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Solid Rocket Motors (SRMs) are known to be prone to the development of flow instabilities during their quasi-steady state phase. Nowadays such issue still represents a major and open problem for many motors currently flying as Ariane 5 P230 and VEGA first stage P80, but also for future ones as P120C, the largest solid rocket motor employing a monolithic grain which will be used as Ariane 6 strap-on booster and next generations VEGA launchers first stage. In order to guarantee the launcher safety and payload comfort, it is actually of paramount importance to carry out a pressure oscillations risk assessment which address all instability sources. In the current state of the art, two physical phenomena are considered to be the major driving mechanism for pressure oscillations onset in launching vehicle SRMs: hydrodynamic instabilities related to vortex shedding and thermoacoustic instabilities driven by aluminum distributed combustion. Hydrodynamic instabilities involve vortical structures generation and dynamics which lock in with chamber acoustics, giving rise to an aeroacoustic feedback loop. Alongside this mechanism, also a thermoacoustic instability is currently considered a pressure oscillations source in SRMs. Modern solid propellants contain metallic fuel particles, mainly aluminum, whose injection in the combustion chamber gives rise to a multiphase reacting flow. Experimental analysis carried out on aluminum combustion have shown that, once the particles are freed from the grain, a certain amount tend to cluster providing agglomerates whose diffusive chemical reaction is strongly influenced by the environment flow condition. As a consequence, a coupling may actually arise if mass and heat release fluctuations produced by the burning droplets are synchronized with the acoustic field. In the past the authors have been working on pressure oscillations in SRMs characterized by aft-finocyl geometries, employing a Q1D, mono-phase formulation named AGAR in which instability source is strictly related to vortex-shedding phenomena. In AGAR, thermoacoustic coupling driven by aluminum combustion is not evaluated, but roughly taken into account thanks to calibration parameters. In order to overcome such limitations a new Q1D model able to deal with pure thermoacoustic feedback loop in solid motors has been developed and validated on the basis of CFD simulations results. The unification of these two Q1D models has lead to a new formulation, named TAHR, which can therefore deal with both hydrodynamic and thermoacoustic instabilities in solid motors. TAHR has been recently validated against Vega P80 SRM, witnessing the model capability to cope with modern and complex solid motors used in the current space transportation system. A full investigation of TAHR model is the ultimate goal of this work. In the final manuscript an aft-finocyl SRM geometry will be taken into account in order to explore the model response, in terms of instability characterization, to different conditions like aluminum amount and size. Particular care will be given to gas and particles unsteady fields in order to highlight the major characteristics able to drive the motor instability. Finally the interaction between the two kinds of pressure oscillations sources will be taken into account. Such work can be considered as a mandatory step within a project that has as its final objective the investigation of pressure oscillations in solid rocket motors by means of a light and reliable tool.

