International Migration, Integration and Social Cohesion online publications
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Perioperative management of upper gastrointestinal surgery
Get PDFDit proefschrift onderzoekt strategieën voor perioperatief management bij chirurgie voor maag- en slokdarmkanker en de impact op postoperatieve uitkomsten. Het richt zich op perioperatief pijnmanagement, waarbij paravertebrale analgesie (PVA) wordt vergeleken met thoracale epidurale analgesie (TEA). We concluderen dat zowel TEA als PVA geschikte opties zijn voor pijnmanagement na minimaal invasieve Ivor Lewis slokdarmresecties. Daarnaast hebben we onderzocht dat anesthesie zonder opiaten vergelijkbare postoperatieve pijnscores geeft als anesthesie met opiaten. Een ander aspect van het onderzoek betreft het vroege postoperatieve traject, waarbij de kwaliteit van herstel na subtotale maagresectie wordt geëvalueerd. Ook wordt de implementatie van een slikvideo met contrast na slokdarmresectie onderzocht, wat de verwijdering van de neusmaagsonde vervroegt zonder de duur van het ziekenhuisverblijf te beïnvloeden. C-reactief proteïne (CRP) wordt onderzocht als een voorspellende marker voor naadlekkage na slokdarmresectie en laat zien dat het een negatieve voorspeller is.Verder wordt gekeken naar factoren die de overleving beïnvloeden, waaronder sarcopenie, lichaamssamenstelling en spierkracht vóór en na neoadjuvante chemoradiotherapie bij slokdarmkankerpatiënten. De studie toont aan dat verminderde spierkracht en een hogere BMI geassocieerd zijn met postoperatieve complicaties en dat verminderde spierkracht en toegenomen visceraal vetweefsel geassocieerd zijn met een slechtere langetermijnoverleving.Tenslotte wordt een nomogram voor conditionele overleving na neoadjuvante chemoradiotherapie en slokdarmresectie ontwikkeld, wat nuttig blijkt voor het voorspellen van overleving tijdens follow-up na chirurgie voor slokdarmkanker. Dit proefschrift benadrukt belangrijke inzichten in pijnmanagement, postoperatieve zorg en factoren die van invloed zijn op de overleving bij chirurgie voor maag- en slokdarmkanker
Modulating the enterohepatic circulation in cholestatic and metabolic liver diseases:Therapeutic perspectives
Get PDFBile salts are synthesized in the liver and temporarily stored in the gall bladder, before they are released in the small intestine upon food intake. Here, they help with the digestion and absorption of food and nutrients. The enterohepatic circulation is the circulation of bile salts from the liver to the gall bladder, the small intestine and back to the liver via the portal vein. The enterohepatic circulation is fully dependent on the presence of multiple bile salt transporters. Sodium taurocholate cotransporting polypeptide (NTCP) is the main hepatic bile salt uptake transporter, while the apical sodium-dependent bile acid transporter (ASBT) is expressed in the small intestine and kidneys, where it prevents bile salts from being secreted in respectively feces and urine. During cholestasis, bile flow from the liver towards the small intestine is disturbed or completely blocked, causing severe liver damage when left untreated. Current treatment strategies are not always effective, and are associated with unwanted side-effects such as diarrhea. In this thesis, we explore new therapeutic strategies involving bile salt transport and signalling, to improve liver health in cholestatic liver diseases such as primary biliary cholangitis (PPC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome but also metabolic liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunctionassociated steatohepatitis (MASH)
Evaluating developments in rectal cancer care in routine clinical practice
Get PDFThe aim of this thesis was to evaluate developments in the multidisciplinary treatment of primary rectal cancer on a national level. Part I focused on the new consensus definition of rectal cancer in the multidisciplinary team meetings, based on the sigmoid take-off landmark. Online training has the potential to improve implementation and unambiguous assessment. By using the sigmoid take-off, 11% of the prior diagnosis of rectal cancer were redefined as sigmoid cancer, with substantial inter-hospital variation and potential implications for multimodality and prognostic value. In part II new developments in the treatment of rectal cancer were evaluated. When comparing two national cohorts with patients with a resection for rectal cancer in 2011 and 2016, an absolute 50% reduction in radiotherapy use for non-locally advanced rectal cancer was observed. This change in neoadjuvant therapy did not compromise cancer-related outcomes and even an improvement in overall survival from 79.6% to 86.4% was observed. Permanent stoma rate and stoma-related complications were evaluated in the two national cohorts. Remarkable hospital variability in permanent stoma rate was observed. Stoma complications were most often observed after a Hartmann’s Procedure (23%), still requiring a significant number of reinterventions even after one year. No beneficial influence of transanal or robot-assisted laparoscopy was found on the permanent stoma rate. Part III addresses the prognostic implications of lateral lymph nodes. Results of an online survey showed vast variation in the awareness, definition of suspicious lateral lymph nodes in rectal cancer and different treatment approaches
