologically. The IMARI study evaluates treatment strategy costs in the first postoperative year and another study highlights that persistent leakages significantly amplify financial burdens, emphasizing the need for preventive, cost-effective interventions
Een kwestie van uitvoering:De gemeente Amsterdam als instrument van de Duitse repressie 1940-1945
Get PDFTijdens de Duitse bezetting van Nederland is de gemeente Amsterdam betrokken geweest bij de onderdrukking, uitsluiting en vervolging van haar eigen burgers. Zo zijn Joodse Amsterdammers door het Bevolkingsregister geregistreerd, door het Bureau voor Sociale Zaken naar werkkampen gestuurd en door de Gemeentepolitie, het Trambedrijf en de Gemeentelijke Gezondheidsdienst naar de deportatiecentra en -treinen vervoerd. Dit roept vragen op naar de verantwoordelijkheid en motieven van de toenmalige bestuurders. De keuzes die destijds door de burgemeester, wethouders en hoofden van gemeentelijke diensten zijn gemaakt worden in dit onderzoek geanalyseerd, met elkaar vergeleken en in een bredere context geplaatst. Waarschijnlijk hebben meerdere factoren een rol gespeeld in de vergaande medewerking van ‘gewone’ Amsterdamse gemeentelijke functionarissen aan de Duitse repressie. Hoewel die functionarissen na de oorlog diverse formele rechtvaardigingen voor hun samenwerking met de vijand hebben gegeven, is de uitkomst van dit onderzoek dat de houding van Nederlandse bestuurders en ambtenaren bovenal bepaald lijkt te zijn geweest door de vrees voor Duits geweld en het besef van eigen machteloosheid. De geschiedenis van het Amsterdamse gemeentelijke apparaat tijdens de Duitse bezetting kan geïnterpreteerd worden als een geschiedenis van menselijke en ambtelijke tekortkomingen. Tegelijkertijd mag echter niet uit het oog verloren worden dat dit apparaat te maken kreeg met een bezetter die over de nodige dwangmiddelen beschikte waarmee hij zijn wil kon trachten door te drijven
Immune stimulation and immunometabolism of the first line of defense in the lung
Get PDFPneumonia is an acute respiratory infection of the bronchial tree and alveoli of the lungs that can be classified as community-acquired pneumonia (CAP), or hospital-acquired pneumonia (HAP), the latter often affecting the immunocompromised or patients on an intensive care unit. In this context, the emergence of multidrug-resistant (MDR) bacteria, such as Klebsiella (K.) pneumoniae or Pseudomonas (P.) aeruginosa, poses a major risk. Apart from the development of new antibiotic agents, there is an increasing interest in drugs that can modulate or “boost” the host immune response; one of such agents is flagellin, a Toll-like receptor (TLR)5 ligand that induces an inflammatory reaction in respiratory epithelial cells upon topical administration. Next to the airway epithelium, alveolar macrophages (AMs) play an important role in the first line of defense in the lung, by phagocytosing pollutants and pathogens, and secreting inflammatory cytokines. Immunometabolic features of AMs, however, are largely unknown, while these could provide targets for improving immune cell function. This thesis seeks to enhance our understanding of innate immunity in the lung, with the specific aim to improve local host defense in the context of pneumonia. In Part I, we investigate the effect of local flagellin administration on the immune response of the airway epithelium, and whether this could serve as an adjunctive therapeutic to antibiotic treatment of bacterial lung infections. Part II focuses on the immunometabolic requirements of human AMs upon stimulation with lipopolysaccharide (LPS), component of the Gram-negative bacterial cell wall, and evaluates a model to generate AM-like cells from human monocytes
An annotated theory of tonal jazz harmony
Get PDFThis work concerns itself with the theory of tonal jazz harmony. It consists of two parts. One part presents a theory in which melodic (horizontal), harmonic (vertical), and stylistic aspects of tonal jazz harmony are integrated and grounded in a solid theoretical foundation. The other part introduces the work and its contexts, followed by a commentary on the harmony theory through extensive annotations. This work’s point of departure is that tonal jazz harmony is a specific variant of Western harmony and does not require a fundamentally new theoretical framework but, rather, crucial modifications of Western harmonic theory to accommodate and explain the musical phenomena adequately. Therefore, it adopts the Harmonielehre-format, a hybrid of speculative theory and pedagogical instruction. The work also touches upon key issues in jazz culture and jazz research, such as the long-standing questions of “ownership” and “entitlement” in jazz, gender, and the recent debates in the US around racism in and through music theory.Two different corpora form the basis of the work. The first is tonal jazz, the core of which consists of “standards” (compositions derived from the Great American Songbook from roughly 1930 to 1960, as performed by jazz musicians ) and tonal jazz compositions. The second corpus is formed by the existing manuals of jazz harmony, reflecting a body of technical know-how loosely labeled “chord-scale theory,” a vocabulary of harmonic possibilities applied by jazz performers. Chord-scale theory’s essential elements are critically evaluated with respect to the theoretical content, stylistic tenability, and practical applicability