Nowadays aft-finocyl solid propellant motors represent an essential asset for European launchers, since their employment in Vega and Ariane 6 launchers. Aft-finocyl solid rocket motors (SRMs) are inherently three-dimensional and geometrically complex. As the propellant burns, the geometry changes in a time-dependent manner, triggering an ongoing flow modification. As a a matter of fact, the internal flowfield of a modern solid motor is characterized by multiphase features. Modern propellants are laden with metal particles, mainly aluminum, that compose up to 20% of the total mass. The primary reason for the inclusion of such fuel particles into the solid propellant stems from the significant heat release obtained as the aluminum particles burn to form aluminum oxides. As the propellant burns, the propellant combustion interface regresses and the particles added to the propellant melt to form liquid droplets. A complex mechanism follows, resulting in the release of aluminum agglomerates and their injection into the accelerating core flow. The final size of the aluminum oxide particles is found to vary from a few micrometers to a few hundred micrometers, providing a polydisperse multiphase flow. Collisions between particles and breakup events near the motor nozzle generate further modification of particles distribution, exacerbating the already complex flowfield. Despite of its favourable effect on specific impulse, inclusion of Al particles in the propellant has some side effects. Indeed, it may lead to slag accumulation in submerged nozzles, thermoacoustic instability due to distributed combustion and, moreover, the alumina droplets are the main source of nozzle scouring from particulate impact, contributing to nozzle erosion. Two-phase flow losses in the nozzle expansion process caused by the velocity- and thermal-lag are also hindering the performance enhancement due to particle addition. Contrary to chemical erosion, mechanical one lacks of comprehensive theoretical/numerical models. Hence a step in this direction would be extremely valuable in achieving an improved understanding of the behavior of nozzle erosion in its entirety. However, such studies present serious challenges. Indeed, beyond the difficulty of defining a model able to cope with the interaction between particles flows and nozzle wall material, the first issue regards the correct assessment of particles trajectory, dimension, and distribution within the motor. In SRMs state of the art, flowfield analyses have been mainly treated using hybrid Eulerian/Lagrangian methods or pure Lagrangians one. Nevertheless, the subjects of such analyses have usually been solid motors with simple geometry or large segmented boosters, thus multiphase flowfield within aft-finocyl solid motors have still to be properly characterized. This work is consequently devoted to the investigation of the internal flowfield of aft-finocyl motors with particular focus on the nozzle region. Multidimensional CFD analyses based on fully Eulerian methods will be the main investigation tools. Since the interest in tracking large droplets characterised by high inertia, such methodology is not suited for accomplish this task due to the risk of generating the so called delta-shocked, thus, in this work, an advanced Eulerian modelling is taken into account. Moreover, thanks to a parametric analysis, focused on several key elements such as particles size and geometry configurations, the most important flow features affecting the motor behavior will be highlighted, contributing to provide a more clear scenario on multiphase flows within aft-finocyl motors class.

This study examines associations between parents’ rejection and control, adolescents’ self-efficacy in their regulation of negative emotions, and maladjustment. Path analyses were employed to test (a) whether adolescents’ dysregulation and self-efficacy regarding anger/sadness regulation mediate the relationship between parental rejection/control and adolescent maladjustment; (b) whether adolescent adjustment mediates the association between parental rejection/control and dysregulation and self-efficacy regarding anger/sadness regulation. Participants included 103 Italian adolescents (Time 1: M age = 15.57; 53% male), their mothers (n = 103), and their fathers (n = 79). Follow up data were assessed one year later (Time 2). At Time 1, adolescent reports of the frequency of mothers’ and fathers’ rejection and control were examined. At Time 2, adolescent-reports of their beliefs about self-efficacy in regulating anger and sadness, as well as anger and sadness dysregulation, were assessed by two methods: questionnaire and mobile ecological momentary assessment. At Time 2, mothers’, fathers’, and adolescents’ reports of adolescents’ aggressive behaviors and depressive problems were also assessed. Maternal rejection was associated with higher one year later aggressive problems, which in turn were associated with higher dysregulation of sadness, and lower self-efficacy in dealing with both anger and sadness. In addition, maternal rejection was associated with higher depressive symptoms one year later, which in turn were associated with lower self-efficacy in dealing with sadness and higher dysregulation of both anger and sadness. Finally, maternal control was associated with higher depressive symptoms, whereas paternal control was associated with lower depressive symptoms.

