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Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
Die Verfasser stellen in ihrem Beitrag die künftig in Kraft tretenden oder schon in Kraft getretenen Gesetzesvorhaben der europäischen Union vor. Vorab werde auf die abgelaufene Frist zur Anpassung von Standardvertragsklausel hingewiesen. Die Anpassung könne ggf. durch den Data Privacy Act der Kommission bewirkt werden, da dieser eine Angemessenheit suggeriere. Neben dem Digital Markets Act, der die Wahrung der Diskriminierungsfreiheit den Gatekeeper-Plattformen bezüglich der Bewerbung von Waren Dritter vorschreibt, sind ebenfalls der Digital Service Act und der Data Governance Act in Kraft getreten und werden künftig wirksam. Letzteres bezweckt den Datenaustausch von nicht-personenbezogenen Daten öffentlich-rechtlicher Datensätze, wobei anders als bei DSA, der die Verbraucherrechte durchsetzen möchte, mangels Verpflichtung die praktische Umsetzung ausbleiben werde. In der Entwurfsphase stecken der Artificial Intelligence Act, der Data Act, sowie der Cyber Resilience Act. Allen drei sei wegen dem weiten Anwendungsspielraum, der Bußgeldandrohung oder der Cyber-Bedrohungslage besondere praktische Relevanz beizumessen. Die Kommission weite durch diese Gesetzesvorhaben ihre Regelungsabsicht auch auf nicht-personenbezogene Daten und dem Datentransfer aus. Im Ergebnis werden die Unternehmen mit mehr Verpflichtungen konfrontiert, zu dessen Umsetzung ein funktionierendes Compliance-Management-System unabdingbar sei.
Datenschutz & Datenrecht – ein Ausblick auf 2023: Nationale Entwicklungen, EuGH-Vorlagen & Aufsicht
(2023)
Die Verfasser vermitteln einen Überblick über die nationalen Gesetzgebungsverfahren und wesentliche EuGH-Vorlagefragen betreffend den Datenschutz und das Datenrecht für das Jahr 2023. Zunächst folgen u.a. Hinweise in Bezug auf den Hinweisgeberschutz, die Verabschiedung der Einwilligungsverwaltungs-Verordnung zur Konkretisierung des § 26 TTDSG und das Mobilitätsdatengesetz. Anschließend werden Vorlagefragen deutscher Gerichte, die dem EuGH vorgelegt und bereits am 12.01.2023 beantwortet wurden, wie etwa C-154/21 und C-132/21 und die EuGH-Entscheidung vom 9.2.2023 (C-453/21), thematisiert. Überdies führen die Autoren wesentliche Entscheidungen des EuGH an, die im Jahr 2023 aus dem Bereich Datenrecht und Datenschutz zu erwarten seien. Auch Aktivitäten der Datenschutzaufsicht auf nationaler und europäischer Ebene finden Erwähnung. Die Verfasser machen abschließend auf besonders interessante Entscheidungen, die 2023 erwartet werden, wie etwa das EuGH-Urteil zum Auskunftsanspruch, sowie auf das Verhältnis des der Whistleblowing-RL umzusetzende Hinweisgeberschutzgesetz einerseits und Vorgaben des Datenschutzes andererseits, aufmerksam. Sie empfehlen, die künftige Rechtsprechung des EuGH im Blick zu behalten.
Umsatzbasierte Bußgelder – wie sonst nur aus dem Kartellrecht bekannt – waren einer der Gründe, warum die Datenschutz-Grundverordnung (DSGVO) vor ihrem Inkrafttreten für erhebliches Aufsehen sorgte. Die vielfach relevanteren Schadensersatzansprüche, die, wie bei „Dieselgate“, aufgrund der Vielzahl von betroffenen Personen und der aus Sicht von Rechtsdienstleistern bestehenden Skalierbarkeit mit weitaus höheren Einbußen für Unternehmen einhergehen können, blieben zunächst unbeachtet. Inzwischen ist der Schadensersatzanspruch gem. Art. 82 DSGVO die Vorschrift, die die meisten Vorlagen zum Europäischen Gerichtshof (EuGH) der letzten Jahre hervorgerufen hat. Am 4.5.2023 hat nun der EuGH (Urteil v. 4.5.2023 - Rs. C-300/21, NWB GAAAJ-41389) in einem Grundsatzurteil über zentrale Fragen rund um den Ersatz immaterieller Schäden als Folge von Datenschutzverstößen entschieden.