SGLT2 independent effects of the SGLT2 inhibitor empagliflozin:Focus on the heart
Get PDFThis thesis explores how sodium glucose cotransporter 2 inhibitors (SGLT2i), particularly empagliflozin (EMPA), reduce cardiovascular risk by investigating their effects on cardiac infarction, hypertrophy, and heart failure (HF). SGLT2i demonstrate significant cardiovascular benefits across diabetic and non-diabetic populations, possibly through off-target effects. The study has reviewed EMPA's acute impact on cardiac physiology, focusing on ion homeostasis, inflammation, oxidative stress, and metabolism. It also investigates EMPA's effects on cardiac metabolism in diabetic hearts, revealing reduced lactate generation and augmented α-ketoglutarate synthesis. EMPA directly inhibits the cardiac sodium hydrogen exchanger 1 (NHE1), albeit with varying results in different experimental setups. Additionally, EMPA attenuates cardiac hypertrophy by inhibiting NHE1 and the RSK pathway. Furthermore, preclinical research and observational studies highlight SGLT2i's role in reducing infarct size, independent of SGLT2 expression. In a murine HF model, EMPA's protective effects involve NHE1, nitric oxide (NO), and interconnected pathways, independent of SGLT2. Notably, EMPA's benefits in HF are not solely reliant on SGLT2 expression. Lastly, the thesis explores how EMPA protects against HF by improving cardiac metabolism, independently of SGLT2. It reveals that EMPA's metabolic alterations precede its mechanical benefits, suggesting SGLT2-independent mechanisms at play. These findings contribute to understanding the multifaceted cardioprotective effects of EMPA and SGLT2i, paving the way for further research in cardiovascular disease management
Out-of-hospital cardiac arrest in women and men:Risk factors, short-term survival, and long-term outcomes
Get PDFLarge sex differences exist in incidence and survival chances of out-of-hospital cardiac arrest (OHCA). Survival rates have increased in recent decades, but it is unclear whether both sexes have benefitted equally. Besides biology, sociocultural factors or improvements in pre-hospital and in-hospital care may contribute to sex differences. Pre-hospital care involves timely start of cardiopulmonary resuscitation, but also guidelines for termination of resuscitation. Further, the rising number of OHCA survivors requires attention for the long-term socioeconomic and mental health changes post-OHCA. Understanding OHCA’s impact on long-term survival can aid design of targeted interventions for women and men. This thesis aimed to assess the OHCA burden in women and men, focusing on the association of sociocultural factors with incidence, and sex differences in short-term survival, and long-term outcomes. Our studies confirmed differences between women and men. For instance, sociocultural characteristics were associated with OHCA incidence, especially among women. Moreover, the short-term survival rates increased for men over time, while remaining unchanged in women. This was associated with differences in proportions of shockable initial rhythm and in-hospital interventions. However, guidelines for termination of resuscitation were equally applicable in both sexes. In the long-term, employment rates and income decreased in women and men, mirroring general population trends, while dispensing of anxiety/depression medication increased disproportionately in women. Long-term survival rates post-OHCA did not differ by sex, but factors associated with survival were sex-specific. Our work may provide targets for prevention and treatment strategies to mitigate sex disparities in OHCA incidence, survival and long-term outcomes
From beads to bedside:Standardizing extracellular vesicle concentration measurements
Get PDFExtracellular vesicles (EVs) are cell-derived particles with a phospholipid bilayer that are present in body fluids, such as blood and urine. Concentrations of EVs in body fluids are potential disease biomarkers and can be measured with flow cytometers (FCMs). To explore the biomarker potential of EV concentrations, reliable and reproducible measurements of EVs are needed. At present, however, measured EV concentrations are incomparable between instruments and institutes. The aim of this thesis is to improve reliability and comparability of EV concentration measurements with flow cytometry by 1) identifying current challenges faced in EV flow cytometry, 2) developing a robust methodology for reliable and comparable EV concentration measurements, and 3) evaluating the developed methodology in an interlaboratory comparison study. In this thesis, we present a filtration procedure to remove residual platelets from blood plasma, thereby improving the quality of plasma for EV research. Furthermore, we introduce a novel methodology to generate reliable and comparable EV concentration measurements by flow cytometry. The newly developed methodology includes a plasma EV test sample and reference materials to calibrate all parameters of an FCM influencing measured EV concentrations. The methodology was evaluated in a global interlaboratory comparison study including 38 FCMs from 24 laboratories. Emphazising the clinical relevance of the developed methodology, we applied the methodology to determine the first-ever reference ranges of cell-type specific EV concentrations in human blood plasma of healthy volunteers. The methodology presented in this thesis opens the door to explore EV concentrations as potential biomarkers for disease