Background Synovial sarcoma (SS) is an aggressive soft tissue tumor with limited therapeutic options in advanced stage. SS18-SSX fusion oncogenes, which are the hallmarks of SS, cause epigenetic rewiring involving histone deacetylases (HDACs). Promising preclinical studies supporting HDAC targeting for SS treatment were not reflected in clinical trials with HDAC inhibitor (HDACi) monotherapies. We investigated pathways implicated in SS cell response to HDACi to identify vulnerabilities exploitable in combination treatments and improve the therapeutic efficacy of HDACi-based regimens. Methods Antiproliferative and proapoptotic effects of the HDACi SAHA and FK228 were examined in SS cell lines in parallel with biochemical and molecular analyses to bring out cytoprotective pathways. Treatments combining HDACi with drugs targeting HDACi-activated prosurvival pathways were tested in functional assays in vitro and in a SS orthotopic xenograft model. Molecular mechanisms underlying synergisms were investigated in SS cells through pharmacological and gene silencing approaches and validated by qRT-PCR and Western blotting. Results SS cell response to HDACi was consistently characterized by activation of a cytoprotective and auto-sustaining axis involving ERKs, EGR1, and the β-endoglycosidase heparanase, a well recognized pleiotropic player in tumorigenesis and disease progression. HDAC inhibition was shown to upregulate heparanase by inducing expression of the positive regulator EGR1 and by hampering negative regulation by p53 through its acetylation. Interception of HDACi-induced ERK-EGR1-heparanase pathway by cell co-treatment with a MEK inhibitor (trametinib) or a heparanase inhibitor (SST0001/roneparstat) enhanced antiproliferative and pro-apoptotic effects. HDAC and heparanase inhibitors had opposite effects on histone acetylation and nuclear heparanase levels. The combination of SAHA with SST0001 prevented the upregulation of ERK-EGR1-heparanase induced by the HDACi and promoted caspase-dependent cell death. In vivo, the combined treatment with SAHA and SST0001 potentiated the antitumor efficacy against the CME-1 orthotopic SS model as compared to single agent administration. Conclusions The present study provides preclinical rationale and mechanistic insights into drug combinatory strategies based on the use of ERK pathway and heparanase inhibitors to improve the efficacy of HDACi-based antitumor therapies in SS. The involvement of classes of agents already clinically available, or under clinical evaluation, indicates the transferability potential of the proposed approaches.

A total of 63 myeloproliferative neoplasms [MPN; 9 polycythemia vera (PV), 32 essential thrombocythemia (ET), and 22 myelofibrosis (MF)] underwent spleen stiffness (SS) measurement by vibration-controlled transient elastography equipped with a novel spleen-dedicated module. Higher SS values significantly correlated with grade 2-3 bone marrow (BM) fibrosis (p=0.035), with hemoglobin level p=0.014) and with white blood cells ≥10,000/μl (p=0.008). Median SS was significantly higher in MF patients compared to ET and PV (p=0.015). SS also correlated with higher JAK2 variant allele frequency (p=0.02). This study identifies SS as a potential noninvasive tool that reflects BM fibrosis and the mutational burden in MPN.

The present study examines parents' self-efficacy about anger regulation and irritability as predictors of harsh parenting and adolescent children's irritability (i.e., mediators), which in turn were examined as predictors of adolescents' externalizing and internalizing problems. Mothers, fathers, and adolescents (N = 1,298 families) from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States) were interviewed when children were about 13 years old and again 1 and 2 years later. Models were examined separately for mothers and fathers. Overall, cross-cultural similarities emerged in the associations of both mothers' and fathers' irritability, as well as of mothers' self-efficacy about anger regulation, with subsequent maternal harsh parenting and adolescent irritability, and in the associations of the latter variables with adolescents' internalizing and externalizing problems. The findings suggest that processes linking mothers' and fathers' emotion socialization and emotionality in diverse cultures to adolescent problem behaviors are somewhat similar. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

