Background Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). Objective To investigate associations among OCT changes, MRI measurements of global and regional brain volume loss, and physical and cognitive impairment in PwMS. Methods 95 PwMS and 52 healthy controls underwent OCT and MRI examinations. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell/inner plexiform layer (GCIPL) volume were measured. In PwMS disability was quantified with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Associations between OCT, MRI, and clinical measures were investigated with multivariable regression models. Results In PwMS, pRNFL and GCIPL were associated with the volume of whole brain ( p  < 0.04), total gray matter ( p  < 0.002), thalamus ( p  ≤ 0.04), and cerebral cortex ( p  ≤ 0.003) –both globally and regionally–, but not white matter. pRNFL and GCIPL were also inversely associated with T2-lesion volume (T2LV), especially in the optic radiations ( p  < 0.0001). The brain volumes associated with EDSS and SDMT significantly overlapped with those correlating with pRNFL and GCIPL. Conclusions In PwMS, pRNFL and GCIPL reflect the integrity of clinically-relevant gray matter structures, underling the value of OCT measures as markers of neurodegeneration and disability in multiple sclerosis.

ABSTRACT Background Large international differences exist in kidney transplantation (KT) rates. We aimed to investigate which factors may explain the total, deceased donor and living donor KT rates over the last decade. Methods KT experts from 39 European countries completed the Kidney Transplantation Rate Survey on measures and barriers and their potential effect on the KT rate in their country. In the analyses, countries were divided into low, middle and high KT rate countries based on the KT rate at the start of study period in 2010. Results Experts from low KT rate countries reported more frequently that they had taken measures regarding staff, equipment and facilities to increase the total KT rate compared with middle and high KT rate countries. For donor type–specific KT, the largest international differences in measures taken were reported for deceased donor KT, with middle and high KT rate countries taking more measures, such as the use of expanded criteria donor kidneys, the presence of transplantation coordinators and (inter)national exchange of donor kidneys. Once a measure was taken, experts’ opinion on its success was similar across the low, middle and high KT rate countries. Experts from low KT rate countries more often reported potential barriers, such as patients’ lack of knowledge and distrust in the healthcare system. Conclusions Particularly in low KT rate countries, the KT rate might be stimulated by optimizing staff, equipment and facilities. In addition, all countries may benefit from measures specific to deceased and living donors.

Objectives Application of ‘treat-to-target’ (T2T) in childhood-onset systemic lupus erythematosus (cSLE) may improve care and health outcomes. This initiative aimed to harmonise existing evidence and expert opinion regarding T2T for cSLE. Methods An international T2T Task Force was formed of specialists in paediatric rheumatology, paediatric nephrology, adult rheumatology, patient and parent representatives. A steering committee formulated a set of draft overarching principles and points-to-consider, based on evidence from systematic literature review. Two on-line preconsensus meeting Delphi surveys explored healthcare professionals’ views on these provisional overarching principles and points-to-consider. A virtual consensus meeting employed a modified nominal group technique to discuss, modify and vote on each overarching principle/point-to-consider. Agreement of >80% of Task Force members was considered consensus. Results The Task Force agreed on four overarching principles and fourteen points-to-consider. It was agreed that both treatment targets and therapeutic strategies should be subject to shared decision making with the patient/caregivers, with full remission the preferred target, and low disease activity acceptable where remission cannot be achieved. Important elements of the points-to-consider included: aiming for prevention of flare and organ damage; glucocorticoid sparing; proactively addressing factors that impact health-related quality of life (fatigue, pain, mental health, educational challenges, medication side effects); and aiming for maintenance of the target over the long-term. An extensive research agenda was also formulated. Conclusions These international, consensus agreed overarching principles and points-to-consider for T2T in cSLE lay the foundation for future T2T approaches in cSLE, endorsed by the Paediatric Rheumatology European Society.

Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.

Tomato powder is produced by dehydrating tomatoes. The powder consists of only one ingredient, it represents the specificity of this product, namely dehydrated natural tomatoes. Among other things, drying as a preservation process is considered one of the best methods, because it ensures ease of use, transportation and storage. As part of the canning and processing of fruits and especially vegetables, tomato products have always occupied a very important place due to the organoleptic and culinary properties of these products, and the nutritional value of tomatoes as a raw material. Compared to other types of vegetables, tomatoes have a high yield, with some varieties even over 90%.The most important factor in tomato dehydration is the dehydration temperature as well as the time interval during which the dehydration process is carried out. In the dehydration process, two varieties of fresh tomatoes from the local market were used, which were dehydrated at temperatures of 50 and 75 °C. In parallel, a comparative physicochemical analysis of fresh tomato samples with dehydrated ground samples of tomato powder was performed. All analyzes in this research work were edited three times, and the mean value was used to display the graphical results.

