735962 research outputs found
Sort by
Speech motor control following surgical treatment for oral cancer:acoustic and kinematic insights
No full textSurgical treatment for tumours in the oral cavity often lead to problems with speech articulation. In this dissertation, we investigated the speech outcomes of speakers who received surgical treatment for oral cancer using a novel method, namely electromagnetic articulography (EMA). EMA is a method whereby small sensors are attached to the tongue, lips, and jaw to measure their movement during speech. The results described in this dissertation show that while tongue mobility decreases after surgery, speakers are able to use the lips and jaw in a compensatory manner. The identification of these compensatory articulatory strategies may be used to design evidence-based speech rehabilitation
Cobalt-mediated mechanical properties in as-deposited Ti alloys:From solid solution to eutectoid strengthening
No full textTo evaluate the influence of the eutectoid-forming element cobalt (Co) on microstructure evolution and mechanical properties of titanium alloys for aerospace applications, a series of Ti-Co alloys with varying Co contents (4.0, 8.4, 12.0 wt%) were designed and fabricated via directed energy deposition (DED). Scanning electron microscopy (SEM) revealed that the as-deposited Ti-4.0Co alloy exhibited continuous grain boundary α-phase, coarse proeutectoid α laths (average width: 9.64 μm), and a fine eutectoid microstructure of α-Ti and Ti2Co phases. Increasing Co to 8.4 wt% induced significant microstructural refinement. Electron backscatter diffraction (EBSD) analysis indicated a 75 % reduction in α-phase size compared to Ti-4.0Co. This refined microstructure in Ti-8.4Co alloy yielded a substantial 27 % increase in yield strength, primarily attributed to synergistic grain boundary and precipitation strengthening, while maintaining reasonable ductility. However, further increasing Co to 12.0 wt% led to continuous segregation of brittle proeutectoid Ti2Co phase along grain boundaries, diminished grain refinement effects, and the formation of coarse Ti2Co precipitates within grains. Although the Ti-12Co alloy achieved an approximate 30 % higher yield strength relative to Ti-4.0Co due to intense precipitation strengthening, its ductility deteriorated severely. Consequently, the Ti-8.4Co alloy demonstrates the optimum balance of strength and ductility among the studied compositions.</p
Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC-4a):results of a randomised, open-label, phase 3, multicentre, non-inferiority trial
No full textBACKGROUND: PORTEC-4a investigated molecular risk profile-based individualised adjuvant treatment for women with high-intermediate risk endometrial cancer, aiming to reduce both overtreatment and undertreatment while optimising locoregional control.METHODS: PORTEC-4a was a randomised, open-label, phase 3, multicentre, non-inferiority trial, conducted across eight European countries. Women (aged ≥18 years and with a WHO performance score of 0-2) with early stage high-intermediate risk endometrial cancer were eligible. Patients were randomly assigned post-surgery in a 2:1 ratio to either adjuvant treatment according to their molecular integrated risk profile or to standard vaginal brachytherapy. Allocation used a biased-coin minimisation with stratification for participating centre, grade, and lymphadenectomy. Adjuvant treatment in the molecular-profile group in case of favourable profile (POLE-mutated or no specific molecular profile [NSMP]-CTNNB1 wildtype) was observation, for intermediate profile (mismatch repair deficient or NSMP-CTNNB1 mutated) was brachytherapy (21 Gy in three fractions of 7 Gy given at 5 to 7 day intervals), and for unfavourable profile (p53 abnormal or substantial lymphovascular space invasion or L1 cell adhesion molecule overexpression) was pelvic radiotherapy (45·0-48·6 Gy in 1·8-2·0 Gy fractions, 5 days per week). The primary endpoint was overall 5-year cumulative incidence of vaginal recurrence as first event. Kaplan-Meier, Cox model, and cumulative incidence with competing risks were used for final analysis in the intention-to-treat population. Patient advocates were involved during grant application and trial conduct. The trial is registered with the Netherlands Trial Registry (NTR5841), the ISRCTN registry (ISRCTN11659025), and ClinicalTrials.gov (NCT03469674), and follow-up is ongoing.FINDINGS: Between June 1, 2016, and Dec 24, 2021, 569 patients were enrolled in PORTEC-4a. After the addition of 23 favourable patients out of PORTEC-4, the final combined PORTEC-4a cohort consisted of 564 eligible and evaluable patients (367 in the molecular profile group and 197 in the standard