Sick (Germany)

Digital technologies for type 2 diabetes mellitus (T2DM) care hold great potential to improve patients' health in the long term. Only a subset of telemedicine offerings are digital interventions that meet the criteria for prescribable digitale Gesundheitsanwendung (digital health apps; DiGAs) in Germany. Digital treatments further provide vast amounts of patient data that are important to generate evidence. This systematic review aims to analyze the efficacy of multimodal digital therapies that mainly meet the DiGA criteria for patients with T2DM and to elicit the potential of such therapies. This includes evidence from randomized controlled trials (RCTs) as well as from real-world data. The outcome of interest was a reduction in glycated hemoglobin (hemoglobin A1c [HbA1c]; long-term blood glucose measurements). A systematic literature search was conducted in the literature bases PubMed, LIVIVO, and Cochrane, based on the predefined PICO (Population; Intervention; Control; Outcome) scheme. Identified studies were assessed for risk of bias, pragmatism, and overall quality of evidence. Meta-analyses were conducted for between group differences using RCTs only, and for within-group differences using RCTs and non-RCTs, to examine the effect of the interventions on HbA1c. In total, 795 records were identified, of which 24 were eligible for this systematic review and 23 studies were eligible for the meta-analysis. The results of the meta-analyses showed significant and clinically relevant reductions in HbA1c in patients with T2DM. Regarding the between-group difference for HbA1c reduction, the pooled effect of the RCTs showed a reduction of -0.36% (95% CI -0.59% to -0.14%; P<.001), favoring app-based interventions. The average mean within-group reduction in HbA1c was -0.79 (95% CI -1.02 to -0.55), with no significant difference between RCTs (-0.69, 95% CI -1.13 to -0.24) and non-RCTs (-0.87, 95% CI -1.16 to -0.57; P<.01, differences between RCTs and RCTs P=.44). A pragmatism rating showed that both study types were on average (very) pragmatic, that is, close to usual care. However, the overall quality of evidence was low to very low. This systematic review shows that digital therapies that mainly meet the DiGA criteria can effectively improve HbA1c in patients with T2DM. The integration of digital health care into usual care holds great potential and should be considered as a complementary option to usual care in the future. PROSPERO CRD42023440203; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=440203.

Abstract Down syndrome (DS, or Trisomy 21) is one of the most common genetic causes of intellectual disability. DS results in both abnormal neurodevelopment and accelerated neurodegeneration, but the molecular mechanisms underlying abnormal cortical construction and aging are incompletely understood. To gain molecular insight into the prenatal neurobiology of DS, we performed single-nucleus sequencing, spatial transcriptomics, and proteomics on mid-gestational prenatal human brain tissue. We captured altered expression dynamics of lineage commitment genes and pronounced de-repression of transposable elements in DS neural progenitor cells, which suggest changes to the fate and functionality of neuronal and glial cells. Given the importance of linking human and model system pathobiology, we also performed highly multiplexed RNA in situ spatial transcriptomics on a well-established trisomic mouse model (Ts65Dn) to study the cellular landscape of the trisomic brain during early life and aging. We profiled the spatial transcriptome of &gt; 240,000 cells in the mouse brain and identified trisomy-associated gene expression patterns in the molecular control of neurogenesis and gliogenesis. Together, our study provides a comprehensive cross-species understanding of the complex multicellular processes underlying DS neurodevelopment.

In logistic environments, diverse applications, reaching from robotics to monitoring and quality assess-ment, benefit from depth information processing. In addition, multiple depth image cameras have been introduced to the market which differ widely in the used imaging technology, quality and price. In this paper, an open source data set is presented, containing calibrated and timely synchronized real world data from seven different depth imaging sensors, including a quantitative evaluation of the quality of each used sensor, in multiple logistic scenarios.

X-linked hypophosphatemia (XLH) is a rare, progressive disorder characterized by excess fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D synthesis. Burosumab is a recombinant human monoclonal antibody that inhibits FGF23, restoring patient serum phosphate levels. Safety data on long-term burosumab treatment are currently limited. This post-authorization safety study (PASS) aims to monitor long-term safety outcomes in children and adolescents (1-17 years) treated with burosumab for XLH. This first interim analysis reports the initial PASS safety outcomes. A 10-year retrospective and prospective cohort study. This PASS utilizes International XLH Registry (NCT03193476) data, which includes standard diagnostic and monitoring practice data at participating European centers. At data cut-off (13 May 2021), 647 participants were included in the International XLH Registry; 367 were receiving burosumab, of which 67 provided consent to be included in the PASS. Mean (SD) follow-up time was 2.2 (1.0) years. Mean (SD) age was 7.3 (4.3) years (range 1.0-17.5 years). Mean duration of burosumab exposure was 29.7 (25.0) months. Overall, 25/67 participants (37.3%) experienced ⩾1 adverse event (AE) during follow-up; 83 AEs were reported. There were no deaths, no AEs leading to treatment withdrawal, nor serious AEs related to treatment. The most frequently reported AEs were classified as 'musculoskeletal and connective tissue disorders', with 'pain in extremity' most frequently reported, followed by 'infections and infestations', with 'tooth abscess' the most frequently reported. In this first interim analysis of the PASS, covering the initial 2 years of data collection, the safety profile of burosumab is consistent with previously reported safety data. The PASS will provide long-term safety data over its 10-year duration for healthcare providers and participants with XLH that contribute to improvements in the knowledge of burosumab safety. European Union electronic Register of Post-Authorisation Studies: EUPAS32190.

