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Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota-driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro-inflammatory and immunomodulatory responses depending on their chemical structures. Herein we report the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol-containing O-antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid-phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whereas pro-inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible "immune modulating" action has been proposed for the peculiar O-antigen portion.

Dendritic cells (DCs) play a pivotal role in immune surveillance, acting as sentinels that coordinate immune responses within tissues. Although differences in the identity and functional states of DC subpopulations have been identified through multiparametric flow cytometry and single-cell RNA sequencing, these methods do not provide information about the spatial context in which the cells are located. This knowledge is crucial for understanding tissue organisation and cellular cross-talk. Recent developments in multiplex imaging techniques can now offer insights into this complex spatial and functional landscape. This review provides a concise overview of these imaging methodologies, emphasising their application in identifying DCs to delineate their tissue-specific functions and aiding newcomers in navigating this field.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Including production considerations in the early design stages of aircraft structures is challenging. Production information is mostly known by experts and rarely formally documented such that it can be effectively used during the design process. Producibility is mostly considered after completing the design, resulting in increased cost and development time due to the late discovery of production issues. This paper presents a new model, called the Manufacturing Information Model (MIM), which supports the automatic inclusion of production considerations into the design process. The MIM provides a single source of truth and a generic structure to capture and organize production-related information in a product system. Furthermore, it provides compatibility analyses to automatically warn for or exclude infeasible designs. Analysis tools use the information stored within the MIM to calculate the mass, costs, and production rate of the product. To show the functionalities of the MIM, it has been applied to the conceptual design of a wing box at a Tier 1 company. This use case shows how the MIM supports trade-off decisions, as it allows for the identification of trends and the ranking of different manufacturing concepts. Overall, the MIM provides a structured and formal approach to include production information in the conceptual design, improving the decision-making process., Flight Performance and Propulsion

During the early design stages of airframe components, many possible design architectures and production methods need to be traded to find the best configuration. Evaluating different production methods can be challenging as different production methods put different requirements on the product to be designed. This paper presents a new methodology that enables the inclusion of manufacturing and assembly in the design process. By extending the architectural design space model with components of the production system, the design choices regarding production are made explicit. Through the modeling of product and production requirements and assigning them a verification method, a dynamic MDAO workflow is formulated. Within a dynamic workflow, the design variables, analysis tools, and constraints change depending on the current design vector. The methodology has been applied to the design and manufacturing of a wing rib in which two manufacturing options were traded: metal machining and composite stamp forming. The dynamic MDAO workflow successfully found the Pareto front for both manufacturing methods. The main benefit is that only one workflow needed to be formulated and executed, whereas previously a separate MDAO workflow needed to be created for each combination of product design and production method. Overall, the newly presented methodology enables the optimization and trade-off between different production methods while ensuring the design complies with the production-specific requirements., Flight Performance and Propulsion, Group Bergsma

Stereotactic needle biopsy (SNB) may be performed to collect tissue samples from lesions not amenable to open surgery. Integration of tractography, intraoperative imaging and fluorescence has been applied to reduce risk of complications and confirm the adequacy of bioptic specimens. Clinical and radiological data from patients who underwent stereotactic needle biopsy with the use of intraoperative CT, tractography and 5-aminolevulinic acid (5-ALA) fluorescence in a single Hospital were retrospectively reviewed to evaluate the accuracy and safety of the procedure. Seven patients were included in the study, and all the collected specimens showed red fluorescence. In six of them, the final histopathological diagnosis was grade 4 glioblastoma IDH-wt and in the other case it was Diffuse large B-Cell Lymphoma. The integration of tractography, intraoperative CT and 5-ALA as an intraoperative marker of diagnostic samples may be suggested in biopsies of suspect gliomas and lymphomas. The cost-effectiveness of the procedure should be evaluated in future studies.

