Showing papers by "Radboud University Nijmegen published in 2023"

Neurological recovery after early versus delayed surgical decompression for acute traumatic spinal cord injury

Abstract: Aims The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Methods Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months. Results The final analyses comprised 159 patients in the early and 135 in the late group. Patients in the early group had significantly more severe neurological impairment before surgical treatment. For unadjusted complete-case analysis, mean change in LEMS was 15.6 (95% confidence interval (CI) 12.1 to 19.0) in the early and 11.3 (95% CI 8.3 to 14.3) in the late group, with a mean between-group difference of 4.3 (95% CI -0.3 to 8.8). Using multiply imputed data adjusting for baseline LEMS, baseline ASIA Impairment Scale (AIS), and propensity score, the mean between-group difference in the change in LEMS decreased to 2.2 (95% CI -1.5 to 5.9). Conclusion Compared to late surgical decompression, early surgical decompression following acute tSCI did not result in statistically significant or clinically meaningful neurological improvements 12 months after injury. These results, however, do not impact the well-established need for acute, non-surgical tSCI management. This is the first study to highlight that a combination of baseline imbalances, ceiling effects, and loss to follow-up rates may yield an overestimate of the effect of early surgical decompression in unadjusted analyses, which underpins the importance of adjusted statistical analyses in acute tSCI research. Cite this article: Bone Joint J 2023;105-B(4):400–411.

The thickness dependence of quantum oscillations in ferromagnetic Weyl metal SrRuO3

Abstract: Abstract In a thin Weyl semimetal, a thickness dependent Weyl-orbit quantum oscillation was proposed to exist, originating from a nonlocal cyclotron orbit via electron tunnelings between top and bottom Fermi-arc surface states. Here, magneto-transport measurements were carried out on untwinned Weyl metal SrRuO 3 thin films. In particular, quantum oscillations with a frequency F s1 ≈ 30 T were identified, corresponding to a small Fermi pocket with a light effective mass. Its oscillation amplitude appears to be at maximum for thicknesses in a range of 10 to 20 nm, and the phase of oscillation exhibits a systematic change with film thickness. The constructed Landau fan diagram shows an unusual concave downward curvature in the 1/ μ 0 H n - n curve, where n is the Landau level index. From thickness and field-orientation dependence, the F s1 oscillation is attributed to be of surface origin. Those findings can be understood within the framework of the Weyl-orbit quantum oscillation effect with non-adiabatic corrections.

A vibrational action spectroscopic study of the Renner–Teller- and spin–orbit-affected cyanoacetylene radical cation HC₃N⁺

Abstract: The linear radical cation of cyanoacetylene, HC 3 N + ( 2 Π), is not only of astrophysical interest, being the, so far undetected, cationic counterpart of the abundant cyanoaceteylene, but also of fundamental spectroscopic interest due to its strong spin–orbit and Renner–Teller interactions. Here, we present the first broadband vibrational action spectroscopic investigation of this ion through the infrared pre-dissociation (IRPD) method using a Ne tag. Experiments have been performed using the FELion cryogenic ion-trap instrument in combination with the FELIX free-electron lasers and a Laservision optical parametric oscillator/optical parametric amplifier system. The vibronic splitting patterns of the three interacting bending modes ( ν 5 , ν 6 , ν 7 ), ranging from 180 to 1600 cm −1 , could be fully resolved revealing several bands that were previously unobserved. The associated Renner–Teller and intermode coupling constants have been determined by fitting an effective Hamiltonian to the experimental data, and the obtained spectroscopic constants are in reasonable agreement with previous photoelectron spectroscopy (PES) studies and ab initio calculations on the HC 3 N + ion. The influence of the attached Ne atom on the infrared spectrum has been investigated by ab initio calculations at the RCCSD(T)-F12a level of theory, which strongly indicates that the discrepancies between the IRPD and PES data are a result of the effects of the Ne attachment.

