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BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.MethodsA total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.ResultsThe in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.ConclusionThis study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.

Purpose Effective training of extracorporeal membrane oxygenation (ECMO) cannulation is key to fighting the persistently high mortality rate of ECMO interventions. Though augmented reality (AR) is a promising technology for improving information display, only a small percentage of AR projects have addressed training procedures. The present study investigates the potential benefits of AR-based, contextual instructions for ECMO cannulation training as compared to instructions used during conventional training at a university hospital. Methodology An AR step-by-step guide was developed for the Microsoft HoloLens 2 that combines text, images, and videos from the conventional training program with simple 3D models. A study was conducted with 21 medical students performing two surgical procedures on a simulator. Participants were divided into two groups, with one group using the conventional instructions for the first procedure and AR instructions for the second and the other group using instructions in reverse order. Training times, a detailed error protocol, and a standardized user experience questionnaire (UEQ) were evaluated. Results AR-based execution was associated with slightly higher training times and with significantly fewer errors for the more complex second procedure (p, International Journal of Computer Assisted Radiology and Surgery, 16 (6), ISSN:1861-6410, ISSN:1861-6429

Eye tracking (ET) has shown to reveal the wearer’s cognitive processes using the measurement of the central point of foveal vision. However, traditional ET evaluation methods have not been able to take into account the wearers’ use of the peripheral field of vision. We propose an algorithmic enhancement to a state-of-the-art ET analysis method, the Object-Gaze Distance (OGD), which additionally allows the quantification of near-peripheral gaze behavior in complex real-world environments. The algorithm uses machine learning for area of interest (AOI) detection and computes the minimal 2D Euclidean pixel distance to the gaze point, creating a continuous gaze-based time-series. Based on an evaluation of two AOIs in a real surgical procedure, the results show that a considerable increase of interpretable fixation data from 23.8 % to 78.3 % of AOI screw and from 4.5 % to 67.2 % of AOI screwdriver was achieved, when incorporating the near-peripheral field of vision. Additionally, the evaluation of a multi-OGD time series representation has shown the potential to reveal novel gaze patterns, which may provide a more accurate depiction of human gaze behavior in multi-object environments., Journal of Eye Movement Research, 14 (1)

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the human retina which in its most aggressive form is associated with the formation of macular neovascularization (MNV) and subretinal fibrosis leading to irreversible blindness. MNVs contain blood vessels as well as infiltrating immune cells, myofibroblasts, and excessive amounts of extracellular matrix proteins such as collagens, fibronectin, and laminin which disrupts retinal function and triggers neurodegeneration. In the mammalian retina, damaged neurons cannot be replaced by tissue regeneration, and subretinal MNV and fibrosis persist and thus fuel degeneration and visual loss. This review provides an overview of subretinal fibrosis in neovascular AMD, by summarizing its clinical manifestations, exploring the current understanding of the underlying cellular and molecular mechanisms and discussing potential therapeutic approaches to inhibit subretinal fibrosis in the future.

Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV‑2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV‑2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV‑2. The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.Aktuelle Studien haben bei ca. 1 % aller COVID-19-Patienten eine Bindehautentzündung beschrieben und spekuliert, dass SARS-CoV‑2 über die Bindehaut übertragen werden kann. In der vorliegenden Arbeit rekapitulieren wir die molekularen Mechanismen des Eintritts von SARS-CoV‑2 in die Wirtszelle und diskutieren die aktuelle Studienlage zu einer möglichen konjunktivalen Transmission. Derzeit geht man davon aus, dass SARS-CoV‑2 das membrangebundene Angiotensin-konvertierende Enzym 2 (ACE2) sowie die Membran-gebundene Serinprotease TMPRSS2 benötigt, um in die Wirtszelle einzudringen. Aktuelle Studien weisen darauf hin, dass COVID-19-Patienten nur selten Virus-RNA im Tränenfilm und Bindehautabstrichen aufweisen und dass ACE2 und TMPRSS2 in der Bindehaut nur in sehr geringen Mengen gebildet werden, was eine konjunktivale Infektion durch SARS-CoV‑2 über diese Mediatoren wenig wahrscheinlich macht. Dennoch halten wir die derzeitige Studienlage für zu begrenzt, um eine abschließende Aussage treffen zu können, und empfehlen konsequente und adäquate Schutzmaßnahmen für medizinisches Personal, das in engem Kontakt mit verdächtigen und bestätigten COVID-19-Patienten steht.

