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“In Other News”: China’s International Media Strategy on Xinjiang — CGTN and New China TV on YouTube
(2023)
In the Western world China stands accused of severe human rights violations regarding its treatment of the Uyghurs and other predominantly Muslim minorities in its northwestern Xinjiang Uyghur Autonomous Region. This is the first article to systematically analyze the response of China’s international state media to these allegations. By studying the YouTube channels of two leading Chinese state media, China Global Television Network (CGTN) and New China TV (operated by Xinhua News Agency), it presents an indepth understanding of how China’s foreign-facing propaganda works in a crucial case. The quantitative content analysis highlights how China reacted to increasing international (mostly United States) pressure regarding its Xinjiang policies by producing higher volumes of videos and putting out new counternarratives. The qualitative analysis that follows provides in-depth treatment of the most important discourses that Chinese media engage in to salvage the nation’s international image, namely those on development, culture, nature, and terrorism. It finds several ways of countering criticism, ranging from presenting a positive image of China, in line with traditional propaganda guidelines and President Xi Jinping’s assignment to state media to “tell the China story well,” to more innovative approaches. Thus the development narrative becomes more personalized, the discourse on culture supports the “heritagization process” to incorporate minority cultures into a harmonized “Chinese civilization,” representations of nature firmly tie Xinjiang into the discourse of “beautiful China,” the “terror narrative” strategically employs shocking footage in an attempt to gain international “discourse power,” etc. The article provides an up-to-date picture of China’s state media strategy on a highly contentious international issue.
Chronic pain conditions are a major reason for the utilization of the health care system. Inflammatory pain states can persist facilitated by peripheral sensitization of nociceptors. The voltage-gated sodium channel 1.9 (NaV1.9) is an important regulator of neuronal excitability and is involved in inflammation-induced pain hypersensitivity. Recently, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (OxPAPC) was identified as a mediator of acute inflammatory pain and persistent hyperalgesia, suggesting an involvement in proalgesic cascades and peripheral sensitization. Peripheral sensitization implies an increase in neuronal excitability. This thesis aims to characterize spontaneous calcium activity in neuronal compartments as a proxy to investigate neuronal excitability, making use of the computational tool Neural Activity Cubic (NA3). NA3 allows automated calcium activity event detection of signal-close-to-noise calcium activity and evaluation of neuronal activity states. Additionally, the influence of OxPAPC and NaV1.9 on the excitability of murine dorsal root ganglion (DRG) neurons and the effect of OxPAPC on the response of DRG neurons towards other inflammatory mediators (prostaglandin E2, histamine, and bradykinin) is investigated. Using calcium imaging, the presence of spontaneous calcium activity in murine DRG neurons was established. NA3 was used to quantify this spontaneous calcium activity, which revealed decreased activity counts in axons and somata of NaV1.9 knockout (KO) neurons compared to wildtype (WT). Incubation of WT DRG neurons with OxPAPC before calcium imaging did not show altered activity counts compared to controls. OxPAPC incubation also did not modify the response of DRG neurons treated with inflammatory mediators. However, the variance ratio computed by NA3 conclusively allowed to determine neuronal activity states. In conclusion, my findings indicate an important function of NaV1.9 in determining the neuronal excitability of DRG neurons in resting states. OxPAPC exposition does not influence neuronal excitability nor sensitizes neurons for other inflammatory mediators. This evidence reduces the primary mechanism of OxPAPC-induced hyperalgesia to acute effects. Importantly, it was possible to establish an approach for unbiased excitability quantification of DRG neurons by calcium activity event detection and calcium trace variance analysis by NA3. It was possible to show that signal-close-to-noise calcium activity reflects neuronal excitability states.
Introduction: This paper addresses the need for reliable user identification in Extended Reality (XR), focusing on the scarcity of public datasets in this area.
Methods: We present a new dataset collected from 71 users who played the game “Half-Life: Alyx” on an HTC Vive Pro for 45 min across two separate sessions. The dataset includes motion and eye-tracking data, along with physiological data from a subset of 31 users. Benchmark performance is established using two state-of-the-art deep learning architectures, Convolutional Neural Networks (CNN) and Gated Recurrent Units (GRU).
Results: The best model achieved a mean accuracy of 95% for user identification within 2 min when trained on the first session and tested on the second.
Discussion: The dataset is freely available and serves as a resource for future research in XR user identification, thereby addressing a significant gap in the field. Its release aims to facilitate advancements in user identification methods and promote reproducibility in XR research.
Introduction: In this study, we investigated the impact of age on mate selection preferences in males and females, and explored how the formation and duration of committed relationships depend on the sex of the person making the selection.
Methods: To this end, we utilized data from the television dating shows The Bachelor and The Bachelorette. In these programs, either a single man (“bachelor”) or a woman (“bachelorette”) has the opportunity to select a potential long-term partner from a pool of candidates. Our analysis encompassed a total of n = 169 seasons from 23 different countries, beginning with the first airing in 2002.
Results: We found that the likelihood of the final couple continuing their relationship beyond the broadcast was higher in The Bachelorette than in The Bachelor, although the duration of these relationships was not significantly influenced by the type of show. On average, women were younger, both when selecting their partner and when being chosen. However, men exhibited a greater preference for larger age differences than women. Furthermore, the age of the chosen male partners significantly increased with the age of the “bachelorettes,” whereas “bachelors” consistently favored women around 25.5 years old, regardless of their own age.
