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Background: Acetaminophen and ibuprofen are the only antipyretics drugs approved in children, and are considered safe and well tolerated. However, data regarding the adverse drug reaction (ADR) profile of these drugs in children are scattered. Aim: The aim of our study is to evaluate the ADRs of acetaminophen and ibuprofen through an observational study over a period of 15 years (January 2005-April 2020). Reports of suspected ADRs to the active substances ‘acetaminophen’ and ‘ibuprofen’ are listed and accessible through the Italian spontaneous reporting database (RAM system) by AIFA (Pharmacovigilance of the Italian Drug Agency). Methods: Acetaminophen ADRs in paediatric populations were 15% of cases, with more frequent involvement of skin and soft tissue (54.36%) and gastrointestinal apparatus (44.09%); liver dysfunction accounts for 5.67%. Results: Ibuprofen paediatric ADRs were 26%: skin and soft tissues in 63.16% of cases, gastrointestinal tract in 47.75%, hematemesis and melena in 6.38%; kidney injury in 2.25% of cases. Conclusion: Children aged 2 to 11 are more frequently affected by ADRs than infants and adolescents. The risk of gastrointestinal and renal side effects is significantly higher with ibuprofen. Hepatobiliary side effects are more frequently linked to acetaminophen. Potentially fatal ADRs have been reported sporadically for both drugs.

This work describes the cooperative/competitive design process that led to the definition of the Krueger flap to be used in the numerical and experimental tests of the European project UHURA. The project requirements are particularly challenging because it is necessary to develop a device with good aerodynamic high-lift characteristics, but it is necessary to consider many constraints of structural and kinematic nature. Indeed, the kinematics for its deployment is quite complex and imposes hard constraints on the Krueger shape, and the structural characteristics must allow it to withstand considerable structural stresses in the deployment phase which is studied in the wind tunnel.

High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9–10/10 HLA-matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, using the locus median to stratify patients with ‘high’ or ‘low’ HED. Patients with high HED-B and -DRB1 showed significantly improved disease-free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.

This manuscript illustrates an optimization procedure carried out on a large-scale wind tunnel model conceived to investigate the aerodynamic and acoustic performance of a Distributed Electric Propulsion (DEP) system installed on the wings of a regional aircraft in high lift conditions. The aim of the optimization process is to obtain the best possible improvements in terms of noise and aerodynamic performance by modifying the propellers' layout of the Wing + DEP wind tunnel model. A multi-objective, multi-point design approach is adopted based on evolutionary computing. The research work is carried out in the framework of the VENUS EU-funded project GA-886019.

This paper presents the multi-objective optimisation of the MH114 high-lift airfoil. We seek the set of Pareto optimal solutions that maximise the airfoil lift and minimise the drag. The lift and drag forces are considered uncertain due to geometrical uncertainties. The uncer- tainty quantification of the probabilistic aerodynamic force values re- quires a large number of samples. However, the prediction of the aero- dynamic forces is expensive due to the numerical solution of the Navier- Stokes equations. Therefore, a multi-fidelity surrogate assisted approach is employed to combine expensive RANS simulations with cheap poten- tial flow calculations. The multi-fidelity surrogate-based approach allows us to economically optimise the aerodynamic design of the airfoil under uncertainty.

Pandemics often put science and scientists at the centre of the public discussion, having relevant effects on the science-society relationships (Metcalfe et al., 2020). For instance, while trust in science as an endeavour may remain stable, trust in scientist may reduce significantly (Eichengreen et al., 2020). During the COVID-19 pandemic, health agencies’ and doctors’ guidelines were crucial in orienting public policies (e.g., lockdowns) and social actions (e.g., wearing a mask). However, their role was surrounded by polemics (Observa, 2020). Being “amateur scientists”, laypeople do not passively accept experts’ opinions, but they actively re-elaborate and resist them (Bauer & Gaskell, 2009). Interestingly, the nature of this re-elaboration is often political (Hamilton & Safford, 2020). By comparing different political positionings, the ongoing research aims to: (1) investigate the contents of the emerging representations of science (themes and key players); (2) highlight the functions and the roles assigned to science-based institutions and scientists; (3) identify laypeople’s perspectives on the different sources of information. We conducted 60 semi-structured interviews with Italian laypeople (30 women; Age M = 44.4) having different political positionings: 30 supporting and 30 opposing the Italian government. Thirty interviews were conducted during the first wave (March-May 2020) and thirty during the second (November-December 2020). Our communication will discuss the results of our thematic analysis (Braun & Clark, 2006) by focusing on two dimensions: (1) the emerging representations of science and scientists in the two waves of infections in Italy and (2) the relationship between these representations and laypeople’s political leaning.

