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Abaloparatide enhances bone regeneration in extraction socket dental implant defects: an experimental in vivo study
No full textCollaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT): global and risk-group stratified course of well-being and mental health during the COVID-19 pandemic in adolescents
No full textObjectiveTo identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide.MethodThis study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization–Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 ResultsAnalyzing 8,115 of 8,762 initiated surveys (representative = 75.1%), the pre-pandemic WHO-5 and P-score remained stable during the study (excluding relevant recall bias/drift), but worsened during the pandemic by 5.55 ± 17.13 (SD) and 6.74 ± 16.06 points, respectively (effect size d = 0.27 and d = 0.28). The proportion of adolescents with WHO-5 scores suggesting depression screening (2 years. The 3 most subjectively effective coping strategies were Internet use, exercise/walking, and social contacts.ConclusionOverall, well-being/mental health worsened (small effect sizes) during the early stages of the COVID-19 pandemic, especially in vulnerable subpopulations. Identified at-risk groups, association with pandemic-related measures, and coping strategies can inform individual behaviors and global public health strategies
Computational study protocol: leveraging synthetic data to validate a benchmark study for differential abundance tests for 16s microbiome sequencing data
No full textBackgroundSynthetic data’s utility in benchmark studies depends on its ability to closely mimic real-world conditions and reproduce results obtained from experimental data. Building on Nearing et al.’s study (1), who assessed 14 differential abundance tests using 38 experimental 16S rRNA datasets in a case-control design, we are generating synthetic datasets that mimic the experimental data to verify their findings. We will employ statistical tests to rigorously assess the similarity between synthetic and experimental data and to validate the conclusions on the performance of these tests drawn by Nearing et al. (1). This protocol adheres to the SPIRIT guidelines, demonstrating how established reporting frameworks can support robust, transparent, and unbiased study planning.MethodsWe replicate Nearing et al.’s (1) methodology, incorporating synthetic data simulated using two distinct tools, mirroring the 38 experimental datasets. Equivalence tests will be conducted on a non-redundant subset of 46 data characteristics comparing synthetic and experimental data, complemented by principal component analysis for overall similarity assessment. The 14 differential abundance tests will be applied to synthetic and experimental datasets, evaluating the consistency of significant feature identification and the number of significant features per tool. Correlation analysis and multiple regression will explore how differences between synthetic and experimental data characteristics may affect the results.ConclusionsSynthetic data enables the validation of findings through controlled experiments. We assess how well synthetic data replicates experimental data, try to validate previous findings with the most recent versions of the DA methods and delineate the strengths and limitations of synthetic data in benchmark studies. Moreover, to our knowledge this is the first computational benchmark study to systematically incorporate synthetic data for validating differential abundance methods while strictly adhering to a pre-specified study protocol following SPIRIT guidelines, contributing to transparency, reproducibility, and unbiased research
Apheresis therapies in MOGAD : a retrospective study of 117 therapeutic interventions in 571 attacks
No full textBackgroundIncomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data on apheresis outcomes in MOGAD attacks remain limited.MethodsWe retrospectively evaluated all apheresis treated attacks occurring in patients with MOGAD between 2008 and 2023 at 18 Neuromyelitis Optica Study Group centres. Treatment response was categorised as complete, partial or no remission. Preattack and follow-up Expanded Disability Status Scale (EDSS) and visual Functional System Scores (FSS) were used to calculate absolute outcomes (ΔEDSS/Δvisual FSS). Predictors of complete remission were analysed using a generalised linear mixed model.ResultsApheresis was used for 117/571 (20.5%) attacks in 85/209 (40.7%) patients. Attacks with simultaneous optic neuritis and myelitis were treated more often with apheresis (42.4%, n=14) than isolated myelitis (25.2%, n=35), cerebral manifestation (21.0%, n=17) or isolated optic neuritis (17.6%, n=51). Apheresis was initiated as first-line therapy in 12% (4.5 (IQR 0–11) days after attack onset), second-line therapy in 62% (15 (IQR 6.75–31) days) and third-line therapy in 26% (30 (IQR 19–42) days). Complete remission was achieved in 21%, partial remission in 70% and no remission in 9% of patients. First-line apheresis (OR 2.5, p=0.040) and concomitant disease-modifying therapy (OR 1.5, p=0.011) were associated with complete remission. Both parameters were also associated with a favourable ΔEDSS. No differences in outcomes were observed between the apheresis types.ConclusionApheresis is frequently used in MOGAD attacks. An early start as first-line therapy and concomitant disease-modifying therapy predict full attack recovery
Germanic rampart or Roman encampment? New geoarchaeological evidence at the Roman conflict site at Kalkriese (NW‐Germany)