Discussion: We discuss these findings within the context of parental investment theory and sexual strategies theory.
What is left after an error? Towards a comprehensive account of goal-based binding and retrieval
(2023)
The cognitive system readily detects and corrects erroneous actions by establishing episodic bindings between representations of the acted upon stimuli and the intended correct response. If these stimuli are encountered again, they trigger the retrieval of the correct response. Thus, binding and retrieval efficiently pave the way for future success. The current study set out to define the role of the erroneous response itself and explicit feedback for the error during these processes of goal-based binding and retrieval. Two experiments showed robust and similar binding and retrieval effects with and without feedback and pointed towards sustained activation of the unbound, erroneous response. The third experiment confirmed that the erroneous response is more readily available than a neutral alternative. Together, the results demonstrate that episodic binding biases future actions toward success, guided primarily through internal feedback processes, while the erroneous response still leaves detectable traces in human action control.
Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients.
In network research, reproducibility of experiments is not always easy to achieve. Infrastructures are cumbersome to set up or are not available due to vendor-specific devices. Emulators try to overcome those issues to a given extent and are available in different service models. Unfortunately, the usability of emulators requires time-consuming efforts and a deep understanding of their functionality. At first, we analyze to which extent currently available open-source emulators support network configurations and how user-friendly they are. With these insights, we describe, how an ease-to-use emulator is implemented and may run as a Network Emulator as a Service (NEaaS). Therefore, virtualization plays a major role in order to deploy a NEaaS based on Kathará.
Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92–1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42–3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58–1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, −0.09–4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters’ perception. However, the study also highlighted the limitations of today’s virtual reality headsets and Visual Blood.
Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis
(2023)
Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care.
Pain-associated approach and avoidance behaviours are critically involved in the development and maintenance of chronic pain. Empirical research suggests a key role of operant learning mechanisms, and first experimental paradigms were developed for their investigation within a controlled laboratory setting. We introduce a new Virtual Reality paradigm to the study of pain-related behaviour and investigate pain experiences on multiple dimensions. The paradigm evaluates the effects of three-tiered heat-pain stimuli applied contingent versus non-contingent with three types of arm movements in naturalistic virtual sceneries. Behaviour, self-reported pain-related fear, pain expectancy and electrodermal activity were assessed in 42 healthy participants during an acquisition phase (contingent movement-pain association) and a modification phase (no contingent movement-pain association). Pain-associated approach behaviour, as measured by arm movements followed by a severe heat stimulus, quickly decreased in-line with the arm movement-pain contingency. Slower effects were observed in fear of movement-related pain and pain expectancy ratings. During the subsequent modification phase, the removal of the pain contingencies modified all three indices. In both phases, skin conductance responses resemble the pattern observed for approach behaviour, while skin conductance levels equal the pattern observed for the self-ratings. Our findings highlight a fast reduction in approach behaviour in the face of acute pain and inform about accompanying psychological and physiological processes. We discuss strength and limitations of our paradigm for future investigations with the ultimate goal of gaining a comprehensive understanding of the mechanisms involved in chronic pain development, maintenance, and its therapy.
To fire action-potential-like electrical signals, the vacuole membrane requires the two-pore channel TPC1, formerly called SV channel. The TPC1/SV channel functions as a depolarization-stimulated, non-selective cation channel that is inhibited by luminal Ca\(^{2+}\). In our search for species-dependent functional TPC1 channel variants with different luminal Ca\(^{2+}\) sensitivity, we found in total three acidic residues present in Ca\(^{2+}\) sensor sites 2 and 3 of the Ca\(^{2+}\)-sensitive AtTPC1 channel from Arabidopsis thaliana that were neutral in its Vicia faba ortholog and also in those of many other Fabaceae. When expressed in the Arabidopsis AtTPC1-loss-of-function background, wild-type VfTPC1 was hypersensitive to vacuole depolarization and only weakly sensitive to blocking luminal Ca\(^{2+}\). When AtTPC1 was mutated for these VfTPC1-homologous polymorphic residues, two neutral substitutions in Ca\(^{2+}\) sensor site 3 alone were already sufficient for the Arabidopsis At-VfTPC1 channel mutant to gain VfTPC1-like voltage and luminal Ca\(^{2+}\) sensitivity that together rendered vacuoles hyperexcitable. Thus, natural TPC1 channel variants exist in plant families which may fine-tune vacuole excitability and adapt it to environmental settings of the particular ecological niche.
Venus Research Station
(2023)
Because of the extreme conditions in the atmosphere, Venus has been less explored than for example Mars. Only a few probes have been able to survive on the surface for very short periods in the past and have sent data. The atmosphere is also far from being fully explored. It could even be that building blocks of life can be found in more moderate layers of the planet’s atmosphere. It can therefore be assumed that the planet Venus will increasingly become a focus of exploration. One way to collect significantly more data in situ is to build and operate an atmospheric research station over an extended period of time. This could carry out measurements at different positions and at different times and thus significantly expand our knowledge of the planet. In this work, the design of a Venus Research Station floating within the Venusian atmosphere is presented, which is complemented by the design of deployable atmospheric Scouts. The design of these components is done on a conceptual basis.
Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. We introduce an advanced human skin equivalent and use tsetse flies to naturally infect the skin with trypanosomes. We detail the chronological order of the parasites’ development in the skin by single-cell RNA sequencing and find a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Here we show that after the establishment of a proliferative population, the parasites enter a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We term these quiescent trypanosomes skin tissue forms, a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.
Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.
Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.
Psychotropic drugs are frequently prescribed ‘off-label’ to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5%) received psychopharmacological treatment. In 53 (8.1%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.
Valence framing effects refer to inconsistent choice preferences in response to positive versus negative formulation of mathematically equivalent outcomes. Here, we manipulate valence framing in a two-alternative forced choice dictator game using gains and losses as frames to investigate the cognitive mechanisms underlying valence framing. We applied a Drift-Diffusion Model (DDM) to examine whether gain (i.e., “take” money) and loss (i.e., “give” money) frames evoke a cognitive bias as previous research did not consistently reveal framing effects using reaction times and response frequency as dependent variables. DDMs allow decomposing the decision process into separate cognitive mechanisms, whereby a cognitive bias was repeatedly associated with a shift in the starting point of the model. Conducting both a laboratory (N = 62) and an online study (N = 109), female participants allocated money between themselves and another person in a prosocial or selfish way. In each study, one group was instructed to give money (give frame), the other to take money (take frame). Consistent with previous studies, no differences were found in response times and response frequencies. However, in both studies, substantial bias towards the selfish option was found in the take frame groups, captured by the starting point of the DDM. Thus, our results suggest that valence framing induces a cognitive bias in decision processing in women, even when no behavioral differences are present.
This paper presents a prototypical implementation of the In-band Network Telemetry (INT) specification in P4 and demonstrates a use case, where a Tofino Switch is used to measure device and network performance in a lab setting. This work is based on research activities in the area of P4 data plane programming conducted at the network lab of HTW Berlin.
Background: Due to the importance of radiologic examinations, such as X-rays or computed tomography scans, for many clinical diagnoses, the optimal use of the radiology department is 1 of the primary goals of many hospitals.
Objective: This study aims to calculate the key metrics of this use by creating a radiology data warehouse solution, where data from radiology information systems (RISs) can be imported and then queried using a query language as well as a graphical user interface (GUI).
Methods: Using a simple configuration file, the developed system allowed for the processing of radiology data exported from any kind of RIS into a Microsoft Excel, comma-separated value (CSV), or JavaScript Object Notation (JSON) file. These data were then imported into a clinical data warehouse. Additional values based on the radiology data were calculated during this import process by implementing 1 of several provided interfaces. Afterward, the query language and GUI of the data warehouse were used to configure and calculate reports on these data. For the most common types of requested reports, a web interface was created to view their numbers as graphics.
Results: The tool was successfully tested with the data of 4 different German hospitals from 2018 to 2021, with a total of 1,436,111 examinations. The user feedback was good, since all their queries could be answered if the available data were sufficient. The initial processing of the radiology data for using them with the clinical data warehouse took (depending on the amount of data provided by each hospital) between 7 minutes and 1 hour 11 minutes. Calculating 3 reports of different complexities on the data of each hospital was possible in 1-3 seconds for reports with up to 200 individual calculations and in up to 1.5 minutes for reports with up to 8200 individual calculations.
Conclusions: A system was developed with the main advantage of being generic concerning the export of different RISs as well as concerning the configuration of queries for various reports. The queries could be configured easily using the GUI of the data warehouse, and their results could be exported into the standard formats Excel and CSV for further processing.
Usability of a mHealth solution using speech recognition for point-of-care diagnostic management
(2023)
The administrative burden for physicians in the hospital can affect the quality of patient care. The Service Center Medical Informatics (SMI) of the University Hospital Würzburg developed and implemented the smartphone-based mobile application (MA) ukw.mobile1 that uses speech recognition for the point-of-care ordering of radiological examinations. The aim of this study was to examine the usability of the MA workflow for the point-of-care ordering of radiological examinations. All physicians at the Department of Trauma and Plastic Surgery at the University Hospital Würzburg, Germany, were asked to participate in a survey including the short version of the User Experience Questionnaire (UEQ-S) and the Unified Theory of Acceptance and Use of Technology (UTAUT). For the analysis of the different domains of user experience (overall attractiveness, pragmatic quality and hedonic quality), we used a two-sided dependent sample t-test. For the determinants of the acceptance model, we employed regression analysis. Twenty-one of 30 physicians (mean age 34 ± 8 years, 62% male) completed the questionnaire. Compared to the conventional desktop application (DA) workflow, the new MA workflow showed superior overall attractiveness (mean difference 2.15 ± 1.33), pragmatic quality (mean difference 1.90 ± 1.16), and hedonic quality (mean difference 2.41 ± 1.62; all p < .001). The user acceptance measured by the UTAUT (mean 4.49 ± 0.41; min. 1, max. 5) was also high. Performance expectancy (beta = 0.57, p = .02) and effort expectancy (beta = 0.36, p = .04) were identified as predictors of acceptance, the full predictive model explained 65.4% of its variance. Point-of-care mHealth solutions using innovative technology such as speech-recognition seem to address the users’ needs and to offer higher usability in comparison to conventional technology. Implementation of user-centered mHealth innovations might therefore help to facilitate physicians’ daily work.
Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128–129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C–X–C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood–brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.
Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review
(2023)
Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.
There is great interest in affordable, precise and reliable metrology underwater:
Archaeologists want to document artifacts in situ with high detail.
In marine research, biologists require the tools to monitor coral growth and geologists need recordings to model sediment transport.
Furthermore, for offshore construction projects, maintenance and inspection millimeter-accurate measurements of defects and offshore structures are essential.
