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Characteristics and Outcomes of 1500 Lung Transplantations in the Leuven Lung Transplant Program: Turning Past Lessons Into Tomorrow's Foundations
No full textLung transplantation has become an established life-saving treatment for selected patients with end-stage pulmonary disease. In December 2024, our center reached the milestone of 1,500 lung transplants, providing an opportunity to evaluate long-term trends, outcomes, and challenges. We analyzed donor and recipient demographics, procedural evolution, and graft survival. Contemporary guidelines and consensus recommendations were also reviewed to contextualize current practice and highlight unmet needs. Median graft survival improved markedly across eras: 3.5 years between 1991 and 2000, 9.9 years between 2001 and 2010, and 11.2 years between 2011 and 2020 (p < 0.0001). Shifts in procedure type, donor selection, and transplant indications mirrored broader developments in the field (all p < 0.0001). Donor and recipient age increased significantly over time, with older recipients experiencing poorer long-term outcomes. Despite these advances, chronic lung allograft dysfunction (CLAD) remains the most important barrier to durable success, with median CLAD-free survival of 6.7 years in the modern era (2010-2024) and a retransplantation rate of 4%. While survival now exceeds a decade in many recipients, extended longevity presents new challenges, including management of comorbidities and optimization of CLAD prevention, treatment, and retransplantation strategies. Continued translational research and evidence-based approaches remain critical to improving long-term results.sponsorship: The author(s) declare that financial support was received for the research and/or publication of this article. AZ is supported by a Transplant Fellowship of the European Society for Organ Transplantation (ESOT). LC is supported by research foundation Flanders (FWO) as a Senior Clinical Researcher (18E2B24N) and by a University chair supported by Medtronic. RV is supported by research foundation Flanders (FWO) as a Senior Clinical Researcher (1803521N) and by a research grant (G060322N). (Transplant Fellowship of the European Society for Organ Transplantation (ESOT), Research foundation Flanders (FWO)|1803521N, Research foundation Flanders (FWO)|G060322N, Research foundation Flanders (FWO)|18E2B24N, Medtronic)status: Publishe
De Dual Active Bridge-omzetter in toekomstige geëlektrificeerde systemen: een vrijheidsgraden- en uitbreidingsbenadering
No full textFuture electrified systems will require either or both high efficiency and high power density. Nevertheless, achieving these goals is not limited to nominal power or traditional operating conditions. Instead, maintaining high efficiency across varying load and voltage conditions will be critical, as modern and emerging applications inherently experience power fluctuations. For instance, in renewable energy generation, power levels change due to meteorological variations, while in electrified transportation, optimizing battery energy usage is important because even a small energy saving can significantly impact the performance, influencing driving/flying range and or oil consumption. This requirement becomes even more stringent in hybrid aerospace vehicles, where power density directly affects fuel efficiency.
The backbone components of these systems are called power electronic converters. Research and development in this field are essential, as the entire system's efficiency depends on them. Driven by ambitious (if not imperative) targets such as net-zero emissions and the increasing demand for energy-efficient applications, power converters must continue evolving. However, rather than completely replacing existing technologies, improving and optimizing traditional converters can help minimize electronic waste and extend their usability.
A highly used converter, the Dual Active Bridge (DAB), was introduced back in the 80s for high-power-density aerospace applications. Its widespread adoption is justified by its performance of minimal switching losses, high voltage gain, and intrinsic safety features enabled by its high-leakage transformer and active bridge implementation. However, when operated using conventional control strategies, the DAB can not maintain its efficiency under light-load conditions. Research efforts have taken two primary approaches to address this issue: developing alternative topologies that compete with the DAB or completely changing its control parameters. Despite various improvements that have been proposed, industrial adoption remains limited due to the mathematical complexity of these approaches and their reliance on nonlinear or discontinuous parameter modifications.
