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The destructive atmospheric entry process is distinguished by the formation of several fragments due to the severe aerothermal loads encountered during the descent. The proximity of debris leads to shock wave interactions and collisions between bodies, influencing the overall dynamics of the fragments and affecting the prediction of demise and ground impact location. To account for these effects, the use of computational fluid dynamics is introduced to resolve the shock interaction patterns by employing a quasi-steady approach, and the use of a simple rigid-body collision model is introduced to represent the dynamics of fragments in the cloud of debris. The quasi-steady approach is assessed and validated by comparative analysis with a few studies in the literature. One of these examples is the rebuilding of the VKI's experiment of a free-flying ring crossing a shock wave generated by the presence of a stationary cylinder. The impact of explicitly modeling collision dynamics in the trajectory of fragments and ground spread distance is validated by considering a set of relevant test cases from the literature and tested them for destructive atmospheric reentry of the Attitude Vernier Upper Module, the launcher VEGA upper stage. [ABSTRACT FROM AUTHOR]

Simple Summary: Anaphylaxis to paclitaxel requires desensitization protocols for safe drug re-administration. Hypersensitivity severity and skin tests (STs) guide desensitization protocol choices. The only study reporting on the basophil activation test (BAT) in diagnosing hypersensitivity to paclitaxel showed unsatisfactory diagnostic performance. Here, we present a modified BAT that shows unprecedented sensitivity (90.91%) and specificity (90.91%) in diagnosing hypersensitivity to paclitaxel and demonstrate that most patients with hypersensitivity to paclitaxel who score ST-negative score BAT-positive. We propose that the present BAT should be used to personalize patient management. Moreover, we predict the interactions of paclitaxel with the degranulation-competent MRGPRX2 receptor using an in silico molecular docking study. Immediate hypersensitivity reactions (iHSRs) to taxanes are observed in 6% and 4% of gynecologic and breast cancer patients, respectively. Drug desensitization is the only option, as no comparable alternative therapy is available. Surfactants in the taxane formulation have been implicated in the immunopathogenesis of iHSRs, although sporadic skin test (ST) positivity and iHSRs to nab-paclitaxel have suggested the involvement of the taxane moiety and/or IgE-mediated pathomechanisms. In vitro diagnostic tests might offer insights into mechanisms underlying iHSRs to taxanes. The aim of the present study was to address this unmet need by developing a novel basophil activation test (BAT). The study included patients (n = 31) undergoing paclitaxel/carboplatin therapy. Seventeen patients presented with iHSRs to paclitaxel (iHSR-Taxpos), and eleven were tolerant (iHSR-Taxneg). Fourteen patients presented with iHSRs to carboplatin (iHSR-Plpos), and fourteen were tolerant (iHSR-Plneg). The BAT median stimulation index (SI) values were 1.563 (range, 0.02–4.11; n = 11) and −0.28 (range −4.88–0.07, n = 11) in iHSR-Taxpos and iHSR-Taxneg, respectively. The BAT median SI values were 4.45 (range, 0.1–26.7; n = 14) and 0 (range, −0.51–1.65; n = 12) in iHSR-Plpos and iHSR-Plneg, respectively. SI levels were not associated with iHSR severity grading. Comparing BAT results in iHSR-Taxpos and iHSR-Taxneg showed the area under the receiver operator characteristic (ROC) curve to be 0.9752 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 90.91% of iHSR-Taxpos patients and 90.91% of iHSR-Taxneg patients. Comparing BAT results for iHSR-Plpos and iHSR-Plneg showed the area under the ROC curve to be 0.9286 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 78.57% of iHSR-Plpos patients and 91.67% of iHSR-Plneg patients. Most iHSR-Taxpos patients for which ST was available (10/11) scored ST-negative and BAT-positive, whereas most iHSR-Plpos patients for which ST was available (14/14) scored both BAT- and ST-positive. This suggested the intervention of non-IgE-mediated mechanisms in iHSR-Taxpos patients. Consistent with this view, an in silico molecular docking analysis predicted the high affinity of paclitaxel to the degranulation-competent MRGPRX2 receptor. This hypothesis warrants further in vitro investigations. In conclusion, the present study provides preliminary proof-of-concept evidence that this novel BAT has potential utility in understanding mechanisms underlying iHSRs to taxanes. [ABSTRACT FROM AUTHOR]