While the process of digitizing individual objects and complete sites on land is well understood and standard methods, such as Structure from Motion or terrestrial laser scanning, are regularly applied, precise underwater surveying with high resolution is still a complex and difficult task.
Applying optical scanning techniques in water is challenging due to reduced visibility caused by turbidity and light absorption.
However, optical underwater scanners provide significant advantages in terms of achievable resolution and accuracy compared to acoustic systems.
This thesis proposes an underwater laser scanning system and the algorithms for creating dense and accurate 3D scans in water.
It is based on laser triangulation and the main optical components are an underwater camera and a cross-line laser projector.
The prototype is configured with a motorized yaw axis for capturing scans from a tripod.
Alternatively, it is mounted to a moving platform for mobile mapping.
The main focus lies on the refractive calibration of the underwater camera and laser projector, the image processing and 3D reconstruction.
For highest accuracy, the refraction at the individual media interfaces must be taken into account.
This is addressed by an optimization-based calibration framework using a physical-geometric camera model derived from an analytical formulation of a ray-tracing projection model.
In addition to scanning underwater structures, this work presents the 3D acquisition of semi-submerged structures and the correction of refraction effects.
As in-situ calibration in water is complex and time-consuming, the challenge of transferring an in-air scanner calibration to water without re-calibration is investigated, as well as self-calibration techniques for structured light.
The system was successfully deployed in various configurations for both static scanning and mobile mapping.
An evaluation of the calibration and 3D reconstruction using reference objects and a comparison of free-form surfaces in clear water demonstrate the high accuracy potential in the range of one millimeter to less than one centimeter, depending on the measurement distance.
Mobile underwater mapping and motion compensation based on visual-inertial odometry is demonstrated using a new optical underwater scanner based on fringe projection.
Continuous registration of individual scans allows the acquisition of 3D models from an underwater vehicle.
RGB images captured in parallel are used to create 3D point clouds of underwater scenes in full color.
3D maps are useful to the operator during the remote control of underwater vehicles and provide the building blocks to enable offshore inspection and surveying tasks.
The advancing automation of the measurement technology will allow non-experts to use it, significantly reduce acquisition time and increase accuracy, making underwater metrology more cost-effective.
Three-dimensional capturing of underwater archeological sites or sunken shipwrecks can support important documentation purposes. In this study, a novel 3D scanning system based on structured illumination is introduced, which supports cultural heritage documentation and measurement tasks in underwater environments. The newly developed system consists of two monochrome measurement cameras, a projection unit that produces aperiodic sinusoidal fringe patterns, two flashlights, a color camera, an inertial measurement unit (IMU), and an electronic control box. The opportunities and limitations of the measurement principles of the 3D scanning system are discussed and compared to other 3D recording methods such as laser scanning, ultrasound, and photogrammetry, in the context of underwater applications. Some possible operational scenarios concerning cultural heritage documentation are introduced and discussed. A report on application activities in water basins and offshore environments including measurement examples and results of the accuracy measurements is given. The study shows that the new 3D scanning system can be used for both the topographic documentation of underwater sites and to generate detailed true-scale 3D models including the texture and color information of objects that must remain under water.
Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.
Understanding the Performance of Different Packet Reception and Timestamping Methods in Linux
(2023)
This document briefly presents some renowned packet reception techniques for network packets in Linux systems. Further, it compares their performance when measuring packet timestamps with respect to throughput and accuracy. Both software and hardware timestamps are compared, and various parameters are examined, including frame size, link speed, network interface card, and CPU load. The results indicate that hardware timestamping offers significantly better accuracy with no downsides, and that packet reception techniques that avoid system calls offer superior measurement throughput.
Humans spontaneously blink several times a minute. These blinks are strongly modulated during various cognitive task. However, the precise function of blinking and the reason for their modulation has not been fully understood. In the present work, I investigated the function of spontaneous blinks through various perceptual and cognitive tasks. Previous research has revealed that blinks rates decrease during some tasks but increase during others. When trying to understand these seemingly contradictory results, I observed that blink reduction occurs when one engages with an external input. For instance, a decrease has been observed due to the onset of a stimulus, sensory input processing and attention towards sensory input. However, for activities that do not involve such an engagement, e.g. imagination, daydreaming or creativity, the blink rate has been shown to increase. To follow up on the proposed hypothesis, I distinguished tasks that involve the processing of an external stimulus and tasks that involve disengagement.
In the first part of the project, I explored blinking during stimulus engagement. If the probability of blinking is low when engaging with the stimulus, then one should find a reduction in blinks specifically during the time period of processing but not during sensory input per se. To this end, in study 1, I tested the influence of task-relevant information duration on blink timing and additionally manipulated the overall sensory input using a visual and an auditory temporal simultaneity judgement task. The results showed that blinks were suppressed longer for longer periods of relevant information or in other words, blinks occurred at the end of relevant information processing for both the visual and the auditory modality. Since relevance is mediated through top-down processes, I argue that the reduction in blinks is a top-down driven suppression. In studies 2 and 3, I again investigated stimulus processing, but in this case, processing was triggered internally and not based on specific changes in the external input. To this end, I used bistable stimuli, in which the actual physical stimulus remains constant but their perception switches between different interpretations. Studies on the involvement of attention in such bistable perceptual changes indicate that the sensory input is reprocessed before the perceptual switch. The results revealed a reduction in eye blink rates before the report of perceptual switches. Importantly, I was able to decipher that the decrease was not caused by the perceptual switch or the behavioral response but likely started before the internal switch. Additionally, periods between a blink and a switch were longer than interblink intervals, indicating that blinks were followed by a period of stable percept. To conclude, the first part of the project revealed that there is a top-down driven blink suppression during the processing of an external stimulus.
In the second part of the project, I extended the idea of blinks marking the disengagement from external processing and tested if blinking is associated with better performance during internally directed processes. Specifically, I investigated divergent thinking, an aspect of creativity, and the link between performance and blink rates as well as the effect of motor restriction. While I could show that motor restriction was the main factor influencing divergent thinking, the relationship between eye blink rates and creative output also depended on restriction. Results showed that higher blink rates were associated with better performance during free movement, but only between subjects. In other words, subjects who had overall higher blink rates scored better in the task, but when they were allowed to sit or walk freely. Within a single subject, trial with higher blink rates were not associated with better performance. Therefore, possibly, people who are able to disengage easily, as indicated by an overall high blink rate, perform better in divergent thinking tasks. However, the link between blink rate and internal tasks is not clear at this point. Indeed, a more complex measurement of blink behavior might be necessary to understand the relationship.
In the final part of the project, I aimed to further understand the function of blinks through their neural correlates. I extracted the blink-related neural activity in the primary visual cortex (V1) of existing recordings of three rhesus monkeys during different sensory processing states. I analyzed spike related multi-unit responses, frequency dependent power changes, local field potentials and laminar distribution of activity while the animal watched a movie compared to when it was shown a blank screen. The results showed a difference in blink-related neural activity dependent on the processing state. This difference suggests a state dependent function of blinks.
Taken altogether, the work presented in this thesis suggests that eye blinks have an important function during cognitive and perceptual processes. Blinks seem to facilitate a disengagement from the external world and are therefore suppressed during intended processing of external stimuli.
Ubiquitylation is a protein post translational modification, in which ubiquitin is covalently attached to target protein substrates resulting in diverse cellular outcomes. Besides ubiquitin, various ubiquitin-like proteins including FAT10 exist, which are also conjugated to target proteins. The underlying modification mechanisms are conserved. In the initial step, ubiquitin or a ubiquitin-like protein is thioester-linked to a catalytic cysteine in the E1activating enzyme in an ATP-dependent manner. The respective protein modifier is then transferred to an E2 conjugating enzyme in a transthioesterification reaction. Finally, an E3 ubiquitin ligase E3 catalyzes the covalent attachment of the protein modifier to a substrate. In the case of ubiquitin, multiple ubiquitin molecules can be attached to a substrate in the form of either linear or branched polyubiquitin chains but also as single ubiquitin modifications. Depending on the nature of the ubiquitin chain, the substrates are destined to various cellular processes such as their targeted destruction by the proteasome but also non-degradative outcomes may occur.
As stated above FAT10 is a ubiquitin-like protein modifier which typically targets proteins for proteasomal degradation. It consists of two ubiquitin-like domains and is mainly expressed in cells of the human immune system. The reported involvement of FAT10 modifications in cancers and other diseases has caught the attention of the scientific community as an inhibition of the FAT10ylation process may provide avenues for novel therapeutic approaches. UBA6 is the E1 activating enzyme that resides at the apex of the FAT10 proteasomal degradation pathway. UBA6 not only recognizes FAT10 but can also activate ubiquitin as efficiently as the ubiquitin specific E1 UBA1. The dual specificity of UBA6 may complicate the inhibition FAT10ylation since targeting the active site of UBA6 will also inhibit the UBA6-catalyzed ubiquitin activation. Therefore, it is important to understand the underlying principles for the dual specificity of UBA6 prior to the development of compounds interfering with FAT10ylation.
In this thesis important novel insights into the structure and function of UBA6 were derived by X-ray crystallography and biochemical methods. The first crystal structure of UBA6 reveals the multidomain architecture of this enzyme in atomic detail. The enzyme is composed of a rigid core including its active and inactive adenylation domains as well as a 4 helix bundle. Overall, the molecule adopts a “Y” shape architecture with the core at the base and the first and second catalytic half domains forming one arm of the “Y” and the ubiquitin fold domain constituting the other arm. While UBA6 shares the same domain architecture as UBA1, substantial differences were revealed by the crystal structure. In particular, the first catalytic half domain undergoes a significant shift to a position more distal from the core. This rigid body movement is assumed to generate room to accommodate the second ubiquitin-like domain of FAT10. Differences are also observed in a hydrophobic platform between the core and the first catalytic half domain and the adenylation active site in the core, which together from the binding sites for ubiquitin and FAT10. Site directed mutagenesis of key residues in these areas altered the UBA6-catalyzed activation of ubiquitin and FAT10. UBA6 variants were generated with the goal of trying to block the activation of FAT10 while still maintaining that of ubiquitin activation, in order to fully explain the dual specificity of UBA6. However, none of these mutations could block the activation of FAT10, while some of these UBA6 variants blocked ubiquitin activation. Preliminary inhibition assays with a group of E1 inhibitors belonging to the adenosyl sulfamate family demonstrated potent inhibition of FAT10ylation for two compounds. The dual specificity of UBA6 hence needs to be further examined by biochemical and structural methods. In particular, the structure of a complex between UBA6 and ubiquitin or FAT10 would provide key insights for further biochemical studies, ultimately allowing the targeted inhibition of the FAT10ylation machinery.