This thesis aims to study several degrees of freedom of the DAB and the expansions proposed in the state of the art, aiming to deliver power at different load levels while maintaining high efficiency, even when operating below their optimal operation point. It also proposes modeling strategies based on artificial intelligence and Fourier component generalization, which help speed up the analysis of the converters handling multiple loads and having high degrees of freedom. Finally, certain topological modifications are proposed for study, providing a detailed comparative analysis. Technological improvements are addressed, including the implementation of variable magnetic devices and novel wide band gap devices. The thesis attempts to push the use of this converter and not discard it yet for future applications; the authors are convinced that the DAB and other old technologies can benefit from the methodology proposed to continue using them from a recycling/keep-using perspective in future applications.status: Publishe
PROTEASEN EN MACROFAGEN - HUN INTERACTIE TIJDENS INFLAMMATIE
No full textNeuroinflammation is characterized by the activation of brain cells and local release of mediators following an inflammatory challenge. When persisting, it leads to demyelination of the central nervous system (CNS), a prevalent process in multiple sclerosis or acquired CNS demyelinating syndromes. Several studies have implicated extracellular proteases and their endogenous regulators, including broad spectrum inhibitors, specific inhibitors, inducers and clearance receptors in neuroinflammation and neurodegeneration. We hypothesize that during neuroinflammation, these molecules and their interplay with proteolytic enzymes can determine disease outcomes, such as the occurrence of onset/relapse and remission phases in MS. We will investigate extracellular protease regulation mechanisms in microglia and (brain-infiltrating) macrophages in in vitro and in vivo models for neuroinflammation and demyelination, and we will validate our obtained results in samples from patients with CNS demyelinating disorders. The outcome of the proposed research has the potential for discovery of new disease targets and diagnostic or prognostic markers.status: Publishe
Eppur si eclissa: Eccentric low-mass companions and time-in-dust selection to explain long secondary periods
No full textsponsorship: L.D., M.E., F.D. and C.L. acknowledge support from the KU Leuven C1 excellence grant BRAVE C16/23/009, KU Leuven Methusalem grant SOUL METH/24/012, and the FWO research grants G099720N and G0B3823N. L.D. acknowledges support from the FWO sabbatical grant and O.V. from the FWO PhD grant 1173025N. D.M.S. and D.D. acknowledge support from the European Union (ERC, LSP-MIST, 101040160). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. (G099720N, G0B3823N, 1173025N, C16/23/009, METH/24/012, LSP-MIST, 101040160)status: Published onlin
Rapid increase in serotype 4 invasive pneumococcal disease among vulnerable young male adults in Belgium (2020-2024)
No full textOBJECTIVES: Invasive pneumococcal disease (IPD) remains a significant global health threat. Although pneumococcal conjugate vaccines have considerably reduced the burden of IPD after their implementation, changes in serotype distribution do occur. This study examines the epidemiology of serotype 4 IPD in Belgium from 2007 to 2024, focusing on a recent and pronounced increase in cases. The aim is to identify and characterize high-risk populations. METHODS: Epidemiologic data from the passive laboratory-based IPD surveillance, as conducted by the national reference center for invasive pneumococci at UZ Leuven, were used to study the evolution of serotype 4 IPD over time. Because clinical and behavioral data are lacking in the nationwide surveillance, this was complemented with a multicenter sub-analysis for 248 serotype 4 cases (2020 to mid-2024), which represented 61% of all serotype 4 IPD cases within that period. Patient records were retrospectively consulted, and information was captured in REDCap. RESULTS: A notable resurgence of serotype 4 IPD cases was noticed, beginning in 2020 and peaked in 2023 as the third most common serotype causing IPD in Belgium. This increase was primarily seen among young adult males (18-49 years old) residing in large urban areas (Brussels Capital Region, Antwerp, Liège, Namur, and Hainaut). The sub-analysis revealed that a high proportion of these patients were unemployed (60.9%), experienced homelessness or unstable housing (30.2%), and reported substance use (72.6%). Tobacco (63.3%) and heavy alcohol consumption (35.1%) were the most reported, whereas a subgroup used hard drugs (26.6%). CONCLUSION: This study identifies a specific population of vulnerable adults at risk for serotype 4 IPD, emphasizing the need for a specific prevention strategy. Vaccination of this risk group with a pneumococcal vaccine targeting serotype 4 is needed to reduce the increasing burden of invasive disease caused by this vaccine serotype.sponsorship: As a national reference center for invasive pneumococci, we are supported by the public health institute Sciensano (through the Funding of RIZIV/INAMI) and are gratefully acknowledged. Nicolas Dauby is clinical researcher of the F.R.S-FNRS. (Public health institute Sciensano (RIZIV/INAMI))status: Accepte
Fotoresist metrologie voor hoge numerieke apertuur (NA) extreme ultraviolet lithografie (EUVL)
No full textThe transition to High Numerical Aperture Extreme Ultraviolet Lithography (High NA EUVL) necessitates the use of ultra thin photoresists (<30 nm) to achieve the patterning requirements. While enabling pattern fidelity at small pitches, thin resists pose significant challenges for electron beam metrology, particularly in critical dimension scanning electron microscopy (CDSEM). Reduced imaging contrast, lower signal-to-noise ratio (SNR), and beam-induced effects, such as charging and shrinkage, degrade the accuracy, precision and throughput of critical dimensions (CD), roughness, and other measurands for the wide array of lithographic features of interest.