We demonstrate solid-state optical phased arrays exploiting 3D-printed facet-attached freeform elements for shaping and deflection of an edge-emitted beam to a surface-normal direction. The concept opens an attractive alternative to widely used grating structures.

Zunehmend suchen Komponentenhersteller nach Lösungen zur Bereitstellung von digitalen Abbildern ihrer realen Komponenten. Ziel ist es, dass Kunden damit ihre Automatisierungskonzepte virtuell validieren und Steuerungssysteme im Entwicklungsprozess anhand einer virtuellen Inbetriebnahme eingehend testen und optimieren können. Simulationswerkzeuge für die virtuelleInbetriebnahme bieten mittlerweile vielfältige Schnittstellen zur Einbindung bestehender Teilmodelle bei der Modellierung eines digitalen Zwillings einer Maschine oder Anlage. In diesem Beitrag wird die Online-Plattform „TwinStore“ für den Austausch von Simulationsmodellen zur virtuellen Inbetriebnahme vorgestellt.

The International Data Spaces (IDS) are virtual data spaces leveraging existing standards and technologies, as well as governance models, well-accepted in the data economy, to facilitate secure and standardized data exchange and data linkage in a trusted business ecosystem. It thereby provides a basis for creating smart service scenarios and facilitating innovative cross-company business processes, while at the same time guaranteeing data sovereignty for data owners. Data sovereignty is a central aspect of the IDS. It can be defined as a natural person’s or corporate entity’s capability of being entirely self-determined with regard to its data. The International Data Spaces initiative proposes a Reference Architecture Model for this particular capability and related aspects, including requirements for secure and trusted data exchange in business ecosystems. Focusing on the generalization of concepts, functionality, and overall processes involved in the creation of a secure “network of trusted data”, the IDS Reference Architecture resides at a higher abstraction level than common architecture models of concrete software solutions do. The document provides an overview supplemented by dedicated architecture specifications defining the individual components of the IDS (Connector, Broker, App Store, etc.) in detail. In compliance with common system architecture models and standards (e.g., ISO 42010, 4+1 view model), the IDS Reference Architecture Model uses a five-layer structure expressing various stakeholders’ concerns and viewpoints at different levels of granularity. The general structure of the IDS Reference Architecture Model is made up of five layers: The <em>Business Layer </em>specifies and categorizes the different roles which the participants of the IDS can assume, and it specifies the main activities and interactions connected with each of these roles. The <em>Functional Layer</em> defines the functional requirements of the IDS, plus the concrete features to be derived from these. The <em>Process Layer </em>specifies the interactions taking place between the different components of the IDS; using the BPMN notation, it provides a dynamic view of the Reference Architecture Model. The <em>Information</em> <em>Layer </em>defines a conceptual model which makes use of linked-data principles for describing both the static and the dynamic aspects of the IDS’s constituents. The <em>System Layer </em>is concerned with the decomposition of the logical software components, considering aspects suchas integration, configuration, deployment, and extensibility of these components. In addition, the IDS Reference Architecture Model comprises three perspectives that need to be implemented across all five layers: <em>Security, Certification, and Governance.</em>

Supply-voltage reduction in digital circuits beyond the minimum energy per operation point is advantageous for supply-voltage-constrained applications and can help to considerably reduce standby power consumption. Schmitt trigger (ST) logic allows for ultra-low voltage (ULV) operation; hardware implementations with supply voltages as low as 62mV have been demonstrated. In this paper, a systematic in-depth analysis of ST logic is presented. First, it is shown that ST logic allows for operation at supply voltages below the ultimate limit of standard digital CMOS circuits, making it-to the best of our knowledge- the only approach proposed to date for operation of digital circuits in this voltage region. The factors critical to the ultimate limit of supply voltage reduction are the ON-to-OFF current ratio of the transistors and the susceptibility to global variability. It is shown that ST logic provides improvements over standard CMOS logic in both of these aspects. The hysteresis that occurs in ST circuits at nominal supply voltage could potentially limit the applicability for ULV operation and is therefore carefully investigated. Furthermore, a systematic approach to optimum sizing of ST gates is presented for the first time. ST gates exhibit inherent overheads with respect to gate area, delay, and leakage, which are carefully evaluated. Compared with standard CMOS gates designed for the same minimum supply voltage, it is shown that ST gates, nevertheless, are the most efficient solution if the target minimum supply voltage is sufficiently low: with respect to area, this limit is at VDD 110 mV and with respect to power/delay at VDD ≈ 75 mV.