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Optical genome mapping enables accurate testing of large repeat expansions.
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318763.pdf (Publisher’s version ) (Open Access)Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed PCR and Southern blotting, are often labor-intensive, locus-specific, and are unable to precisely determine long repeat expansions. Sequencing-based methods, although capable of genome-wide detection, are limited by inaccuracy (short-read technologies) and high associated costs (long-read technologies). This study evaluated optical genome mapping (OGM) as an efficient, accurate approach for measuring STR lengths and assessing somatic stability in 85 samples with known pathogenic repeat expansions in DMPK, CNBP, and RFC1, causing myotonic dystrophy types 1 and 2 and cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), respectively. Three workflows-manual de novo assembly, local guided assembly (local-GA), and a molecule distance script-were applied, of which the latter two were developed as part of this study to assess the repeat sizes and somatic repeat stability. OGM successfully identified 84/85 (98.8%) of the pathogenic expansions, distinguishing between wild-type and expanded alleles or between two expanded alleles in recessive cases, with greater accuracy than standard of care (SOC) for long repeats and no apparent upper size limit. Notably, OGM detected somatic instability in a subset of DMPK, CNBP, and RFC1 samples. These findings suggest OGM could advance diagnostic accuracy for large repeat expansions, providing a more comprehensive genome-wide assay for repeat expansion disorders by measuring exact repeat lengths and somatic instability across multiple loci simultaneously
Structured Randomness
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320377.pdf (Publisher’s version ) (Open Access)Imagine I want to send you a message over an insecure channel, such as the public Internet. I do not want anyone other than you to be able to learn its content. To achieve that, you and I share a secret and use it to transform the message in a way that is unpredictable to anyone who does not know the secret.
A natural idea is to pick a transformation at random and let the secret be that random choice. But describing such a choice requires far too many symbols to be practical. Instead, we build a transformation that relies on a much smaller amount of randomness, yet still looks as if it were chosen completely at random.
This thesis explores how such transformations are constructed and how their security can be assessed. It presents several analyses of the building blocks used in modern cryptographic design and takes a closer look at their underlying structure. It also introduces two new designs, each suited to different practical needs, that aim to strike the right balance between structure and randomness.Radboud University, 03 juli 2025Promotor : Daemen, J.J.C.ix, 217 p
Roadmap on quantum magnetic materials
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321166.pdf (Publisher’s version ) (Open Access
Terugvordering van uitkering en verdragsrechtelijk eigendomsrecht
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Validating candidate endpoints for intermediate age-related macular degeneration trials in a multi-centre setting-lessons from the MACUSTAR study
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320860.pdf (Publisher’s version ) (Open Access)For the conduct of future interventional age-related macular degeneration (AMD) trials, the availability of clinical study endpoints is key. However, no endpoints have been accepted by regulators for evaluation of treatment for intermediate (i) AMD, i.e. the AMD stage at highest risk of developing irreversible geographic atrophy or macular neovascularization. The European MACUSTAR consortium has recruited more than 700 individuals to develop and validate structural, functional and patient-reported endpoints, enabling future iAMD trials based on a prospective observational, multi-centre cohort study. Reliably assessing candidate endpoints in a setting that involves multiple clinical sites across countries comes with a plurality of challenges in the study set-up, quality of data, recruitment of participants and study conduct. Therefore, the MACUSTAR consortium has established a framework that successfully addresses these topics, provides relevant insights into the natural history of iAMD and its sub-phenotypes, and will open new regulatory pathways. The MACUSTAR study is registered on ClinicalTrials.gov under NCT03349801
Current use of donor lymphocyte infusions after allogenic stem cell transplantation in Europe: a survey on behalf of the cellular therapy and immunobiology working party of the EBMT
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319108.pdf (Publisher’s version ) (Open Access)23 maart 20255 p
Preventieve inzet bestuursrecht bij demonstraties. Onrechtmatig en ongewenst. Reactie op 'Van repressie naar preventie. een bestuursrechtelijk perspectief op demonstraties
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319889.pdf (Publisher’s version ) (Open Access)3 p
The structures that matter. Identifying relevant syntactic units for the study of L2 French phraseology
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320334.pdf (Publisher’s version ) (Open Access)15 p
Impact of Continuation Versus Interruption of Oral Anticoagulation During TAVI on Health-Related Quality of Life.
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319231.pdf (Publisher’s version ) (Closed access)BACKGROUND: One-third of patients undergoing TAVR have a concomitant indication for oral anticoagulation. The impact of continuation as compared to interruption of oral anticoagulation during TAVR on health-related quality of life is unknown. AIMS: To investigate the impact of continuation as compared to interruption of oral anticoagulation on health-related quality of life. METHODS: The POPular PAUSE TAVI (Periprocedural Continuation vs. Interruption of Oral Anticoagulant Drugs during Transcatheter Aortic Valve Implantation) trial was an international, open-label, randomized, clinical trial performed at 22 European sites. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Short Form-12 (SF-12) before, and at 1 and 3 months after TAVR. RESULTS: A total of 8 patients were included: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. Before TAVR, the mean overall KCCQ summary score was 53.6 (±26.0). At 1 month, the mean change in KCCQ summary score as compared to baseline was +11.4 points (95% confidence interval [CI] 8.0-14.8) in the continuation group and +12.2 points (95% CI 8.8-15.6) in the interruption group (difference -0.7 points; 95% CI -4.6 to 3.1). At 3 months, the mean change was +11.0 points (95% CI 7.3-14.6) versus +13.8 points (95% CI 10.2-17.4), respectively (difference -2.8 points; 95% CI -7.1 to 1.5). Mean changes in SF-12 physical and mental component summary scores showed no differences between both groups at 1 and 3 months after TAVR. CONCLUSIONS: In patients undergoing TAVR with a concomitant indication for oral anticoagulation, continuation as compared to interruption of oral anticoagulation during TAVR did not significantly impact health-related quality of life up to 3 months after TAVR
Preoperative physical resilience indicators and their associations with postoperative outcomes.
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320546.pdf (Publisher’s version ) (Open Access)The health benefit of surgery in older adults may be outweighed by negative effects on cognitive or physical function. Physical resilience is defined as the potential for recovery after a stressor such as surgery. We assessed associations between physical resilience measured by orthostatic blood pressure (BP) and cerebral oxygenation recovery or grip work (sustained hand grip strength; GW) and postoperative outcome in two cohorts of (older) surgical patients. The first cohort (CTC) consisted of patients undergoing complex cardiothoracic surgery. The second cohort (GRR) held geriatric outpatients undergoing various surgical procedures. Outcome measures were length of stay (LoS) and postoperative complications. Negative binomial (LoS) and ordinal (complications) regression models were used to determine associations. 261 patients (113 CTC and 148 GRR) underwent surgery. Median LoS was 10 (CTC) and 5 days (GRR). Postoperative complications occurred in 80% (CTC) and 45% (GRR) of patients. In CTC, 10 mmHg higher systolic BP recovery was associated with a 12% shorter LoS (incidence rate ratio (IRR) 0.88 (95% CI 0.78-0.98)). 10 s longer sustained hand grip was associated with a 5% shorter LoS in GRR (IRR 0.95 (0.90-1.00)), but a 7% longer LoS in CTC (IRR 1.07 (1.03-1.11)). No significant associations were found with postoperative complications. Orthostatic cerebral oxygenation recovery in CTC was not significantly associated with any postoperative outcome. Our results imply that resilience indicators might be associated with LoS after surgery. Future research should seek to replicate our findings and investigate whether adding resilience parameters to preoperative assessment can support postoperative outcome prediction.01 juni 202