Abstract Objectives Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist. We aimed to inventory transitional care programs for rare CTDs across Europe. Methods In April 2023, the ERN ReCONNET Transition of Care Task Force, consisting of expert clinicians, patient advocates and coordination team members, created a survey to assess transitional care practices. The survey was distributed to ERN ReCONNET and ERN RITA centres and responses received by 15 March 2024 were analysed. Results A total of 67 responses from 59 centres across 20 European countries were collected. Paediatric rheumatologists typically initiated the transition process (49% of centres). Twenty centres had joint clinics. Despite positive self-assessments of transitional programs, significant limitations were noted. Transition policies varied, with only 40% of centres having a formal standardized policy and less than half of the centres adhering to available transition of care guidelines. Transfer readiness was evaluated using validated questionnaires in 13% of centres, while 29% transitioned patients based solely on age without any readiness assessments. The main challenges included finding adult-oriented centres and the lack of guidelines or engagement from adult centres. Adult healthcare providers also noted a lack of training in adolescent medicine. Conclusion The survey highlighted diverse transition practices and resources across centres, with challenges in readiness evaluation and the use of guidelines. Despite these obstacles, respondents rated ongoing transition processes positively. Enhancing patient perspectives in the transition process is crucial to meet their needs during this critical phase.

Background Atherosclerosis of the coronary arteries is a chronic, progressive condition characterized by the buildup of plaque within the arterial walls. Coronary artery disease (CAD), more specifically coronary atherosclerosis (CATS), is one of the leading causes of death worldwide. Computational modeling frameworks have been used for simulation of atherosclerotic plaque progression and with the advancement of agent-based modeling (ABM) the simulation results became more accurate. However, there is a need for optimization of resources for predictive modeling, hence surrogate models are being built to substitute lengthy computational models without compromising the results. Objective This study explores the development of a surrogate model for atherosclerotic plaque progression using ABM simulation data. Method The dataset used for this study contains samples from latin-hypercube sampling based generated simulation parameters used in conjunction with 15 patient-specific geometries and corresponding plaque progression data. The developed surrogate model is based on deep learning using artificial neural networks (ANN). Results The surrogate model achieved an accuracy of 95.4% in benchmarking with the ABM model it was built upon which indicates the robustness of the framework. Conclusion Adoption of surrogate models with high accuracy in practice opens an avenue for utilization of high-fidelity decision support systems for predicting atherosclerotic plaque progression in real-time.

Purpose The purpose of this study was to determine the relationship between linear and change-of-direction sprinting performance with dribbling performance and Dribble Deficit in professional female handball players. Methods Eleven professional female handball players (mean age: 21.12 ± 4.34 years; body height: 171.59 ± 4.52 cm; body weight: 66.29 ± 5.73 kg) participated in the study. Each participant completed several linear (sprint over 10, 20, and 30 m) and change-of-direction tests (slalom test, zig-zag test, 505 test), first without the ball (sprinting performance) followed by ball dribbling (dribbling performance). Dribble Deficit was calculated indirectly as the time difference between the best trial while dribbling minus the best trial without dribbling. Results A large to very large correlation was observed between the linear sprint and dribbling performance (r = 0.53–0.78), as well as between change-of-direction sprinting performance and dribbling performance (r = 0.66–0.88). The study also showed a moderate to perfect relationship between linear dribbling performance and Dribble Deficit (r = 0.46–0.93), and a large relationship between change-of-direction dribbling performance and Dribble Deficit (r = 0.54–0.55), while the relationships between linear sprinting performance and Dribble Deficit (r = −0.51–0.21) and between change-of-direction sprinting performance and Dribble Deficit (r = −0.14–0.26) were small and non-significant. Conclusion In summary, Dribble Deficit reflects dribbling ability independent of sprinting ability and refines its application for practical use in assessing dribbling skills in female handball players.

Background A subset of developmental disorders (DD) is characterized by disease-specific genome-wide methylation changes. These episignatures inform on the underlying pathogenic mechanisms and can be used to assess the pathogenicity of genomic variants as well as confirm clinical diagnoses. Currently, the detection of these episignature requires the use of indirect methylation profiling methodologies. We hypothesized that long-read whole genome sequencing would not only enable the detection of single nucleotide variants and structural variants but also episignatures. Methods Genome-wide nanopore sequencing was performed in 40 controls and 20 patients with confirmed or suspected episignature-associated DD, representing 13 distinct diseases. Following genomic variant and methylome calling, hierarchical clustering and dimensional reduction were used to determine the compatibility with microarray-based episignatures. Subsequently, we developed a support vector machine (SVM) for the detection of each DD. Results Nanopore sequencing-based methylome patterns were concordant with microarray-based episignatures. Our SVM-based classifier identified the episignatures in 17/19 patients with a (likely) pathogenic variant and none of the controls. The remaining patients in which no episignature was identified were also classified as controls by a commercial microarray assay. In addition, we identified all underlying pathogenic single nucleotide and structural variants and showed haplotype-aware skewed X-inactivation evaluation directs clinical interpretation. Conclusion This proof-of-concept study demonstrates nanopore sequencing enables episignature detection. In addition, concurrent haplotyped genomic and epigenomic analyses leverage simultaneous detection of single nucleotide/structural variants, X-inactivation, and imprinting, consolidating a multi-step sequential process into a single diagnostic assay. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-024-01419-z.