In this study, the impact of reconstruction sharpness on the visualization of the appendicular skeleton in ultrahigh-resolution (UHR) photon-counting detector (PCD) CT was investigated. Sixteen cadaveric extremities (eight fractured) were examined with a standardized 120 kVp scan protocol (CTDI\(_{vol}\) 10 mGy). Images were reconstructed with the sharpest non-UHR kernel (Br76) and all available UHR kernels (Br80 to Br96). Seven radiologists evaluated image quality and fracture assessability. Interrater agreement was assessed with the intraclass correlation coefficient. For quantitative comparisons, signal-to-noise-ratios (SNRs) were calculated. Subjective image quality was best for Br84 (median 1, interquartile range 1–3; p ≤ 0.003). Regarding fracture assessability, no significant difference was ascertained between Br76, Br80 and Br84 (p > 0.999), with inferior ratings for all sharper kernels (p < 0.001). Interrater agreement for image quality (0.795, 0.732–0.848; p < 0.001) and fracture assessability (0.880; 0.842–0.911; p < 0.001) was good. SNR was highest for Br76 (3.4, 3.0–3.9) with no significant difference to Br80 and Br84 (p > 0.999). Br76 and Br80 produced higher SNRs than all kernels sharper than Br84 (p ≤ 0.026). In conclusion, PCD-CT reconstructions with a moderate UHR kernel offer superior image quality for visualizing the appendicular skeleton. Fracture assessability benefits from sharp non-UHR and moderate UHR kernels, while ultra-sharp reconstructions incur augmented image noise.
Ultra-high-resolution photon-counting detector CT arthrography of the ankle: a feasibility study
(2023)
This study was designed to investigate the image quality of ultra-high-resolution ankle arthrography employing a photon-counting detector CT. Bilateral arthrograms were acquired in four cadaveric specimens with full-dose (10 mGy) and low-dose (3 mGy) scan protocols. Three convolution kernels with different spatial frequencies were utilized for image reconstruction (ρ\(_{50}\); Br98: 39.0, Br84: 22.6, Br76: 16.5 lp/cm). Seven radiologists subjectively assessed the image quality regarding the depiction of bone, hyaline cartilage, and ligaments. An additional quantitative assessment comprised the measurement of noise and the computation of contrast-to-noise ratios (CNR). While an optimal depiction of bone tissue was achieved with the ultra-sharp Br98 kernel (S ≤ 0.043), the visualization of cartilage improved with lower modulation transfer functions at each dose level (p ≤ 0.014). The interrater reliability ranged from good to excellent for all assessed tissues (intraclass correlation coefficient ≥ 0.805). The noise levels in subcutaneous fat decreased with reduced spatial frequency (p < 0.001). Notably, the low-dose Br76 matched the CNR of the full-dose Br84 (p 0.999) and superseded Br98 (p < 0.001) in all tissues. Based on the reported results, a photon-counting detector CT arthrography of the ankle with an ultra-high-resolution collimation offers stellar image quality and tissue assessability, improving the evaluation of miniscule anatomical structures. While bone depiction was superior in combination with an ultra-sharp convolution kernel, soft tissue evaluation benefited from employing a lower spatial frequency.
Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research
(2023)
A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.
Explaining the baryon asymmetry of the Universe has been a long-standing problem of particle physics, with the consensus being that new physics is required as the Standard Model (SM) cannot resolve this issue. Beyond the Standard Model (BSM) scenarios would need to incorporate new sources of \(CP\) violation and either introduce new departures from thermal equilibrium or modify the existing electroweak phase transition. In this thesis, we explore two approaches to baryogenesis, i.e. the generation of this asymmetry.
In the first approach, we study the two-particle irreducible (2PI) formalism as a means to investigate non-equilibrium phenomena. After arriving at the renormalised equations of motions (EOMs) to describe the dynamics of a phase transition, we discuss the techniques required to obtain the various counterterms in an on-shell scheme. To this end, we consider three truncations up to two-loop order of the 2PI effective action: the Hartree approximation, the scalar sunset approximation and the fermionic sunset approximation. We then reconsider the renormalisation procedure in an \(\overline{\text{MS}}\) scheme to evaluate the 2PI effective potential for the aforementioned truncations. In the Hartree and the scalar sunset approximations, we obtain analytic expressions for the various counterterms and subsequently calculate the effective potential by piecing together the finite contributions. For the fermionic sunset approximation, we obtain similar equations for the counterterms in terms of divergent parts of loop integrals. However, these integrals cannot be expressed in an analytic form, making it impossible to evaluate the 2PI effective potential with the fermionic contribution. Our main results are thus related to the renormalisation programme in the 2PI formalism: \( (i) \)the procedure to obtain the renormalised EOMs, now including fermions, which serve as the starting point for the transport equations for electroweak baryogenesis and \( (ii) \) the method to obtain the 2PI effective potential in a transparent manner.