Cell-free DNA and immune cell dynamics in acute graft-versus-host disease and systemic inflammation
Get PDFAcute graft-versus-host disease (aGvHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Affecting 30-50% of allo-HSCT recipients, aGvHD limits the broader use of this treatment. The pathogenesis of aGvHD is complex, involving donor immune cells attacking recipient tissues in the context of systemic inflammation. However, predicting the onset and severity of aGvHD remains a challenge, and ongoing efforts focus on identifying reliable biomarkers and refining biomarker panels. The work in this thesis explores the role of cell-free DNA (cfDNA) as a potential biomarker for aGvHD. We show that cell-free DNA (cfDNA) is increased in systemic inflammation, sepsis, and around the onset of aGvHD. We propose that cfDNA initially originates from a hematopoietic source followed by the release from damaged parenchymal tissue. By determining both the quantity and origin of cfDNA, we aim to enhance the prediction of aGvHD and evaluation of treatment efficacy in aGvHD. The second part of this thesis focuses on immune cell profiling in the context of aGvHD using multi-panel flow cytometry. We identify immune cell subsets that correlate with aGvHD in a small cohort of allo-HSCT patients, providing promising insights, though further investigation is warranted. Focusing on innate lymphoid cells (ILC), our work suggests that grafts rich in ILC, particularly ILC3, are significantly correlated to a reduced risk of aGvHD development. The use of adoptive transfer of ILC is an interesting treatment of aGvHD prevention to explore in the future
Patients’ rights protection and artificial intelligence in the European Union
Get PDFEuropean patients are increasingly confronted with the algorithmisation of healthcare. This transformation of healthcare presents both significant opportunities and substantial risks. Before fully embracing this revolution, it is important to pause and think about the actual implications of introducing artificial intelligence (AI) in healthcare, reflecting on whose needs are being addressed, and whose rights might be overlooked in the process. The topic of this dissertation is the safeguarding of the rights of patients in the European Union (EU) in light of the increasing use of AI technologies in healthcare, within the context of expanding EU integration through the Digital Single Market. The central aim is to assess whether the current EU legal frameworks adequately protect patients' rights against the algorithmisation of healthcare. Additionally, it proposes alternative legal approaches to ensure more robust protections for patients in this rapidly evolving sector
New Insights from Old Programs:The Structure of The First ALGOL 60 System
Get PDFIt 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
Metaphor use in aphasia
Get PDFIn the conceptual metaphor theory (CMT), one tenant is that metaphors are ubiquitous in our everyday language. This dissertation tried to make a thorough investigation into how linguistic metaphors are used by people with aphasia (PWA). Aphasia is an acquired language disorder that affects people’s language production and understanding; it can be divided into two types: non-fluent and fluent, according to the fluency of sufferers’ speech. Some former studies have revealed deficiencies of certain word classes produced by these two groups of PWA. Apart from linguistic metaphors, the metaphor use in aphasia can be also discussed under the scope of CMT: in people’s speech about aphasia, aphasia treatment, and rehabilitation, we can find conceptual metaphors and analyse them to see how aphasia is conceptualized in discourse. The overall research goal of this dissertation is to examine how metaphors are used in aphasia from two perspectives: linguistic and conceptual.Results have shown features of PWA’s production of linguistic metaphors in some word classes; in some word classes, metaphor distribution is not balanced in different types of aphasia. By analysing the interaction between metaphor, word class, and participant group in English and Mandarin data, we can have a deeper understanding of metaphor use by PWA. As for the analysis of metaphorical framings about aphasia and aphasia recovery, it can be helpful for practitioners and family caregivers to communicate with PWA in the rehabilitation process. Moreover, metaphorical framings on aphasia can shape how we think about aphasia and PWA