Although the influence of infill masonry on horizontal load structure behavior is well-documented, current standards and regulations have yet to fully incorporate or explicitly define the load-bearing capacity of this complex system. Canadian and American standards present more comprehensive and specific methodologies for calculating the load-bearing capacity of infill masonry and frame systems. In contrast, European standards tend to focus on offering general guidelines for the design of these systems without delving into the detailed calculation procedures. However, extensive data and experimental studies on this topic are available in the literature. The primary aim of this paper was to compile a database of experiments involving frames with different types of infill masonry. Subsequently, the empirical results obtained through the application of analytical expressions from various standards are compared to the experimental data included in the compiled database. The obtained load-bearing values were compared to different standards and work conducted by various researchers found in the literature in order to assess their reliability. Based on the obtained results, important conclusions were drawn, specifically to the most accurate equivalent diagonal model used and the analytical expressions to be used in the assessment of the masonry-infilled steel frame behavior. The equivalent diagonal model, utilized in all analytical expressions, can provide highly accurate estimations of load-bearing capacities that closely align with the experimental results. Regardless of the type of infill element, the analytical expressions consistently overestimated the load-bearing capacity. In the presence of longitudinal force, analytical expressions tend to be conservative, providing significantly lower load-bearing values compared with experimental results, which ensures a safety margin. The database can be utilized to develop numerical models, which can subsequently serve as the foundation for probabilistic methods used in conducting reliability assessments.

: Ophiolitic mélanges of the Ozren and Borja-Mahnjača massifs comprise Middle Triassic, Lower Jurassic, and Middle Jurassic radiolarites. The Middle Triassic radiolarites from clastic components in the mélange of the Ozren ophiolite complex (OOC) predominantly contain the species Annulotriassocampe and Triassocampe species, together with marker species of the Ladinocampe multiperforata Zone, belonging to the Illyrian. These Middle Triassic radiola-rites are remnants of the Maliac Ocean, which opened during the Late Anisian. The inferred continuation of the Middle Triassic radiolarian sedimentation to the Early Jurassic is recorded by radiolarites from block-in-matrix in the mélange of the Borja-Mahnjača ophiolite complex (BMOC). Their Sinemurian–Pliensbachian age is indicated by species of the genera Canoptum, Katroma, Droltus , Lantus, Gorgasium , Charlottea , Bipetis , Paleosaturnalis and Paroanella . Such Lower Jurassic radiolarites were so far unknown from the Dinaric ophiolite complexes. The Middle Jurassic radio-larites cover the pillow basalts of the OOC. Their microfauna indicates the Bathonian–early Callovian age based on the LADs of Mizukidella kamoensis and Hemicyrtocapsa carpathica and FADs of Transhuum brevicostatum , Cinguloturris cf. carpathica , Loopus venustus and Protunuma turbo within the UAZ 6–7 Zone. The Middle Jurassic radiolarites are also interbedded in the pillow lavas of the BMOC. In addition to common species of the UAZ 6–7 Zone (e.g., Transhuum maxwelli , Eucyrtidiellum unumaense , Unuma gordus ), they also contain the species Takemuraella veghae and Eoxitus cf. baloghi, which are limited to the Bathonian. Considering the radiolarites from the pillow basalts, the OOC and BMOC are interpreted as the mélanges with the reworked clasts of the Middle Triassic to Lower Jurassic radiolarites, but also with the Middle Jurassic radiolarites. The Middle Triassic radiolarites of the OOC and the Lower Jurassic radiolarites of the BMOC represent rare remnants after the closure of the Middle Triassic to Lower Jurassic Maliac Ocean of the Neo - tethys. The newly-formed Neotethyan oceanic crust was terminated by the Middle Jurassic radiolarian deposition in an inferred fore-arc/back-arc basin until the Bathonian to early Callovian.

A genomic and transcriptomic analysis of patients with clear-cell renal cell carcinoma reveals clinically relevant patterns of nongenetic evolution, including progressive immune dysfunction and cGAS–STING suppression.

