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When lack of control leads to uncertainty: Explaining the effect of anomie on support for authoritarianism.
No full textStudies have shown that anomie, that is, the perception that a society's leadership and social fabric are breaking down, is a central predictor of individuals' support for authoritarianism. However, causal evidence for this relationship is missing. Moreover, previous studies are ambiguous regarding the mediating mechanism and lack empirical tests for the same. Against this background, we derive a set of integrative hypotheses: First, we argue that perceptions of anomie lead to a perceived lack of political control. The repeated failure to exert control in the political sphere leads to feelings of uncertainty about the functioning and meaning of the political world. This uncertainty heightens people's susceptibility to authoritarianism because, we argue, the latter promises a sense of order, meaning, and the guidance of a "strong leader." We support our hypothesis in a large-scale field study with a representative sample of the German population (N = 1,504) while statistically ruling out alternative explanations. Adding internal validity, we provide causal evidence for each path in our sequential mediation hypothesis in three preregistered, controlled experiments (conducted in the United States, total N = 846). Our insights may support policymakers in addressing the negative political consequences of anomie. (PsycInfo Database Record (c) 2026 APA, all rights reserved).status: Published onlin
Veilig Meerpartijrekenen, In en Buiten het Hoofd
No full textThe PhD investigates MPC and ZK systems operating over the ring of integers modulo powers of two, and the links between MPC and ZK in this setting. The goal is to develop practical and efficient protocols, paving the way towards wider public adoption.status: Publishe
Verschillende gradaties van glucose-intolerantie tijdens de zwangerschap: een visie op het toekomstige risico op diabetes en hart- en vaatziekten
No full textGestational diabetes (GDM) is a form of diabetes that develops during pregnancy. GDM is associated with increased risks for pregnancy complications such as big baby's and preterm birth. Women with a history of GDM have a high risk to develop a type 2 diabetes (T2DM) within the next ten years after delivery. The children are also at increased risk of developing obesity and T2DM later in life. Studies are needed to find more accurate predictors for the metabolic risk later in life. This will help to individualize the follow-up and to develop tailored prevention strategies in women and offspring with a history of GDM. In this research project we will therefore investigate how the long-term metabolic risk can more accurately be predicted in a follow-up cohort of the 'Belgian Diabetes in Pregnancy study' (BEDIP-N). We will study the relationship between maternal weight, degree of body fat and degree of evaluated sugar levels in pregnancy on the long-term metabolic risk of at least 375 women and offspring pairs 3-7 years after the delivery across different gestational glucose tolerance groups based on the 2013 WHO criteria in pregnancy. In addition, we will study whether a promising new biomarker, glycated CD59, is a good predictor for the long-term metabolic risk.status: Publishe
What makes teaching students with special educational needs special? An investigation and comparison of effectively teaching students with special educational needs in mainstream and special education settings.
No full textEffective teaching is widely recognized as a crucial factor contributing to students' learning and development, placing teachers and their teaching behaviors at the center of educational research. While effective teaching is often considered as a one-size-fits-all practice, recent research has endorsed the importance of teaching contingency. Under this assumption, the effectiveness of teaching is considered as dependent upon the unique classroom context in which it is implemented, including the students in the classroom and the classroom setting. Considering both components, this doctoral project has a twofold objective: (1) to conceptualize effective teaching for students with special educational needs (SEN), a specific group of learners who greatly benefit from effective teaching but is largely overlooked in most teacher effectiveness research; and (2) to compare the teaching behaviors of teachers who teach students with SEN in two distinct classroom settings: mainstream education teachers (MET) and special education teachers (SET). The general effective teaching principles defined in the Great Teaching Toolkit (GTT, Coe et al., 2020) are taken as a starting point to investigate effective SEN teaching throughout five studies. In the first two studies, effective teaching for students with SEN and differences between MET and SET are examined from both theoretical and practical perspectives. Study 1 involves a scoping review with the aim of providing a comprehensive overview of the literature on effective teaching focused on improving reading comprehension outcomes for students with SEN. In Study 2 interviews are conducted with MET and SET to gather and compare their perspectives on effective SEN teaching. Findings from these two studies are then used in Study 3 to develop a classroom observation instrument that aims to outline effective teaching behaviors implemented by teachers of students with SEN during reading comprehension lessons. Consequently, the instruments' use is illustrated in Study 4 by investigating the frequency of and variations in the implementation of teaching behaviors through viewing and scoring real lesson observations. Finally, in Study 5, teachers' reasons behind the implementation of specific teaching behaviors and their perceptions on barriers and facilitators to adapt their teaching to students with SEN are investigated and compared between MET and SET. The findings of the five studies support the application of the general principles defined in the GTT model to effectively teach students with SEN. However, what makes teaching to students with SEN special is the translation of these principles into detailed, context-specific teaching behaviors. It is at this more fine-grained level of effective teaching that meaningful differences are identified between teachers who teach students with SEN in different classroom settings. This doctoral dissertation concludes with a critical reflection on the complex concept of effective teaching and its measurement for students with SEN in particular. The findings of this doctoral project have the potential to make a valuable contribution to the delivery of more adequate and high-quality education for students with SEN in every classroom setting, ensuring that every student with SEN is provided with effective, high-quality teaching to learn and reach its highest potential.status: Publishe
Biologie van synoviaal sarcoom en het onderzoek naar nieuwe therapeutische mogelijkheden voor deze zeldzame ziekte.