Objective  Electrical cardiometry is an impedance-based monitoring technique that provides data on several hemodynamic parameters in a noninvasive way. There is limited information on clinical utility of the application of this technique in neonates. Study Design  In this study, we describe the case of a preterm neonate born at 30 2/7 weeks of gestational age who developed severe systemic infection with fluid refractory septic shock on day 2 of life. Discussion  Electrical cardiometry was used and proved very helpful in real-time guiding the choice and the dosing of the most appropriate inotrope drugs in this patient. In addition, it promptly underlined an abrupt drop of systemic vascular resistances occurring after administration of the first dose of antibiotic, thus warning the attending neonatologist to institute appropriate treatment before the clinical conditions could further worsen. Conclusion  This case report suggests that electrical cardiometry could be a useful tool in assessing, monitoring, and guiding care of neonates who develop severe septic shock. We suggest that electrical cardiometry is a promising approach in the management strategies of such patients that warrants informative clinical trials. Key Points Electrical cardiometry was helpful in real-time decision-making. Electrical cardiometry reported hemodynamic perturbations before worsening of clinical conditions. Electrical cardiometry should be included in the management of critical patients. [ABSTRACT FROM AUTHOR]

A data-driven adaptive reduced order modelling approach is presented for the reconstruction of impulsively started and vortex-dominated flows. A residual-based error metric is presented for the first time in the framework of the adaptive approach. The residual-based adaptive Reduced Order Modelling selects locally in time the most accurate reduced model approach on the basis of the lowest residual produced by substituting the reconstructed flow field into a finite volume discretisation of the Navier–Stokes equations. A study of such an error metric was performed to assess the performance of the resulting residual-based adaptive framework with respect to a single-ROM approach based on the classical proper orthogonal decomposition, as the number of modes is varied. Two- and three-dimensional unsteady flows were considered to demonstrate the key features of the method and its performance. [ABSTRACT FROM AUTHOR]

The effect of thermal nonequilibrium on shock interactions of carbon dioxide (CO2) hypersonic flows is investigated. Given the relatively low characteristic vibrational temperature of the CO2 molecule, it is expected that excited vibrational modes play a significant role in the physics of shock/shock and shock/boundary layer interactions. The shock interference mechanism resulting from a CO2-dominated flow over different double-wedge geometries is investigated by numerically solving the Navier–Stokes equations within the framework of a two-temperature model that considers translational energy–vibrational energy transfer. To assess the impact of vibrational relaxation, a comparative assessment of the patterns obtained with three thermo-physical models is presented, with the two-temperature model flow pattern being compared to thermally perfect and perfect ideal gas ones. Results obtained with the two-temperature model show that increasing the aft angle significantly enlarges the separated region in the compression corner and generates numerous secondary shock waves and shear layers. Peaks of heat flux and pressure occur along the surface due to boundary layer reattachment downstream of the compression corner, except for the case of the higher angle, which results in the largest peaks due to shock impingement. Different assumptions on the excitation of vibrational modes are shown to largely influence the size of the recirculation bubble in the compression corner, shock interaction mechanism, and surface loads. The more energy transferred to the vibrational mode, the lower post-shock temperatures are obtained, which tends to reduce the post-shock density, leading to weaker shock interactions characterized by delayed onsets of separation, reduced separation regions, and smaller standoff distances. [ABSTRACT FROM AUTHOR]

The Web has evolved into a huge mine of knowledge carved in different forms, the predominant one still being the free-text document. This motivates the need for intelligent Web-reading agents: hypothetically, they would skim through disparate Web sources corpora and generate meaningful structured assertions to fuel knowledge bases (KBs). Ultimately, comprehensive KBs, like Wikidata and DBpedia, play a fundamental role to cope with the issue of information overload. On account of such vision, this paper depicts the Fact Extractor, a complete natural language processing (NLP) pipeline which reads an input textual corpus and produces machine-readable statements. Each statement is supplied with a confidence score and undergoes a disambiguation step via entity linking, thus allowing the assignment of KB-compliant URIs. The system implements four research contributions: it (1) executes n-ary relation extraction by applying the frame semantics linguistic theory, as opposed to binary techniques; it (2) simultaneously populates both the T-Box and the A-Box of the target KB; it (3) relies on a single NLP layer, namely part-of-speech tagging; it (4) enables a completely supervised yet reasonably priced machine learning environment through a crowdsourcing strategy. We assess our approach by setting the target KB to DBpedia and by considering a use case of 52 , 000 Italian Wikipedia soccer player articles. Out of those, we yield a dataset of more than 213 , 000 triples with an estimated 81.27 % F 1 . We corroborate the evaluation via (i) a performance comparison with a baseline system, as well as (ii) an analysis of the T-Box and A-Box augmentation capabilities. The outcomes are incorporated into the Italian DBpedia chapter, can be queried through its SPARQL endpoint, and/or downloaded as standalone data dumps. The codebase is released as free software and is publicly available in the DBpedia association repository. [ABSTRACT FROM AUTHOR]