Background. Discussion on the impact of pocket money on positive behaviors is still debated.Objective. To investigate the effect of diverse money allowance schemes on risky behaviors (smoking, alcohol, binge drinking, drug use, gambling) during adolescence.Method. 989 students aged 15 from Lombardy (Italy) reported information on money availability in the 2018 wave of the Health Behaviour in School-aged Children study. To analyze the relationship between money availability and risky behaviors we computed odds ratios and 95% confidence intervals through unconditional multiple logistic regression models.Results. Spending more than 10(sic) weekly was associated with higher likelihood to smoke, binge drink or gamble. Receiving pocket money (rather than receiving money upon request) was related to higher likelihood to engage in risky behaviors.Conclusions. Pocket money may have a negative impact on adolescents, particularly with a substantial amount of money. More research is needed to understand why providing money only if needed may serve as a protective factor against risky behaviors.

The present study explores the concurrent contribution to sleep problems of individual-related, family-related, and school-related factors in adolescence. Gathering from the Italian 2018 Health Behavior in School-Aged Children (HBSC) data collection, we used hierarchical logistic regression on a sample of 3397 adolescents (51% females, Mage = 13.99, SD = 1.62) to explore the contribution to sleep problems of the individual (Model 1: alcohol use, smoking, screen time, physical activity), familial (Model 2: parental communication, parental support), and school-related (Model 3: peer support, schoolmates/students support, teacher support and school pressure) variables. 28.3 percent of adolescents reported having sleep difficulties. Overall, Model 3 significantly improved over Model 2 and Model 1. Data showed that increasing smoking (OR = 1.11; 95% CI: 1.03–1.20) and screen time (OR = 1.05; 95% CI: 1.02–1.08) were associated with sleep difficulties but not alcohol use and physical activity. Also, impaired communication with both parents and increasing parental support (OR = 0.84; 95% CI: 0.78–0.90) were associated with decreased odds of sleep problems. Finally, both increases in school pressure (OR = 1.40; 95% CI: 1.26–1.56) and lack of student support (OR = 1.25; 95% CI: 1.10–1.42) were associated with a higher likelihood of sleep problems, while peer support and teacher support were not. Conclusion: Our findings highlight the importance of an integrated approach to the study of sleep difficulties in adolescence that includes specific psychosocial contributors such as the quality of parental communication and perceived parental support and considers the quality of the day-to-day relationship with schoolmates and the school level of demands.What is Known:• Adolescents' are at-risk of more significant sleep difficulties, and recent literature highlights the importance of an integrated approach to understanding this phenomenon, including biological, psychosocial, and cont

Calcineurin (CN) inhibitors currently used to avoid transplant rejection block the activation of adaptive immune responses but also prevent the development of tolerance toward the graft, by directly inhibiting T cells. CN, through the transcription factors of the NFAT family, plays an important role also in the differentiation dendritic cells (DCs), the main cells responsible for the activation of T lymphocytes. Therefore, we hypothesized that the inhibition of CN only in DCs and not in T cells could be sufficient to prevent T cell responses, while allowing for the development of tolerance. Here, we show that inhibition of CN/NFAT pathway in innate myeloid cells, using a new nanoconjugate capable of selectively targeting phagocytes in vivo, protects against graft rejection and induces a longer graft acceptance compared to common CN inhibitors. We propose a new generation of nanoparticles-based selective immune suppressive agents for a better control of transplant acceptance.

Systemic vasculitis are rare heterogeneous disorders potentially involving any organ and system with a relevant burden of mortality and comorbidity. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis.