No full textSoft tissue sarcoma represents a very heterogeneous group of tumors of mesenchymal origin and accounts for about 1% of all adult cancers. Despite the heterogeneity in soft tissue sarcomas, the standard treatment options are very uniform and have limited efficacy. There is a need for a more subtype-specific approach to develop more effective treatment options. In this PhD project, we focused specifically on one of the more common subtypes of soft tissue sarcoma: synovial sarcoma. It is characterized by a translocation between the SYT gene on the 18th chromosome and one of the SSX genes on the X chromosome, resulting in the pathognomonic SS18::SSX fusion. For localized synovial sarcoma, treatment typically consists of surgery, combined with chemo-or radiotherapy in some cases. Patients with metastatic synovial sarcoma are usually treated with systemic chemotherapy and although synovial sarcoma can respond to systemic therapy, the outcome of patients with metastatic disease remains very poor.
The first aim of this research project was to explore the clinical disease course of 134 adult patients diagnosed with synovial sarcoma and treated at the University Hospitals Leuven, Belgium, between 1987 and 2018. This retrospective series confirmed that most patients were diagnosed with localized disease, but although they received treatment with curative intent at a sarcoma reference center, almost half of these patients developed metastases. Treatment options in advanced and metastatic setting resulted in poor outcomes. This clearly emphasized the need to develop better treatment strategies for these patients.
The development of T cell receptor therapies will hopefully improve the outcome of patients with SynSa in the future. A better understanding of the expression of this treatment's targets is needed to understand which patients might be eligible for this therapy and which clinicopathological factors might influence the expression. We provided one of the first real-world data on this topic. Secondly, also the expression of other potentially actionable targets such as bromodomain-containing protein 9, chemokine receptor 4 and key regulators of the Hippo pathway: yes associated protein 1 and transcriptional co-activator with PDZ-binding motif were investigated. All evaluated markers were expressed in a clinically meaningful proportion of cases represented in our samples, supporting the relevance of ongoing preclinical and clinic research with novel agents directed against these targets.
The third aim of this research project focused on the expansion of the currently available preclinical models of synovial sarcoma and the creation of novel preclinical models, such as tumoroids. Several patient-derived preclinical models of synovial sarcoma were created within this project: primary cell cultures, tumoroids and patient-derived xenografts. These models are well characterized, ensuring the key characteristics of the original patient's tumor are present and corresponding clinicopathological information is available. Most of these models can be exchanged with collaborators and used for subsequent experiments as highlighted in one of the subchapters. Given the rarity of this disease, these models are very valuable. The creation of tumoroids from synovial sarcoma only had limited success and required an extensive optimization of the culture conditions. Based on this experience, an active working group connecting researchers working with tumoroid models of sarcoma was founded and recommendations to guide others working on this topic were written.
In conclusion, this thesis offered a deeper insight into the clinical presentation of patients with synovial sarcoma. We explored the expression of several novel actionable targets, enhancing our understanding of potential therapeutic opportunities. Secondly, preclinical models were developed and characterized to evaluate novel treatment approaches. Lastly, this work established strong foundations for ongoing and future collaborations.status: Publishe
De rol van mestcellen in het prikkelbaredarmsyndroom
No full textIrritable bowel syndrome (IBS) is one of the most prevalent disorders of the gut-brain axis, affecting on average 4% of the world population and 3% of Belgians (1). IBS is characterised by recurrent abdominal pain that is associated with a change in stool frequency and/or form (2). Patients are categorised based on their defecation pattern in an attempt to stratify the highly heterogeneous group and aid in treatment selection and scientific research. These subgroups include diarrhoea-predominant (IBS-D) patients, constipation-predominant (IBS-C) patients, and patients with alternating periods of diarrhoea and constipation (IBS-M). Patients who cannot be classified based on their defecation pattern are referred to as IBS-U. Abdominal pain is the hallmark symptom of IBS and is often caused by increased pain perception in the gut, also called visceral hypersensitivity (VHS) (3). Current clinical management of IBS consists of dietary and lifestyle advice and drugs that normalise defecation or reduce cramping (4). Treatment options targeting abdominal pain are limited, exhibit modest efficacy or are prone to cause more severe side effects. A more complete understanding of IBS pathophysiology would greatly improve the development of effective treatments.