This thesis investigates the origin of contrast degradation in thin resist stacks, quantifies materials and thickness dependent effects, and develops methodologies to enhance metrology performance. Monte Carlo simulations are combined with experimental measurements to provide comprehensive understanding. For thin resists in the range of 15 nm, both the resist and underlayer properties strongly influence the imaging contrast. Experimental yield curves are measured, and show a higher metal oxide resist (MOR) yield compared to chemically amplified resist (CAR), thus confirming the superior visibility of MOR when imaged using CDSEM.
Different strategies are explored to overcome those SNR limitations present in low visibility resists. First, switching to low voltage SEM (LVSEM) can enhance the contrast in some stacks, but it requires careful optimization to balance the charging and shrinkage effects. Second, machine learning denoising techniques, either supervised or unsupervised, enable accurate roughness extraction from images captured with low number of frames, matching the images captured with a higher number of frames (hence 16 times improved throughput). Third, using high probe current can also increase the emitted signal and improve unbiasing fidelity, as shown by using power spectral density (PSD) analysis matching methodology between two CDSEMs with different columns design. Those strategies are compared to the existing standard benchmark criteria, stating that the SNR should be above 2 to ensure the reliable roughness extraction, and the measurement precision should be below 1% of the measured CD value itself. These criteria are applied to the above strategies to benchmark them to the existing approaches.
Considering other features, besides line and spaces (LS), such as contact hole (CH) and tip-to-tip (T2T), metrology becomes more complex for such features. For contact holes, optimal scanning strategies, beam energies, and complementary metrology confirm the interplay between charging, shrinkage, and feature profile effects, paving the way to the use of new measurement approaches such as the random measurement acquisition (RMA). Monte Carlo simulations support these findings and shows material-dependent charge polarity reversal induced by beam energy. T2T features exhibit intrinsically higher variability, with measurement and process conditions, such as pixel size, resist thickness, and post exposure bake (PEB) temperature, all significantly influencing LCDU. Analysis of variance across lithographic conditions identifies key contributors to T2T variability, including stochastic effects, mask contributions, and metrology limitations.