ZusammenfassungAktuelle Studien haben bei ca. 1 % aller COVID-19-Patienten eine Bindehautentzündung beschrieben und spekuliert, dass SARS-CoV‑2 über die Bindehaut übertragen werden kann. In der vorliegenden Arbeit rekapitulieren wir die molekularen Mechanismen des Eintritts von SARS-CoV‑2 in die Wirtszelle und diskutieren die aktuelle Studienlage zu einer möglichen konjunktivalen Transmission. Derzeit geht man davon aus, dass SARS-CoV‑2 das membrangebundene Angiotensin-konvertierende Enzym 2 (ACE2) sowie die Membran-gebundene Serinprotease TMPRSS2 benötigt, um in die Wirtszelle einzudringen. Aktuelle Studien weisen darauf hin, dass COVID-19-Patienten nur sehr selten Virus-RNA im Tränenfilm und Bindehautabstrichen aufweisen und dass ACE2 und TMPRSS2 in der Bindehaut nur in sehr geringen Mengen gebildet werden, was eine konjunktivale Infektion durch SARS-CoV‑2 über diese Mediatoren wenig wahrscheinlich macht. Dennoch halten wir die derzeitige Studienlage für zu begrenzt, um eine abschließende Aussage treffen zu können, und empfehlen konsequente und adäquate Schutzmaßnahmen für medizinisches Personal, das in engem Kontakt mit verdächtigen und bestätigten COVID-19-Patienten steht.

Purpose To describe the clinical presentation and novel anatomical features of a patient with chronic central serous chorioretinopathy (CSCR) complicated by retinal neovascularization (RNV). Observations A 48 year-old patient with a long-standing history of bilateral CSCR presented to our clinic complaining about a sudden onset of tiny floaters. Multimodal imaging including fundus autofluorescence (FAF), fundus fluorescein (FA) and ICG angiography (ICG) and spectral domain optical coherence tomography (SD-OCT) confirmed the diagnosis of CSCR and revealed a pre-retinal neovascularization and concurring vitreous hemorrhage. Swept source OCT angiography (OCTA) and 3D reconstruction virtual reality determined the retinal origin of the neovascularization. Follow-up examination revealed clearing of the vitreous hemorrhage and spontaneous obliteration of the RNV without any treatment three months following the initial presentation. Conclusion and importance To the best of our knowledge, this is the first report of a RNV associated with CSCR which was determined by three-dimensional (3D) OCTA reconstruction

For an in-depth, AOI-based analysis of mobile eye tracking data, a preceding gaze assignment step is inevitable. Current solutions such as manual gaze mapping or marker-based approaches are tedious and not suitable for applications manipulating tangible objects. This makes mobile eye tracking studies with several hours of recording difficult to analyse quantitatively. We introduce a new machine learning-based algorithm, the computational Gaze-Object Mapping (cGOM), that automatically maps gaze data onto respective AOIs. cGOM extends state-of-the-art object detection and segmentation by mask R-CNN with a gaze mapping feature. The new algorithm’s performance is validated against a manual fixation-by-fixation mapping, which is considered as ground truth, in terms of true positive rate (TPR), true negative rate (TNR) and efficiency. Using only 72 training images with 264 labelled object representations, cGOM is able to reach a TPR of approx. 80% and a TNR of 85% compared to the manual mapping. The break-even point is reached at 2 hours of eye tracking recording for the total procedure, respectively 1 hour considering human working time only. Together with a real-time capability of the mapping process after completed training, even hours of eye tracking recording can be evaluated efficiently., Journal of Eye Movement Research, 11 (6)

In order to enable the ATLAS experiment to successfully track charged particles produced in high-energy collisions at the High-Luminosity Large Hadron Collider, the current ATLAS Inner Detector will be replaced by the Inner Tracker (ITk), entirely composed of silicon pixel and strip detectors. An extension of the tracking coverage of the ITk to very forward pseudorapidity values is proposed, using pixel modules placed in a long cylindrical layer around the beam pipe. The measurement of long pixel clusters, detected when charged particles cross the silicon sensor at small incidence angles, has potential to significantly improve the tracking efficiency, fake track rejection, and resolution of the ITk in the very forward region. The performance of state-of-the-art pixel modules at small track incidence angles is studied using test beam data collected at SLAC and CERN.

Robustness and reliability are essential requirements of today's embedded systems. Especially errors in the control flow of a program, e.g. caused by transient errors, may lead to a faulty system behavior potentially with catastrophic consequences. Several methods for control flow checking have been proposed during the last decades. However, these techniques mostly focus on a correct sequence of application parts but not on the correct timing behavior of the control flow, which is essential for hard real-time systems. In this paper, we present a new approach which introduces fine-grained on-line timing checks for hard real-time systems combined with a lightweight control flow monitoring technique. The proposed approach is a hybrid hardware-software technique: We instrument the application code at compile-time by adding checkpoints, which contain temporal and logical information of the control flow. During run-time, a small hardware check unit connected to the core reads the instrumented data in order to verify the correctness of the application's control flow and timing behavior. The finegrained functionality of our mechanism allows a detection of many transient errors, associated with very low detection latency. It is no longer necessary to redundantly execute code in order to monitor anomalies. The hardware overhead is limited to a small check unit (only 0.5 % of chip space compared to the processor core); according to experimental results, the execution time overhead is only 10.6 % in the average case while the memory overhead is 12.3 %.

