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ProRail als privaatrechtelijk ZBO: Reflecties op een wetsvoorstel
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315498.pdf (Author’s version preprint ) (Open Access)Tweede Kamer: Ronde Tafel ProRail, 23 januari 202
Development and validation of a machine learning-based, point-of-care risk calculator for post-ERCP pancreatitis and prophylaxis selection.
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315829.pdf (Publisher’s version ) (Closed access)BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.01 januari 202
Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study.
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316813.pdf (Publisher’s version ) (Open Access)BACKGROUND: There is an unmet need for high-quality data from prospective studies on the safety and effectiveness of direct oral anticoagulants (DOACs) for the treatment of cerebral venous thrombosis (CVT). We aimed to compare the safety and effectiveness of DOACs versus vitamin K antagonists (VKAs) for the treatment of CVT in a setting that reflects daily clinical practice. METHODS: DOAC-CVT was an international, prospective, observational cohort study done in 65 hospitals in 23 countries across five continents. Eligible patients were adults (aged ≥18 years) with radiologically confirmed CVT starting oral anticoagulant treatment with either DOACs or VKAs, as per local practice, within 30 days after diagnosis. Exclusion criteria were previous use of anticoagulants at the time of CVT diagnosis or an absolute contraindication to DOACs (eg, pregnancy and lactation, or severe renal or liver disease). Data were collected during routine clinical visits or telephone consultations at CVT diagnosis (baseline) and at 3 months, 6 months, and 12 months after CVT diagnosis. The primary endpoint was a composite of symptomatic venous thromboembolism and major bleeding events (International Society on Thrombosis and Haemostasis criteria) at 6 months. Main outcomes were adjusted for the confounders age, renal function, active cancer, CNS infections, concomitant antiplatelet use, country of inclusion's income status, Glasgow Coma Scale score, intracranial haemorrhage, antiphospholipid antibodies, previous major bleeding, and previous venous thromboembolism using inverse probability-of-treatment weighting. This study is registered at ClinicalTrials.gov (NCT04660747) and is ongoing. FINDINGS: Between Jan 27, 2021, and Jan 15, 2024, 619 patients were included; 401 (65%) patients started DOAC treatment, and 218 (35%) patients started VKA treatment. 390 (63%) of 619 patients were female and 229 (37%) of 619 patients were male. Patients' median age was 41 years (IQR 28-51). 6-month follow-up data were available for 617 (>99%) of 619 patients. 12 (3%) of 401 patients in the DOAC group and seven (3%) of 218 patients in the VKA group had a primary outcome event (weighted odds ratio [OR] 0·99 [95% CI 0·37-3·38]). Three (1%) of 401 patients in the DOAC group died versus three (1%) of 218 patients in the VKA group (weighted OR 0·55 [95% CI 0·11-2·80]). INTERPRETATION: The rate of recurrent thrombosis and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. This study adds to the increasing evidence that DOACs are a reasonable treatment option for CVT alongside VKAs. FUNDING: Netherlands Thrombosis Foundation
Towards a sustainable future for plastics: A global material flow and life cycle assessment perspective
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310290.pdf (Publisher’s version ) (Open Access)
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310290 supplementary data.pdf (Publisher’s version ) (Open Access)Plastics are versatile, lightweight, inexpensive, and robust. Because of these properties, they are produced in large quantities and used in all industrial sectors. Despite their positive properties, the use of plastics is also sometimes associated with negative environmental impacts, such as climate change and pollution. Methods for quantifying these negative impacts include spatial pollution modelling, measurements, material flow analysis (MFA), and life cycle assessment (LCA). The advantages of plastics underline the importance of finding good solutions for the negative impacts of their use. First, the negative environmental impacts must be addressed in a comprehensive manner. This requires developing methods (MFA and LCA) for sources of plastic pollution and their impact on a global scale. Second, when applying these methods, the effectiveness of solutions to climate change and pollution must be assessed. This PhD thesis aims to contribute to the assessment of the environmental impact of plastics. This will support decisions for a sustainable future for plastics, where ‘sustainable’ means minimising negative environmental impact from both climate change and pollution.Radboud University, 13 januari 2025Promotor : Huijbregts, M.A.J. Co-promotor : Emmerik, T.H.M. va
Absolute membrane protein abundance of P-glycoprotein, breast cancer resistance protein, and multidrug resistance proteins in term human placenta tissue and commonly used cell systems: Application in physiologically based pharmacokinetic modeling of placental drug disposition.
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315908.pdf (Publisher’s version ) (Open Access)The placenta acts as a barrier, excluding noxious substances while actively transferring nutrients to the fetus, mediated by various transporters. This study quantified the expression of key placental transporters in term human placenta (n = 5) and BeWo, BeWo b30, and JEG-3 placenta cell lines. Combining these results with pregnancy physiologically based pharmacokinetic (PBPK) modeling, we demonstrate the utility of proteomic analysis for predicting placental drug disposition and fetal exposure. Using targeted proteomics with quantification concatemer standards, we found significant expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein (MRP) 2, MRP4, and MRP6 in the human placenta (0.05-0.25 pmol/mg membrane protein) with only regional differences observed for P-gp. Unexpectedly, both P-gp and BCRP were below the limit of quantification in the regularly used BeWo cells, indicating that this cell line may not be suitable for the study of placental P-gp and BCRP-mediated transport. In cellular and vesicular overexpression systems, P-gp and BCRP were detectable as expected. Vesicle batches showed consistent P-gp expression correlating with functional activity (N-methyl-quinidine transport). However, BCRP activity (estrone 3-sulfate transport) did not consistently align with expression levels. Incorporating in vitro transporter kinetic data, along with placental transporter abundance, into a PBPK model enabled the evaluation of fetal exposure. Simulation with a hypothetical drug indicated that estimating fetal exposure relies on the intrinsic clearances of relevant transporters. To minimize interlaboratory discrepancies, expression data was generated using consistent proteomic methodologies in the same lab. Integration of this data in pregnancy PBPK modeling offers a promising tool to investigate maternal, placental, and fetal drug exposure. SIGNIFICANCE STATEMENT: This study quantified the expression of key placental transporters in human placenta and various placental cell lines, revealing significant expression variations. By integrating these data with physiologically based pharmacokinetic modeling, the study highlights the importance of transporter abundance data in understanding and predicting placental drug disposition, essential for maternal and fetal health during pregnancy.01 januari 202
Diagnostic Accuracy of 4D-MRA for the Detection and Localization of Spinal Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis.
