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Nutriënt-gemedieerde modulatie van de orale microbiologie
No full textPeriodontal diseases are a significant public health burden, of which severe periodontitis is the 6th-most prevalent disease, affecting 11% of the global population. Periodontitis is defined as infections of the tooth supporting tissue, leading to destruction of the connective tissue and alveolar bone, eventually resulting in tooth loss. While dental biofilm are known to play a major role in the development of periodontal diseases, the exact microbial etiology is still unknown. The ecological plaque hypothesis states that the host, the environment, the presence of periodontal pathogens and the absence of beneficial bacteria are the most important factors in the development of periodontal diseases. The shift from a homeostatic microbial composition towards a dysbiotic microbiota in a susceptible host will lead to the development of periodontitis. To date, standard periodontal therapy focuses mainly on the reduction and elimination of the bacterial load with subsequent improvement in clinical parameters. However, fast bacterial translocation and recolonization increases the risk of recurrence of disease, making maintenance therapy a lifelong requirement for the patients. One new treatment strategy focuses on controlling recolonization by means of probiotic bacteria. Although the use of certain probiotic bacteria resulted in an improvement in clinical parameters as well as in a delayed recolonization by pathogenic bacteria, the colonization of probiotic bacteria in the oral cavity is only temporary. Therefore, the stimulation of the protective and beneficial properties of the natural resident microbiota might reveal a new treatment approach. The prebiotic concept has already been introduced in gastrointestinal health. By means of specific food ingredients, selective changes in the composition or activity of the indigenous gastrointestinal are induced, thus conferring health benefits to the host.
The main aim of this thesis was to investigate if the prebiotic concept can be transferred to oral health to reveal an alternative treatment approach for periodontitis.
To identify potential prebiotic compounds for oral health, Phenotype MicroArrays were used as a high-throughput method to monitor the change in respiratory activity of 16 oral bacteria in response to 759 nutritional compounds. Multivariate statistical analysis was employed to investigate metabolic associations within and among bacterial groups, analyzing collaborative or competitive interactions of bacteria. Further, compounds were selected based on their selective stimulation of individual bacteria in metabolic activity, growth and biofilm formation. Seven compounds were subsequently used in dual species competition assays of beneficial and pathogenic bacteria. N-acetyl-D-mannosamine, L-arginine, and beta-methyl-D-galactoside selectively stimulated beneficial oral bacteria, leading to a suppression of pathogenic species. Hence, mixed species biofilm communities were shifted towards a composition dominated by beneficial oral bacteria at in vitro level. To validate the selective stimulatory effect of beneficial bacteria, a chemostat culture containing 14 model bacteria was developed. Nine potential prebiotic substrates were tested on these multispecies biofilms, and biofilm composition was analyzed by vitality qPCR. N-acetyl-D-mannosamine, succinic acid, and the di-peptide Met-Pro were able to stimulate the beneficial proportion of the biofilm to above 95%. Additionally, the effect of environmental factors, such as pH, nutrient availability, oxygen concentration and prebiotic dose, on the efficacy of the prebiotic substances was evaluated. Throughout the experiments, N-acetyl-D-mannosamine could be identified as the most promising prebiotic compound, shifting the biofilm composition despite changing conditions towards a beneficial dominated community of 97%. In addition, the potential of N-acetyl-D-mannosamine to increase the resistance of established beneficial biofilms to invading pathogens was analyzed. Incorporation of pathogenic species was significantly decreased when compared to the control treatment, thus, possibly enabling the use of prebiotics to control or prevent the translocation and recolonization of pathogenic bacteria in the oral cavity. Although the exact mechanism of the prebiotic treatment needs to be investigated, data indicated that N-acetyl-D-mannosamine also interferes with the co-aggregation of beneficial and pathogenic bacteria. The prebiotic concept shows promising potential as a new treatment approach for periodontal diseases by shifting the bacterial composition of mixed biofilm communities towards a health associated microbiota and preventing the incorporation of pathogenic bacteria into established biofilms.status: Publishe
Towards a Framework for Powerful Learning Environments for Struggling Students in Middle School: A Systematic Review
No full textstatus: Publishe
Digital Mapping of Toponyms in Paradoxographical Texts: The Case of the Paradoxographus Florentinus
No full textstatus: Accepte
Predicting Transformer HotSpot Temperature: A Comparative Study of FNN and LSTM-PCA
No full textstatus: Accepte
Een meccanodoos vol verschalende kreeften. Hoe een debat in Quebec de aanzet kan vormen voor een 'historiografisch moment' in de Vlaamse geschiedschrijving
No full textDebatten, aldus de Nederlandse geschiedfilosoof Chris Lorenz, vormen de basis van een historiografische analyse. Ze stellen ons in staat om bepaalde historiografische conventies en praktijken te observeren en te analyseren. Anders gezegd: debatten laten ons toe om een ‘historiografisch moment’ vast te leggen.