During the aircraft conceptual design phase, many different design options need to be explored and compared in a short time frame. To speed up this process, efforts have been made in the past decades to digitalize parts of the design process, with a focus on the automation of the repetitive and non-creative tasks inherent to the iterative design process. Whilst many of the newly developed methodologies focus on specific parts of the design process, a holistic model-based design framework, incorporating the latest design technology developments, is lacking. To fill this gap, this paper presents the latest version of the Design and Engineering Engine (DEE) framework, originally proposed in the early 2000s and progressively matured through the experience of several international research collaborations. The DEE enables the setup and execution of Multidisciplinary Design Analysis and Optimization (MDAO) problems for aircraft (sub)systems, leveraging the automated, rule-based modeling capabilities offered by Knowledge-Based Engineering (KBE) and recent developments in the automatic formulation and integration of MDAO workflows. While the traditional MDAO process focuses on a given product architecture, the DEE allows also architectural design studies and makes use of Model-Based Systems Engineering (MBSE) principles to address the whole design process, from requirements modeling up to the automatic verification of the requirements. In practice, the DEE provides a single conceptual framework or template from which specific design framework instances can be formulated and executed, according to the user's needs. This paper describes the DEE architecture and its implementation concepts. Furthermore, it demonstrates the application of the DEE template to four different scenarios, ranging from a simple requirement verification study, up to the simultaneous synthesis and optimization of an aircraft system and its production process, including multiple system architecture optio, Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Flight Performance and Propulsion

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

This paper discusses the approach for architecture design space optimization of aeronautical systems investigated in the DEFAINE project. In system architecture optimization problems, hierarchical relations between design variables may exist. This means that the quantity and type of some variables are dependent on the value of other variables. To address this challenge, a nested optimization strategy is proposed, where an outer loop deals with the independent design variables and an inner loop with the dependent ones. As the characteristics of the dependent variables may become known only during workflow execution, a dynamic workflow formulation approach is developed to introduce these variables into the MDAO workflow, automatically, during execution. The proposed methodology is implemented using a suite of technologies provided by partners of the DEFAINE consortium to enable formulation and execution of collaborative MDAO problems. This implementation is then applied to the design and optimization of the structural layout of a UAV aileron. The goal is to minimize the aileron mass, subjected to failure criteria constraints. In this use case, hierarchical relations between variables are present. The aileron skin is discretised into material zones, each one defined by a (dependent) design variable. The number of zones, hence the number of design variables, is not known a priori as it depends on the number and position of ribs and spars(both independent variables). A preliminary implementation of the proposed approach proved effective in dealing with the hierarchical mixed-integer design space. Trade off studies comparing different aileron architectures could be efficiently set up and executed. Some limitations in the implemented workflow management technology, however prevent performing a full nested architecture optimization. Therefore, to demonstrate the effectiveness of the proposed nested approach, a parallel study was conducted on the same aileron, using a less g, The research presented in this paper has partially been performed in the framework of the DEFAINE (Design Exploration Framework based on AI for front-loaded Engineering) project and has received funding from ITEA 3 programme (Call 6 project 19009)., Flight Performance and Propulsion

This article proposes a novel approach to support Knowledge Based Engineering (KBE) application development based on Model-Based Systems Engineering (MBSE). In this methodology, the related knowledge is captured in a well-structured Systems Modeling Language (SysML) model, instead of (static) documents. The knowledge model is then automatically translated to application (skeleton) code using a model-to-code tool developed in this research. The proposed methodology is applied to a use case at GKN Fokker Elmo for the development of a KBE application to design Electrical Wiring Interconnection Systems (EWIS) architectures for aircraft. The results show that the proposed MBSE approach improves the knowledge acquisition process, reduces the time needed for developing new KBE applications (initial knowledge model and code skeleton) by almost 50%, and enables traceability of requirements within the KBE application and knowledge model. These benefits allow effective project-to-project knowledge transfer while mitigating the black-box effect often experienced by KBE application users. In the next phase of this research, reverse engineering capabilities will also be incorporated to enable code-to-model translation, so as to guarantee the application code and knowledge model synchronization throughout the application's lifetime., Flight Performance and Propulsion