Providing healthcare services frequently involves cognitively demanding tasks, including diagnoses and analyses as well as complex decisions about treatments and therapy. From a global perspective, ethically significant inequalities exist between regions where the expert knowledge required for these tasks is scarce or abundant. One possible strategy to diminish such inequalities and increase healthcare opportunities in expert-scarce settings is to provide healthcare solutions involving digital technologies that do not necessarily require the presence of a human expert, e.g., in the form of artificial intelligent decision-support systems (AI-DSS). Such algorithmic decision-making, however, is mostly developed in resource- and expert-abundant settings to support healthcare experts in their work. As a practical consequence, the normative standards and requirements for such algorithmic decision-making in healthcare require the technology to be at least as explainable as the decisions made by the experts themselves. The goal of providing healthcare in settings where resources and expertise are scarce might come with a normative pull to lower the normative standards of using digital technologies in order to provide at least some healthcare in the first place. We scrutinize this tendency to lower standards in particular settings from a normative perspective, distinguish between different types of absolute and relative, local and global standards of explainability, and conclude by defending an ambitious and practicable standard of local relative explainability.
To fulfil the CO2 emission reduction targets of the European Union (EU), heavy-duty (HD) trucks need to operate 15% more efficiently by 2025 and 30% by 2030. Their electrification is necessary as conventional HD trucks are already optimized for the long-haul application. The resulting hybrid electric vehicle (HEV) truck gains most of the fuel saving potential by the recuperation of potential energy and its consecutive utilization. The key to utilizing the full potential of HEV-HD trucks is to maximize the amount of recuperated energy and ensure its intelligent usage while keeping the operating point of the internal combustion engine as efficient as possible. To achieve this goal, an intelligent energy management strategy (EMS) based on ECMS is developed for a parallel HEV-HD truck which uses predictive discharge of the battery and adaptive operating strategy regarding the height profile and the vehicle mass. The presented EMS can reproduce the global optimal operating strategy over long phases and lead to a fuel saving potential of up to 2% compared with a heuristic strategy. Furthermore, the fuel saving potential is correlated with the investigated boundary conditions to deepen the understanding of the impact of intelligent EMS for HEV-HD trucks.
Using scenarios is vital in identifying and specifying measures for successfully transforming the energy system. Such transformations can be particularly challenging and require the support of a broader set of stakeholders. Otherwise, there will be opposition in the form of reluctance to adopt the necessary technologies. Usually, processes for considering stakeholders' perspectives are very time-consuming and costly. In particular, there are uncertainties about how to deal with modifications in the scenarios. In principle, new consulting processes will be required. In our study, we show how multi-criteria decision analysis can be used to analyze stakeholders' attitudes toward transition paths. Since stakeholders differ regarding their preferences and time horizons, we employ a multi-criteria decision analysis approach to identify which stakeholders will support or oppose a transition path. We provide a flexible template for analyzing stakeholder preferences toward transition paths. This flexibility comes from the fact that our multi-criteria decision aid-based approach does not involve intensive empirical work with stakeholders. Instead, it involves subjecting assumptions to robustness analysis, which can help identify options to influence stakeholders' attitudes toward transitions.