In de jaren 1990 vonden er zowel in de Canadese provincie Quebec als Vlaanderen debatten plaats onder historici. De discussie in Quebec over de rol van de invloedrijke priester-historicus Lionel Groulx vormde de aanleiding om te reflecteren over de invulling van nationalisme en geschiedenis in de overwegend Franstalige samenleving. In Vlaanderen was het debat tussen journalist-historicus Marc Reynebeau en de historicus en politicus Eric Defoort volgens Marnix Beyen een “leerrijke polemiek”.
Dit artikel vergelijkt deze twee debatten en plaatst ze in de bredere historiografische context van de twee regio’s, om zo een ‘historiografisch moment’ te capteren.
Het focust in het bijzonder op de verschillen tussen de geschiedfilosofische visies en de historiografische praktijk die daaruit zijn voortgekomen. Ik zal immers beargumenteren dat het gangbare uitgangspunt van de Vlaamse geschiedschrijving haaks staat op de Quebecse historiografie. In Quebec ligt de nadruk voornamelijk op het concept van determinisme, in Vlaanderen daarentegen is het uitgangspunt tegenovergesteld. De focus ligt in de eerste plaats op het contingente. Het veronderstelt dat, hoewel structuren aanwezig zijn, toeval en individuele beslissingen de bovenhand nemen op structurele determinanten.
Het verschil, zo zal ik argumenteren, heeft deels te maken met de blijvende invloed van de Vlaams-nationalistische politicus en historicus Hendrik Elias op de hedendaagse geschiedpraktijk. Aan de hand van een analyse van de drie edities van de Encyclopedie van de Vlaamse beweging, zal geïllustreerd worden dat Elias’ geschiedvisie (en de historiografische ‘oerknal’ die hij had veroorzaakt) tot vandaag nog een hoeksteen vormt van de historiografische praktijk. Dit onderliggend aspect toelichten, kan helpen om het conventionele beeld uit te dagen en sterker stil te staan bij mogelijke alternatieve benaderingen voor de Vlaamse historiografie.status: Publishe
A Footnote on Plato? Kant’s Comparison of Philosophy and Chemistry in the 1787 Preface of the Critique of Pure Reason
No full textCommentaries on the B-Preface of the Critique of Pure Reason tend to focus on Kant’s so-called Copernican turn. Much less attention has been paid to the fact that the B-Preface compares the achievement of the Critique to two different scientific procedures: the act of demonstrating a counter-intuitive hypothesis and the act of verifying its correctness by means of a cross-check. Whereas the first procedure seeks to prove that objective cognitions of noumena are impossible, the second procedure seeks to confirm the result of the first. In an allusive and elliptical footnote, Kant compares the second procedure to a procedure carried out by chemists. Deviating from the interpretations put forward by Falkenburg and Schmid, my reconstruction of this footnote puts Kant’s use of the terms ‘metaphysician’ and ‘separated’ center stage. Drawing on Kant’s distinction between general and special metaphysics in the B-Preface and the Architectonic, his comments on Plato, and other relevant texts, I argue that the footnote addresses, in an extremely compressed manner, Kant’s largely implicit conception of the relation between the history of metaphysics, its projected scientific elaboration, and the tasks carried out in the Critique of Pure Reason.status: Published onlin
Programmatische toetsing implementeren: de kloof tussen theorie en praktijk overbruggen
No full textIntroduction
Programmatic assessment is an instructional approach, where the assessment purpose requires the alternation between assessments for learning (or low-stakes assessments) and assessments of learning (high-stakes). Low-stakes assessments are intended to support trainees' further development, while high-stakes assessments are used to take decisions on trainees' progression, based on aggregated information. By combining assessment stakes in a continuum, PA aspires to create a fit-for-purpose approach, integrating both the learning and decision-making purpose of assessment. Although literature on PA has dominated medical education research, early implementation evidence indicates barriers. Alternating the assessment stakes, along with difficulties to engage workplace stakeholders, namely trainees and trainers, posit challenges to PA, when it is applied in practice. Therefore, designing and implementing a PA framework that aligns with stakeholders' needs is crucial for enhancing assessment practices in postgraduate medical education. Such stakeholder-centric PA framework can help bridge the gap between theoretical knowledge and practical application, ensuring that the assessment process fulfils its dual purpose.
