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Abstract Background By transmitting various types of data, telemedical care enables the provision of care where physicians and patients are physically separated. In nursing homes, telemedicine has the potential to reduce hospital admissions in nonemergency situations. In this study, telemedicine devices were implemented with the new 5G mobile communications standard in selected wards of a large nursing home in Northwest Germany. The main aim of this study is to investigate which individual and organizational factors are associated with the use of telemedicine devices and how users perceive the feasibility and implementation of such devices. Moreover, it is investigated whether the telemedical devices help to reduce the number of emergency admissions. Methods Telemedicine devices are implemented over an 18-month period using a private 5G network, and all users receive training. This study uses qualitative and quantitative methods: To assess the individual and organizational factors associated with the use of telemedicine devices, survey data from employees before and after the implementation of these devices are compared. To assess the perception of the implementation process as well as the feasibility and usability of the telemedical devices, the nursing staff, physicians, medical assistants and residents are interviewed individually. Moreover, every telemedicine consultation is evaluated with a short survey. To assess whether the number of emergency admissions decreased, data from one year before implementation and one year after implementation are compared. The data are provided by the integrated dispatch centre and emergency medical services (EMS) protocols. The interview data are analysed via structured qualitative content analysis according to Kuckartz. Survey data are analysed using multivariable regression analysis. Discussion Learnings from the implementation process will be used to inform future projects implementing telemedicine in care organizations, making the final telemedicine implementation and care concept available to more nursing homes and hospitals. Moreover, the study results can be used to provide use cases for appropriate and targeted application of telemedicine in nursing homes and to define the role of 5G technologies in these use cases. If the intervention is proven successful, the results will be used to promote 5G network rollout. Trial registration German Clinical Trials Register – trial registration number: DRKS00030598.

The rapid digitalization of the mobility and transport ecosystem generates an escalating volume of data as a by-product, presenting an invaluable resource for various stakeholders. This mobility and transport data can fuel data-driven services, ushering in a new era of possibilities. To facilitate the development of these digitalized mobility services, we propose a novel conceptual framework for Mobility Data Science. Our approach seamlessly merges two distinct research domains: 1) mobility and transport science, and 2) data science. Mobility Data Science serves as a connective tissue, bridging the digital layers of physical mobility and transport artefacts such as people, goods, transport means, and infrastructure with the digital layer of data-driven services. In this paper, we introduce our conceptual framework, shaped by insights from domain experts deeply immersed in the mobility and transport ecosystem. We present a practical application of our framework in guiding the implementation of a driving style detection service, demonstrating its effectiveness in translating theoretical concepts into real-world solutions. Furthermore, we validate our framework’s versatility by applying it to various real-world cases from the scientific literature. Our demonstration showcases the framework’s adaptability and its potential to unlock value by harnessing mobility and transport data, enabling the creation of impactful data-driven services. We believe our framework offers valuable insights for researchers and practitioners: It provides a structured approach to comprehend and leverage the potential of mobility and transport data for developing impactful data-driven services, which we refer to as digitalized mobility services.

Abstract Human interleukin-1β (hIL-1β) is a pro-inflammatory cytokine involved in many diseases. While hIL-1β directed antibodies have shown clinical benefit, an orally available low-molecular weight antagonist is still elusive, limiting the applications of hIL-1β-directed therapies. Here we describe the discovery of a low-molecular weight hIL-1β antagonist that blocks the interaction with the IL-1R1 receptor. Starting from a low affinity fragment-based screening hit 1, structure-based optimization resulted in a compound (S)-2 that binds and antagonizes hIL-1β with single-digit micromolar activity in biophysical, biochemical, and cellular assays. X-ray analysis reveals an allosteric mode of action that involves a hitherto unknown binding site in hIL-1β encompassing two loops involved in hIL-1R1/hIL-1β interactions. We show that residues of this binding site are part of a conformationally excited state of the mature cytokine. The compound antagonizes hIL-1β function in cells, including primary human fibroblasts, demonstrating the relevance of this discovery for future development of hIL-1β directed therapeutics.