group). All patients were female, the median age was 69·0 years (IQR 63·0-73·5), and data on race and ethnicity were not collected. Median follow-up was 58·1 months (IQR 40·7-63·6). In the molecular profile group 168 (46%) patients had a favourable profile, 148 (40%) had an intermediate profile, and 51 (14%) had an unfavourable profile. The 5-year cumulative incidence of vaginal recurrence was 4·5% (95% CI 2·23-6·76) in the molecular profile group and 1·6% (0·00-3·32) in the standard group (HR 2·71 [95% CI 0·79-9·34]). The upper-bound of the one-sided confidence interval of the difference (5·3%) was below the predefined-equivalence margin of 7·0% (p non-inferiority=0·005). The second primary analysis in patients with a favourable molecular profile showed 5-year vaginal recurrence of 4·1% (95% CI 0·81-7·37) in the molecular profile group versus 0·9% (0·00-2·78) in the standard group (HR 3·97 [95% CI 0·48-32·95]). Adverse events were mainly grades 1-2, with grade 3 or above related genitourinary toxicities in four (1%) of 367 versus four (2%) of 197, without substantial differences between groups. Five serious adverse events occurred, of which one was possibly related to treatment (vaginal scar dehiscence). No treatment-related deaths occurred. INTERPRETATION: Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment.FUNDING: KWF Dutch Cancer Society.</p
Longa manu en c.p. in het licht van de legitimatieleer en het toedoenbeginsel als grondslagen voor derdenbescherming
No full textDe auteur bespreekt de verschillen in derdenbescherming tussen de levering longa manu en c,p. van roerende zaken, en betoogt dat bij beiden bescherming uit hoofde van art. 3:86 BW niet mogelijk zou moeten zijn
Acute Carotid Stenting for Tandem Lesions in Patients Randomized to Endovascular Treatment With or Without Thrombolysis:Results From the IRIS Individual Participant Data Meta-Analysis
No full textBACKGROUND: Equipoise persists whether patients with stroke with carotid tandem lesions undergoing endovascular treatment (EVT) should undergo acute carotid stenting, and whether intravenous thrombolysis (IVT) before EVT should influence this decision. We assessed functional and safety outcomes of acute carotid stenting in patients with carotid tandem lesions randomized to IVT plus EVT or EVT alone.METHODS: Individual participant data meta-analysis of 6 randomized clinical trials conducted in Asia, Europe, and Oceania between 2017 and 2021 investigating IVT plus EVT versus EVT alone in patients with carotid tandem lesions presenting directly to EVT-capable centers. The primary outcome was the 90-day modified Rankin Scale score, assessed with mixed-effect ordinal regression models. Safety outcomes were any intracranial hemorrhage and symptomatic intracranial hemorrhage. A secondary analysis used inverse probability of treatment weighting. Treatment effect heterogeneity between IVT plus EVT and EVT alone was assessed in a 2-step meta-analysis.RESULTS: Overall, 340 of 2267 (15%) patients had carotid tandem lesions with 113 of 329 (34%) undergoing acute carotid stenting. Stenting was associated with better 90-day functional outcomes (adjusted common odds ratio, 1.60 [95% CI, 1.03-2.47]), confirmed in inverse probability of treatment weighting analysis (adjusted common odds ratio, 1.66 [95% CI, 1.08-2.54]). Patients undergoing stenting had no statistically significant higher rates of any intracranial hemorrhage (44% versus 35%; adjusted odds ratio, 1.30 [95% CI, 0.79-2.15]) and symptomatic intracranial hemorrhage (6.3% versus 3.7%; adjusted odds ratio, 2.09 [95% CI, 0.78-5.59]). No heterogeneity in treatment effect was observed in patients randomized to IVT plus EVT (adjusted common odds ratio, 2.07 [95% CI, 1.06-4.07]) or EVT alone (1.21 [95% CI, 0.59-2.50]; P interaction=0.81). CONCLUSIONS: In this international individual participant data meta-analysis of patients with carotid tandem lesions randomized to EVT alone or IVT followed by EVT, acute carotid stenting during EVT was associated with better functional outcomes, and this association was not modified by prior treatment with IVT.</p
Complex coacervate tissue adhesives: effect of polycation chemistry and ionic strength on cytocompatibility
No full textSpectral decomposition of human BCL2 bonded to a PROTAC