This paper compares optimum control surface layouts designed and sized to obtain the same Flying Qualities (FQs) performance with different Control Allocation (CA) methods, and proposes novel layouts for staggered box-wing aircraft aimed at transonic commercial flight. Box-wings allow the installation of redundant control surfaces for which no explicit role can be defined a priori, but present challenges related to aerodynamic interaction and interference effects. To evaluate the impact of different CA methods on top-level layout parameters, the cumulative control surface span and the properties of the Attainable Moment Set (AMS) corresponding to each control surface layout are used. A physics-based multi-disciplinary optimization framework is developed to size the control surface layout. FQs are evaluated through non-linear flight dynamics simulation, using a variable-architecture flight control system that allows their assessment as a function of different CA methods. The most traditional Mechanical Gearing and Ganging (MGG) approach, the Constrained Pseudo-Inverse (CPI) method and the Direct Control Allocation (DCA) method are compared. Results show that different optimum layouts exist with comparable cumulative span, for a given CA method and same FQs requirements. The traditional MGG approach requires the largest cumulative control surface span, but retains the best ability to generate coupled roll-pitch moments. DCA requires the smallest cumulative control surface span, with the largest AMS volume. By using this method, a novel layout featuring a mid-wing rear elevon has been discovered, which reduces the total required control surface span by about 13%, results in a 3.7% increase of span available for flaps on the front wing, and avoids detrimental aerodynamic interaction effects near the wing-tail intersection region., Flight Performance and Propulsion

The present study explores the concurrent contribution to sleep problems of individual-related, family-related, and school-related factors in adolescence. Gathering from the Italian 2018 Health Behavior in School-Aged Children (HBSC) data collection, we used hierarchical logistic regression on a sample of 3397 adolescents (51% females, Mage = 13.99, SD = 1.62) to explore the contribution to sleep problems of the individual (Model 1: alcohol use, smoking, screen time, physical activity), familial (Model 2: parental communication, parental support), and school-related (Model 3: peer support, schoolmates/students support, teacher support and school pressure) variables. 28.3 percent of adolescents reported having sleep difficulties. Overall, Model 3 significantly improved over Model 2 and Model 1. Data showed that increasing smoking (OR = 1.11; 95% CI: 1.03-1.20) and screen time (OR = 1.05; 95% CI: 1.02-1.08) were associated with sleep difficulties but not alcohol use and physical activity. Also, impaired communication with both parents and increasing parental support (OR = 0.84; 95% CI: 0.78-0.90) were associated with decreased odds of sleep problems. Finally, both increases in school pressure (OR = 1.40; 95% CI: 1.26-1.56) and lack of student support (OR = 1.25; 95% CI: 1.10-1.42) were associated with a higher likelihood of sleep problems, while peer support and teacher support were not.Conclusion: Our findings highlight the importance of an integrated approach to the study of sleep difficulties in adolescence that includes specific psychosocial contributors such as the quality of parental communication and perceived parental support and considers the quality of the day-to-day relationship with schoolmates and the school level of demands.

BackgroundNeuronavigation of preoperative MRI is limited by several errors. Intraoperative ultrasound (iUS) with navigated probes that provide automatic superposition of pre-operative MRI and iUS and three-dimensional iUS reconstruction may overcome some of these limitations. Aim of the present study is to verify the accuracy of an automatic MRI - iUS fusion algorithm to improve MR-based neuronavigation accuracy.MethodsAn algorithm using Linear Correlation of Linear Combination (LC2)-based similarity metric has been retrospectively evaluated for twelve datasets acquired in patients with brain tumor. A series of landmarks were defined both in MRI and iUS scans. The Target Registration Error (TRE) was determined for each pair of landmarks before and after the automatic Rigid Image Fusion (RIF). The algorithm has been tested on two conditions of the initial image alignment: registration-based fusion (RBF), as given by the navigated ultrasound probe, and different simulated course alignments during convergence test.Results Except for one case RIF was successfully applied in all patients considering the RBF as initial alignment. Here, mean TRE after RBF was significantly reduced from 4.03 (+/- 1.40) mm to (2.08 +/- 0.96 mm) (p = 0.002), after RIF. For convergence test, the mean TRE value after initial perturbations was 8.82 (+/- 0.23) mm which has been reduced to a mean TRE of 2.64 (+/- 1.20) mm after RIF (p < 0.001).ConclusionsThe integration of an automatic image fusion method for co-registration of pre-operative MRI and iUS data may improve the accuracy in MR-based neuronavigation.