RESUMEN Introducción: Múltiples estudios demostraron una relación “protectora” del índice de masa corporal (IMC) incrementado por sobre el IMC normal o bajo en el desarrollo y el pronóstico de la insuficiencia cardíaca. Las categorías de IMC de la población adulta no son adecuadas en la población anciana. Nos proponemos comparar la incidencia de mortalidad global y de reinternación por insuficiencia cardíaca durante el primer año según la categoría de IMC en esta población. Materiales y métodos: Estudio observacional y analítico de una cohorte retrospectiva de pacientes mayores de 65 años internados en la unidad de cuidados intensivos cardiológicos del Hospital Italiano de Buenos Aires (HIBA) con diagnóstico de síndrome de insuficiencia cardíaca aguda (SICA) entre enero de 2013 y diciembre de 2017. Resultados: Se incluyeron 409 pacientes. Los subgrupos con mayor IMC presentaron menor mortalidad al año (peso insuficiente: 53%, normopeso: 41%, sobrepeso: 33%, obesos: 27%, p = 0,008). En el análisis multivariado, el HR para mortalidad anual ajustado por edad, sexo, reinternaciones, insuficiencia renal y tipo de insuficiencia cardíaca fue de 0,51 (IC95% 0,29-0,90) en los pacientes con sobrepeso y de 0,36 (IC95% 0,19-0,67) en los pacientes obesos con respecto a los de peso insuficiente. No hubo diferencias en la mortalidad intrahospitalaria ni en las reinternaciones al año entre los diferentes subgrupos de IMC. Conclusión: En la población de ancianos con SICA, los subgrupos con mayor IMC tienen mejor pronóstico durante el primer año, por lo que se cumple la “paradoja de la obesidad”. ABSTRACT Background: Multiple studies have demonstrated a “protective” relationship of increased body mass index (BMI) over normal or low BMI in the development and prognosis of heart failure. The BMI categories of the adult population are not adequate in the elderly population. We propose to compare the incidence of global mortality and/or readmission for heart failure during the first year according to the BMI category in this population. Methods: This was an observational and analytical study of a retrospective cohort of patients ≥65 years admitted to the cardiology intensive care unit of Hospital Italiano de Buenos Aires with a diagnosis of Acute Heart Failure Syndrome (AHFS) between January 2013 and December 2017. Results: The study included 409 patients. The subgroups with higher BMI had lower mortality at one year (Underweight: 53%, Normal weight: 41%, Overweight: 33%, Obese: 27%, p = 0.008). In the multivariate analysis, annual mortality HR adjusted for age, gender, readmissions, kidney failure and type of heart failure was 0.51 (95% CI 0.29-0.90) for overweight patients and 0.36 (95% CI 0.19-0.67) for patients with obesity compared with underweight patients. There were no differences in inhospital mortality or in readmissions at one year between the different BMI subgroups. Conclusion: In the elderly population with AHFS, the subgroups with higher BMI have a better prognosis during the first year, fulfilling the “obesity paradox”.

Women with bipolar disorder are at high risk for relapse throughout pregnancy and in the postpartum period, especially when mood stabilizer medication is discontinued. Postpartum disruption of circadian rhythms, immune dysregulation, and abrupt fluctuation of reproductive hormones can precipitate postpartum psychosis, a psychiatric emergency with an increased risk of suicide and a 4% risk of infanticide. Fortunately, effective treatments exist for managing bipolar disorder in pregnancy, with the aim of preventing episode recurrence and maintaining function. Risks associated with psychotropic medication in pregnancy must be balanced against risks of untreated bipolar illness. In this review, we present risk profiles of existing treatments for bipolar disorder in pregnancy and breast-feeding, concluding with key evidence-based resources for clinicians and patients. [ Psychiatr Ann. 2019;49(9):392–398.]

In order to obtain an anticorrosive film produced according to the sol–gel method for protection of steel alloys, some parameters of the process were tested, which resulted in a crackless film with effective corrosion protection. The parameters studied were sol formulation, aging time of the sol, withdrawal speed using dip-coating technique, and heat treatment temperature. After the conduction of preliminary experiments, the formulation with a molar ratio of TEOS:glycerol:NH4OH of 3:3:1 was selected, due to the lack of cracks when analyzed with an optical microscope. The evaluation of the other parameters (aging time of the sol, withdrawal speed after the immersion in the sol using dip-coating technique, and heat treatment temperature) was realized with the help of a Taguchi design. Aiming for the evaluation of the effectiveness of the corrosion protection, experiments of accelerated corrosion in sulfuric acid aqueous solution were conducted. The samples covered with the film aged in 96 h, heat treated at 150 °C, and with withdrawal speed of 10 cm.min−1 presented the most satisfactory results.

In a Hilbert space X, we consider the abstract problem M∗ddt(My(t))=Ly(t)+f(t)z,0≤t≤τ,My(0)=My0, where L is a closed linear operator in X and M∈L(X) is not necessarily invertible, z∈X. Given the additional information Φ[My(t)]=g(t) wuth Φ∈X∗, g∈C1([0,τ];C). We are concerned with the determination of the conditions under which we can identify f∈C([0,τ];C) such that y be a strict solution to the abstract problem, i.e., My∈C1([0,τ];X), Ly∈C([0,τ];X). A similar problem is considered for general second order equations in time. Various examples of these general problems are given.