Modelling passengers in air-rail multimodality

Air-rail mobility has the potential to play a significant role in addressing European mobility challenges such as emissions reduction and capacity shortages. Rail can complement the air network in different ways: enlarging airport catchment areas, supporting operations in case of disruption or replacing air links to obtain environmental benefits. There is, however, still a need to better understand the potential role of rail when substituting current air links both from a strategic and a tactical mobility perspective, particularly when passenger connections are considered. This was initially assessed, considering passengers' door-to-door itineraries, as part of the Modus project (H2020 - SESAR 2020) with an innovative approach towards data driven, integrated air-rail modelling. Further considerations, such as the evaluation of strategic and tactical multimodal solutions, will be explored in the MultiModX project (Horizon Europe - SESAR 3). This discussion paper presents the modelling challenges addressed in Modus and the approach defined for MultiModX to evaluate and model multimodal door-to-door solutions

Modus D5.2 Final project results report

The Final Project Results Report of the Modus project provides a comprehensive overview of the project. First, it outlines the operational context, the project scope and the objectives in order to show the relevance of the project to the ATM Master Plan as well as other European high-level strategic mobility agendas. Based on this scope and the objectives, the report describes the work performed and discusses the key project results, including a list of all technical deliverables. Based on the work performed and the results, the report contains a detailed maturity gate assessment which described the Modus solution and how this solution has been achieved. Furthermore, the report describes the overall conclusions of the project, the technical lessons learned and identifies further R&D needs

Multi-objective fuzzy rule-based prediction and uncertainty quantification of aircraft taxi time

The ever growing air traffic demand and highly connected air transportation networks put considerable pressure for the sector to optimise air traffic management (ATM) related performances and develop robust ATM systems. Recent efforts made in accurate aircraft taxi time prediction have shown significant advancement in generating more efficient taxi routes and schedules, benefiting other key airside operations, such as runway sequencing and gate assignment. However, little study has been devoted to quantification of uncertainty associated with taxiing aircraft. Routes and schedules generated based on deterministic and accurate taxi time prediction for an aircraft may not be resilient under uncertainties due to factors such as varying weather conditions, operational scenarios and pilot behaviours, impairing system-wide performance as taxi delays can propagate throughout the network. Therefore, the primary aim of this paper is to utilise multi-objective fuzzy rule-based systems to better quantify such uncertainties based on historic aircraft taxiing data. Preliminary results reveals that the proposed approach can capture uncertainty in a more informative way, and hence represents a promising tool to further develop robust taxi planning to reduce delays due to uncertain taxi times

Modus D4.2 Mobility models description

Air-rail multimodal mobility has the potential to play a significant role in addressing European mobility challenges such as emissions reduction goals, and capacity shortages, and in moving towards a wider European multimodal transport network. There is still a need to better understand the potential role of rail when substituting current air links both from a strategic and a full, tactical mobility perspective, particularly when passenger connections are considered. Here we present the development of an innovative approach towards data driven, integrated air-rail modelling, considering passenger door-to-door itineraries

Future multimodal mobility scenarios within Europe

The European transport system faces multiple pressing challenges, including the need for significant emissions reduction in the sector and the provision of a seamless, multimodal journey to travellers. In order to address these challenges, a thorough understanding and assessment of different development pathways are required. This paper elaborates on four different scenarios developed within the scope of the Modus project. Based on these as well as additional insights from experts of the air and rail sector, initial implications for emissions reduction potential, travel times, or technological options are discussed

Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naive T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults

The acoustical and perceptual features of snore-related sounds in patients with obstructive sleep apnea sleeping with the dynamic mandibular advancement system MATRx plus®

Purpose: The effect of snoring on the bed partner can be studied through the evaluation of in situ sound records by the bed partner or unspecialized raters as a proxy of real-life snoring perception. The aim was to characterize perceptual snore events through acoustical features in patients with obstructive sleep apnea (OSA) with an advanced mandibular position. Methods: Thirty-minute sound samples of 29 patients with OSA were retrieved from overnight, in-home recordings of a study to validate the MATRx plus® dynamic mandibular advancement system. Three unspecialized raters identified sound events and classified them as noise, snore, or breathing. The raters provided ratings for classification certainty and annoyance. Data were analyzed with respect to respiratory phases, and annoyance. Results: When subdividing perceptual events based on respiratory phase, the logarithm-transformed Mean Power, Spectral Centroid, and Snore Factor differed significantly between event types, although not substantially for the spectral centroid. The variability within event type was high and distributions suggested the presence of subpopulations. The general linear model (GLM) showed a significant patient effect. Inspiration segments occurred in 65% of snore events, expiration segments in 54%. The annoyance correlated with the logarithm of mean power (r = 0.48) and the Snore Factor (0.46). Conclusion: Perceptual sound events identified by non-experts contain a non-negligible mixture of expiration and inspiration phases making the characterization through acoustical features complex. The present study reveals that subpopulations may exist, and patient-specific features need to be introduced

Perceptual snoring as a basis for a psychoacoustical modeling and clinical patient profiling

Purpose The perceptual burden and social nuisance for mainly the co-sleeper can affect the relationship between snorer and bedpartner. Mandibular advancement devices (MAD) are commonly recommended to treat sleep-related breathing such as snoring or sleep apnea. There is no consensus about the definition of snoring particularly with MAD, which is essential for assessing the effectiveness of treatment. We aimed to stablish a notion of perceptual snoring with MAD in place. Methods Sound samples, each 30 min long, were recorded during in-home, overnight, automatic mandibular repositioning titration studies in a population of 29 patients with obstructive sleep apnea syndrome (OSAS) from a clinical trial carried out to validate the MATRx plus. Three unspecialized and calibrated raters identified sound events and classified them as noise, snore, or breathing as well as providing scores for classification certainty and annoyance. Data were analyzed with respect to expiration-inspiration, duration, annoyance, and classification certainty. Results A Fleiss' kappa (>0.80) and correlation duration of events (>0.90) between raters were observed. Prevalence of all breath sounds: snore 55.6% (N = 6398), breathing sounds 31.7% (N = 3652), and noise 9.3% (N = 1072). Inspiration occurs in 88.3% of events, 96.8% contained at least on expiration phase. Snore and breath events had similar duration, respectively 2.58s (sd 1.43) and 2.41s (sd 1.22). Annoyance is lowest for breathing events (8.00 sd 0.98) and highest for snore events (4.90 sd 1.92) on a VAS from zero to ten. Conclusion Perceptual sound events can be a basis for analysis in a psychosocial context. Perceived snoring occurs during both expiration as well as inspiration. Substantial amount of snoring remains despite repositioning of the mandible aimed at the reduction of AHI-ODI

IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1− B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1− ΔIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1 and outcome is the older age of participants in our population. The impact of ΔIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617

Adult-type granulosa cell tumor of the ovary : a FOXL2-centric disease

Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one-third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole-genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon-based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle-related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.Peer reviewe