In the second approach, we study baryogenesis via leptogenesis. Here, an asymmetry in the lepton sector is generated, which is then converted into the baryon asymmetry via the sphaleron process in the SM. We proceed to consider an extension of the SM along the lines of a scotogenic framework. The newly introduced particles are charged odd under a \(\mathbb{Z}_2\) symmetry, and masses for the SM neutrinos are generated radiatively. The \(\mathbb{Z}_2\) symmetry results in the lightest BSM particle being stable, allowing for a suitable dark matter (DM) candidate. Furthermore, the newly introduced heavy Majorana fermionic singlets provide the necessary sources of \(CP\) violation through their Yukawa interactions and their out-of-equilibrium decays produce a lepton asymmetry. This model is constrained from a wide range of observables, such as consistency with neutrino oscillation data, limits on branching ratios of charged lepton flavour violating decays, electroweak observables and obtaining the observed DM relic density. We study leptogenesis in this model in light of the results of a Markov chain Monte Carlo scan, implemented in consideration of the aforementioned constraints. Successful leptogenesis in this model, to account for the baryon asymmetry, then severely constrains the available parameter space.
The chirality of the interlocked bay-arylated perylene motif is investigated upon its material prospect and the enhancement of its chiroptical response to the NIR spectral region. A considerable molecular library of inherently chiral perylene bisimides (PBIs) was utilized as acceptors in organic solar cells to provide decent device performances and insights into the structure-property relationship of PBI materials within a polymer blend. For the first time in the family of core-twisted PBIs, the effects of enantiopurity on the device performance was thoroughly investigated. The extraordinary structural sensitivity of CD spectroscopy served as crucial analytical tool to bridge the highly challenging gap between molecular properties and device analytics by proving the excitonic chirality of a helical PBI dimer. The chirality of this perylene motif could be further enhanced on a molecular level by both the expansion and the enhanced twisting of the π-scaffold to achieve a desirable strong chiroptical NIR response introducing a new family of twisted QBI-based nanoribbons. These achievements could be substantially further developed by expanding this molecular concept to a supramolecular level. The geometrically demanding supramolecular arrangement necessary for the efficient excitonic coupling was carefully encoded into the molecular design. Accordingly, the QBIs could form the first J-type aggregate constituting a fourfold-stranded superhelix of a rylene bisimide with strong excitonic chirality. Therefore, this thesis has highlighted the mutual corroboration of experimental and theoretical data from the molecular to the supramolecular level. It has demonstrated that for rylene bisimide dyes, the excitonic contribution to the overall chiroptical response can be designed and rationalized. This can help to pave the way for new organic functional materials to be used for
chiral sensing or chiral organic light-emitting devices.
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.
Non-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug–drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient’s skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.
In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cells (HBMVEC) and immortalized pericytes, both of human origin. The TTFields at a frequency of 100 kHz administered for 72 h increased the permeability of our human-derived BBB model. The integrity of the BBB had already recovered 48 h post-TTFields, which is earlier than that observed in cerebEND. The data presented herein validate the previously observed effects of TTFields in murine models. Moreover, due to the fact that human cell-based in vitro models more closely resemble patient-derived entities, our findings are highly relevant for pre-clinical studies.
The great progress in organic photovoltaics (OPV) over the past few years has been largely achieved by the development of non‐fullerene acceptors (NFAs), with power conversion efficiencies now approaching 20%. To further improve device performance, loss mechanisms must be identified and minimized. Triplet states are known to adversely affect device performance, since they can form energetically trapped excitons on low‐lying states that are responsible for non‐radiative losses or even device degradation. Halogenation of OPV materials has long been employed to tailor energy levels and to enhance open circuit voltage. Yet, the influence on recombination to triplet excitons has been largely unexplored. Using the complementary spin‐sensitive methods of photoluminescence detected magnetic resonance and transient electron paramagnetic resonance corroborated by transient absorption and quantum‐chemical calculations, exciton pathways in OPV blends are unravelled employing the polymer donors PBDB‐T, PM6, and PM7 together with NFAs Y6 and Y7. All blends reveal triplet excitons on the NFA populated via non‐geminate hole back transfer and, in blends with halogenated donors, also by spin‐orbit coupling driven intersystem crossing. Identifying these triplet formation pathways in all tested solar cell absorber films highlights the untapped potential for improved charge generation to further increase plateauing OPV efficiencies.
Alignment strategies for primary total knee arthroplasty (TKA) have changed significantly over time with a shift towards a more individualized alignment goal. At the same time, computer-assisted surgery (CAS) has gained interest for intraoperative control and accuracy in implant positioning and limb alignment. Despite the often discussed benefits and drawbacks of robotics and navigation for TKA, the routine use of these new devices on a day-to-day basis remains obscure. Therefore, nationwide hospital billing data based on the Operation Procedure Classification System (OPS) were retrieved from the Federal Statistical Office of Germany for the period from 2010 to 2021. OPS codes for primary total knee arthroplasty (OPS code: 5-822*) were further analyzed regarding the usage of computer navigation (additional OPS code: 5-988) or robotic devices (additional OPS code: 5-987). Gender and age at the time of surgery were also assessed. The results show a total of 2,226,559 primary TKAs were implanted between 2010 and 2021, of which 2,044,914 were performed conventionally (91.84% of all TKAs). A total of 170,276 TKAs were performed using navigation technique (7.65% of all TKAs) and another 11,369 TKAs were performed using robotics (0.51% of all TKAs). For the period from 2018 to 2021, a substantial increase in robot-assisted TKA (R-TKA) was observed, with an average increase rate of 84.74% per year, while the number of navigated TKAs declined (−3.67% per year). Computer-assisted surgery, and particularly robotics for TKA, are seeing growing popularity and stepwise translation into routine clinical use in Germany, with a steep increase rate of more than 80% per year since 2018. Nevertheless, the majority of TKAs are still performed using manual instrumentation, rendering conventional TKA the currently unchanged gold standard.
Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report
(2023)
Background
Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively.
Case presentation
We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab.
Conclusion
Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive.
The fact that photovoltaics is a key technology for climate-neutral energy production can be taken as a given. The question to what extent perovskite will be used for photovoltaic technologies has not yet been fully answered. From a photophysical point of view, however, it has the potential to make a useful contribution to the energy sector. However, it remains to be seen whether perovskite-based modules will be able to compete with established technologies in terms of durability and cost efficiency. The additional aspect of ionic migration poses an additional challenge. In the present work, primarily the interaction between ionic redistribution, capacitive properties and recombination dynamics was investigated. This was done using impedance spectroscopy, OCVD and IV characteristics as well as extensive numerical drift-diffusion simulations. The combination of experimental and numerical methods proved to be very fruitful. A suitable model for the description of solar cells with respect to mobile ions was introduced in chapter 4.4. The formal mathematical description of the model was transferred by a non-dimensionalization and suitable numerically solvable form. The implementation took place in the Julia language. By intelligent use of structural properties of the sparse systems of equations, automatic differentiation and the use of efficient integration methods, the simulation tool is not only remarkably fast in finding the solution, but also scales quasi-linearly with the grid resolution. The software package was released under an open source license. In conventional semiconductor diodes, capacitance measurements are often used to determine the space charge density. In the first experimental chapter 5, it is shown that although this is also possible for the ionic migration present in perovskites, it cannot be directly understood as doping related, since the space charge distribution strongly depends on the preconditions and can be manipulated by an externally applied voltage. The exact form of this behavior depends on the perovskite composition. This shows, among other things, that experimental results can only be interpreted within the framework of conventional semiconductors to a very limited extent. Nevertheless, the built-in 99 potential of the solar cell can be determined if the experiments are carried out properly. A statement concerning the type and charge of the mobile ions is not possible without further effort, while their number can be determined. The simulations were applied to experimental data in chapter 6. Thus, it could be shown that mobile ions make a significant contribution to the OCVD of perovskite solar cells. j-V characteristics and OCVD transients measured as a function of temperature and illumination intensities could be quantitatively modeled simultaneously using a single global set of parameters. By the simulations it was further possible to derive a simple experimental procedure to determine the concentration and the diffusivity of the mobile ions. The possibility of describing different experiments in a uniform temperaturedependent manner strongly supports the model of mobile ions in perovskites. In summary, this work has made an important contribution to the elucidation of ionic contributions to the (photo)electrical properties of perovskite solar cells. Established experimental techniques for conventional semiconductors have been reinterpreted with respect to ionic mass transport and new methods have been proposed to draw conclusions on the properties for ionic transport. As a result, the published simulation tools can be used for a number of further studies.
Objectives: Positron emission tomography (PET) is currently considered the non-invasive reference standard for lymph node (N-)staging in lung cancer. However, not all patients can undergo this diagnostic procedure due to high costs, limited availability, and additional radiation exposure. The purpose of this study was to predict the PET result from traditional contrast-enhanced computed tomography (CT) and to test different feature extraction strategies. Methods: In this study, 100 lung cancer patients underwent a contrast-enhanced \(^{18}\)F-fluorodeoxyglucose (FDG) PET/CT scan between August 2012 and December 2019. We trained machine learning models to predict FDG uptake in the subsequent PET scan. Model inputs were composed of (i) traditional “hand-crafted” radiomics features from the segmented lymph nodes, (ii) deep features derived from a pretrained EfficientNet-CNN, and (iii) a hybrid approach combining (i) and (ii). Results: In total, 2734 lymph nodes [555 (20.3%) PET-positive] from 100 patients [49% female; mean age 65, SD: 14] with lung cancer (60% adenocarcinoma, 21% plate epithelial carcinoma, 8% small-cell lung cancer) were included in this study. The area under the receiver operating characteristic curve (AUC) ranged from 0.79 to 0.87, and the scaled Brier score (SBS) ranged from 16 to 36%. The random forest model (iii) yielded the best results [AUC 0.871 (0.865–0.878), SBS 35.8 (34.2–37.2)] and had significantly higher model performance than both approaches alone (AUC: p < 0.001, z = 8.8 and z = 22.4; SBS: p < 0.001, z = 11.4 and z = 26.6, against (i) and (ii), respectively). Conclusion: Both traditional radiomics features and transfer-learning deep radiomics features provide relevant and complementary information for non-invasive N-staging in lung cancer.
The Fifth Generation (5G) communication technology, its infrastructure and architecture, though already deployed in campus and small scale networks, is still undergoing continuous changes and research. Especially, in the light of future large scale deployments and industrial use cases, a detailed analysis of the performance and utilization with regard to latency and service times constraints is crucial. To this end, a fine granular investigation of the Network Function (NF) based core system and the duration for all the tasks performed by these services is necessary. This work presents the first steps towards analyzing the signaling traffic in 5G core networks, and introduces a tool to automatically extract sequence diagrams and service times for NF tasks from traffic traces.
In this paper, we work to understand the global IPX network from the perspective of an MVNO. In order to do this, we provide a brief description of the global architecture of mobile carriers. We provide initial results with respect to mapping the vast and complex interconnection network enabling global roaming from the point of view of a single MVNO. Finally, we provide preliminary results regarding the quality of service observed under global roaming conditions.
Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be
attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.