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Companies receive numerous customer inquiries and regulatory requirements while attempting to offer new services to enhance sustainability, leading in total to an increase in the number of product-related requirements. Digital Twins serve as enablers for meeting these requirements, whereas new challenges arise for companies through the introduction of Digital Twins. Digital Twins represent an order-specific configuration and must be structured differently according to requirements and thus as modularly as possible. This paper aims to provide a systemic approach with a concept for a Modular Digital Twin for generating and exploiting Product Sustainability Information to leverage sustainability potentials towards Service-oriented Business Models. The approach is concretised by means of a selected use case regarding energy-efficient production control of an automated model factory. We can show with this use case that the systemic approach with the concept of a Modular Digital Twin is applicable for energy consumption of machinery motors' simulation and for the calculation of an optimised motor speed. [ABSTRACT FROM AUTHOR]

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection.

Background: Following non-pharmaceutical interventions (NPI) lifting in 2021, an important surge in childhood lower respiratory tract infections (LRTI) was reported in several countries, raising major concerns about the middle-term consequences of such interventions. Whether this recent upsurge overwhelms the initial benefit of NPI remains unknown. Methods: We conducted an interrupted time-series analysis based on exhaustive national surveillance systems. All hospitalisations from January 2015 to March 2023 and all ambulatory visits for LRTI from a network of 110 paediatricians from June 2017 to March 2023 were included. The main outcome was the monthly incidence of children hospitalised for LRTI per 100,000 over time, assessed by a seasonally adjusted quasi-Poisson regression model. Results: We included 845,047 hospitalisations. The incidence of hospitalisation for LRTI significantly decreased during the NPI period (− 61.7%, 95% CI − 98.4 to − 24.9) and rebounded following NPI lifting, exceeding the pre-NPI baseline trend (+ 12.8%, 95% CI 6.7 to 19.0). We observed similar trends for hospitalisation due to bronchiolitis, pneumonia and pneumonia with pleural effusion, along with ambulatory LRTI. Overall, despite the recent rebound, 31,777 (95% CI, 25,375 to 38,179) hospitalisations for paediatric LRTI were averted since NPI implementation up to 2023. Conclusions: Three years after their implementation, despite an increase in LRTI incidence, the middle-term impact of NPI remains highly beneficial in preventing overall paediatric LRTI. The implementation of some societally acceptable NPI, particularly during epidemics, may be considered in the future to further reduce the burden of paediatric LRTI. [ABSTRACT FROM AUTHOR]

Aim: Height velocity is considered a key auxological tool to monitor growth, but updated height velocity growth charts are lacking. We aimed to derive new French height velocity growth charts by using a big‐data approach based on routine measurements. Methods: We extracted all growth data of children aged 1 month–18 years from the electronic medical records of 42 primary care physicians, between 1 January 1990 and 8 February 2018, throughout the French metropolitan territory. We derived annual and biannual height velocity growth charts until age 15 years by using the Lambda‐Mu‐Sigma method. These new growth charts were compared to the 1979 French and 2009 World Health Organisation (WHO) ones. Results: New height velocity growth charts were generated with 193 124 and 209 221 annual and biannual values from 80 204 and 87 260 children, respectively, and showed good internal fit. Median curves were close to the 1979 French or 2009 WHO ones, but SD curves displayed important differences. Similar results were found with the biannual height velocity growth charts. Conclusion: We produced new height velocity growth charts until age 15 years by using a big‐data approach applied to measurements routinely collected in clinical practice. These updated growth charts could help optimise growth‐monitoring performance. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the suitability of cerebral oximetry using near-infrared spectroscopy (NIRS) compared to traditional pulse oximetry (SpO2) for measuring cerebral oxygen saturation during hypoxia testing, aiming to enhance safety during flight operations and training. Material and Methods: The study included 106 participants aged 18–60 years at the Aerospace Medicine Training Center in Königsbrück. Cerebral oxygen saturation (rSO2) and peripheral oxygen saturation (SpO2) were measured using the INVOS™ 5100C cerebral oximeter and Masimo™ MS5 pulse oximeter, respectively. Measurements were taken at baseline, during hypoxia at 25,000 feet, and post recovery. Data analysis included regression analysis, Bland–Altman plots, and concordance correlation coefficients (CCC). Ethical approval was obtained from the Hannover Medical School. Data from 100 participants were analyzed. Results: Baseline SpO2 was 97.5 ± 1.5%, and baseline rSO2 was 77.25 ± 6.4%. During hypoxia, SpO2 dropped significantly, while rSO2 showed higher values. SpO2 recovered faster than rSO2. Deviations in rSO2 between the right and left sides during hypoxia were minimal. Lin's CCC indicated moderate to substantial concordance. NIRS measurements were more stable and less prone to disturbances, with 95 disruptions in pulse oximetry, 25 of which were potentially critical. Conclusions: NIRS is a reliable method for detecting cerebral oxygen saturation, offering significant advantages over traditional pulse oximetry in stability and reliability during hypoxia testing. NIRS is less error-prone, supporting its use for continuous monitoring in aviation settings and enhancing flight safety by providing more accurate hypoxia detection. [ABSTRACT FROM AUTHOR]