Fast Degradable Calcium Phosphate Cement for Maxillofacial Bone Regeneration

Abstract: The aim of this preclinical study was to test the applicability of calcium phosphate cement (CPC)-poly(lactic-co-glycolic acid) (PLGA)-carboxymethylcellulose (CMC) as a bone substitute material for guided bone regeneration (GBR) procedures in a clinically relevant mandibular defect model in minipigs. In the study, a predicate device (i.e., BioOss®) was included for comparison. Critical-sized circular mandibular bone defects were created and filled with either CPC-PLGA-CMC without coverage with a GBR membrane or BioOss covered with a GBR membrane and left to heal for 4 and 12 weeks to obtain temporal insight in material degradation and bone formation. Bone formation increased significantly for both CPC-PLGA-CMC and BioOss with increasing implantation time. Further, no significant differences were found for bone formation at either 4 or 12 weeks between CPC-PLGA-CMC and BioOss. Finally, bone substitute material degradation increased significantly for both CPC-PLGA-CMC and BioOss from 4 to 12 weeks of implantation, showing the highest degradation for CPC-PLGA-CMC (∼85%) compared to BioOss (∼12%). In conclusion, this minipig study showed that CPC-PLGA-CMC can be used as a bone-grafting material and stimulates bone regeneration to a comparable extent as with BioOss particles. Importantly, CPC-PLGA-CMC degrades faster compared to BioOss, is easier to apply into a bone defect, and does not need the use of an additional GBR membrane. Consequently, the data support the further investigation of CPC-PLGA-CMC in human clinical trials. Guided bone regeneration (GBR) is a frequently used dental surgical technique to regenerate the alveolar ridge to allow stable implant installation. However, stabilization of the GBR membrane and avoidance of bone graft movement remain a challenge. Consequently, there is need for the development of alternative materials to be used in GBR procedures that are easier to apply and induce predictable bone regeneration. In this minipig study, we focused on the applicability of calcium phosphate cement-poly(lactic-co-glycolic acid)-carboxymethylcellulose as an alternative bone substitute material for GBR procedures without the need of an additional GBR membrane.

Molecular Engineering of pH-Responsive Anchoring Systems onto Poly(ethylene glycol) Corona

Abstract: An adaptive surface that can sense and respond to environmental stimuli is integral to smart functional materials. Here, we report pH-responsive anchoring systems onto the poly(ethylene glycol) (PEG) corona of polymer vesicles. The hydrophobic anchor, pyrene, is reversibly inserted into the PEG corona through the reversible protonation of its covalently linked pH-sensing group. Depending on the pKa of the sensor, the pH-responsive region is engineered from acidic to neutral and basic conditions. The switchable electrostatic repulsion between the sensors contributes to the responsive anchoring behavior. Our findings provide a new responsive binding chemistry for the creation of smart nanomedicine and a nanoreactor.

Casting shadows: later-life outcomes of stature

Abstract: The central question in this special issue is a relatively new one in anthropometric history: how did body height affect the life course? This raises the issue of whether such an effect merely captures the underlying early-life conditions that impact growth, or whether some independent effect of stature can be discerned. Further, the effects of height on later-life outcomes need not be linear. These effects may also differ by gender, by context (time and place), and among life course domains such as occupational success, family formation or health in later life. The ten research articles in this issue use a plethora of historical sources on individuals, such as prison and hospital records, conscript records, genealogies and health surveys. These articles employ a variety of methods to distinguish between early-life and later-life effects, between intra- and intergenerational processes and between biological and socio-economic factors. Importantly, all articles discuss the impact of the specific context on their results to understand these effects. The overall conclusion is that independent later-life outcomes of height are rather ambiguous, and seem to stem more from the perception of physical strength, health and intelligence associated with height than from height itself. This special issue also reflects on intergenerational effects of the later-life outcomes of height. As populations have grown taller, it is possible that height and later-life outcomes have formed a ‘virtuous cycle’, resulting in taller, healthier and wealthier populations. So far, however, our research offers little support for this hypothesis.

Discovering a pregnancy after 30 weeks: a qualitative study on explanations for unperceived pregnancy

Abstract: “Unperceived pregnancy” names the phenomenon when a person becomes pregnant unintentionally and is not aware of being pregnant. Scientific explanations are roughly based on two hypotheses: psychological and physiological. We aim to gain a better understanding of unperceived pregnancy by studying the perspectives of people who experienced an unperceived pregnancy and obstetric professionals. Seventeen semi-structured interviews were conducted: eight with women who had experienced an unperceived pregnancy (≥30 weeks’ gestation), six with midwives, and three with gynecologists. Our findings show that women’s explanations for not noticing their pregnancy center around the absence of pregnancy symptoms. The failure to recognize more subtle signs of pregnancy was enforced by inattention, physical distractions, and psychological factors. In contrast, psychological explanations are dominant among obstetric professionals. Our study demonstrates a discrepancy in the explanations provided by women who had experienced an unperceived pregnancy and obstetric professionals. Potentially, this could result in people being unheard and misunderstood. We recommend that future research moves beyond a focus on “denial of pregnancy” to consider both psychological and physiological factors, and how these could potentially interrelate. This broadened approach will enhance our understanding of unperceived pregnancy and can contribute to improved counseling by obstetric professionals.

