Constraining the systematics of (acoustic) wave heating estimates in the solar chromosphere

Acoustic wave heating is believed to contribute significantly to the missing energy input required to maintain the solar chromosphere in its observed state. We studied the propagation of waves above the acoustic cutoff in the upper photosphere into the chromosphere with ultraviolet and optical spectral observations interpreted through comparison with three dimensional radiative magnetohydrodynamic (rMHD) \emph{Bifrost} models to constrain the heating contribution from acoustic waves in the solar atmosphere. Sit-and-stare observations taken with the Interface Region Imaging Spectrograph (IRIS) and data from the Interferometric BIdimensional Spectrograph (IBIS) were used to provide the observational basis of this work. We compared the observations with synthetic observables derived from the Bifrost solar atmospheric model. Our analysis of the \emph{Bifrost} simulations show that internetwork and enhanced network regions exhibit significantly different wave propagation properties, which are important for the accurate wave flux estimates. The inferred wave energy fluxes based on our observations are not sufficient to maintain the solar chromosphere. We point out that the systematics of the modeling approaches in the literature lead to differences which could determine the conclusions of this type of studies, based on the same observations.Comment: Accepted for publication in Ap

Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m2/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m^{2}/14 days) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care

Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action

Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function

CHANNEL CAPACITY OF THE MACRO-DIVERSITY SC SYSTEM IN THE PRESENCE OF KAPPA-MU FADING AND CORRELATED SLOW GAMMA FADING

In this paper macrodiversity system consisting of two microdiversity SC (Selection Combiner) receivers and one macrodiversity SC receiver are analyzed. Independent κ-μ fading and correlated slow Gamma fading are present at the inputs to the microdiversity SC receivers. For this system model, analytical expression for the probability density of the signal at the output of the macrodiversity receiver SC, and the output capacity of the macrodiversity SC receiver are calculated. The obtained results are graphically presented to show the impact of Rician κ factor, the shading severity of the channel c, the number of clusters µ and correlation coefficient ρ on the probability density of the signal at the output of the macrodiversity system and channel capacity at the output of the macrodiversity system. Based on the obtained results it is possible to analyze the real behavior of the macrodiversity system in the presence of  κ-μ fading

Predictors and moderators of outcome of psychotherapeutic interventions for mental disorders in adolescents and young adults : protocol for systematic reviews

Background: Adolescence and young adulthood is a risk period for the emergence of mental disorders. There is strong evidence that psychotherapeutic interventions are effective for most mental disorders. However, very little is known about which of the different psychotherapeutic treatment modalities are effective for whom. This large systematic review aims to address this critical gap within the literature on non-specific predictors and moderators of the outcomes of psychotherapeutic interventions among adolescents and young adults with mental disorders. Methods: The protocol is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. PubMed and PsycINFO databases will be searched for randomized controlled and quasi-experimental/naturalistic clinical trials. Risk of bias of all included studies will be assessed by the Mixed Methods Appraisal Tool. The quality of predictor and moderator variables will be also assessed. A narrative synthesis will be conducted for all included studies. Discussion: This systematic review will strengthen the evidence base on effective mental health interventions for young people, being the first to explore predictors and moderators of outcome of psychotherapeutic interventions for a wide range of mental disorders in young people.Peer reviewe

Inflammation, lipid (per)oxidation and redox regulation

Significance: Inflammation increases during the aging process. It is linked to mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Mitochondrial macromolecules are critical targets of oxidative damage; they contribute to respiratory uncoupling with increased ROS production, redox stress, and a cycle of senescence, cytokine production, and impaired oxidative phosphorylation. Targeting the formation or accumulation of oxidized biomolecules, particularly oxidized lipids, in immune cells and mitochondria could be beneficial for age-related inflammation and comorbidities. Recent Advances: Inflammation is central to age-related decline in health and exhibits a complex relationship with mitochondrial redox state and metabolic function. Improvements in mass spectrometric methods have led to the identification of families of oxidized phospholipids (OxPLs), cholesterols, and fatty acids that increase during inflammation and which modulate nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPARγ), activator protein 1 (AP1), and NF-κB redox-sensitive transcription factor activity. Critical Issues: The kinetic and spatial resolution of the modified lipidome has profound and sometimes opposing effects on inflammation, promoting initiation at high concentration and resolution at low concentration of OxPLs. Future Directions: There is an emerging opportunity to prevent or delay age-related inflammation and vascular comorbidity through a resolving (oxy)lipidome that is dependent on improving mitochondrial quality control and restoring redox homeostasis

Monocyte Distribution Width (MDW) as novel inflammatory marker with prognostic significance in COVID-19 patients

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p < 0.001), fibrinogen (p < 0.001) and ferritin (p < 0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66\u20130.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73\u201313.96; OR = 7.14, 95% CI: 2.06\u201324.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients