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Dynamische risicovoorspelling van bloedbaaninfecties met behulp van elektronische patiëntendossiers
No full textCentral line-associated blood stream infections (CLA-BSI) cause prolonged hospital stays, morbidity, and cost. We envisage an actionable trigger-based warning system that helps to reduce the incidence of CLA-BSI, and its negative impact on patients. We will develop a dynamic risk model that estimates CLA-BSI risk at any moment, using baseline characteristics at catheter placement and later observations during the patient stay (eg parenteral nutrition, admission to intensive care). We will compare regression and machine learning algorithms. Models will be developed on electronic health records (EHR) from 60,000 patient stays between 2014-2017 in Leuven. Validation will be performed on Leuven data from 2018-2020, as well as in hospitals from the Flemish Hospital Network and from the Netherlands. Through a decision analysis, we assess the model's impact on clinical and financial outcomes. Finally, we aim to implement the model into the UZ Leuven EHR system.status: Publishe
The impact of systemic blockade of dopamine receptors on the acquisition of two-way active avoidance in male rats
No full textActive threat avoidance is a core aspect of adaptive and maladaptive behavior, yet its underlying mechanisms are not fully understood. Prior studies concluded that pharmacologically blocking dopaminergic receptors (DRs) disrupted avoidance acquisition, but it remains unclear whether such effects on learning persist during a drug-free follow-up test. To assess the involvement of D1R and D2R in avoidance acquisition, we conducted two experiments. In Experiment 1, thirty-six male Wistar rats underwent a single avoidance training session involving 30 tone-shock pairings. Rats could avoid the shock by moving to the opposite compartment of the shuttle box. Twenty minutes before training, rats received either D1R antagonist SCH23390 (0.05 mg/kg), D2R antagonist sulpiride (20 mg/kg), or vehicle. While sulpiride did not affect avoidance, 0.05 mg/kg SCH23390 significantly reduced the number of avoidance responses. In a separate test, 0.05 mg/kg SCH23390 also reduced locomotor activity. In Experiment 2 (N = 24), a lower dose of SCH23390 (0.025 mg/kg) was administered, and a drug-free avoidance test under continued reinforcement was added 24 h later to test for sustained effects of D1R blockade on avoidance in the absence of acute drug effects. Although animals avoided less with SCH23390 in the system, this effect did not persist 24 h later, suggesting that effects of D1R blockade during avoidance training might reflect an acute disruption of secondary processes involved in the performance of avoidance behavior rather than an actual impairment of avoidance learning.sponsorship: This work was supported by KU Leuven Research Grant 3H190245, KU Leuven starting grant STG/14/035 and Research Foundation - Flanders (FWO) PhD fellowship 11G7124N. (KU Leuven Research Grant|3H190245, KU Leuven starting grant|STG/14/035, Research Foundation - Flanders (FWO) PhD fellowship|11G7124N)status: Publishe
Does the online direct channel cannibalize or synergize the retail Network? The moderating impact of retailer competitive strength
No full textManufacturers in the retailing sector extensively use online sales points of their own, known as online direct channels. This form of manufacturer encroachment offers consumers the possibility to purchase directly from the manufacturer and hence may cannibalize retailer sales. However, it may also create synergy effects by increasing brand awareness, which may create additional retailer sales. In this research, we investigate the cannibalistic versus synergetic nature of the relationship between an established online direct channel and the retail network and assess whether retailer characteristics related to competitive strength impact this relationship. Using unique sales data from the toy industry and vector autoregressive modeling, we find that the short-term cross-channel price elasticity of online direct channels on retailer sales is negative and significant, indicating a synergetic relationship on average. However, the impact is heterogenous across retailers. Our analysis reveals that acquisition utility components of competitive strength, such as price and innovativeness, especially for large items, can enhance synergetic effects and mitigate the risk of cannibalization. Transaction utility components, such as online presence or the number of physical stores, do not play a moderating role.sponsorship: We gratefully acknowledge financial support from KU Leuven [grant number OT/13/021] and the Flemish Organization for Scientific Research (FWO) [grant number G069617N] . (KU Leuven|OT/13/021, Flemish Organization for Scientific Research (FWO)|G069617N)status: Publishe
Fostering postcolonial historical thinking through museum education: exploring prospective teachers' design practices
No full textstatus: Publishe
Ontwikkeling van een microfluïdisch systeem voor interactie met de hersenen.
No full textBrain disorders, such as neurodegenerative diseases and brain tumours, represent a major societal and healthcare challenge due to their enormous economic burden and the lack of effective treatments. A critical hurdle in developing brain therapies is the difficulty of delivering drugs across the blood-brain barrier (BBB) and sampling cerebrospinal fluid (CSF) for disease biomarkers. This workaddresses these challenges by presenting a novel microcatheter platform for enhanced brain drug delivery and long-term CSF sampling in preclinical models.
The microcatheter platform features a micronozzle fabricated using two-photon polymerization, enabling precise control over drug delivery and distribution. In vitro experiments using agarose brain surrogates demonstrated that the microcatheter significantly reduced backflow and improved fluid distribution compared to conventional catheters. In vivo infusions in mice further confirmed that the micronozzle increased drug spread, reduced backflow, and successfully targeted brain regions such as the anterior olfactory nucleus and thalamus. Additionally, we showed through an olfactory study in rodents that chronic infusion of artificial cerebrospinal fluid (aCSF) through the microcatheter had no adverse effects on behaviour, while conventional methods disrupted these parameters.
In parallel, we developed a microcatheter for chronic CSF sampling to enable longitudinal liquid biopsies. This system allowed repeated CSF collection for over 200 days without causing brain barrier disruption or significant tissue damage. Collected samples were consistent in their nucleic acid and protein content, facilitating biomarker analysis. Long-term monitoring of amyloid-beta levels and cytokine profiles provided valuable insights into neuroinflammation dynamics in mice.
Overall, the novel microcatheter platform presented in this thesis offers a versatile and minimally invasive tool for both drug delivery and biomarker sampling in the brain. This technology has the potential to improve the treatment of brain disorders by enabling localized therapy and real-time monitoring of disease progression.status: Publishe
Bestuderen van Cykels met Computationele Grafentheorie
No full textIn applications of graph theory, computational methods seem to be an inevitability, but despite the growing popularity of computer methods in various areas and the general increase in computing power, such methods are still often underutilised in the domain of structural graph theory.
In this thesis, we aim to push the state-of-the-art structural graph theory research by utilising computational methods alongside a more theoretical approach. In particular, we design and implement algorithms in order to check structural properties of graphs or generate them exhaustively and use computations to obtain examples and gain a better understanding of certain graph classes. These computational results can then in turn be used as a foundation for creating and proving mathematical theorems. We applied this methodology to several topics within graph theory, more specifically on topics in which cycles play a significant role. Cycles are an important concept within the theoretical study of graph theory, but also appear in a lot of applications such as the travelling salesperson problem, which is for example used in routing, logistics and genome assembly. Cycles also play a role in the design of fault-tolerant networks as they are a source of redundancy and many other such examples can be given. We divide the topics we study into three parts.
The first part is on K2-hypohamiltonian graphs. These are graphs which are non-hamiltonian, but every subgraph obtained by deleting an edge and its two endpoints is hamiltonian. Their study is motivated by a long-standing and difficult conjecture of Grünbaum from 1974. We develop an algorithm for checking whether a graph satisfies this property and an algorithm which generates these graphs exhaustively. Using these results, we completely classify the orders for which K2-hypohamiltonian graphs exist in the general case, as well as in the case of cubic graphs and snarks and describe or give lower bounds for smallest examples in the planar or cubic planar case.
The second part is on 2-factors, i.e. spanning subgraphs in which every vertex has degree 2. A first work is on the Frank number, a parameter for 3-edge-connected graphs which refines k-edge-connectivity. An edge e of a graph G is deletable for some orientation if its restriction to G - e is still strongly connected. The Frank number of G is defined as the minimum number of orientations of G such that every edge of G is deletable in at least one of the orientations. Hörsch and Szigeti showed that every 3-edge-connected graph G has Frank number at most 7 and if they are 3-edge-colourable that their Frank number is at most 3. We strengthen both of these results, by showing that every 3-edge-connected graph has Frank number at most 4 and 3-edge-connected 3-edge-colourable graphs have Frank number precisely 2. Moreover, we develop two sufficient conditions for a cyclically 4-edge-connected cubic graph to have Frank number 2, based on the structure of the 2-factors of the graph. Using these conditions we develop an algorithm for determining whether or not a graph has Frank number at most 2 and use it to determine that, apart from the Petersen graph, all cyclically 4-edge-connected cubic graphs up to order 36 have Frank number exactly 2.
A second work involving 2-factors is on cycle permutation graphs. These are cubic graphs of order n containing a 2-factor consisting of two induced cycles of length n/2. We develop a specialised algorithm for generating non-hamiltonian cycle permutation graphs and permutation snarks, i.e. non-3-edge-colourable cycle permutation graphs. On the one hand, we use the algorithm to completely settle a question posed by Klee in 1972 on the orders for which non-hamiltonian cycle permutation graphs exist. On the other hand, we improve on earlier computational results by Brinkmann et al. who generated permutation snarks up to order 34 using a generator-filter approach, by generating these graphs up to order 46. This gives computational evidence for the non-existence of permutation snarks on orders 6 mod 8 (which is still an open problem) and yields 736 extra examples in the class of cyclically 5-edge-connected permutation snarks, whereas only 13 such graphs had been generated in previous work.
The third part is on the absence of cycles. In a first work, we consider HISTs. These are spanning trees of a graph not containing any vertices of degree 2. We study these structures, which are antithetical to hamiltonian cycles, in the same spirit as hypohamiltonian graphs. We define HIST-critical graphs, which are graphs not containing a HIST, but every vertex-deleted subgraph does. We create an algorithm that checks whether a graph contains a HIST or whether it is HIST-critical and use this to give a near-characterisation of the orders for which HIST-critical graphs exist. We give an infinite family of planar HIST-critical graphs in which all but few vertices have degree 4, giving insight into the HIST-analogue of a theorem by Thomassen on planar hypohamiltonian graphs. We also provide computational evidence to a conjecture of Malkevitch stating that all 4-connected planar graphs contain a HIST.
A second work is on the fault-tolerance of networks. In certain applications the cost of a network is determined by their nodes of degree at least 3. Therefore spanning trees in which the number of branches and therefore the number of leaves is minimal are of interest. In this context we study what happens when a node fails. The fault cost is a measure of how many degree changes are required to obtain a new spanning tree with minimum number of leaves after a node is removed from the network. We develop an algorithm for determining the fault cost of a graph and use this to exhaustively determine the fault cost of small graphs. We show that any non-negative fault cost can occur and give infinite families of graphs with fault cost 1 and cubic graphs with fault cost 3.
These works show the merit of computational approaches in structural graph theory and that a good balance between computational and theoretical methods can be optimal for advancing the state-of-the-art research in an efficient way.status: Publishe
Ontwikkeling van nieuwe strategieën om de precisie en de mechanische performantie van metalen onderdelen geproduceerd via selectief laser smelten te verhogen
No full textLaser Powder Bed Fusion (LPBF) is an Additive Manufacturing (AM) technique that allows the fabrication of metal parts with unparalleled design freedom. Despite its advantages, the fatigue strength of LPBF-produced parts is often limited by their poor surface quality. Post-AM surface finishing is commonly an essential step for enhancing the parts' surface quality and thus fatigue strength. However, this increases the production time and costs, and is sometimes not feasible for the complex geometries of LPBF parts. This thesis addresses these challenges by developing an in-process remelting strategy to improve the surface quality - and thereby the fatigue strength - of parts with up-facing inclined surfaces directly during printing. The research explores the use of pulsed laser-induced shock waves to remove powder from inclined surfaces in order to enable subsequent remelting.
The first part of the thesis deals with a dual laser PBF (DLPBF) strategy, which employs remelting as a single surface finishing step once the part is built. Laser remelting allows significant improvements in fatigue life compared to reference samples with as-built, electrical discharge machined, and mechanically polished surface conditions by up to a factor of 36, 10 and 3, respectively. Moreover, the strategy can be applied for improving the fatigue life of parts made from various AM materials (Ti64, M300, M789). Furthermore, simultaneous improvements in productivity, surface quality and fatigue life can be achieved by combining high speed LPBF using a high layer thickness of 120 μm with remelting. Despite these advances, the DLPBF strategy is considered impractical for treating larger parts.
The second part of the thesis addresses these limitations by advancing the strategy towards remelting at defined height steps during printing. This so-called incremental dual laser PBF strategy (IDLPBF) enables fully automated remelting during printing and is applicable for theoretically any part height, inclinations up to 60°, and for surfaces located in the shadow zone. Significant fatigue life improvements can be achieved compared to as-built samples via surface quality improvement, subsurface pore healing, and leveraging of phase change induced compressive surface stresses.status: Publishe
Developing Cognition From Its Original Seeds: Kant’s Conception of the Synthetic Method in the Critique of Pure Reason
No full textIn the Prolegomena, Kant contrasts the synthetic procedure employed in the Critique of Pure Reason with the analytic procedure carried out in the Prolegomena itself. Given the tangle of analyses, arguments, and alleged proofs that make up the Critique itself, however, it is hard to relate Kant’s remarks on the method to the way he actually proceeds in this work. Unlike Merritt and Gava, among others, I argue that Kant’s innovative use of the synthetic method consists not in the unification of two previously separated elements, but in the act of generating a sum total of cognitions without relying on anything given. Even though Kant in the Critique does not proceed synthetically in all regards, he arguably develops sets of synthetic a priori cognitions from a consideration of the functions of the pure understanding and pure reason per se. I support this reading by clarifying in which sense Kant actually proceeds synthetically in the Doctrine of Elements, in particular as regards his derivation of the synthetic a priori judgments generated by the pure understanding and pure reason. In the latter context, I focus on Kant’s metaphysical deductions of the categories and the ideas of pure reason on which these judgments are based.status: Published onlin
Convergeren van expertise in de zorg: orthogeriatrisch co-management voor ouderen met een majeure osteoporotische fractuur
No full textAs the population ages, the number of older adults experiencing major osteoporotic fractures continues to rise. These fractures pose significant challenges for both patients and society, affecting health, well-being, and healthcare systems. Orthogeriatric co-management, a collaborative approach between surgical and geriatric teams, has emerged as a promising model to improve patient outcomes by providing comprehensive, multidisciplinary care. However, its effectiveness, costeffectiveness and success of implementation in real-world hospital settings remain key areas of investigation. Therefore, the overall aim of this PhD project was to investigate the impact of orthogeriatric co-management in patients aged 75 years and older hospitalized due to a major osteoporotic fracture. To address this overall aim, two studies were conducted with the following aims: to evaluate the effectiveness, costs, and success of implementation of a nurse-led orthogeriatric co-management program in a tertiary care hospital setting (Part I) and to evaluate the effectiveness and costeffectiveness of systematic collaboration (systematic consultation or integrated care) between surgical and geriatric teams compared to consultation on request, the standard of care in Belgium (Part II).
In Part I, we performed a hybrid type II effectiveness-implementation observational prepost study to evaluate the implementation, effectiveness, and costs of a newly implemented proactive nurse-led orthogeriatric co-management model (G-COMAN) on the trauma ward of the University Hospital Leuven. First, we recruited 108 older patients with a major osteoporotic fracture receiving usual care (reactive geriatric consultation on request). Thereafter, implementation of the G-COMAN intervention started, and a feasibility study was conducted to ensure that the healthcare professionals delivered the intervention as intended, to identify barriers to its adoption, and to generate valuable insights for healthcare professionals aiming to implement orthogeriatric co-management. We conducted a multi-method feasibility study, which demonstrated 1) high fidelity to three out of four program core components and to the majority of the care processes, 2) that healthcare professionals perceived G-COMAN both as feasible and acceptable, and 3) that 32 key implementation determinants influenced uptake. Given these findings, we concluded that G-COMAN was implemented as intended, allowing us to proceed with evaluating its impact on patient outcomes and to start with recruitment of 108 older patients receiving G-COMAN. The primary aim was to determine whether G-COMAN could reduce in-hospital complications for older patients admitted with any type of major osteoporotic fracture compared to standard of care (geriatric consultation on request). Additionally, we evaluated adherence to hospital care processes, secondary outcomes, and costs at discharge. Finally, we examined post-discharge secondary outcomes and secondary fracture prevention measures at 1-, 3-, 6-, and 12-months post-surgery. We observed that this proactive nurse-led orthogeriatric co-management intervention led to a significant decrease of 13% in delirium incidence, although this was not statistically significant after correction for multiple testing, yet in-hospital complication rates remained similar in both groups. Moreover, the broader benefits of this care model were visible, such as improved adherence to geriatric protocols and enhanced patientcentered care compared to reactive geriatric consultation on request. This approach also significantly resulted in lower declines in both iADL scores and cognitive scores at discharge, while maintaining similar costs despite a longer length of stay. While this nurse-led orthogeriatric co-management intervention did not improve overall postdischarge outcomes, it was linked with fewer 30-day readmissions for patients with non-hip fractures and strengthened secondary fracture prevention efforts across fracture types. These findings support the growing recognition that integrating geriatric expertise into non-geriatric wards through structured co-management models like GCOMAN can enhance care processes and secondary fracture prevention while maintaining comparable clinical outcomes and costs to geriatric consultation on request.
In Part II, we performed a retrospective, population-based data registry study to assess the effectiveness and cost-effectiveness of systematic collaboration (i.e., systematic consultation or integrated care) between surgical and geriatric teams for older patients with a major osteoporotic fracture compared to consultation on request, the standard of care in Belgium. Before conducting the data-registry study, a survey was distributed to 95 Belgian hospitals to map six care models, including consultation on request, systematic consultation, and integrated care, implemented either on a surgical or a geriatric ward. We obtained a response rate of 88% (n=84/95). After exclusion of hospitals that did not have one specific care model, we used the data of 8,302 older patients hospitalized with a major osteoporotic fracture in the 60 remaining hospitals. Findings from this real-world, population-based study underscore the benefits of integrated care on a surgical ward, demonstrating that collaboration between surgical and geriatric teams for patients with osteoporotic fractures reduces emergency department visits while maintaining similar length of stay, mortality rates, institutionalization rates, and unplanned readmission rates compared to the standard of care in Belgium, where geriatric consultation is provided upon request on a surgical ward. From a health-economic perspective, surgical consultation on request with admission to a geriatric ward was the most cost-effective model in terms of total adjusted cost per life year survived within one year. However, absolute differences between models were minimal, suggesting comparable health-economic outcomes. These results suggest that while systematic collaboration provides clinical benefits, the optimal organization of orthogeriatric care depends on both clinical outcomes and costeffectiveness considerations. Nonetheless, these results advocate for embedding geriatric expertise into routine surgical care through co-management, leveraging the complementary strengths of both specialties.
In summary, this PhD project highlights the positive impact of orthogeriatric comanagement for older patients with a major osteoporotic fracture. The evaluation of the nurse-led G-COMAN model in a tertiary care hospital showed improved adherence to proactive geriatric protocols, better management of complex needs, and enhanced patient-centered care, while maintaining similar costs. Though post-discharge outcomes remained unchanged, proactive geriatric care improved inpatient functional and cognitive outcomes and strengthened secondary fracture prevention. The population-based study across Belgian hospitals further confirmed the advantages of orthogeriatric co-management, with integrated care on a surgical ward reducing emergency department visits without negatively impacting mortality, institutionalization, or readmission rates. While the choice of the optimal model requires balancing clinical effectiveness and cost-effectiveness, these findings reinforce the growing recognition that embedding geriatric care into routine surgical practice enhances the quality and sustainability of care for older patients with osteoporotic fractures.status: Publishe