Background The COMET-CTO trial was a randomized prospective study that assessed long-term follow-up in patients with chronic total occlusion (CTO) in coronary arteries treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT). During the 9-month follow-up, the incidence of major adverse cardiac events (MACE) did not differ between the two groups; no death or myocardial infarction (MI) was observed. There was a significant difference in quality of life (QoL), assessed by the Seattle Angina Questionnaire (SAQ), in favor of the PCI group. Here we report long-term follow-up results (56 ± 12 months). Methods Between October 2015 and May 2017, a total of 100 patients with CTO were randomized into two groups of 50 patients: PCI CTO or OMT group. The primary endpoint of the current study was the incidence of MACE defined as cardiac death, MI, and revascularization [PCI or coronary artery bypass graft (CABG)]. As the secondary exploratory outcome, we analyzed all the cause-mortality rate. Results Out of 100 randomized patients, 92 were available for long-term follow-up (44 in the PCI group and 48 in the OMT group). The incidence of MACE did not differ significantly between the two groups (p = 0.363). Individual components of MACE were distributed, respectively: cardiac death (OMT vs. PCI group, 6 vs. 3, p = 0.489), MI (OMT vs. PCI group, 1 vs. 0, p = 1), and revascularization (PCI: OMT vs. PCI group, 2 vs. 2, p = 1; CABG: OMT vs. PCI group, 1 vs. 1, p = 1). There was no significant difference between the two groups regarding the individual component of MACE. Six patients died from non-cardiac causes [five deaths were reported in the OMT group and one death in the PCI group (p = 0.206)]. Kaplan-Meier survival curves for MACE did not differ significantly between the study groups (log-rank 0.804, p = 0.370). Regarding the secondary exploratory outcome, a total of 15 patients died at 56 ± 12 months (11 in the OMT and 4 in the PCI group) (p = 0.093). The Kaplan-Meier survival curves for all-cause mortality rates did not differ significantly between the two groups (log rank 3.404, p = 0.065). There were no statistically significant differences between OMT and PCI groups in all five SAQ domains. There was a significant improvement in three SAQ domains in the PCI group: PL (p < 0.001), AF (p = 0.007), and QoL (p = 0.001). Conclusion After 56 ± 12 months of follow-up, the incidence of MACE, as well as QoL measured by SAQ, did not differ significantly between the PCI and OMT groups.

For an integer $r\ge 2$, the space of $r$-immersions of $M$ in $\R^n$ is defined to be the space of immersions of $M$ in $\R^n$ such that at most $r-1$ points of $M$ are mapped to the same point in $\R^n$. The space of $r$-immersions lies ``between"the embeddings and the immersions. We calculate the connectivity of the layers in the homological Taylor tower for the space of $r$-immersions in $\mathbb R^n$ (modulo immersions), and give conditions that guarantee that the connectivity of the maps in the tower approaches infinity as one goes up the tower. We also compare the homological tower with the homotopical tower, and show that up to degree $2r-1$ there is a ``Hurewicz isomorphism"between the first non-trivial homotopy groups of the layers of the two towers.

Despite the success of neural-based combinatorial optimization methods for end-to-end heuristic learning, out-of-distribution generalization remains a challenge. In this paper, we present a novel formulation of Combinatorial Optimization Problems (COPs) as Markov Decision Processes (MDPs) that effectively leverages common symmetries of COPs to improve out-of-distribution robustness. Starting from a direct MDP formulation of a constructive method, we introduce a generic way to reduce the state space, based on Bisimulation Quotienting (BQ) in MDPs. Then, for COPs with a recursive nature, we specialize the bisimulation and show how the reduced state exploits the symmetries of these problems and facilitates MDP solving. Our approach is principled and we prove that an optimal policy for the proposed BQ-MDP actually solves the associated COPs. We illustrate our approach on five classical problems: the Euclidean and Asymmetric Traveling Salesman, Capacitated Vehicle Routing, Orienteering and Knapsack Problems. Furthermore, for each problem, we introduce a simple attention-based policy network for the BQ-MDPs, which we train by imitation of (near) optimal solutions of small instances from a single distribution. We obtain new state-of-the-art results for the five COPs on both synthetic and realistic benchmarks. Notably, in contrast to most existing neural approaches, our learned policies show excellent generalization performance to much larger instances than seen during training, without any additional search procedure.

A search for nonresonant Higgs boson pair production in the $b\bar{b}b\bar{b}$ final state is presented. The analysis uses 126 fb$^{-1}$ of $pp$ collision data at $\sqrt{s}={13}$ TeV collected with the ATLAS detector at the Large Hadron Collider, and targets both the gluon-gluon fusion and vector-boson fusion production modes. No evidence of the signal is found and the observed (expected) upper limit on the cross-section for nonresonant Higgs boson pair production is determined to be 5.4 (8.1) times the Standard Model predicted cross-section at 95% confidence level. Constraints are placed on modifiers to the $HHH$ and $HHVV$ couplings. The observed (expected) $2\sigma$ constraints on the $HHH$ coupling modifier, $\kappa_\lambda$, are determined to be $[-3.5, 11.3]$ ($[-5.4, 11.4]$), while the corresponding constraints for the $HHVV$ coupling modifier, $\kappa_{2V}$, are $[-0.0, 2.1]$ ($[-0.1, 2.1]$). In addition, constraints on relevant coefficients are derived in the context of the Standard Model effective field theory and Higgs effective field theory, and upper limits on the $HH$ production cross-section are placed in seven Higgs effective field theory benchmark scenarios.