Background: allogeneic HSCT is the only potentially curative treatment for many non-malignant diseases (NMD), either inherited or acquired. However, many patients lack an HLA-matched donor (familiar (MFD) or unrelated (MUD)) and the outcome of children transplanted from an HLA-haploidentical relative (haplo) was historically inferior to that of transplants from a MFD or a MUD. We previously published promising results in a cohort of 23 children with NMD given this type of allograft (Bertaina et al., Blood 2014), demonstrating a low transplant-related mortality (TRM) and high cure rates. Here, we report the outcome of a large cohort of children affected by NMD who received a TBdepl-haploHSCT at our Center (NCT01810120). Patients and methods: Between February 2011 and June 2020, 80 consecutive patients affected by NMD received TBdepl-haploHSCT from an HLA-partially matched relative at Ospedale Pediatrico Bambino Gesù in Rome, Italy. Patients had many different disorders (see Table for details on patient- and transplant-related characteristics). Median time from diagnosis to transplant for the whole cohort was 12 months (range 1-177), while it was 2.5 months (range 1.3-11.2) for SCID patients. All patients, including children with SCID, received a conditioning regimen, which varied according to the original disease. Pre-transplant anti-thymocyte globulins (from day -4 to day -2) were given to modulate bi-directional donor/recipient alloreactivity, while rituximab (on day -1) was administered to prevent PTLD. Moreover, no post-transplant pharmacological GvHD prophylaxis was given. Results: fifty-eight patients (72.5%) achieved primary donor cell engraftment, while 3 patients experienced secondary graft failure (GF); the cumulative incidence of either primary or secondary GF was 27.8% (95% CI 17.2-37.0). Median time to neutrophil and platelet recovery was 13.5 (range 9-33) and 10 days (range 7-51), respectively. As expected, GF occurred more frequently in children with disorders known to be associated with an increased GF risk (i.e., HLH, thalassemia, SAA or osteopetrosis) (see also Figure 1A). Three children (4%) experiencing GF died because of infectious complications before retransplant. Sixteen of the 22 patients with either primary or secondary GF were successfully retransplanted (2 with a mismatched unrelated cord blood unit, the other having received a second TBdepl-haploHSCT from either the same donor or the other parent). Since 3 other patients died [all because of infectious complications, 2 due to disseminated adenovirus infection and 1 to CMV pneumonia)], TRM is 7.8% (95% CI 1.6-13.7). Eighteen patients experienced acute GVHD of any grade, the cumulative incidence of this complication being 22% (95% CI 13.5-31.8); 10/18 patients developed grade II acute GVHD (no patient developed grade III or IV aGVHD), this resulting into a cumulative incidence of 12.9% (95% CI 6.6-21.4). Only one patient at risk developed mild chronic GVHD. Twenty-two and 7 patients developed clinically-relevant (i.e., with a viral load > 1000 copies/ml and/or requiring specific antiviral-treatment) CMV and adenovirus infection, respectively, at a median time of 4 (range 0-16) and 1 (range 1-4) weeks from HSCT. Time averaged area under the curve (i.e., viral burden under the curve/weeks at risk for infection) for CMV and ADV are reported in Figure 1B. With a median follow-up of 36 months (range 2 - 110), the 5-year probability of overall survival and event-free survival for the entire cohort of patients is 92.1% (95% CI 83.3-96.4) (Figure 1C) and 68.1% (95% CI 56.4-77.2), respectively. Considering the 16/22 given a successful 2nd allograft, the 5-year disease-free survival is 88.4% (95% CI 78.9-93.8). Details on reconstitution of CD3+, CD4+ and CD8+ lymphocytes are reported in Figure 1D. Conclusions: TBdepl-haploHSCT is an effective option for children with different NMD. GF (either primary or secondary) is a challenging problem in a sub-group of patients at risk (i.e., those with HLH, thalassemia, SAA or osteopetrosis): thus, new strategies to overcome this problem are desirable. However, a second transplant is able to rescue most of these patients. Prompt availability of this type of transplant, limiting infectious risk, low incidence of both acute and chronic GvHD preserving a good quality of life in patients makes this strategy an attractive choice in patients with NMD. Figure 1 Disclosures Merli: Bellicum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria; Sanofi-Genzyme: Honoraria; Atara Therapeutics: Honoraria. Algeri:BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; Atara Therapeutics: Membership on an entity's Board of Directors or advisory committees. Locatelli:Jazz Pharmaceeutical: Speakers Bureau; Medac: Speakers Bureau; Miltenyi: Speakers Bureau; Bellicum Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Uncertainty-based optimisation techniques provide optimal airfoil de- signs that are less vulnerable to the presence of uncertainty in the operational conditions (i.e., Mach number, angle-of-attack, etc.) at which an airfoil is func- tioning. These uncertainty-based techniques typically require numerous function evaluations to accurately calculate the statistical measure of the quantity of inter- est. To render the computational burden down, the design optimisation of the air- foil is performed by a multi-fidelity surrogate-based technique. The high-fidelity aerodynamic performance is calculated with a compressible RANS solver using a fine grid. At the low-fidelity level a coarser grid is used. To obtain accurate drag predictions despite the lower grid resolution the so-called far-field drag approxi- mation is employed.

[Excerpt] This book contains book chapters from selected and extended contributions presented at the EUROGEN 2019 International Conference, that took place at the University of Minho at the historical town of Guimarães in the north of Portugal on September 12-14, 2019. EUROGEN 2019 was the 13th of a series of International Conferences previously held in Las Palmas de Gran Canaria (1995), Trieste (1997), Jyväskylä (1999), Athens (2001), Barcelona (2003), Munich (2005), Jyväskylä (2007), Kracow (2009), Capua (2011), Las Palmas de Gran Canaria (2013), Glasgow (2015) and Madrid (2017) mainly focused on Evolutionary and Deterministic Computing for Industrial Applications. This conference aims at bringing together specialists from universities, research institutions and industries developing or applying evolutionary and deterministic methods in design optimization and control and emphasizing industrial and societal applications. This series of conferences was originally launched by the EC –Strategic/Prospective Network INGENET in 1998. EUROGEN 2019 is, also, an ECCOMAS Thematic Conference also co-ordinated by the Special Interest Group (SIG) with ERCOFTAC (European Research Community on Flow, Turbulence and Combustion). The conference included the following topics: metaheuristics and evolutionary algorithms, multiobjective evolutionary algorithms and constraint handling techniques, adjoint-based including oneshot methods, hybrid optimisation methods, high-performance computing, goal-oriented optimization for mesh and meshless methods, game strategies, surrogate models for optimisation, parallel and distributed evolutionary algorithms, multi-disciplinary optimization methods, design optimization under uncertainties, multi-criteria decision making and topology optimization. [...], CCHRB -Chicago Committee on High Rise Buildings(734205)