1 Placental pharmacology studies to characterize the effects and disposition of pharmaceuticals: lessons from human tissues and cells for improving drug safety in pregnancy

Abstract: The placenta plays a key role in maintaining a healthy pregnancy. In order to improve drug safety during pregnancy, it is therefore relevant to understand to which extent and at which rate drugs are transferred across the placenta and how pharmaceuticals may affect placental function. Translational and predictive pharmacology studies based on human tissues and cells are becoming increasingly important in characterizing the effects and disposition of pharmaceuticals. With regard to the placenta, such approaches may for example be readily combined with physiology-based pharmacokinetic (PBPK) modeling to predict fetal exposure of drugs, as well as placental tissue exposure in the clinic. In addition, placental tissue and cells can be used to study potential effects of drugs, as well. The current presentation, will highlight several studies that investigated the placental disposition and effects of both small and large molecule pharmaceuticals, as well as how such data can help to better understand the clinical pharmacology of therapeutics.

Calculating Required Purification Effort to Turn Source Water Into Drinking Water Using an Adapted CCME Water Quality Index

Abstract: The 2000 European Union Water Framework Directive (WFD) states that “Member States shall ensure the necessary protection for the bodies of water identified with the aim of avoiding deterioration in their quality in order to reduce the level of purification treatment required in the production of drinking water.” However, it does not specify how to evaluate or quantify this level of purification treatment. We propose a novel water quality index (WQI) to quantify the level of purification treatment required to prepare drinking water from source water. It is based on the WQI of the Canadian Council of Ministers of the Environment (CCME WQI). Our WQI compares measured contaminant concentrations in source water to drinking water guidelines and any exceedance is weighted by a measure of the resilience of that contaminant to the treatment processes, which is not possible in the CCME WQI. Furthermore, it accommodates for varying sampling frequencies that are characteristic of the ongoing monitoring program. These adaptations make our index robust and sensitive to relevant changes in source water quality. We calculated index scores for source water from the Rhine and the Meuse and found no general decrease in required purification treatment levels since the introduction of the WFD.

Cerebrospinal Fluid Panel of Synaptic Proteins in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Abstract: Background: Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) share pathogenic pathways related to amyloid-β deposition. Whereas AD is known to affect synaptic function, such an association for CAA remains yet unknown. Objective: We therefore aimed to investigate synaptic dysfunction in CAA. Methods: Multiple reaction monitoring mass spectrometry was used to quantify cerebrospinal fluid (CSF) concentrations of 15 synaptic proteins in CAA and AD patients, and age- and sex-matched cognitively unimpaired controls. Results: We included 25 patients with CAA, 49 patients with AD, and 25 controls. Only neuronal pentraxin-2 levels were decreased in the CSF of CAA patients compared with controls (p = 0.04). CSF concentrations of 12 other synaptic proteins were all increased in AD compared with CAA or controls (all p≤0.01) and were unchanged between CAA and controls. Synaptic protein concentrations in the subgroup of CAA patients positive for AD biomarkers (CAA/ATN+; n = 6) were similar to AD patients, while levels in CAA/ATN- (n = 19) were comparable with those in controls. A regression model including all synaptic proteins differentiated CAA from AD at high accuracy levels (area under the curve 0.987). Conclusion: In contrast to AD, synaptic CSF biomarkers were found to be largely unchanged in CAA. Moreover, concomitant AD pathology in CAA is associated with abnormal synaptic protein levels. Impaired synaptic function in AD was confirmed in this independent cohort. Our findings support an apparent differential involvement of synaptic dysfunction in CAA and AD and may reflect distinct pathological mechanisms.

