158 research outputs found
Fully anisotropic unstructured grid generation with application to aircraft design
No full textThis paper describes a fully automatic 3D anisotropic mesh generation method for domains of arbitrary shape. The spacing of the boundary mesh is computed by the analysis of the principal curvatures and directions of the boundary surfaces. The spacing in the domain is obtained by interpolation of the spacing at the boundaries on a suitably constructed background mesh. Examples which illustrate the performance of the proposed methodology are presented
L'HARMONIE DES ORGUES. SUONI, CORPI E SENSAZIONI NEL PENSIERO MUSICALE DI DESCARTES
No full textThe importance of René Descartes's (1596-1650) metaphysics, physics and methodology is common knowledge in the Humanities: the author of the revolutionary Discours sur la méthode (1637) is universally celebrated as the father of modern Rationalism. Therefore, since the second part of the XVII Century, all cartesian interests and studies were focused on the Meditationes de prima philosophia (1641) and the Principia philosophiae (1644), the most philosophically pregnant Descartes's works. On the contrary, his ideas about music and sound theory, developed in the Compendium musicae (1618) and in the Correspondence (mostly in the letter exchanges with Marin Mersenne in the 1630's), were generally considered a back burner research area. In 1907 the author of the first monography on this subject, André Pirro (A. Pirro, Descartes et la musique, Paris 1907), actually accused the french philosopher of carelessness about sonorous and auditive phaenomena. The historical studies on cartesian music dramatically increased in the last decades of the XX Century mainly thanks to Fréderic de Buzon's survey (F. De Buzon, Descartes, Beeckman et l’acoustique, «Archives de philosophie», 4 BC X, 1981; Sympathie et antipathie dans le Compendium Musicae, «Archives de philosophie», XLVI, 1983; Fonctions de la mémoire dans les traités théoriques au XVII siècle, «Revue de musicologie», 76/2, 1990). These researches highlighted the prominent role played by the music theory in the constitution of the Descartes's greatest philosophy.
Moving from these studies, recently revived in Bologna by Paolo Gozza (author of the crucial article Una matematica rinascimentale: la musica di Descartes, «Il saggiatore musicale», II/2, 1995), my PhD thesis has two principal aims: (i) To reconstruct the Descartes's musical thought, scattered in a disorganic way, throught his whole production; (ii) To utilize the conception of human being that emerges from Descartes's music theory as a test for the anthropology described in the metaphysical works. Descartes's music theory offers a theorical direction to clarify this problem and suggests a potential answer. Since the early Compendium musicae, the music creation and perception are described as homogeneous actions that implicate a mind-body cooperation. The human being can play an instrument, sing, listen music, dance only because he is deeply unitary: it is composed by a third nature (different by mind and body too) that upsets the dualism rules. Cartesian music depicts an organic anti-dualist and anti-rationalist man in a rigid sense. Therefore and lastly, I claim that this research on Descartes's music thought is useful not only to enrich the studies on cartesian anthropology, but also to definitively eject the common mismatch on the René Descartes philosophy as a monolithic and ingenuous rationalism
Is cognitive function linked to serum free copper levels? A cohort study in a normal population.
No full textMuch research on copper-dependent neurodegeneration has focused on the study of total copper levels in the organism. However, recent evidence suggests that the portion of copper that does not bind to ceruloplasmin and is loosely transported by micronutrients (free copper) may play a more significant role than copper as a whole. In this paper, we measured markers of copper metabolism in the sera of a group of cognitively normal women to test whether abnormal amounts of free copper have detectable effects on the mental state of clinically normal people.We measured serum levels of free and ceruloplasmin-bound copper in 64 women whose normal mental state had been assessed via a battery of neuropsychological tests representing the major cognitive domains.Results show a significant inverse correlation of the serum levels of free copper with both Mini-Mental State Examination (MMSE) and attention-related neuropsychological tests scores. Bound copper, instead, did not correlate with either MMSE scores or any cognitive domain.Free copper appears to be a player in cognitive decline.This evidence suggests the need for a shift of focus from total to free copper levels in the study of mental decline and sustains the notion that free copper may be a risk factor in the development of impaired cognition
A Dangerous Consequence of the Recent Pandemic: Early Lung Fibrosis Following COVID-19 Pneumonia – Case Reports
No full textChiara Scelfo,1 Matteo Fontana,1 Eleonora Casalini,1 Francesco Menzella,1 Roberto Piro,1 Alessandro Zerbini,2 Lucia Spaggiari,3 Luca Ghidorsi,1 Giulia Ghidoni,1 Nicola C Facciolongo1 1Department of Medical Specialties, Pneumology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 3Department of Radiology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyCorrespondence: Chiara Scelfo Email [email protected]: The outbreak of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in China in December 2019. COVID-19 patients at presentation show a wide spectrum of clinical and pathological involvement. We report two cases of respiratory insufficiency due to COVID-19 pneumonia that occurred in adults without a history of respiratory diseases. Although these patients improved and were discharged from the acute ward, during the hospitalization they both progressed with a subsequent clinical and radiological worsening, pointing out one of the main concerns for these patients at discharge: the possibility of developing persistent lung abnormalities also in healthy people not having other risk factors. In conclusion, these cases represent two examples of early lung fibrosis in patients with COVID-19 pneumonia with different severity disease evolution and highlight the need for long-term follow-up strategies. The etiology of this fibrosis is under discussion: we suppose that it could be due to either a possible outcome of natural history of lung damage produced by ARDS, or to the lung injury related to high oxygen level or to the lung damage directly induced by viral infection or finally to the autoimmune response. At this moment, it is not possible to predict how many people will have consequences due to COVID-19 pneumonia, and therefore we believe that careful follow-up should be mandatory.Keywords: COVID-19, pulmonary fibrosis, critical care, viral disease, computed tomography, follow-u
Disruption of retinoic acid receptor alpha reveals the growth promoter face of retinoic acid.