Background: Aerobic training has been widely indicated to patients with type 2 diabetes. However, there are still few studies comparing acute glycemic and blood pressure effects of different methods of aerobic training. The aim is to compare glycemic and pressure acute responses of continuous aerobic exercise to interval aerobic exercise in patients with type 2 diabetes.Materials and Methods: This study is a randomized, crossover clinical trial. Fourteen patients with type 2 diabetes performed two sessions of aerobic training with different methods (continuous and interval). Continuous session had duration of 35 minutes with intensity of 85–90% of heart rate corresponding to anaerobic threshold (HRAT), while interval session had 45 minutes, with stimulus in intensity of 85–90% of HRATwith recovery in intensity under 85% of HRAT. Capillary glycemia, systolic and diastolic blood pressure were analyzed before and after the sessions.Results: Patients were 63.5 ± 9.8 years old. Glycemia was reduced in both sessions (p < 0.001). Only glycemia measured at 25 minutes after continuous session was not lower than pre-session values. Systolic blood pressure was also reduced in both sessions (p = 0.010) with similar behavior between them. In the diastolic blood pressure, there were differences only between the values measured immediately after exercise and the values measured 20 minutes (p = 0.002) and 30 minutes after exercise (p = 0.008).Conclusion: Both continuous and interval aerobic exercise, in a same intensity, are effective for glycemic and pressure acute reductions in individuals with type 2 diabetes. For patients with greater risk of hypertension, we believe that the interval method is safer. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to evaluate the diagnostic performances of manual and instrumental measurement of reticulocyte percentage (Ret%), reticulocyte number (Ret#) and reticulocyte production index (RPI) to differentiate regenerative anaemia (RA) from non-regenerative anaemia (NRA) in cats. Methods Data from 106 blood samples from anaemic cats with manual counts (n = 74; 68 NRA, six RA) or instrumental counts of reticulocytes (n = 32; 25 NRA, seven RA) collected between 1995 and 2013 were retrospectively analysed. Sensitivity, specificity and positive likelihood ratio (LR+) were calculated using either cut-offs reported in the literature or cut-offs determined from receiver operating characteristic (ROC) curves. Results All the reticulocyte parameters were significantly higher in cats with RA than in cats with NRA. All the ROC curves were significantly different (P <0.001) from the line of no discrimination, without significant differences between the three parameters. Using the cut-offs published in literature, the Ret% (cut-off: 0.5%) was sensitive (100%) but not specific (<75%), the RPI (cut-off: 1.0) was specific (>92%) but not sensitive (<15%), and the Ret# (cut-off: 50 × 10³/µl) had a sensitivity and specificity >80% and the highest LR+ (manual count: 14; instrumental count: 6). For all the parameters, sensitivity and specificity approached 100% using the cut-offs determined by the ROC curves. These cut-offs were higher than those reported in the literature for Ret% (manual: 1.70%; instrumental: 3.06%), lower for RPI (manual: 0.39; instrumental: 0.59) and variably different, depending on the method (manual: 41 × 10³/µl; instrumental: 57 × 10³/µl), for Ret#. Using these cut-offs, the RPI had the highest LR+ (manual: 22.7; instrumental: 12.5). Conclusions and relevance This study indicated that all the reticulocyte parameters may confirm regeneration when the pretest probability is high, while when this probability is moderate, RA should be identified using the RPI providing that cut-offs <1.0 are used. [ABSTRACT FROM AUTHOR]

Introduction Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab – an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein – failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients’ propensity to respond to abagovomab. Materials and methods The immune system status was assessed as percentage and absolute count of CD8 + T cells producing IFN-γ after stimulation with Staphylococcal Enterotoxin B (SEB) in 80 patients on abagovomab and 31 patients on placebo from the MIMOSA trial ahead of treatment. Optimal cutoffs of the two variables were calculated by the web application “Cutoff Finder” as the points with most significant (log-rank test) splits based on relapse-free survival (RFS). The Kaplan–Meier curves and log-rank test served to estimate and compare RFS in patients with percentage and absolute count of IFN-γ producing CD8 + T cells around the cutoffs. Results Patients on abagovomab with IFN-γ producing CD8 + T cell percentage above the cutoff had a better RFS (p = 0.042) than those with IFN-γ producing CD8 + T cell percentage below the cutoff. Patients on abagovomab with IFN-γ producing CD8 + T cell absolute count above the cutoff had a better RFS (p = 0.019) than those with IFN-γ producing CD8 + T cell absolute counts below the cutoff. Consistently, the RFS of patients on abagovomab with IFN-γ producing CD8 + T cell percentage and absolute counts values below the respective cutoffs was identical to that of patients on placebo. Neither the percentage nor the absolute count of IFN-γ producing CD8 + T cells correlated with RFS in patients on placebo. Conclusions A robust immune system is essential to obtain a clinical response in OC patients undergoing abagovomab immunotherapy whereas a robust immune system does not confer per se a survival advantage. Further work will clarify whether the results shown here apply only in the present setting or extend to other types of cancer and/or immunotherapeutic agents. [ABSTRACT FROM AUTHOR]