Single molecule reactivity studies of metallo-porphyrins at solid-liquid interfaces

Abstract: Metallo-porphyrins are among the most widely investigated molecules in homogeneous and biochemical catalysis. This overview will focus on the reactive properties of individual metallo-porphyrins when they are adsorbed in a monolayer at a solid-liquid interface. With the help of scanning tunneling microscopy (STM), structural and electronic changes of metallo-porphyrins when they participate in a chemical reaction will be elucidated at the highest detail possible. In particular reactions that take place at the metal center of the porphyrin will be highlighted. Reactivity will be investigated with conventional liquid-STM (tip, sample and an apolar organic supernatant) and with electrochemical STM (additional control over surface potential, and a polar or aqueous supernatant) setups.

A Quenched Size‐Expanded Nucleotide Reports Activity of the Leukemia Biomarker Terminal Deoxynucleotidyl Transferase (TdT)**

Abstract: Terminal deoxynucleotidyl Transferase (TdT) is a template-independent DNA polymerase that plays an essential role in the human adaptive immune system and is upregulated in several types of leukemia. It has therefore gained interest as a leukemia biomarker and potential therapeutic target. Herein, we describe a FRET-quenched fluorogenic probe based on a size-expanded deoxyadenosine that reports directly on TdT enzymatic activity. The probe enables real-time detection of primer extension and de novo synthesis activity of TdT and displays selectivity over other polymerase and phosphatase enzymes. Importantly, TdT activity and its response to treatment with a promiscuous polymerase inhibitor could be monitored in human T-lymphocyte cell extract and Jurkat cells using a simple fluorescence assay. Finally, employing the probe in a high-throughput assay resulted in the identification of a non-nucleoside TdT inhibitor.

Religionsfreiheit, Religionskritik und Blasphemie

Abstract: ReligionReligionReligionsfreiheit bzwBürgerrechteund Religionsfreiheit. derenBlasphemie Praktiken haben immer ReligionskritikReligionReligionskritik zur Folge gehabt. Religionskritik hat ihrerseits oft den Vorwurf der Blasphemie auf sich gezogen, aber der Blasphemieverdacht war (und ist) ebenfalls ein religionsinternes Mittel der Orthodoxieapologie und der Häresieabwehr.

A Companion to Boniface. Edited by MichelAaij and ShannonGodlove. Brill's Companions to the Christian Tradition 92. Leiden and Boston: Brill. 2020. xviii + 562 pp. + 1 b/w ill. + 16 colour ill. €239; $ 288. ISBN 978 90 04 42513 2 (ebook); 978 90 04 33851 7 (hardback).

Abstract: Early Medieval EuropeVolume 31, Issue 1 p. 145-148 Book review A Companion to Boniface. Edited by Michel Aaij and Shannon Godlove. Brill's Companions to the Christian Tradition 92. Leiden and Boston: Brill. 2020. xviii + 562 pp. + 1 b/w ill. + 16 colour ill. €239; $ 288. ISBN 978 90 04 42513 2 (ebook); 978 90 04 33851 7 (hardback). Sven Meeder, Sven Meeder Radboud University NijmegenSearch for more papers by this author Sven Meeder, Sven Meeder Radboud University NijmegenSearch for more papers by this author First published: 09 January 2023 https://doi.org/10.1111/emed.12606Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume31, Issue1February 2023Pages 145-148 RelatedInformation

Sportethik

Abstract: WoSportethik individuelles, kollektives und institutionelles Handeln einem Praxisbereich zugeordnet werden kann, der sich von anderen Praxisbereichen hinreichend klar unterscheidet, entsteht auch das Erfordernis einer entsprechenden Bereichsethik. Unweigerlich stellt sich dann nämlich die Frage, welchen Kriterien das bereichsspezifische Handeln zu genügen hat, um als gutes und richtiges Handeln gelten zu können. Sobald sich diese Frage nicht mehr mit einem Hinweis auf bekanntes Praxiswissen gleichsam von selbst erledigt, sondern zum Gegenstand methodisch geleiteter Reflexionen wird, die ihrerseits alle möglichen – also nicht nur bereichsfunktionale – Kriterien zur Ermittlung des Guten und Richtigen einbeziehen, da wurde der Schritt hin zu einer Bereichsethik bereits vollzogen.