No full textIn this study, we have decomposed the linear infrared spectra and two-dimensional infrared spectroscopy of a VHL-recruiting Proteolysis-targeting chimera (PROTAC) complex with BCL-2 to understand the spectral signatures of this complex. Our findings show that both VHL and BCL-2 units have distinct spectral signatures that contribute to the total spectra in different regions. Furthermore, we observed that the interaction between VHL and BCL-2 within the PROTAC complex leads to unique spectral features, indicating a strong synergistic effect. Through detailed analysis, specific bands were identified that correspond to the vibrational modes of the individual components, as well as their interactive modes within the complex. This study provides valuable insight into the molecular interactions within the PROTAC complex, offering a deeper understanding of its structure and function. These insights could be pivotal in designing more efficient PROTACs for targeted protein degradation in therapeutic applications.</p
Bat-human encounters:Exploring practices of conservation, coexistence and care in urban spaces in the Netherlands
No full textThis thesis explores the dynamic relationships between humans and bats in urban environments in the Netherlands, highlighting how encounters, perceptions, and emotional experiences influence conservation outcomes. While urban wildlife conservation typically focuses on managing species at a broader level, this research emphasizes the emotional, ethical, and spatial aspects of human-bat interactions, areas that have largely been overlooked.The study involves three participant groups: bat advocates, residents, and students, and it utilizes multiple theoretical frameworks. Actor-Network Theory is employed to examine how the interactions among bats, humans, spaces, and technologies shape conservation practices. The Ethics of Care emphasizes empathy, responsibility, and attentiveness in shared living environments, while Compassionate Conservation considers coexistence within the context of design, legislation, and the agency of bats. Environmental Literacy underscores the importance of affective educational practices in promoting understanding and advocacy for urban bat conservation.Through a qualitative approach, the research reveals how emotions, knowledge, and spatial contexts interact to transform traditional conservation models. It demonstrates that bats actively participate in socio-ecological networks and that human-bat relationships are deeply rooted in place-based care and long-term engagement. The thesis advocates for recognizing bats as co-designers of urban spaces and partners in conservation efforts. By integrating human values, bat agency, and relational ethics, it envisions urban conservation as a collaborative, multispecies effort, promoting more inclusive and vibrant city spaces that support diverse forms of life
Faint Object Detection in Multidimensional Astronomical Data
No full textThis thesis addresses the challenges of detecting faint objects in modern astronomical surveys like LSST and Euclid, which produce vast, complex, multi-wavelength datasets. Traditional pixel-based analysis methods struggle with crowded fields, overlapping sources, and variable backgrounds, leading to missed detections and biased measurements.The core innovation is a paradigm shift from pixel-based to hierarchical, structure-aware analysis using the max-tree data structure. This framework organizes an image into nested components based on intensity, preserving topological relationships and the intrinsic geometry of astronomical emissions.Three key contributions are presented. First, a novel method called Multi-band Max-Tree Objects (MMTO) is introduced for multi-spectral source segmentation. It accurately (98%) identifies correlated sources across wavelengths with a 31x computational speed-up, enabling scalable analysis of petabyte-scale surveys. Second, a morphological background model is developed that uses the max-tree to distinguish background light from source emission, yielding more accurate flux measurements than standard tools. Third, a hierarchical deblending algorithm operates on the max-tree to separate overlapping sources without parametric shape assumptions, preserving faint, nested structures.Beyond astronomy, these techniques offer a versatile framework for analyzing complex, multi-scale data in fields like medical imaging and remote sensing. Future work may integrate deep learning and extend the methods for larger datasets. Ultimately, this thesis bridges the gap between data acquisition and discovery by providing robust, scalable tools to explore the faint universe, ensuring scientific rigor in the era of big-data astronomy
Defying the Landlords:Leftwing Radicalism in the Countryside, 1880-1950
No full textRurale gemeenschappen worden in populaire beeldvormingen vaak voorgesteld als conservatieve ecosystemen gehecht aan tradities en bestaande structuren. De geschiedenis van onder andere de Amerikaanse prairies en de Mississippi Delta en de Noord-Nederlandse veen- en landbouwgebieden vertellen echter een ander verhaal. Daar schoot links gedachtegoed wortel aan het eind van de negentiende eeuw