Aircraft holding around busy airports may be requested to sustain as much as 45 min of icing before landing or being diverted to another airport. In this paper, a three-dimensional mesh deformation scheme, based on a structural frame analogy, is proposed for the numerical simulation of ice accretion during extended exposure to adverse weather conditions. The goal is to provide an approach that is robust and efficient enough to delay or altogether avoid re-meshing while preserving (enforcing) nearly orthogonal elements at the highly distorted ice surface. Robustness is achieved by suitably modifying the axial and torsional stiffness components of the frame elements in order to handle large and irregular grid displacements typical of in-flight icing. Computational efficiency is obtained by applying the mesh displacement to an automatically selected small subset of the entire computational domain. The methodology is validated first in the case of deformations typical of fluid-structure interaction problems, including wing bending, a helicopter rotor in forward flight, and the twisting of a high-lift wing configuration. The approach is then assessed for aero-icing on two swept wings and compared against experimental measurements where available. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Centroidal Voronoi tessellation, leave-one-out cross validation, proper orthogonal decomposition, and multidimensional interpolation are integrated to define a reduced-order modeling approach for the parametric evaluation of steady aerodynamic loads. The proper orthogonal decomposition-based methodology allows reducing the number of degrees of freedom of the problem while maintaining good accuracy for the solution of complex three-dimensional viscous turbulent flows. As a result, it yields fairly accurate solutions at a fraction of the time required by standard computational fluid dynamics approaches. Three-dimensional examples for fixed- and rotary-wing cases of industrial relevance are used to assess the method in the cases of subsonic and transonic flow conditions. [ABSTRACT FROM AUTHOR]

Erratum: "Effect of thermal nonequilibrium on the shock interaction mechanism for carbon-dioxide mixtures on double-wedge geometries" [Phys. REFERENCES 1 C. Garbacz, F. Morgado, and M. Fossati, " Effect of thermal nonequilibrium on the shock interaction mechanism for carbon dioxide mixtures on double-wedge geometries", Phys. A correction is required to the abstract of the original published paper.[1] According to the content of the paper, the last sentence of the abstract, "The more energy is transferred to the vibrational mode, the lower post-shock temperatures are obtained, which tends to reduce the post-shock density, leading to weaker shock interactions characterized by delayed onsets of separation, reduced separation regions and smaller standoff distances" should read instead: "The more the energy is transferred to the vibrational mode, the lower post-shock temperatures are obtained, which tends to increase the post-shock density, leading to weaker shock interactions characterized by delayed onsets of separation, reduced separation regions, and smaller standoff distances.". [Extracted from the article]

Steady and unsteady three-dimensional viscous turbulent aero-icing simulations are computationally expensive, especially for certification campaigns when broad parametric studies are needed. To overcome the computational effort of such investigations, a Reduced Order Modeling approach, based on Proper Orthogonal Decomposition and Kriging interpolation, is proposed. Using a database of high-fidelity numerical simulations, experimental data, or combinations of both, the proposed technique allows approximating solutions by linear combination of a limited number of eigenfunctions. Bayesian Kriging, a recent variant, is used to obtain the scalar coefficients for the expansion. The accuracy of the proposed method is assessed against reference solutions from two- and threedimensional aero-icing simulations as well as against experimental data. [ABSTRACT FROM AUTHOR]