Mast cell (MC) activation in the gastrointestinal tract is known to play a key role in IBS pathophysiology, mainly characterised by a greater number of MCs close to enteric and extrinsic nerve terminals and an increase in MC activation (5). This results in the release of MC mediators such as histamine, with sensitisation of visceral afferents and increased pain signalling. In a pilot study, we previously reported clinical improvement by treatment with the histamine receptor H1 (HRH1) antagonist ebastine (6). In chapter 3, we report the results of a multicentre trial in which we compared the treatment effect of ebastine to placebo in non-constipated IBS patients. We show that a 12-week treatment of ebastine (20 mg daily) significantly increased the proportion of patients with a clinical response, especially in the last 6 weeks of treatment. Ebastine also had a significant treatment effect on the weekly abdominal pain scores compared to placebo, but not on stool consistency and quality of life. This would indicate that HRH1-antagonism can reduce VHS and represents a novel therapeutic option for managing IBS-related abdominal pain.
Our group previously provided evidence that MCs in the intestinal mucosa of IBS patients are sensitised with dietary antigen-specific immunoglobulin E (IgE) and therefore more prone to degranulation upon food antigen stimulation (7). However, MCs can also undergo degranulation via an IgE-independent pathway, for example via the Mas-related G-protein-coupled receptor X2 (MRGPRX2). In chapter 4, we report the presence of MCs expressing MRGPRX2 in the human colon. Activation of the receptor in situ leads to MC degranulation, and subsequent sensitisation of transient receptor potential vanilloid 1 (TRPV1), indicating MRGPRX2 is functional in the human gut and might contribute to VHS. While expression levels of the receptor in rectal biopsies were similar between IBS patients and healthy subjects, we did observe increased levels of MRGPRX2 agonistic activity in rectal biopsy supernatant when comparing calcium responses before and after incubation with an MRGPRX2 antagonist in MRGPRX2-expressing Chinese Hamster Ovary cells. Additionally, we show evidence of increased levels of substance P in IBS patient samples, which is a known MRGPRX2 agonist and possibly involved in stress-induced abdominal pain. Our results suggest a potential role for MRGPRX2-mediated MC activation in IBS, implying that MRGPRX2-antagonists may represent a novel therapeutic approach to treat IBS patients.
As we know from our results in chapter 3, a significant proportion of patients do not improve with ebastine. Therefore, other mediators such as proteases might be involved in the development of VHS. From research in mouse models of VHS, we know that histamine and tryptase, two MC mediators, can sensitise neurons and induce VHS via sensitisation of the TRP channels TRPV1 and TRPV4, and TRPA1 (6,8-11). While proteases in the gut are primarily known for their role in food digestion, they can also mediate processes that depend on cellular communication (12). Trypsin and tryptase are suggested to play a role in this pathway based on increased expression levels in the intestinal mucosa and increased activity levels measured with substrate-based kinetics (13-17).
In chapter 5, we confirm these previous findings of increased trypsin-like activity levels and show no significant increase in chymotrypsin- and elastase-like activity levels, the two other subclasses of serine proteases. Additionally, our data strongly suggest that the increased trypsin-like activity in IBS patient samples is more likely to originate from proteases with trypsin- and tryptase-like substrate preferences, rather than thrombin-like proteases. Using an activity-based probe to unambiguously identify active proteases in the complex proteome of rectal biopsy supernatant, preliminary results suggest increased levels of trypsin-2 and chymotrypsin-like elastase 3A in a subgroup of IBS patients displaying high trypsin-like activity levels. These findings support the involvement of proteases in IBS and guide the development of protease inhibitors as potential new treatment options for IBS management.