Premature ventricular complex (PVC) is a frequent finding in the general population. The atrial conduction time (ACT) is the period between the electrocardiographic P wave and the atrial mechanical contraction, and its prolongation indicates an atrial electromechanical delay (EMD). In our study, we compared atrial conduction parameters by echocardiographic methods between patients with frequent PVC and healthy control subjects.

The shipping sector has become one of the corner-stone aspects of modern production systems, which has been impacting economic growth over the past decades. Its digitalization is expected to make significant improvements in ship control safety and reliability by enabling autonomous operations. Nonetheless, there are still many challenges that need to be thoroughly studied, and in this paper, we focus on one of them, i.e., the communication between barges, ports, and services, as the increased network latency and the limitations on the bandwidth imposed by satellite communications could result in significant risks for accident occurrence. Thus, we present one of the first attempts to leverage the potential of 5G systems for automating barge operations, starting from teleoperation as an enabler of automation, toward creating and validating a cellular-based automated barge control system in a real-life environment.

To properly orchestrate challenging services such as those deployed for Vehicle-to-Everything (V2X) use cases, MANO systems need to be intelligent and automated. Network Function Virtualization (NFV) and Machine Learning (ML) provide opportunities for automating MANO operations, and this paper presents our MI-enhAnced Edge Service orchesTRatiOn (MAESTRO) algorithm that makes proactive ML-driven decisions for edge service relocation to ensure Quality of Service (QoS) guarantees for V2X services. Moreover, to validate the effectiveness of our proposed solution, we have performed the experimentation using real-life testbeds for high computing and smart mobility i.e., Smart Highway and Virtual Wall, located in Antwerp and Gent, Belgium. The contribution of our paper is two-fold: i) we study the interrelation between the Key Performance Indicators (KPIs) measured at the vehicle client side, and the infrastructure metrics at the edge computing nodes and ii) we propose and evaluate an ML-based quality-aware algorithm that automates edge service orchestration to decrease average latency while guaranteeing high service availability and reliability.

Vehicular communication is a core technology of Intelligent Transportation Systems (ITS). Vehicle-to-vehicle (V2V) communication still needs to develop resilience, such that communication is safe and efficient, in time-critical applications. The radio-based systems, such as cellular V2X (C-V2X) and Dedicated Short Range Communication (DSRC), which are used classically for vehicular communication suffer from performance degradation in traffic scenarios where traffic is dense. In recent years, Line of Sight (LoS) technologies such as Visible Light Communication (VLC) are considered complementary technology to Radio Frequency (RF). VLC utilizes the light-emitting diodes (LEDs) headlamps and tail lights that are standard on modern vehicles to exchange information with the predecessor and subsequent vehicle. This work-in-progress paper highlights the need to combine RF and LoS technologies to improve the stability and reliability of $V2 V$ communication. Therefore, we discuss the different LoS and RF technologies, and we present the combinations that can be used for communication. Finally, we propose a hybrid strategy that combines the best properties of individual technologies.

Vehicular Edge Computing (VEC) brings cloud infrastructure to the vehicular edge, resulting in better performances and avoiding network congestions. In this work-in-progress paper, the benefits of edge computing over cloud computing are discussed in a vehicular environment context, and they are leveraged by creating a Cooperative, Connected and Automated Mobility (CCAM) performance measurement framework. This measurement tool can follow vehicles by moving across different devices, enabling measurements on Key Performance Indicators (KPIs) using edge computing. We already used this tool to evaluate latencies of both a stationary and driving vehicle, moving over the Smart Highway testbed in Antwerp, Belgium. When driving, smart-edge-following algorithms can be deployed to choose the nearest Road Side Unit (RSU) using broadcasted Cooperative Awareness Messages (CAMs) of the vehicle. While driving on the Smart Highway, the application monitors important performance metrics such as throughput, latency, packet loss, packet delivery rate and more. We compare short-range vehicular communications technologies on the Smart Highway (ITS-G5 and LTE-V2X PC5) against the cellular. Our preliminary results demonstrate the benefits in terms of latency by using short-range communications technologies in VEC applications. These results validate that moving applications to the edge is truly beneficial, since our results confirmed up to 90% lower latency using ITS-G5, up to 50% using LTE-V2X PC5. Future deployments of 5G in the Smart Highway are planned, which would further improve the performance edge computing technologies.