The computational cost of viscous turbulent aeroicing simulations is a limitation that needs to be addressed more extensively using computational fluid dynamics (CFD) for aircraft in-flight icing certification. To overcome this computational burden, a reduced-order modeling (ROM) approach, based on proper orthogonal decomposition and kriging interpolation techniques, is applied to the computation of the water impact pattern of supercooled large droplets on aircraft. Relying on an appropriate database of high-fidelity, full-order simulations, the ROM approach provides an accurate lower-order approximation of the system in terms of a linear combination of appropriate functions. The resulting surrogate solution is successfully compared with experimental and CFD results for two-dimensional and three-dimensional cases, including a complete aircraft case. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-1/PD-L1 axis blockade immunotherapy leverages on assessment of tumour PD-L1 status by immunohistochemistry for identifying cancer patients' who would benefit most from this therapy. Because some PD-L1 negative cancer patients also benefit from the treatment, it has been postulated that spatial heterogeneity of PD-L1 expression in tumour tissue may reduce the predictive value of the test. Here we demonstrate for the first time the presence of PD-L1+ circulating tumor–derived microvesicles in the blood stream of high grade serous ovarian cancer patients and propose the assessment of tumor-derived circulating PD-L1+ microvesicles to be inserted in predictive algorithms for complementing tumour PD-L1 status. Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1+ tumour cells (TC) and infiltrating PD-L1+ leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status. Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1+ MVs (range: 1.4–178.8 MVs/μL and 6.2–504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients (n = 63), using a sensitive flow cytometry platform. The concentration of PD-L1+ MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1+ MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1+ MVs of platelet origin (10.3–2409.6 MVs/μL). Conclusions: The enumeration of circulating PD-L1+ MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1+ MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies. [ABSTRACT FROM AUTHOR]

SU2-NEMO, a recent extension of the open-source SU2 multiphysics suite's set of physical models and code architecture, is presented with the aim of introducing its enhanced capabilities in addressing high-enthalpy and high-Mach number flows. This paper discusses the thermal nonequilibrium and finite-rate chemistry models adopted, including a link to the Mutation++ physio-chemical library. Further, the paper discusses how the software architecture has been designed to ensure modularity, incorporating the ability to introduce additional models in an efficient manner. A review of the numerical formulation and the discretization schemes utilized for the convective fluxes is also presented. Several test cases in two- and three-dimensions are examined for validation purposes and to illustrate the performance of the solver in addressing complex nonequilibrium flows. [ABSTRACT FROM AUTHOR]

The presence of complex geometries and/or multiple bodies during atmospheric reentry may lead to complex and directional flow features, such as shock waves and shear layers, that need to be correctly predicted to ensure accurate calculation of the aerothermal loads during reentry. Central in ensuring reliable numerical prediction of loads is the adoption of meshes that ensure grid independence and minimize the misalignment between the directional flow features and the grid cell interfaces, a situation that is known to give rise to nonphysical behaviors and spurious oscillations. The use of anisotropic unstructured grid adaptation is here presented as a means to ensure appropriate grid resolution and alignment with directional flow features for cases where the use of structured grids is not always possible or practical. Results highlight the effectiveness and reliability of anisotropic mesh adaptation in successfully predicting the location of shock discontinuities as well as surface aerothermodynamic quantities, while providing results comparable with established approaches relying on structured meshes. Results are presented for single- and multiple-body cases through comparison with experimental data and reference numerical solutions. [ABSTRACT FROM AUTHOR]

The aerothermodynamic environment surrounding bodies undergoing destructive atmospheric entry is characterized by multiple interacting shock waves generated by the presence of several fragments moving close to one another at high speed. Shock interaction and impingement produce highly localized surface loads, influencing the overall dynamics of the fragment, its temperature, and in turn its demise. To account for the relevant physics during the reentry process of fragmenting bodies, a multifidelity framework is presented that allows for selecting the most appropriate level of fidelity, between high-fidelity solutions or low-fidelity aerothermodynamic metamodels. A physics-informed approach is implemented to automatically choose between the two fidelity levels on the basis of the intersection of shock wave envelopes. The complete framework is validated on relevant test cases from the literature and its performance is demonstrated for destructive atmospheric reentry cases, such as the case of the Attitude Vernier Upper Module and the Automated Transfer Vehicle from the European Space Agency. [ABSTRACT FROM AUTHOR]

Predicting shock/shock and shock/boundary-layer interactions in gas flows that surround high-speed vehicles is key in aerodynamic design. Under typical hypersonic conditions, these flow structures are influenced by complex nonequilibrium phenomena leading to high-temperature effects. In this work, the conceptual Bedford wing-body vehicle is studied to analyze flow patterns in shock/shock and shock/boundary-layer interactions with thermochemical nonequilibrium. A parametric computational fluid dynamics study is carried out for different hypersonic operating conditions, with respect to the freestream Mach number. Simulations are performed with the SU2-NEMO solver coupled to the Mutation++ library, which provides all the necessary thermodynamic, kinetic, and transport properties of the mixture and chemical species. The Adaptive Mesh Generation library is used for automatic anisotropic mesh adaptation. Numerical results show that increasing the freestream Mach number from 4 to 10 leads to changes in the shock layer, locations of shock impingement, and regions of boundary-layer separation. Despite these changes, the change in freestream Mach number has little impact on the overall shock interaction structures. [ABSTRACT FROM AUTHOR]