No full textKalkriese, near Osnabrueck (NW Germany), is considered the location of the ‘Battle of Varus’, where a coalition of Germanic tribes, under the leadership of Arminius, defeated three Legions under the command of Varus in 9 ad. Roman coinage and remains of military equipment prove that the Oberesch site at Kalkriese saw military operations between Germanic tribes and the Roman legions during Early Imperial times, but the sequence and magnitude of the military operations still remain unclear. In this study, we present for the first time absolute dates from the Oberesch site to decipher the general sequence of the Holocene landscape development at Kalkriese, identify the antique surface, and evaluate the ‘Germanic Rampart Theory’ and the ‘Roman Encampment Theory’. The geoprofile encompasses the entire stratigraphic sequence from the Pleistocene base, indicating intensive agricultural use of the area since the Early Neolithic. A fossil topsoil of late Pre-Roman Iron Age to Roman Imperial Age was identified, which probably represents the antique surface of the Roman conflict site. Our results do not support either the ‘Germanic Rampart Theory’ or the ‘Roman Encampment Theory’, as both linear structures seem to be of High Middle Age origin
H2-roaming dynamics in the formation of H+ 3 following twophoton double ionization of ethanol and aminoethanol
No full textRoaming reactions involving a neutral fragment of a molecule that transiently wanders aroundanother fragment before forming a new bond are intriguing and peculiar pathways for molecularrearrangement. Such reactions can occur for example upon double ionization of small organicmolecules, and have recently sparked much scientific interest. We have studied the dynamics of theH2-roaming reaction leading to the formation of H+3 after two-photon double ionization of ethanoland 2-aminoethanol, using an XUV-UV pump-probe scheme. For ethanol, we find dynamics similarto previous studies employing different pump-probe schemes, indicating the independence of theobserved dynamics from the method of ionization and the photon energy of the disruptive probepulse. Surprisingly, we do not observe a kinetic isotope effect in ethanol-D6, in contrast to previous experiments on methanol where such an effect was observed. This distinction indicates fundamental differences in the energetics of the reaction pathways as compared to the methanol molecule.The larger number of possible roaming pathways compared to methanol complicates the analysisconsiderably. In contrast to previous studies, we additionally analyze a broad range of dissociativeionization products, which feature distinct dynamics from that of H+3 and allow initial insight into the action of the disruptive UV-probe pulse
Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults
No full textAnti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy
Shaping the peaceful city: (post)colonial and transnational entanglements of security governance and spatial economic restructuring in urban Colombia
No full textThis contribution examines the impact of transnational actors, policies, and discourses on the dynamics of urban renewal and governance in Colombia’s conflict-ridden cities. Emphasizing local and global encounters in policymaking, we understand initiatives of spatial economic restructuring as central components of a larger project oriented towards cities’ adjustment to the requirements of global markets. Frequently, the rationality of such policies, based on a liberal approach that conceives of peace and development in terms of pacification and economic liberalisation rather than democratic transformation, has been successful in accommodating a violent context instead of confronting it. Based on an analysis of the Colombian towns of Pereira and Santa Marta and of national and municipal planning documents, we disentangle the ways such policies are embedded in as well as contribute to the perpetuation of historical, (post)colonial hierarchies traversing the spatiality and exclusionary urban politics in cities affected by conflict. These hierarchies in urban governance, as well as their transnational linkages, are a largely overlooked aspect in the literature on the Colombian conflict
MEMS pressure sensors with novel TSV design for extreme temperature environments
No full textThis study introduces a manufacturing process based on industrial MEMS technology, enabling the production of diverse sensor designs customized for a wide range of absolute pressure measurements. Using monocrystalline silicon as the structural material minimizes thermal stresses and eliminates temperature-dependent semiconductor effects, as silicon functions solely as a mechanical material. Integrating a eutectic bonding process in the sensor fabrication allows for a reliable operation at temperatures up to 350 °C. The capacitive sensor electrodes are enclosed within a silicon-based Faraday cage, ensuring effective shielding against external electrostatic interference. An innovative Through-Silicon Via (TSV) design, sealed using gold–gold (Au-Au) diffusion and gold–silicon (Au-Si) eutectic bonding, further enhances the mechanical and thermal stability of the sensors, even under high-temperature conditions. The unfilled TSV structure mitigates mechanical stress from thermal expansion. The sensors exhibited excellent performance, achieving a linearity of 99.994%, a thermal drift of −0.0164% FS (full scale)/K at full load and 350 °C, and a high sensitivity of 34 fF/kPa. These results highlight the potential of these sensors for high-performance applications across various demanding environments