The objective of this study was to evaluate the bait preference of three selected bait types by local dogs and the induced immunogenicity of the oral rabies vaccine strain SPBN GASGAS in Morocco. The vaccine strain, combined with different bait types, has been tested in many different settings, but not yet in northern Africa. Overall, bait consumption and preference were similar in other studies using the same materials (bait type and sachet). The intestine bait had the highest acceptance rate (97.6%, 95%CI: 87.4–99.9), followed by the egg bait (83.0%, 95%CI: 69.2–92.4). Only 52% (95%CI: 37.4–66.3) of the dogs showed an interest in the fish meal bait. However, considering the successful release of the contents of the sachet (blue-dyed water) into the oral cavity, the egg bait (65.7%, 95%CI: 47.8–80.9) scored better than the intestine bait (51.7%, 95%CI: 32.5–70.6). The dogs selected for the immunogenicity study were offered the egg bait containing a sachet filled with SPBN GASGAS (3.0 mL, 107.5 FFU/mL) or were given the same dose by direct oral administration (d.o.a.). In addition, several dogs were vaccinated by the parenteral route (s.c.) using a commercially available inactivated rabies vaccine. Unfortunately, due to the COVID-19 pandemic and subsequent travel restrictions, it was not possible to collect blood samples directly after vaccination. The blood samples were collected pre-vaccination and on five occasions between 450 and 1088 days post vaccination. The seroconversion rate, as determined for rabies-virus-neutralizing antibodies by the FAVN test, was significantly lower than that found for binding antibodies, as determined by ELISA, for all blood samples collected post vaccination. No treatment effect (bait, d.o.a., s.c.) could be seen in the seroconversion rate. At 15 months post vaccination, 84.2% of the dogs offered vaccine bait still tested sero-positive in ELISA. Only after 3 years was a clear drop in the seroconversion rate observed in all three treatment groups. This study confirms the long-term immunogenicity of the oral rabies vaccine SPBN GASGAS in dogs under field conditions.

New digital technologies, the internet age, and ever-increasing customer expectations are changing industries worldwide. Companies in the apparel industry must digitally transform to remain competitive. Traditional approaches will no longer work in the face of change because digital transformation is inevitable, irreversible, enormously fast, and unfortunately marked by challenges in implementation and uncertainties in execution. However, it also brings many benefits for which it is worth striving for the complete digitization of the value chain. This research paper aims to clarify the benefits and challenges companies face in digital transformation. For this purpose, it shows a report on the current state of digitalization in the apparel industry. The article ends with an approach on the implementation of digitization in the apparel companies.

Driver behaviour monitoring is a broad area of research, with a variety of methods and approaches. Distraction from the use of electronic devices, such as smartphones for texting or talking on the phone, is one of the leading causes of vehicle accidents. With the increasing number of sensors available in vehicles, there is an abundance of data available to monitor driver behaviour, but it has only been available to vehicle manufacturers and, to a limited extent, through proprietary solutions. Recently, research and practice have shifted the paradigm to the use of smartphones for driver monitoring and have fuelled efforts to support driving safety. This systematic review paper extends a preliminary, previously carried out author-centric literature review on smartphone-based driver monitoring approaches using snowballing search methods to illustrate the opportunities in using smartphones for driver distraction detection. Specifically, the paper reviews smartphone-based approaches to distracted driving behaviour detection, the smartphone sensors and detection methods applied, and the results obtained.

Distracted driving is known to be one of the leading causes of vehicle accidents. With the increase in the number of sensors available within vehicles, there exists an abundance of data for monitoring driver behaviour, which, however, have so far only been comparable across vehicle manufacturers to a limited extent due to proprietary solutions. A special role in distraction is played by the smartphone, which is repeatedly a source of distraction for drivers through calls and messages. However, the smartphone can be used for driver behaviour monitoring (like driver distraction detection) too, as current developments show. As vehicle manufacturer-independent device, which is usually equipped with adequate sensor technology, smartphones can provide significant advantages, however, an overview of such approaches is missing so far. Thus, this work carries out an author-centric literature review of 16 research papers to illustrate the opportunities in using smartphones to detect driver distraction.