This study evaluates neuromechanical control and muscle-tendon interaction during energy storage and dissipation tasks in hypergravity. During parabolic flights, while 17 subjects performed drop jumps (DJs) and drop landings (DLs), electromyography (EMG) of the lower limb muscles was combined with in vivo fascicle dynamics of the gastrocnemius medialis, two-dimensional (2D) kinematics, and kinetics to measure and analyze changes in energy management. Comparisons were made between movement modalities executed in hypergravity (1.8 G) and gravity on ground (1 G). In 1.8 G, ankle dorsiflexion, knee joint flexion, and vertical center of mass (COM) displacement are lower in DJs than in DLs; within each movement modality, joint flexion amplitudes and COM displacement demonstrate higher values in 1.8 G than in 1 G. Concomitantly, negative peak ankle joint power, vertical ground reaction forces, and leg stiffness are similar between both movement modalities (1.8 G). In DJs, EMG activity in 1.8 G is lower during the COM deceleration phase than in 1 G, thus impairing quasi-isometric fascicle behavior. In DLs, EMG activity before and during the COM deceleration phase is higher, and fascicles are stretched less in 1.8 G than in 1 G. Compared with the situation in 1 G, highly task-specific neuromuscular activity is diminished in 1.8 G, resulting in fascicle lengthening in both movement modalities. Specifically, in DJs, a high magnitude of neuromuscular activity is impaired, resulting in altered energy storage. In contrast, in DLs, linear stiffening of the system due to higher neuromuscular activity combined with lower fascicle stretch enhances the buffering function of the tendon, and thus the capacity to safely dissipate energy.
Magnetic detection structure for Lab-on-Chip applications based on the frequency mixing technique
(2018)
A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
For performing point-of-care molecular diagnostics, magnetic immunoassays constitute a promising alternative to established enzyme-linked immunosorbent assays (ELISA) because they are fast, robust and sensitive. Simultaneous detection of multiple biomolecular targets from one body fluid sample is desired. The aim of this work is to show that multiplex magnetic immunodetection based on magnetic frequency mixing by means of modular immunofiltration columns prepared for different targets is feasible. By calculations of the magnetic response signal, the required spacing between the modules was determined. Immunofiltration columns were manufactured by 3D printing and antibody immobilization was performed in a batch approach. It was shown experimentally that two different target molecules in a sample solution could be individually detected in a single assaying step with magnetic measurements of the corresponding immobilization filters. The arrangement order of the filters and of a negative control did not influence the results. Thus, a simple and reliable approach to multi-target magnetic immunodetection was demonstrated.
In modern bioanalytical methods, it is often desired to detect several targets in one sample within one measurement. Immunological methods including those that use superparamagnetic beads are an important group of techniques for these applications. The goal of this work is to investigate the feasibility of simultaneously detecting different superparamagnetic beads acting as markers using the magnetic frequency mixing technique. The frequency of the magnetic excitation field is scanned while the lower driving frequency is kept constant. Due to the particles’ nonlinear magnetization, mixing frequencies are generated. To record their amplitude and phase information, a direct digitization of the pickup-coil’s signal with subsequent Fast Fourier Transformation is performed. By synchronizing both magnetic beads using frequency scanning in magnetic frequency mixing technique magnetic fields, a stable phase information is gained. In this research, it is shown that the amplitude of the dominant mixing component is proportional to the amount of superparamagnetic beads inside a sample. Additionally, it is shown that the phase does not show this behaviour. Excitation frequency scans of different bead types were performed, showing different phases, without correlation to their diverse amplitudes. Two commercially available beads were selected and a determination of their amount in a mixture is performed as a demonstration for multiplex measurements.
Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection
(2019)
Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more
than 700 ng/ml.
It has been shown that muscle fascicle curvature increases with increasing contraction level and decreasing muscle–tendon complex length. The analyses were done with limited examination windows concerning contraction level, muscle–tendon complex length, and/or intramuscular position of ultrasound imaging. With this study we aimed to investigate the correlation between fascicle arching and contraction, muscle–tendon complex length and their associated architectural parameters in gastrocnemius muscles to develop hypotheses concerning the fundamental mechanism of fascicle curving. Twelve participants were tested in five different positions (90°/105°*, 90°/90°*, 135°/90°*, 170°/90°*, and 170°/75°*; *knee/ankle angle). They performed isometric contractions at four different contraction levels (5%, 25%, 50%, and 75% of maximum voluntary contraction) in each position. Panoramic ultrasound images of gastrocnemius muscles were collected at rest and during constant contraction. Aponeuroses and fascicles were tracked in all ultrasound images and the parameters fascicle curvature, muscle–tendon complex strain, contraction level, pennation angle, fascicle length, fascicle strain, intramuscular position, sex and age group were analyzed by linear mixed effect models. Mean fascicle curvature of the medial gastrocnemius increased with contraction level (+5 m−1 from 0% to 100%; p = 0.006). Muscle–tendon complex length had no significant impact on mean fascicle curvature. Mean pennation angle (2.2 m−1 per 10°; p < 0.001), inverse mean fascicle length (20 m−1 per cm−1; p = 0.003), and mean fascicle strain (−0.07 m−1 per +10%; p = 0.004) correlated with mean fascicle curvature. Evidence has also been found for intermuscular, intramuscular, and sex-specific intramuscular differences of fascicle curving. Pennation angle and the inverse fascicle length show the highest predictive capacities for fascicle curving. Due to the strong correlations between pennation angle and fascicle curvature and the intramuscular pattern of curving we suggest for future studies to examine correlations between fascicle curvature and intramuscular fluid pressure.