Method
This PhD project was based on the principles of the educational design research (EDR) within the General Practitioner's (GP) Training context. Embracing the complexity of real learning environments, EDR attempts to pursue practical and scientific goals for specific contexts through the phases of analysis, design, and evaluation. Therefore, this PhD project began by thoroughly analysing the existing assessment structures within the GP Training (Chapter 1 and Chapter 2). Subsequently, it proceeded to designing customized solutions to address stakeholders' assessment needs (Chapter 3, Chapter 4, and Chapter 5), and, lastly, it concluded with evaluating these solutions (Chapter 6, Chapter 7, Chapter 8, and Chapter 9).
Results
Starting with the first high-stakes assessment and problem analysis, our validity study demonstrated that a multicomponent proficiency-testing exam can provide valid performance evidence, setting trainees' learning agenda. Our focus group study showed that low-stakes workplace assessments need toestablish clear learning outcomes, allow frequent assessments, and enhance feedback processes, to meet workplace stakeholders' needs. During the design phase, amidst the COVID-19 pandemic, our comparative study on proctoring systems suggested that online proctoring could be a viable solution for high-stakes assessments. Furthermore, our Delphi study indicated that the CanMEDS competency framework is context-dependent and challenging for low-stakes workplace assessments. Our co-design study aimed to bridge the gap between CanMEDS and practice by designing an Entrustable Professional Activities (EPAs) framework with clinical competence committee members, trainers, and trainees, highlighting the importance of collaborative efforts. This study showed that involving various stakeholders in the design phase of an educational intervention can identify implementation barriers. In the evaluation phase, our longitudinal study assessed the EPA intervention's implementation, revealing that stakeholders' perceptions changed over time and were divergent between trainees and trainers. Additionally, our mixed-method study on feedback demonstrated that EPAs can provide high-quality feedback. Furthermore, our first qualitative study with semi-structured interviews provided evidence on trainees' agency during EPAs. Trainees' agency was multifaceted, and was influenced by internal and external factors. Finally, our second qualitative study with semi-structured interviews highlighted challenges with e-portfolios in implementing PA. User profile, limited functionalities of the e-portfolio, and time constraints were factors influencing not only utilization of e-portfolios, but also PA implementation.