Turning performance measurement on its head: From the measurement of performance to the performativity of measuring

Abstract: This paper develops a performativist metaphysical grounding of NPM-based performance measurement as a radical alternative to a representationalist grounding, an alternative that turns performance measurement on its head. Performance measurement turns from an act of representation characterized by a metaphor of reflection into an ethical practice of mattering characterized by a metaphor of diffraction. In performativism, performance measurement does not (imperfectly) represent performance as a base for knowing and intervention from afar (both in terms of space and time) but is somehow performative of who and what come to count in the world. Its exclusionary character makes it an inherently ethical practice. We contrast a performativist grounding of performance measurement with a representationalist grounding and rework concepts of responsibility and accountability. We illustrate a performativist grounding of performance measurement with examples from academia and healthcare and provide a direction for future research.

Clinical and radiological assessment of scoliosis in Koolen‐de Vries syndrome

Abstract: The Koolen-de Vries syndrome (KdVS) is a multisystem disorder characterized by developmental delay, intellectual disability, characteristic facial features, epilepsy, cardiovascular and urogenital malformations, and various musculoskeletal disorders. Scoliosis is a common feature. The aim of this study is to fill the gap in the current knowledge about scoliosis in individuals with KdVS and to provide recommendations for management and follow-up. In total, 54 individuals with KdVS were included in the study, with a mean age of 13.6 years (range 1.9–38.8 years). Spine radiographs, MR scans, and corresponding radiology reports were analyzed retrospectively for scoliosis and additional anomalies. The presence of scoliosis-related clinical conditions was assessed in participants' medical records and by use of a parent survey. Scoliosis was present in 56% of the participants (30/54) with a mean age of onset of 10.6 years and curve progression during the growth spurt. Prevalence at age 6, 10, and 18 years was, respectively, 9%, 41%, and 65%. Most participants were diagnosed with a single curve (13/24, 54%), of which five participants had a long C-curve type scoliosis. No significant risk factors for development of scoliosis could be identified. Severity was mostly classified as mild, although 29% (7/24) of the curves were larger than 30° at last follow-up. Bracing therapy was received in 13% (7/54), and surgical spinal fusion was warranted in 6% (3/54). Remarkably, participants with scoliosis received less often physical therapy compared to participants without scoliosis (P = 0.002). Scoliosis in individuals with KdVS should be closely monitored and radiologic screening for scoliosis and vertebrae abnormalities is recommended at diagnosis of KdVS, and the age of 10 and 18 years.

Measurements of the clumped isotopic composition of atmospheric methane

Abstract: Atmospheric methane (CH4) is the second most important anthropogenic greenhouse gas after CO&#173;2. Global scale measurements of CH4 mole fraction show an increasing trend since pre-industrial times. Various studies have attempted to attribute the temporal change to variations in the balance between different CH4 sources and atmospheric sink reactions. Measurements of bulk isotopic composition (&#948;13C and &#948;D) are used for this purpose, but due to the overlap of source signatures, it is difficult to distinguish between biogenic, thermogenic, and pyrogenic CH4. With the advancement of high-resolution mass spectrometry, it is now possible to measure the two most abundant clumped isotopologues of CH4: 13CDH3 and CD2H2. The clumping anomalies denoted as &#916;13CD and &#916;DD can be used as an additional tool to constrain CH4 sources.Most of the clumped isotope studies so far, have focused on high-concentration samples, which can easily deliver the large quantity of pure CH4 (several mL) needed to measure the clumped isotopologues. But these measurements could be particularly interesting for atmospheric CH4, for which the explanations of the recent variations are still under debate. As shown by a recent modeling study (1), clumping anomalies, especially &#916;DD, have the potential to help distinguish between the main drivers of change in the atmospheric CH4 burden.In our laboratory, we use the 253-Ultra mass spectrometer to measure the clumped isotopologues of CH4. These measurements require 4-5 mL of pure CH4 to achieve a precision of 0.3 &#177; 0.1 &#8240; for &#916;13CD and 2.4 &#177; 0.8 &#8240; for &#916;DD. For atmospheric air at 2 ppm, this translates to extracting CH4 from at least 2000 L of air.We have recently developed a method for extracting and purifying CH4 from this large quantity of air, without modifying its isotopic composition. We will present the current capabilities of this extraction system, and the first results of the clumped isotopic composition of the ambient air.Reference:1. Chung, E & Arnold, T 2021, 'Potential of Clumped Isotopes in Constraining the Global Atmospheric Methane Budget', Global Biogeochemical Cycles, vol. 35, no. 10, https://doi.org/10.1029/2020GB006883