Driver inattention and distraction are the main causes of road accidents, many of which result in fatalities. To reduce road accidents, the development of information systems to detect driver inattention and distraction is essential. Currently, distraction detection systems for road vehicles are not yet widely available or are limited to specific causes of driver inattention such as driver fatigue. Despite the increasing automation of driving due to the availability of increasingly sophisticated assistance systems, the human driver will continue to play a longer role as supervisor of vehicle automation. With this in mind, we review the published scientific literature on driver distraction detection methods and integrate the identified approaches into a holistic framework that is the main contribution of the paper. Based on published scientific work, our driver distraction detection framework contains a structured summary of reviewed approaches for detecting the three main distraction detection approaches: manual distraction, visual distraction, and cognitive distraction. Our framework visualizes the whole detection information chain from used sensors, measured data, computed data, computed events, inferred behavior, and inferred distraction type. Besides providing a sound summary for researchers interested in distracted driving, we discuss several practical implications for the development of driver distraction detection systems that can also combine different approaches for higher detection quality. We think our research can be useful despite - or even because of - the great developments in automated driving.

For many people, driving a vehicle is an indispensable part of everyday life. However, sometimes everyday life does not go as expected, as a lot of accidents happen on the public roads. Most of the accidents are due to inattentive driver behavior. Modern driver monitoring systems evaluate driver behavior by means of distinctive sensor technology and, if necessary, indicate undesirable driving behavior. However, many roadworthy vehicles do not have the possibility to implement such systems. Therefore, it seems to be interesting to investigate the implementation of such systems on the basis of commodity hardware, e.g. smartphones, because nowadays almost every driver has a powerful smartphone equipped with many sensors. Furthermore, advances in machine learning made it possible to analyze large amounts of data and to generate new conclusions. This work is dedicated to the topic of how machine learning can be used for driver behavior recognition by improving an already existing driver monitoring system with machine learning techniques. We propose to use Microsoft Azure platform to analyze the data generated by a Driver Monitoring System.

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies.

Oral vaccination of wildlife has shown to be a very effective management tool in rabies control. Evaluation of the genetic stability of vaccine viruses before distributing vaccine baits in the environment is essential because all available oral rabies vaccines, including the genetically engineered rabies virus vaccine strain SPBN GASGAS (Rabitec), are based on replication-competent viruses. To evaluate the genetic stability of this vaccine strain, five serial passages of the Master Seed Virus (MSV) in the production cell line BHK21 Cl13 were performed. Furthermore, to test possible reversion to virulence, a back-passage study in suckling mouse brain (SMB) was performed. Subsequently, the pooled 5th SMB passage was inoculated intracerebrally (i.c.) in adult and suckling mice. The full genome sequences of the isolated 5th passage, in vivo and in vitro, were compared at both the consensus and the quasispecies level with the MSV. Additionally, the full genome sequence of the 6th SMB passage from the individual animals was determined and compared. Full-length integration of the double glycoprotein and modified base substitutions at amino acid position 194 and 333 of the glycoprotein could be verified in all 5th and 6th passage samples. Overall, 11 single nucleotide polymorphisms (SNPs) were detected in the 5th pooled SMB passage, 4 with frequency between 10 and 20%, and 7 with between 2.5 and 10%. SNPs that resulted in amino acid exchange were found in genes: N (one SNP), G (four SNPs), and L (three SNPs). However, none of these SNPs were associated with reversion to virulence since all adult mice inoculated i.c. with this material survived. In the individual samples of the 6th SMB passage 24 additional SNPs (>2.5%) were found, of which only 1 SNP (L-gene, position 6969) had a prevalence of >50% in 3 of 17 samples. The obtained results confirmed the stable expression of genetic modifications and the genetic stability of the consensus strain after serial in vivo and in vitro passaging.