While it is clear that activation of the protease-activated receptor 2 (PAR2) is necessary for TRPV1, TRPV4, or TRPA1 sensitisation in murine models, it is uncertain how proteases mediate sensitisation of TRP channels in humans. Especially as it appears that proteases in colonic biopsy supernatant from IBS patients could only activate human enteric neurons via PAR1, and not PAR2 (18-20). As human dorsal root ganglion neurons are hard to obtain, and experiments with enteric neurons and stem cells are highly time-intensive, we decided to modify the Human Embryonic Kidney cell line, which has neuronal characteristics (21). In chapter 6, we describe in detail the stable incorporation of human TRPV1, TRPV4, and TRPA1 with a C-terminal hemagglutinin-tag under an inducible promotor and the calcium indicator GCaMP6m-Xc under a constitutive promotor, determining optimal TRP expression and confirming functionality of the new model, which enables functional assessment of protease-mediated TRP sensitisation.
In summary, the results of this thesis provide new insights into the mechanisms underlying abdominal pain in IBS. We show that HRH1 antagonism should be considered as a novel treatment option for IBS patients. Additionally, our results indicate two novel therapeutic strategies for managing IBS-related abdominal pain, specifically antagonism of MRGPRX2 and inhibition of overactive proteases, highlighting promising new avenues for targeted treatment approaches.
References:
1. Sperber, A. D. et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology 160, 99-114.e3 (2021).
2. Drossman, D. A. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Gastroenterology 150, 1262-1279.e2 (2016).
3. Farzaei, M. H., Bahramsoltani, R., Abdollahi, M. & Rahimi, R. The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments. J Neurogastroenterol Motil 22, 558-574 (2016).
4. Black, C. J. & Ford, A. C. Best management of irritable bowel syndrome. Frontline Gastroenterol 12, 303-315 (2021).
5. Aguilera-Lizarraga, J., Hussein, H. & Boeckxstaens, G. E. Immune activation in irritable bowel syndrome: what is the evidence? Nat Rev Immunol 22, 674-686 (2022).
6. Wouters, M. M. et al. Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome. Gastroenterology 150, 875-887.e9 (2016).
7. Aguilera-Lizarraga, J. et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature 2021 590:7844 590, 151-156 (2021).
8. Balemans, D., Boeckxstaens, G. E., Talavera, K. & Wouters, M. M. Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 312, G635-G648 (2017).
9. Cattaruzza, F. et al. Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice. AJP: Gastrointestinal and Liver Physiology 298, G81-G91 (2010).
10. Cenac, N. et al. Quantification and potential functions of endogenous agonists of transient receptor potential channels in patients with irritable bowel syndrome. Gastroenterology 149, 433-444.e7 (2015).
11. Kawao, N. et al. Modulation of Capsaicin-Evoked Visceral Pain and Referred Hyperalgesia by Protease-Activated Receptors 1 and 2. J Pharmacol Sci 94, 277-285 (2004).
12. Vergnolle, N. Protease inhibition as new therapeutic strategy for GI diseases. Gut 65, 1215-1224 (2016).
13. Barbara, G. et al. Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome. Gastroenterology 132, 26-37 (2007).
14. Rolland-Fourcade, C. et al. Epithelial expression and function of trypsin-3 in irritable bowel syndrome. Gut 66, 1767-1778 (2017).
15. Buhner, S. et al. Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome. Gastroenterology 137, 1425-1434 (2009).
16. Lee, J. W. et al. Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase. Dig Dis Sci 55, 2922-2928 (2010).
17. Bian, Z. X. et al. Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients. J Gastroenterol 44, 666-674 (2009).
18. Mueller, K. et al. Activity of protease-activated receptors in the human submucous plexus. Gastroenterology 141, 2088-2097.e1 (2011).
19. Kugler, E. M. et al. Activity of protease-activated receptors in primary cultured human myenteric neurons. Front Neurosci 6, 1-8 (2012).