Dependability is a crucial requirement of today's embedded systems. To achieve a higher level of fault tolerance, it is necessary to develop and integrate mechanisms for a reliable fault detection. In the context of hard real-time computing, such a mechanism should also guarantee correct timing behavior, an essential requirement for these systems. In this paper, we present results of the fault coverage of a lightweight timing and control flow checker for hard real-time systems. An experimental evaluation shows that more than 30% of injected faults can be detected by our technique, while the number of errors leading to an endless loop is reduced by around 80 %. The check mechanism causes only very low overhead concerning additional memory usage (15.0% on average) and execution time (12.2% on average).

Hard real-time applications in safety-critical domains — namely avionics, automotive, and machinery — require high-performance and timing analysability. We present research results of the parallelisation and WCET analysis of an industrial hard real-time application, i.e. the control code of a large drilling machine from BAUER Maschinen GmbH. We reached a quad-core speedup of 2.62 for the maximum observed execution time (MOET) and 1.93 on the WCET compared to the sequential version. For the WCET analysis we used the measurement-based WCET analysis tool RapiTime.

Future computing systems (Teradevices) will probably contain more than 1000 cores on a single die. To exploit this parallelism, threaded dataflow execution models are promising, since they provide side-effect free execution and reduced synchronization overhead. But the terascale transistor integration of such chips make them orders of magnitude more vulnerable to voltage fluctuation, radiation, and process variations. This means reliability techniques have to be an essential part of such future systems, too.In this paper, we conceptualize a fault tolerant architecture for a scalable threadeddataflow system. We provide methods to detect permanent, intermittent, and transientfaults during the execution. Furthermore, we propose a recovery technique for dataflow threads.

Multicore processors can deliver higher performance than single-core processors by exploiting thread level parallelism (TLP): applications are split into independent threads, each of which is mapped into a different core, reducing the execution time and potentially its worst-case execution time (WCET). Unfortunately, inter-thread interferences generated by simultaneous accesses to shared resources from different threads may completely destroy the performance benefits brought by TLP. This paper proposes a software/hardware cache partitioning approach that reduces the inter-thread memory interferences generated in hard real-time software-pipelined parallel applications. Our results show that our approach effectively reduces memory interferences, while still guaranteeing a predictable timing behaviour, achieving a WCET estimation reduction of 28% for a software pipelined version of the LU decomposition application with respect to the single-threaded version.

Ubiquitous systems build on the vision that great amounts of fixed and mobile microchips and sensors will be integrated in everyday objects. Developing services on basis of sensor nodes and limited devices is an arduous task. A program running on such a device is static and limited to a single service. If a new service needs to be performed, devices have to be fundamentally reprogrammed and reloaded. For dynamic service distribution a mobile agent system is devised and services are distributed by mobile agents. The idea in this paper is to load a service on a limited device or sensor node when it is needed and to switch services dynamically. The service comes in form of an agent to each device. We developed a mobile agent system called UbiMASS that is downsized to run on sensor nodes. UbiMASS was evaluated on the sensor nodes ESB430 which has multiple sensors and actuators on-board. For real test scenarios, we could investigate the possibility and advantages of service changes on a wireless sensor network using mobile agents. UbiMASS offers an easy and convenient way to dynamically reprogram tiny devices with wireless connections.

The Merasa project aims to achieve a breakthrough in hardware design, hard real-time support in system software, and worst-case execution time analysis tools for embedded multicore processors. The project focuses on developing multicore processor designs for hard real-time embedded systems and techniques to guarantee the analyzability and timing predictability of every feature provided by the processor.

Multi-cores are the contemporary solution to satisfy high performance and low energy demands in general and embedded computing domains. However, currently available multi-cores are not feasible to be used in safety-critical environments with hard real-time constraints. Hard real-time tasks running on different cores must be executed in isolation or their interferences must be time-bounded. Thus, new requirements also arise for a real-time operating system (RTOS), in particular if the parallel execution of hard real-time applications should be supported. In this paper we focus on the MERASA system software as an RTOS developed on top of the MERASA multi-core processor. The MERASA system software fulfils the requirements for time-bounded execution of parallel hard real-time tasks. In particular we focus on thread control with synchronisation mechanisms, memory management and resource management requirements. Our evaluations show that all system software functions are time-bounded by a worst-case execution time (WCET) analysis.