The outbreak of Sars-CoV-2 (COVID-19) poses serious challenges to people's health worldwide. The management of the disease is mostly supportive, and respiratory failure from acute respiratory ...distress syndrome is the leading cause of death in a significant proportion of affected patients. Preliminary data point out that dramatic increase in IL-6 and subsequent cytokine release syndrome may account for the development of fatal interstitial pneumonia. Inhibition of IL-6 by blocking its specific receptor with monoclonal antibodies has been advocated as a promising attempt. Here we assess the potential utility of myo-Inositol, a polyol already in use for treating the newborn Respiratory Distress Syndrome, in downregulating the inflammatory response upon Sars-CoV-2 infection. Myo-Inositol proved to reduce IL-6 levels in a number of conditions and to mitigate the inflammatory cascade, while being devoid of any significant side effects. It is tempting to speculate that inositol could be beneficial in managing the most dreadful effects of Sars-CoV-2 infection.
Dag Prawitz’s theory of grounds proposes a fresh approach to valid inferences. Its main aim is to clarify nature and reasons of their epistemic power. The notion of ground is taken to denote what one ...is in possession of when in a state of evidence, and valid inferences are described in terms of operations that make us pass from grounds we already have to new grounds. Thanks to a rigorously developed proof-as-chains conception, the ground-theoretic framework permits Prawitz to overcome some conceptual difficulties of his earlier proof-theoretic explanation. Though from different points of view, anyway, the two accounts share an issue of recognizability of relevant operational properties.
The estimation of expected seismic losses at regional scale represents a critical issue for the assessment of the seismic risk and for the evaluation of the seismic resilience of large communities. ...In a performance-based approach, the assessment of economic losses requires the computation of the building performances in terms of engineering demand parameters such as interstory drift ratios and peak floor accelerations in order to assess the distribution and the extent of the damage experienced by various building components. The Stick-IT model (Stick for Infilled frames Typologies) was recently proposed to predict the response, in terms of engineering demand parameters, for infilled RC building typologies. The Stick-IT is a MDOF system consisting of a series of lumped masses connected by nonlinear shear link elements. The model parameters can be defined for building typologies starting from low-level information that can be easily retrieved at the large scale via image-based processing techniques integrated with information about typical construction features, such as in plan dimensions, the number of stories or the percentage of infills openings and considering the infills consistency.
This paper adopts the Stick-IT model within a probabilistic framework to predict damage and expected losses for a set of residential buildings located in L'Aquila town that suffered damage during the 2009 L'Aquila earthquake. By comparing the predicted losses with the actual repair costs, the application shows the advantages and the potentiality of the proposed model when adopted for large scale loss assessments.
•A probabilistic framework to predict the seismic losses for RC buildings is proposed.•The building response is simulated adopting the Stick-IT model.•The framework allows to account accounts for propagation of uncertainties.•The framework is tested using actual cost data from the 2009 L'Aquila earthquake.•The method provides a more accurate prediction with respect to conventional ones.
Celebrated as a courtesan and poet, and as a woman of great intelligence and wit, Tullia d'Aragona (1510–56) entered the debate about the morality of love that engaged the best and most famous male ...intellects of sixteenth-century Italy. First published in Venice in 1547, but never before published in English, Dialogue on the Infinity of Love casts a woman rather than a man as the main disputant on the ethics of love. Sexually liberated and financially independent, Tullia d'Aragona dared to argue that the only moral form of love between woman and man is one that recognizes both the sensual and the spiritual needs of humankind. Declaring sexual drives to be fundamentally irrepressible and blameless, she challenged the Platonic and religious orthodoxy of her time, which condemned all forms of sensual experience, denied the rationality of women, and relegated femininity to the realm of physicality and sin. Human beings, she argued, consist of body and soul, sense and intellect, and honorable love must be based on this real nature. By exposing the intrinsic misogyny of prevailing theories of love, Aragona vindicates all women, proposing a morality of love that restores them to intellectual and sexual parity with men. Through Aragona's sharp reasoning, her sense of irony and humor, and her renowned linguistic skill, a rare picture unfolds of an intelligent and thoughtful woman fighting sixteenth-century stereotypes of women and sexuality.
Context Coupling is a widely discussed metric by software engineers while developing complex software systems, often referred to as a crucial factor and symptom of a poor or good design. ...Nevertheless, measuring the logical coupling among microservices and analyzing the interactions between services is non-trivial because it demands runtime information in the form of log files, which are not always accessible. Objective and Method In this work, we propose the design of a study aimed at empirically validating the Microservice Logical Coupling (MLC) metric presented in our previous study. In particular, we plan to empirically study Open Source Systems (OSS) built using a microservice architecture. Results The result of this work aims at corroborating the effectiveness and validity of the MLC metric. Thus, we will gather empirical evidence and develop a methodology to analyze and support the claims regarding the MLC metric. Furthermore, we establish its usefulness in evaluating and understanding the logical coupling among microservices.
Abstract Dry eye disease (DED), a multifactorial disease of the tears and ocular surface, is common and has a significant impact on quality of life. Reduced aqueous tear flow and/or increased ...evaporation of the aqueous tear phase leads to tear hyperosmolarity, a key step in the vicious circle of DED pathology. Tear hyperosmolarity gives rise to morphological changes such as apoptosis of cells of the conjunctiva and cornea, and triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. This exacerbates tear film instability and drives the cycle of events that perpetuate the condition. Traditional approaches to counteracting tear hyperosmolarity in DED include use of hypotonic tear substitutes, which have relatively short persistence in the eye. More recent attempts to counteract tear hyperosmolarity in DED have included osmoprotectants, small organic molecules that are used in many cell types throughout the natural world to restore cell volume and stabilize protein function, allowing adaptation to hyperosmolarity. There is now an expanding pool of clinical data on the efficacy of DED therapies that include osmoprotectants such as erythritol, taurine, trehalose and L-carnitine. Osmoprotectants in DED may directly protect cells against hyperosmolarity and thereby promote exit from the vicious circle of DED physiopathology.
To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye.
Case control study.
Seventy-five female subjects divided into 3 groups: ...group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD).
A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate.
Conjunctival expression of MMP9 and TG2.
MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS.
The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.
To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA).
Observational, cross-sectional study.
...Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan.
Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2).
Fixation location and stability.
The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P < 0.01). Both PRL eccentricity and fixation stability were linearly associated with BCVA: every 1° increase in PRL eccentricity was associated with a 0.07 logarithm of the minimum angle of resolution (logMAR) worse BCVA (P < 0.0001) while every 1°2 increase in 95% BCEA was associated with a 0.01 logMAR worse BCVA (P < 0.001). No significant intereye correlation was found for PRL eccentricity and fixation stability, as well as no association between the patient's age and fixation parameters.
We demonstrated that most eyes affected by BVMD retain a central stable fixation and provided evidence that both fixation eccentricity and stability are strongly associated with visual acuity in BVMD. These parameters may serve as secondary end points for future clinical trials.
Proprietary or commercial disclosure may be found after the references.
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