No full textRetinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA
Mechanical power ratio threshold for ventilator-induced lung injury
No full textAbstract Rationale Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MP ratio ). Objective To define a threshold value of MP ratio leading to the development of VILI. Methods In a population of 82 healthy pigs, a threshold of MP ratio for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MP ratio above or below the threshold. Measurements and main results We measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MP ratio threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p 4.5 MP ratio in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.Open-Access-Publikationsfonds 202
Does the Intensity of Therapy Correspond to the Severity of Acute Respiratory Distress Syndrome (ARDS)?
No full textObjectives: The intensity of respiratory treatment in acute respiratory distress syndrome (ARDS) is traditionally adjusted based on oxygenation severity, as defined by the mild, moderate, and severe Berlin classifications. However, ventilator-induced lung injury (VILI) is primarily determined by ventilator settings, namely tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP). All these variables, along with respiratory elastance, are included in the concept of mechanical power. The aim of this study is to investigate whether applied mechanical power is proportional to oxygenation severity. Methods: We analyzed 291 ARDS patients (71 mild, 155 moderate, and 65 severe). We defined low, middle, and high mechanical power by dividing the entire population into tertiles with a similar number of patients. In each oxygenation class, we measured computed tomography (CT) anatomy, gas exchange, respiratory mechanics, mechanical power, and mortality rate. Results: ARDS severity was proportional to lung anatomy impairment, as defined by quantitative CT scans (i.e., lung volume and well-aerated tissue decreased across the ARDS classes, while respiratory elastance increased, as did mortality). Mechanical power, however, was similarly distributed across the severity classes, as the decrease in tidal volume in severe ARDS was offset by an increase in respiratory rate. Within each ARDS class, mortality increased from low to high mechanical power (roughly 1% for each J/min increase). Conclusions: Both lung severity and mechanical power independently impact mortality rates. It is tempting to speculate that ARDS severity primarily reflects the natural course of the disease, while mechanical power primarily reflects the risk of VILI
Predictors of VILI risk: driving pressure, 4DPRR and mechanical power ratio—an experimental study
No full textAbstract Background Ventilator-induced lung injury (VILI) is one of the side effects of mechanical ventilation during ARDS; a prerequisite for averting it is the quantification of its risk factors associated with a given ventilatory setting. Many clinical variables have been proposed as predictors of VILI, of which driving pressure is the most widely used. In this study, we compared the performance of driving pressure, four times the driving pressure added to respiratory rate (4DPRR) and mechanical power ratio. Results In a study population of 121 previously healthy pigs exposed to harmful ventilation, we compared the association of driving pressure, 4DPRR and mechanical power ratio to lung weight, lung wet-to-dry and total histological score. All the three variables were associated with these outcomes. Driving pressure, 4DPRR and mechanical power ratio increase linearly with the lung weight (adjusted R 2 of 0.27, 0.36 and 0.40, respectively), the lung wet-to-dry ratio (adjusted R 2 of 0.19, 0.25 and 0.37) and the total histological score (adjusted R 2 of 0.26, 0.38 and 0.26). Using a multiple linear regression model with forward analysis, starting with tidal volume and progressively adding respiratory rate and positive end-expiratory pressure, and comparing the topic with the outcome variables, we obtained R 2 values, respectively, of 0.07, 0.20, 0.42 for lung weight, 0.09, 0.19, 0.26 for lung wet-to-dry ratio and 0.07, 0.27, 0.43 for total histological score. Conclusions Driving pressure, 4DPRR and mechanical power ratio, were all associated with lung injury in healthy animals undergoing mechanical ventilation.Open-Access-Publikationsfonds 202
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