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316837.pdf (Publisher’s version ) (Open Access)BACKGROUND: The gold standard for the diagnosis and detailed evaluation of spinal dural arteriovenous fistula (SDAVF) is a digital subtraction angiography (DSA). However, this procedure is time-consuming and effortful. A time-resolved contrast enhanced 4D magnetic resonance angiography (4D-MRA) can be used to increase the diagnostic accuracy of spinal magnetic resonance imaging for the detection and localization of a SDAVF. The goal of this study is to assess the diagnostic accuracy of 4D-MRA for the detection and localization of a SDAVF in comparison to DSA based on a systematic review of the literature. METHODS: We performed a systematic review and meta-analysis on the diagnostic accuracy of 4D-MRA compared to DSA. Literature was reviewed from the PubMed, Cochrane, and EMBASE databases. RESULTS: In comparison with DSA, the pooled sensitivity of MRA was 98.2% (95% confidence interval [CI] 91.5%-99.6%), with a pooled specificity of 88.2% (95% CI 57.5%-97.6%) for the diagnosis of SDAVFs. The side and level of the SDAVFs were correct in 91% (95% CI: 86%-94%) and 76% (95% CI: 71%-80%), respectively. CONCLUSIONS: Current literature indicates that 4D-MRA has a high sensitivity and specificity for the detection and localization of a SDAVF. It can serve to guide DSA to shorten the procedural time, reduce the risk of complications, and decrease patient discomfort.01 januari 202
BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection
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316205.pdf (Publisher’s version ) (Open Access
The Southern Twenty-centimetre All-sky Polarization Survey (STAPS): Survey description and maps (2025)
No full textItem does not contain fulltextWe present data processing and verification of the Southern Twenty-centimetre All-sky Polarization Survey (STAPS) conducted with Murriyang, the Parkes 64-m telescope. The survey covers the sky area of -89{deg}<Dec<0{deg} and the frequency range of 1.3-1.8GHz split into 1-MHz channels. STAPS was observed commensally with the S-band Polarization All-Sky Survey (S-PASS). The survey is composed of long azimuth scans, which allows us to absolutely calibrate Stokes Q and U with the data processing procedure developed for S-PASS. We obtained I, Q, and U maps on both the flux density scale (Jy/beam) and the main beam brightness temperature scale (K), for the 301 frequency channels with sufficiently good data. The temperature scale is tied to the Global Magneto-ionic Medium Survey (GMIMS) high-band north sky survey conducted with the Dominion Radio Astrophysical Observatory 26-m telescope. All the STAPS maps are smoothed to a common resolution of 20'. The root mean square (rms) noise per channel ranges from about 16mK to 8mK for I, and from about 8mK to 5mK for Q and U, at frequencies from 1.3 to 1.8GHz. The rms noise in Q and U varies with declination and reaches minimum at declination of -89{deg}. We also ran rotation measure (RM) synthesis and RM clean to obtain peak polarized intensity and Faraday depth maps. The whole STAPS data processing was validated by comparing flux densities of compact sources, pixel flux density versus pixel flux density for Cen A, pixel temperature versus pixel temperature for the entire survey area, and the RMs of extragalactic sources between STAPS and other measurements. The uncertainty of the flux density scale is less than 10%. STAPS delivers an L-band ({lambda}20cm) multifrequency polarization view of the Galaxy, and will help advance our understanding of the Galactic magnetic field and magnetized interstellar medium
Auditory working memory in noise in cochlear implant users: Insights from behavioural and neuronal measures.
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315961.pdf (Publisher’s version ) (Open Access)OBJECTIVE: We investigated auditory working-memory using behavioural measures and electroencephalography (EEG) in adult Cochlear Implant (CI) users with varying degrees of CI performance. METHODS: 24 adult CI listeners (age: M = 61.38, SD = 12.45) performed the Sternberg auditory-digit-in-working-memory task during which EEG, accuracy, and promptness were captured. Participants were presented with 2, 4, or 6 digits at Signal-to-Noise Ratios (SNR) of 0, +5 and +10dB. They had to identify a probe stimulus as present in the preceding sequence. ANOVA models were used to compare conditions. RESULTS: ANOVA revealed that increasing memory load (ML) led to decreased task performance and CI performance interacted with ML and SNR. Centro-parietal alpha power increased during memory encoding but did not differ between conditions. Frontal alpha power was positively correlated with accuracy in conditions most affected by SNR (r = 0.57, r = 0.52) and theta power in conditions most affected by ML (r = 0.55, r = 0.57). CONCLUSIONS: While parietal alpha power is modulated by the task, it is frontal alpha that relates quantitatively to sensory aspects of processing (noise) and frontal theta to memory load in this group of CI listeners. SIGNIFICANCE: These results suggest that alpha and theta show distinct relationships to behaviour, providing additional insight into neurocognitive (auditory working-memory) processes in CI users.01 februari 202
Understanding patterns of engagement in the citizen humanities. The civil records of Suriname
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312105.pdf (Publisher’s version ) (Open Access)16 p