Speaking the news:How conversational agents influence trust and issue salience
Get PDFThis dissertation studies the role of conversational agents (CAs), such as Google Assistant, as news recommender systems and their impact on public issue salience and trust in recommender systems. Chapter 1 establishes the research framework, emphasizing the influence of CAs as information gatekeepers and highlighting the research gap in understanding CAs’ role as news recommenders. Chapter 2 examines the societal implications of news recommendations provided by CAs, focusing on how trust in these agents shapes public perceptions of important issues (i.e., issue salience). It compares the effects of CAs with other news sources, such as social media and traditional websites, and evaluates the moderating role of general media trust and channel-specific trust. Chapter 3 explores how the interface—whether a CA or a traditional website—impacts trust in news recommenders, evaluating specifically the influence of CAs’ dialogic interactions. Chapter 4 investigates the effects of global and local explanation types across different modalities (audio and text), considering the regulatory context and its impact on user trust. Chapter 5 integrates findings from the previous chapters, concluding that CAs, due to their uniqueness, can potentially influence issue salience. Additionally, CAs can negatively influence trust in news recommenders through factors such as perceived enjoyment. The dissertation also identifies perceived personalization and privacy concerns as important determinants of trust. However, the modality or the dialogic interaction with CAs does not significantly affect these factors. As CAs evolve, future research should further investigate trust in CAs, mainly focusing on how different dialogic features (e.g., content) can affect user enjoyment
Just business redux:Transnational corporate responsibility decoded through relational justice
Get PDFPrivate law theory is hesitant to delve into questions of business and human rights; except for the theory of relational justice by Hanoch Dagan and Avihay Dorfman. Their theory articulates private law as the law of just interpersonal conduct—and subsequently articulates corporate responsibility for upholding human rights in such interpersonal relationships.This PhD thesis extends this theory to articulate supply chain responsibility for human rights harms. It introduces the concept of cascading responsibility stating that large transnational corporations do not have an arbitrary limit to their responsibilities depending on tiers of a supply chain where human rights harms occur. Such corporations have responsibilities travelling through the entirety of their supply chain.Further, the thesis states that transnational corporations have a responsibility to prevent and mitigate such human rights harms. They must undertake human rights due diligence in their business decisions and relationships by taking seriously the concerns of the far away workers or people who may be affected downstream.It is then shown that the UN Guiding Principles on Business and Human Rights mirrors this private law theory understanding through its articulation responsibility for directly linked impacts. Further, it is demonstrated that case law like Nevsun v Araya and Begum v Maran reflect such an understanding of cascading corporate responsibility. Lastly, it is also shown that legislation like the French devoir de vigilance law and the German supply chain due diligence law reflect the normative understanding of the thesis
The everyday politics of urban shrinkage:Negotiating “decline” in two medium-sized cities
Get PDFThis thesis examines the everyday reality of urban shrinkage and the associated power struggles within urban spaces. Drawing on ethnographic studies in Dieppe and Nevers, two medium-sized French cities experiencing long-term shrinkage, the research explores how residents experience and negotiate this phenomenon in their daily lives.Building on existing scholarship on urban shrinkage, this work introduces new perspectives by highlighting everyday urban shrinkage and its politics. Using approaches from urban studies, geography, and anthropology, a new conceptual framework is developed, presenting urban shrinkage as a lived, political, and ordinary process of urban change. This process involves unequal power relations and unfolds in non-spectacular ways within ordinary cities.Four key themes are identified in residents’ everyday experiences and negotiations of urban shrinkage: the selective production and mobilisation of symbols of “decline”; the negotiation of territorial stigmatisation; the recomposition of social capital; and the negotiation of socio-spatial change through sensory politics. These themes show that urban shrinkage shapes urban experiences profoundly and prompts diverse negotiation strategies.Negotiating change involves power struggles between various groups at different scales, from the national level to domestic spaces. Urban inequalities are central to the differentiated experiences and negotiations of shrinkage. The everyday politics of shrinkage are often inconspicuous and informal, reflecting inequalities in social capital, power to impose or contest urban representations, and capacities to craft pleasing urban environments