20. Buhner, S. et al. Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients. PLoS One 13, 1-16 (2018).
21. Shaw, G., Morse, S., Ararat, M. & Graham, F. L. Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. Faseb J 16, 869-71 (2002).status: Publishe
Children’s emerging sociolinguistic expectations around social roles: a triangulated approach
No full textstatus: Published onlin
Op parelmoer geïnspireerde synthese en modificatie van vulstoffen voor beter presterende polymeercomposieten
No full textLighter, better performing, and more sustainable materials are a key market need in this era. Nature provides marvellous source of inspiration to develop such materials as many natural systems possess extraordinary properties, features, or appearances such as excellent mechanical strength and/or toughness, self-cleaning, self-healing, etc. Nacre, forming the inner layer of shells, is one such source of inspiration with its biomineralization, structure and strengthening mechanism. Even though nacre consists of 95 % brittle inorganic mineral (CaCO3), it exhibits a toughness of about 3000 times higher than that of CaCO3 thanks to its brick and mortar structure with organic polymer (5%). Recently, nacre-inspired crystals, fibres, films and bulk composites have been developed. However, due to nacre's complex structure, development of nacre-like bulk composites requires complicated manufacturing processes. Consequently, nacre-inspired synthesis and modifications of fillers are explored in this research.status: Publishe
Beyond dichotomies in generalization research: A reply to Lee and Schlegelmilch (2024)
No full textLee and Schlegelmilch (2025) reanalyzed data from Zaman, Yu, and Verheyen (2023), arguing that the role of perception in generalization is overemphasized and that higher level cognitive processes (in the form of a similarity-based rule) provide a better account. In this reply, we make the argument that their reanalysis contains flaws and inconsistencies and present additional evidence for consideration. While acknowledging the role of higher level cognition in generalization, we maintain that the available evidence supports stimulus perception and memory as important predictors. We view this exchange as a reminder that stimulus representation and higher level cognition exist on a spectrum, with their relative importance varying across contexts. Consequently, more research into the interactions between these processes is necessary. We argue that rather than adhering to existing theoretical frameworks, researchers should continue to challenge our understanding of human generalization by incorporating new evidence and insights into existing models and comparing them across diverse contexts. This approach will foster a more comprehensive and nuanced understanding of human generalization processes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).sponsorship: Kenny Yu is supported by a FWO research project(coprincipal investigator Jonas Zaman, Grant G079520N). Jonas Zaman is a Postdoctoral Research Fellow of the Research Foundation Flanders (FWO,Grant 12P8623N) and received funding from the Alexander von HumboldtStiftung. Kenny Yu is partially supported by a grant from the Research Council of KU Leuven (C14/23/062) (FWO research project|G079520N, Postdoctoral Research Fellow of the Research Foundation Flanders (FWO)|12P8623N, Alexander von HumboldtStiftung, Research Council of KU Leuven|C14/23/062)status: Publishe
Onderzoek naar automatische planning van radiotherapie behandelingen voor slokdarmkanker: een focus op protontherapie en online adaptieve workflows
No full textMore than half of the patients treated for cancer receive external Beam Radiation Therapy (EBRT) during the course of their disease. EBRT is typically characterized by highly standardized protocols and relies on the precise daily delivery of high energy X-rays combined with volumetric imaging tools. In order to further improve cancer care in Belgium, the UZ Leuven and the Cliniques Universitaires Saint-Luc have recently built in partnership the first Belgian proton therapy center, called ParTICLe, which is located on the Gasthuisberg campus in Leuven. The chosen manufacturer was IBA, a former spin-off from UCLouvain in 1986 and now the world leader in the construction of proton therapy centers. The first patient is expected by March 2020. Proton therapy (PT) sets itself as a major player in the therapeutic arsenal available to clinicians on both sides of the linguistic border to treat their patients with one of the most advanced technologies. In comparison to photon therapy with X-rays (XT), proton physics allows a high concentration of the dose delivered in the target volumes resulting in a better sparing of the surrounding healthy tissues and a better therapeutic ratio. However, the added value of PT is not systematic and depends on anatomical and clinical parameters which are specific to each patient. In addition, patients with similar baseline profiles may respond differently to treatment. So, a patient under treatment with XT might develop unexpected toxicities which urges switch to PT. Optimal usage of such advanced technology therefore requires to determine, before and during treatment, the patients who could benefit the most from PT. The aim of the project is to develop a clinical decision support system, largely automated by artificial intelligence, which allows to objectively assess the added value of PT compared to XT at any time during treatment, for every individual patient. This assessment will be accomplished using published toxicity and tumor control prediction models that will be updated based on longitudinal imaging data and biological markers (i.e., acquired during treatment). The tumor site chosen for the proof-of-concept is oesophageal cancer, which is already the focus of several ParTICLe researchers. Furthermore, we will participate in a European randomized clinical trial in which patients with oesophageal cancer will be randomized between PT and XT. The role of artificial intelligence is to address some bottleneck steps in the usual treatment planning procedure, which normally requires human intervention. These manual operations are typically slow, tedious, and prevent fast simulation of the treatment planning chain. Such manual steps are for instance the delineation of organs at risk, the contouring of target volumes, the fine adjustment of the plan objectives to get a clinically acceptable dose.status: Publishe