Hazard vulnerability assessment of critical infrastructures (CIs) is crucial for ranking infrastructures based on their level of criticality, enabling the urban managers to prioritize CIs for allocating funds in the hazard mitigation/recovery process. This study aims to provide a framework for ranking CIs based on a rapid and preliminary flood vulnerability assessment by introducing a methodology for classifying CIs according to their vulnerability to riverine flooding. An indicator‐based vulnerability curve is calculated both quantitatively (using Fuzzy Logic Toolbox in MATLAB) and qualitatively (using susceptibility–exposure matrix), based on which CIs prioritization is accomplished with a focus on functional flood vulnerability considering structural/nonstructural damages. Besides, this study addresses the consequences that a damaged infrastructure may have on the rest of CIs and estimates their vulnerability given the additive impact of the surrounding failed infrastructures considering their interdependence. The methodology was applied to Berat (Albania) and Sarajevo (Bosnia‐Herzegovina) with findings compared to those of a multi‐criteria decision‐making‐based approach commonly used in CI ranking literature. The obtained results from both methods represent that roads are the most vulnerable studied infrastructure in the case of Berat, while regarding the city of Sarajevo, road infrastructures are considered the least vulnerable to riverine floods compared to bridges and schools.

Embedded systems, particularly when integrated into the Internet of Things (IoT) landscape, are critical for projects requiring robust, energy-efficient interfaces to collect real-time data from the environment. As these systems become complex, the need for dynamic reconfiguration, improved availability, and stability becomes increasingly important. This paper presents the design of a framework architecture that supports dynamic reconfiguration and “on-the-fly” code execution in IoT-enabled embedded systems, including a virtual machine capable of hot reloads, ensuring system availability even during configuration updates. A “hardware-in-the-loop” workflow manages communication between the embedded components, while low-level coding constraints are accessible through an additional abstraction layer, with examples such as MicroPython or Lua. The study results demonstrate the VM’s ability to handle serialization and deserialization with minimal impact on system performance, even under high workloads, with serialization having a median time of 160 microseconds and deserialization having a median of 964 microseconds. Both processes were fast and resource-efficient under normal conditions, supporting real-time updates with occasional outliers, suggesting room for optimization and also highlighting the advantages of VM-based firmware update methods, which outperform traditional approaches like Serial and OTA (Over-the-Air, the ability to update or configure firmware, software, or devices via wireless connection) updates by achieving lower latency and greater consistency. With these promising results, however, challenges like occasional deserialization time outliers and the need for optimization in memory management and network protocols remain for future work. This study also provides a comparative analysis of currently available commercial solutions, highlighting their strengths and weaknesses.

When nonsequential double ionization is treated using the strong-field approximation and the saddle-point (SP) method, the transition amplitude can be expressed as a coherent sum of the partial amplitudes corresponding to different SP solutions. For the case of the recollision excitation with subsequent ionization (RESI) mechanism of the nonsequential double ionization, we examine the partial contributions of the SP solutions which correspond to the electron responsible for the excitation. For a monochromatic linearly polarized laser field, we find that, in addition to the pair of the SP solutions with the shortest travel time, other SP solutions may also make a significant contribution to the photoelectron yield. Moreover, the SP solutions appear in pairs and exhibit notable modifications in comparison to those observed in high-order above-threshold ionization. Furthermore, for a bichromatic linearly polarized driving field, we investigate the intensity range obtained using the simpleman’s model for which the RESI mechanism is dominant. We find that this range must be modified if the photoelectron yield corresponding to the SP solution for which the photoelectron has the highest energy upon return to the parent ion is small. This is particularly the case for the excitation channels involving loosely bound excited states.

Designing controllers that accomplish tasks while guaranteeing safety constraints remains a significant challenge. We often want an agent to perform well in a nominal task, such as environment exploration, while ensuring it can avoid unsafe states and return to a desired target by a specific time. In particular we are motivated by the setting of safe, efficient, hands-off training for reinforcement learning in the real world. By enabling a robot to safely and autonomously reset to a desired region (e.g., charging stations) without human intervention, we can enhance efficiency and facilitate training. Safety filters, such as those based on control barrier functions, decouple safety from nominal control objectives and rigorously guarantee safety. Despite their success, constructing these functions for general nonlinear systems with control constraints and system uncertainties remains an open problem. This paper introduces a safety filter obtained from the value function associated with the reach-avoid problem. The proposed safety filter minimally modifies the nominal controller while avoiding unsafe regions and guiding the system back to the desired target set. By preserving policy performance while allowing safe resetting, we enable efficient hands-off reinforcement learning and advance the feasibility of safe training for real world robots. We demonstrate our approach using a modified version of soft actor-critic to safely train a swing-up task on a modified cartpole stabilization problem.

This study examines the urgency of strengthening Indonesia's presidential institution to enhance governance and adapt to contemporary challenges. The research aims to assess the institution's capacity to ensure political stability, promote democratic values, and address corruption and centralization of power. Utilizing mixed methods, the study combines surveys, in-depth interviews, and direct observation, supported by thematic and statistical analysis. Key findings indicate that improving inter-institutional collaboration, adopting innovative decision-making strategies, and leveraging technology for transparency are crucial for addressing governance challenges. The study concludes that reforms in legal frameworks and accountability mechanisms are vital for enhancing public trust and institutional responsiveness. These findings provide actionable insights for policymakers to advance democratic governance and institutional resilience