Conclusion
This PhD project added to the current literature on PA by describing a stepwise design and implementation process. Each chapter of this dissertation delineates the stepwise process of implementing PA, by not only outlining the necessary steps, but also by offering profound insights into curriculum planning and process evaluation, aimed at fostering sustainable and enduring results.status: Publishe
Neutrofielen: ondergewaardeerde spelers in de pathogenese van multiple sclerose
No full textMultiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system (CNS), affecting about 2.8 million people worldwide, of which 13.000 in Belgium. Unfortunately, no curing treatment is available, leaving these patients with a treatment strategy to reduce symptoms and slow down neurodegeneration, which is far from ideal. Despite decades of research, the exact pathogenesis and cause of this disease is not fully understood, leaving a multitude of unanswered questions. With the adaptive immune system always thought to be most important for driving MS disease course, the innate immune system is left seriously understudied. Belonging to this innate arm are neutrophils, the first-responding cells to fight infection or inflammation in the body, and the most numerous circulating leukocytes. With their short lifespan, they are challenging to study in a laboratory environment and in situ. Hence, this cell type is often overlooked in chronic inflammatory or autoimmune conditions, such as MS. However, in animal models of MS, a significant body of evidence was already gathered, supporting the importance of neutrophils in the early phases of disease. Therefore, the aim of this PhD project was to elucidate the involvement of neutrophils in the pathogenesis of MS.
We explored the involvement of neutrophils in the broader context of MS through various approaches. Our findings revealed that circulating neutrophils from MS patients exhibit increased expression of CD62L compared to those from healthy donors. Additionally, single-cell RNA sequencing identified multiple distinct neutrophil subsets within the circulation, each characterized by unique transcriptional signatures. Notably, we observed differential expression of interesting genes such as ANXA1, IFITM3 and S100P, in neutrophils from untreated RRMS patients compared to those from natalizumab-treated patients or healthy donors. Furthermore, we demonstrated that BTK inhibitors, an upcoming group of therapy for autoimmune diseases, interfere with neutrophil's fundamental effector functions in vitro. This finding may have important implications for patients receiving BTK inhibitors, particularly regarding their immune response to infections. Moreover, this research suggests a novel mechanism of action for BTK inhibitors in autoimmune diseases, as they may attenuate activated neutrophils in pro-inflammatory environments. Lastly, we explored the possible involvement of neutrophils in one of the main hallmarks of MS pathology: demyelination. We discovered that human neutrophils take up myelin (debris) via complement-dependent pathways, specifically through the C3/CR3 pathway. Prolonged exposure to myelin debris induced a dose-dependent pro-inflammatory phenotype in neutrophils, characterized by an increased oxidative burst, NET release, chemokine production and inflammatory gene expression. Our research demonstrates that neutrophils are more than simple first-line defending cells; they may play a substantial role in various aspects of MS disease progression, potentially influencing disease outcomes and providing new targets for therapeutic intervention.
Altogether, this PhD research highlighted the critical involvement of human neutrophils in various aspects of MS pathogenesis, offering valuable insights into their potential contribution to disease progression. This work lays a foundation for further investigations in patient samples or animal models, in an attempt to bridge knowledge gaps and contribute to the development of new therapeutic options for all MS patients.status: Publishe
Cultural psychiatry in Flanders, Belgium: an exploratory focus group study and position statement
No full textstatus: Accepte
Het verkennen van routes naar schaalbare ferro-elektrische perovskietmaterialen
No full textIn recent years, there has been a renewed interest in ferroelectrics in low power integrated electronics such as memory. The discovery of ferroelectric hafnia has led to further scaling of layers to sub 10 nm thicknesses. However, the multiphasic nature of hafnia yields poor endurance and across-wafer repeatability. Complex oxides such as perovskites offer a an extremely flexible structure class of materials that offer a wide variety of ferroelectrics with tunable dielectric properties. However, dead-layer effects, negative conduction band offsets with Si, and complex stoichiometries, make the integration and scaling of these materials challenging on devices in large wafer production. Ferroelectricity has been observed in ultrathin films in epitaxy but polycrystalline films, which are preferred in production, have yet to be demonstrated. The development of complex oxide-based materials will be undertaken targeting ferroelectricity in ultrathin layers for devices. Pulsed laser deposition (PLD) will be used on 200mm wafer scale to deposit and optimise complex oxide, perovskite-based materials. Interfacial and strain engineering will be used to minimise dead-layers, and other phenomena that could negatively effect ferroelectricity in these layers. Understanding the growth, structural mechanisms, the role of strain and interfacial chemistries on the ferroelectric response will be key to building a knowledge library and proof-of-concept for the operation of ultrathin ferroelectric complex oxides.status: Accepte