Low emission zones and truck bans, the rising price of diesel and increases in road tolls: all of these factors are putting serious pressure on the transport industry. Commercial vehicle manufacturers and their suppliers are in the process of identifying new solutions to these challenges as part of their efforts to meet the EEV (enhanced environmentally friendly vehicle) limits, which are currently the most robust European exhaust and emissions standards for trucks and buses.
Germany is a frontrunner in setting frameworks for the transition to a low-carbon system. The mobility sector plays a significant role in this shift, affecting different people and groups on multiple levels. Without acceptance from these stakeholders, emission targets are out of reach. This research analyzes how the heterogeneous preferences of various stakeholders align with the transformation of the mobility sector, looking at the extent to which the German transformation paths are supported and where stakeholders are located.
Under the research objective of comparing stakeholders' preferences to identify which car segments require additional support for a successful climate transition, a status quo of stakeholders and car performance criteria is the foundation for the analysis. Stakeholders' hidden preferences hinder the derivation of criteria weightings from stakeholders; therefore, a ranking from observed preferences is used. This study's inverse multi-criteria decision analysis means that weightings can be predicted and used together with a recalibrated performance matrix to explore future preferences toward car segments.
Results show that stakeholders prefer medium-sized cars, with the trend pointing towards the increased potential for alternative propulsion technologies and electrified vehicles. These insights can guide the improved targeting of policy supporting the energy and mobility transformation. Additionally, the method proposed in this work can fully handle subjective approaches while incorporating a priori information. A software implementation of the proposed method completes this work and is made publicly available.
GHEtool is a Python package that contains all the functionalities needed to deal with borefield design. It is developed for both researchers and practitioners. The core of this package is the automated sizing of borefield under different conditions. The sizing of a borefield is typically slow due to the high complexity of the mathematical background. Because this tool has a lot of precalculated data, GHEtool can size a borefield in the order of tenths of milliseconds. This sizing typically takes the order of minutes. Therefore, this tool is suited for being implemented in typical workflows where iterations are required.
GHEtool also comes with a graphical user interface (GUI). This GUI is prebuilt as an exe-file because this provides access to all the functionalities without coding. A setup to install the GUI at the user-defined place is also implemented and available at: https://www.mech.kuleuven.be/en/tme/research/thermal_systems/tools/ghetool.
In general aviation, too, it is desirable to be able to operate existing internal combustion engines with fuels that produce less CO₂ than Avgas 100LL being widely used today It can be assumed that, in comparison, the fuels CNG, LPG or LNG, which are gaseous under normal conditions, produce significantly lower emissions. Necessary propulsion system adaptations were investigated as part of a research project at Aachen University of Applied Sciences.
Auch in der allgemeinen Luftfahrt wäre es wünschenswert, die bereits vorhandenen Verbrennungsmotoren mit weniger CO₂-trächtigen Kraftstoffen als dem heute weit verbreiteten Avgas 100LL betreiben zu können. Es ist anzunehmen, dass im Vergleich die unter Normalbedingungen gasförmigen Kraftstoffe CNG, LPG oder LNG deutlich weniger Emissionen produzieren. Erforderliche Antriebssystemanpassungen wurden im Rahmen eines Forschungsprojekts an der FH Aachen untersucht.