The findings of this thesis provide both fundamental understanding of thin resist electron e-beam interactions and practical strategies for enhancing CDSEM metrology in the High NA EUVL era. The proposed approaches combining material-based process optimization/investigation, hardware tuning, simulations, and artificial intelligence (AI)-enabled image enhancement allow accurate, efficient, and low-dose measurements, ultimately supporting the reliable characterization of scaled resist features for the next generation semiconductor manufacturing.status: Publishe
Dislocation and repair after nuclear accidents: The discursive struggle over nuclear power in Belgium in the wake of Three Mile Island, Chernobyl and Fukushima
No full textSince the early 1970s, the use of nuclear power to generate electricity has been the subject of ongoing public controversy. These debates about energy provision are rooted in a deeper clash between hegemonic and counterhegemonic worldviews regarding an energy-intensive society and, ultimately, humanity's relationship with the natural environment. This clash becomes especially pronounced after nuclear accidents. Large-scale accidents are interesting case studies because they put the technology's advocates on the defensive while providing its opponents with opportunities to challenge the status quo. This article presents a discourse-theoretical analysis of the public debate in Belgium following three such accidents: Three Mile Island (1979), Chernobyl (1986), and Fukushima (2011). The analysis identifies three discursive strategies for handling the accidents discursively, each with its own implications with regard to maintaining the status quo or pursuing social change. The first strategy protects the technology by focusing narrowly on the affected reactors and suggesting that the accidents are exceptional misfortunes without deeper implications. The second strategy allows discussion of the technology's societal desirability, but avoids scrutiny of the underlying worldview. The third strategy most radically challenges the status quo by representing nuclear accidents as emblematic of humans' problematic relationship with their natural environment. This shows that the debate on nuclear power is ultimately a deeper conflict between competing worldviews regarding humans' relationship with their socio-ecological nvironment. The article concludes that the mechanisms of discursive struggle identified in this nuclear power case study are relevant to debates on energy and complex technologies more broadly.status: Published onlin
A scalable tool for fast and flexible variant identification in mass spectrometry Mass spectrometry
No full textstatus: Published onlin
An international placebo-controlled randomized multicenter trial of nimorazole with accelerated chemo-radiotherapy for locally advanced HPV-negative squamous cell carcinoma of the head and neck (HNSCC)
No full textPURPOSE: To evaluate the benefit of the hypoxic radiosensitizer nimorazole (NIM) with accelerated concomitant chemo-radiotherapy in patients with advanced squamous cell carcinoma of the head and neck (HNSCC). MATERIALS AND METHODS: Patients with stage III-IV laryngeal, hypopharyngeal or HPV-negative oropharyngeal SCC were randomized between NIM or placebo, given concomitantly with moderately accelerated chemo-radiotherapy delivered using IMRT (70 Gy in 6 weeks). Total cisplatin dose was 200 mg/m2 either weekly (40 mg/m2) or 3-weekly (100 mg/m2). NIM/placebo was given with 1.2 mg/m2 daily. RESULTS: Between Aug 2014 and Jan 2018, when the trial closed prematurely, a total of 194 patients (92 oropharynx, 59 hypopharynx and 43 larynx) were randomized (97 NIM, 97 placebo) out of 640 planned. Most patients had T3-T4 (76%) and N2-3 (66%) tumors. The three-year incidence of locoregional failure was 20.7% (95% Cl: 12.8-29.8) in the NIM arm and 33.8% (24.1-43.8) in the placebo arm. Corresponding disease specific survival were 76.7% and 74.3% and overall survival 62.4% and 61.5% for NIM and placebo, respectively. Multivariable analysis demonstrated significant locoregional benefit of NIM (adjusted HR 0.51; 95% Cl: 0.27-0.95) together with good WHO performance and weekly cisplatin. Compliance with treatment did not differ significantly depending on NIM/placebo allocation and cisplatin regimen, nor did treatment related morbidity except for acute nephrotoxicity which appeared to be higher in the 3-weekly cisplatin regimen. CONCLUSION: NIM improved locoregional control in advanced HPV-negative HNSCC, but without significant survival improvement. This finding underscore that hypoxic radiosensitization plays a role in chemo-radiotherapy for HNSCC. The incompleteness of the study precluded further detailed analysis.sponsorship: This trial benefited from a research grant from Azanta A/S, Denmark. (Azanta A/S, Denmark)status: Accepte
Use of advanced technology for the treatment of type 1 diabetes in pregnancy
No full textAutomated insulin delivery (AID) systems have led to a paradigm shift for the management of type 1 diabetes outside pregnancy. As more women use AID at preconception, it is important to have data on the efficacy and safety of AID systems in pregnancy. A large randomized controlled trial (RCT) with the CamAPS® FX showed a 10 % increase in time in range compared to standard insulin therapy in pregnant women with type 1 diabetes. The CamAPS® FX is currently the only AID approved for use in pregnancy. An RCT with the MiniMed™ 780 G demonstrated additional benefits compared to standard insulin therapy. Recent data suggest that AID can be safely continued during labor and postpartum. It is yet unclear whether AID use can improve maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and postpartum.sponsorship: Acknowledgments KB received a fundamental clinical investigatorship from FWO Flanders (1800220N) . (FWO Flanders|1800220N)status: Publishe