The Sec translocon, consisting of a heterotrimeric transmembrane channel (SecYEG) and an associated ATPase (SecA), catalyzes the export of unfolded proteins from the cytosol in bacteria. Kinetically resolving protein translocation at high resolution yields mechanistic insight into the process. Translocation is typically followed by measuring the protection of proteins transported into lipid vesicles, which only allows visualization of translocation after it has already been completed and limits time resolution. Here, we describe the implementation of an assay for measuring translocation in real-time. By priming the reconstituted translocon with suitably engineered substrate proteins, the kinetics of the actual translocation process can be resolved at high resolution. To analyze translocation kinetics, we developed a detailed kinetic model of the process that includes on-pathway and off-pathway processes. Together, this experimental protocol and model permit detailed mechanistic analyses of Sec-dependent protein translocation.Graphic abstract:Synchronized real-time measurements, combined with a detailed kinetic model, enable a mechanistic analysis of protein transport.

Background:. We tested the workflow and comparability of compression garments (CG) automatically knitted from 3D-body-scan data (3DBSD) versus manually measured data for scar treatment. Industry 4.0 has found its way into surgery, enhancing the trend toward personalized medicine, which plays an increasingly important role in CG scar therapy. Therefore, we conducted a study to evaluate the workflow from 3DBSD to fast and precisely knitted CG and compared it with standard of care. Methods:. A randomized controlled crossover feasibility study was conducted as part of the individual medical technology research project “Smart Scar Care.” Objective and patient-reported outcome measures were documented for 10 patients with hypertrophic burn scars at baseline and after wearing CG automatically knitted from 3DBSD versus CG from manually measured data for one month. Results:. The “scan-to-knit” workflow and the study design were feasible in 10 of 10 patients. No adverse effects were found. 3DBSD showed a bias of half a centimeter compared with manually measured data and wider limits of agreement. With respect to fit, comfort, suitability, Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, stiffness and microcirculation, this was a promising pilot study. Stiffness and blood flow were increased in scars compared with normal skin. The highest rank correlations were found between pain and itch, stiffness and Patient and Observer Scar Assessment Scale, Vancouver Scar Scale, and pain. Conclusions:. These results indicate that automatically knitted CG using 3DBSD could become an alternative to the standard of care, especially with regard to economical and faster patient care. The produced scan data opens the door for objective scar science.

Im Zusammenhang mit der Covid-19-Pandemie wurde die Aktualität der Lehren des ethischen Hedonismus der epikureischen Tradition betont. Der Beitrag möchte die Aspekte dieses Hedonismus aufzeigen, die in der aktuellen Krise relevant sein könnten, und dabei auf ihre theoretische Begründung und historische Fundierung eingehen. Zentral ist zunächst die Beschäftigung mit der eigenen Sterblichkeit. Der Tod wird ständig vergegenwärtigt; Epidemien sind seit der Antike ein klassisches Beispiel zur Illustration der Bedeutung der Todesakzeptanz für das Lebensglück. Das „gute Leben“ beinhaltet die „Selbstisolation“, hier verstanden als die Konzentration auf einen kleinen Kreis von Menschen, die einander helfen, ein freudeerfülltes Leben zu realisieren. Im Vordergrund steht zudem die permanente Selbstbeschränkung auf die Befriedigung der wirklich notwendigen und natürlichen Bedürfnisse zur Therapie der eigenen Leidenschaften. Auf diesem Fundament lassen sich Grundsätze für den sozialen und politischen Umgang mit epidemischen Gefahren formulieren, etwa die stärkere Berücksichtigung der Notwendigkeit der Bedürfnisbefriedigung im materiellen und zwischenmenschlichen Sinne, die Präferenz für die Gesundheitsversorgung gegenüber anderen öffentlich finanzierten Bereichen, aber auch philosophische Aufklärung gegen die verbreitete Todesverdrängung.

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.

To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (106.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (103.0 MICLD50/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia.

Interlayer exchange coupling of two ferromagnetic electrodes separated by a thin MgO tunnel barrier is investigated using magneto-optical Kerr effect. We find that the coupling field can be reduced by more than 40% as the thickness of a top Ta capping layer increases from 0.5 to 1.2 nm. In contrast, a similar film stack with an additional 3 nm Ru capping layer displays no such dependence on Ta thickness. Transmission electron microscopy study shows that the oxidation of the exposed Ta capping layer induces changes in the crystalline structures of the underlying films, giving rise to the observed reduction of the interlayer coupling field.