A simple morphodynamic model for sand banks and large-scale sand pits subject to asymetrical tides

We extend existing knowledge on theoretical growth characteristics of tidal sand banks by including asymmetrical tides with an M0, M2 and M4-constituent, thus allowing for migration. Furthermore, in the context of the continuously increasing demand on the Dutch sand market, we show that creating a large-scale offshore sand pit has long-term morphological implications, both for the pit itself and the surrounding area. The pit deepens, while around it a sand bank pattern emerges, spreading at a constant rate of the order of tens to hundred metres per year

Entwicklung eines nanoliposomalen Trägersystems zur gezielten siRNA-Therapie des nicht-kleinzelligen Bronchialkarzinoms

Einleitung: Das Bronchialkarzinom ist mit einer Inzidenz über 50.000 jährlich die häufigste Krebserkrankung in Deutschland. Die aktuellen multimodalen Therapieschemata führen zu keiner wesentlichen Prognoseverbesserung. Ein vielversprechendes innovatives Konzept sind Therapien auf der Basis der RNA- Interferenz. Die Applikation von small interfering RNAs (siRNA) kann die Expression von an der Tumorgenese beteiligten Genen gezielt inhibieren. Aktuell ist jedoch die Gewährleistung der Bioverfügbarkeit der siRNAs in den Tumoren problematisch. Das Ziel dieser Arbeit war die Entwicklung eines nanoliposomalen Trägersystems für die siRNA-Therapie des nicht-kleinzelligen Bronchialkarzinoms. Methodik: In den vorliegenden Versuchen wurden unterschiedliche Lipidmischung für die Nanoliposomen (egg phosphatidylcholine (EPC)-, hydrogenated soy phosphatidyl-choline (HSPC)-, Polyethylenglykol (PEG) und Transfektionsreagenzien (INTERFERin®, DOTAP) auf verschiedenen Zelllinien (HUVEC, A549-Zellen, Ea.hy926-Zellen) getestet. Untersucht wurde die Transfektionseffizienz und die Reduktion der Genexpression verschiedener Adhäsionsmoleküle (vascular adhesion molecule 1 (VCAM-1), E-Selektin und intercellular adhesion molecule 1 (ICAM-1)) durch spezifische enkapsulierte siRNAs. Zur Kontrolle wurden zusätzlich die Zellviabilität und die Größe der Nanoliposomen überprüft. Ergebnisse: Die PEG-Nanoliposomen (50 μM) mit der enkapsulierten ICAM-1- siRNA erzielten mit einer 57 % Reduktion der ICAM-1-Genexpression, im Vergleich zu anderen getesteten Nanoliposomenmischungen, die besten Effekte. Die durchschnittliche Größe der Nanoliposomen betrug 53 nm. Die Zellviabilität lag abhängig von der Konzentration der PEG-Nanoliposomen zwischen 67 % und 78 %. Zusätzlich erzielten HSPC-Nanoliposomen (10mM) mit enkapsulierter VCAM-1 siRNA eine maximale Reduktion der VCAM-1-Genexpression von 67%, jedoch mit einer signifikant erhöhten Zelltoxizität. Schlussfolgerung: Die Versuche zeigen, dass die Genexpression in humanen Endothelzellen durch siRNA-tragende Nanoliposomen signifikant und spezifisch reduziert werden kann. Das entwickelte Trägersystem ist für die systemische Applikation von spezifischen siRNAs geeignet, die die Chemotaxis und damit die Ausbreitung von Tumorzellen stören. Daraus ergeben sich neue multimodale Therapiemöglichkeiten im Rahmen der Lungenkrebs-Therapie

Probabilistic sequence learning in mild cognitive impairment

Mild Cognitive Impairment (MCI) causes slight but noticeable disruption in cognitive systems, primarily executive and memory functions. However, it is not clear if the development of sequence learning is affected by an impaired cognitive system and, if so, how. The goal of our study was to investigate the development of probabilistic sequence learning, from the initial acquisition to consolidation, in MCI and healthy elderly control groups. We used the Alternating Serial Reaction Time task (ASRT) to measure probabilistic sequence learning. Individuals with MCI showed weaker learning performance than the healthy elderly group. However, using the reaction times only from the second half of each learning block – after the reactivation phase - we found intact learning in MCI. Based on the assumption that the first part of each learning block is related to reactivation/recall processes, we suggest that these processes are affected in MCI. The 24-hour offline period showed no effect on sequence-specific learning in either group but did on general skill learning: the healthy elderly group showed offline improvement in general reaction times while individuals with MCI did not. Our findings deepen our understanding regarding the underlying mechanisms and time course of sequence acquisition and consolidation

The complexity of measuring reliability in learning tasks: an illustration using the Alternating Serial Reaction Time task

Despite the fact that reliability estimation is crucial for robust inference, it is underutilized in neuroscience and cognitive psychology. Appreciating reliability can help researchers increase statistical power, effect sizes, and reproducibility, decrease the impact of measurement error, and inform methodological choices. However, accurately calculating reliability for many experimental learning tasks is challenging. In this study, we highlight a number of these issues, and estimate multiple metrics of internal consistency and split-half reliability of a widely used learning task on a large sample of 180 subjects. We show how pre-processing choices, task length, and sample size can affect reliability and its estimation. Our results show that the Alternating Serial Reaction Time Task has respectable reliability, especially when learning scores are calculated based on reaction times and two-stage averaging. We also show that a task length of 25 blocks can be sufficient to meet the usual thresholds for minimally acceptable reliability. We further illustrate how relying on a single point estimate of reliability can be misleading, and the calculation of multiple metrics, along with their uncertainties, can lead to a more complete characterization of the psychometric properties of tasks

Canine Saliva as a Possible Source of Antimicrobial Resistance Genes

While the One Health issues of intensive animal farming are commonly discussed, keeping companion animals is less associated with the interspecies headway of antimicrobial resistance. With the constant advance in veterinary standards, antibiotics are regularly applied in companion animal medicine. Due to the close coexistence of dogs and humans, dog bites and other casual encounters with dog saliva (e.g., licking the owner) are common. According to our metagenome study, based on 26 new generation sequencing canine saliva datasets from 2020 and 2021 reposited in NCBI SRA by The 10,000 Dog Genome Consortium and the Broad Institute within Darwin's Ark project, canine saliva is rich in bacteria with predictably transferable antimicrobial resistance genes (ARGs). In the genome of potentially pathogenic Bacteroides, Capnocytophaga, Corynebacterium, Fusobacterium, Pasteurella, Porphyromonas, Staphylococcus and Streptococcus species, which are some of the most relevant bacteria in dog bite infections, ARGs against aminoglycosides, carbapenems, cephalosporins, glycylcyclines, lincosamides, macrolides, oxazolidinone, penams, phenicols, pleuromutilins, streptogramins, sulfonamides and tetracyclines could be identified. Several ARGs, including ones against amoxicillin-clavulanate, the most commonly applied antimicrobial agent for dog bites, were predicted to be potentially transferable based on their association with mobile genetic elements (e.g., plasmids, prophages and integrated mobile genetic elements). According to our findings, canine saliva may be a source of transfer for ARG-rich bacteria that can either colonize the human body or transport ARGs to the host bacteriota, and thus can be considered as a risk in the spread of antimicrobial resistance.European Union's Horizon 2020 research and innovation program [874735]The research was supported by the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 874735 (VEO)

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy