Nuove acquisizioni in termini di insufficienza mitralica: complicanze tromboemboliche dopo chirurgia della valvola mitrale: incidenza, predittori e implicazioni cliniche

Objectives: to define in patients undergoing surgery for mitral regurgitation (MR) the risk of thrombo-embolic complications, particularly ischemic stroke (IS) compared to that in the general population. Background: MR is frequent, occurs mostly in the elderly and guidelines recommend surgery in asymptomatic patients but IS risks are unknown. Methods: in 1344 patients (65±12 years) consecutively operated for MR (procedures: 897 valve repair, MRep; 447 valve replacement, 231 mechanical, MVRm; 216 biological, MVRb), thrombo-embolic complications particularly IS (diagnosed by a neurologist) during follow-up were assessed early (<30 days), mid-term (30-180 days) and long-term (180 days). Results: IS occurred in 130 patients and IS or transient ischemic attack in 201. IS rates were 1.9±0.4% and 2.7±0.5%, at 30 and 180 days and 8.1±0.8% at 5 years. IS rates were lowest after MRep vs. MVRb and MVRm (6.1±0.9, 8±2.1 and 16.1±2.7% at 5 years, p<0.001). Comparison to IS expected rates in the population showed high risk within 30 days of surgery (Risk-ratio 41[26-60], p<0.001 but p>0.10 between procedures) and moderate risk after 30 days (risk-ratio 1.7 overall, p<0.001; 1.3 for MRep, p=0.07; 0.98 for MVRb, p=0.95; 4.8 for MVRm, p<0.001). Beyond 180 days, IS risk declined further and was not different from the general population for MRep (1.2, p=0.30) and for MVRb (0.9, p=0.72). Risk of IS or transient ischemic attack was higher than the general population in all groups up to 180 days. The risk of bleeding beyond 30 days was lowest in MRep vs. MVRb and MVRm (7±1, 14±4 and 16±3% at 10 years, p<0.001). Conclusion: thrombo-embolic complications after MR surgery are both reason for concern and encouragement. IS risk is notable early, irrespective of the procedure performed, but long-term is not higher than in the general population after MRep and MVRb. Preference for MRep should be emphasized and trials aimed at preventing IS should be conducted to reduce the thrombo-embolic and hemorrhagic risk in patients undergoing surgery for MR.

Ricezione e Finzione. Una teoria della lettura tra struttura e risposta estetica

Attraverso l’analisi di teorie della lettura “centripete” e “centrifughe”, tra fenomenologia, semiotica e teoria della risposta estetica, questa ricerca punta a definire la lettura come un’esperienza estetica di una variabile e plurale letterarietà, o per essere più precisi, come una relazione estetica ad una funzione nel linguaggio, che di volta in volta diviene immanente e trascendente rispetto al linguaggio, immanente nella percepibilità espressiva del segno e trascendente nella sua ristretta finzionalità o fittività, aperta alla dimensione del senso. Così, la letterarietà è vista, dal punto di vista di una teoria della lettura, come una funzione che nega o sovverte il linguaggio ordinario, inteso come contesto normale, ma anche una funzione che permette il supplemento di senso del linguaggio. Ciò rende la definizione di cosa sia letteratura e di quali testi siano considerabili come letterari come una definizione dipendente dalla lettura, ed anche mette in questione la classica dicotomia tra linguaggio standard e linguaggio deviante, di secondo grado e figurativo, comportamento che distinguerebbe la letteratura. Questi quattro saggi vorrebbero dimostrare che la lettura, come una pratica estetica, è l’espressione di una oscillazione tra una Finzione variabile nei suoi effetti ed una Ricezione, la quale è una risposta estetica controllata dal testo, ma anche una relazione estetica all’artefatto a natura verbale. Solo in questo modo può essere compresa la caratteristica paradossale della lettura, il suo stare tra una percezione passiva ed un’attiva esecuzione, tra un’attenzione aspettuale ed una comprensione intenzionale. Queste modalità si riflettono anche sulla natura dialettica della lettura, come una dialettica di apertura e chiusura, ma anche di libertà e fedeltà, risposta ad uno stimolo che può essere interpretato come una domanda, e che presenta la lettura stessa come una premessa dell’interpretazione, come momento estetico. Così una teoria della lettura dipende necessariamente da una teoria dell’arte che si presenta come funzionale, relativa più al Quando vi è arte?/Come funziona? piuttosto che al Che cosa è Arte?, che rende questo secondo problema legato al primo. Inoltre, questo Quando dell’Arte, che definisce l’opera d’arte come un’arte- all’-opera, dipende a sua volta, in un campo letterario, dalla domanda Quando vi è esperienza estetica letteraria? e dalla sue condizioni, quelle di finzione e ricezione.

Mechanosensitivity in the myenteric plexus of the guinea pig ileum

The enteric nervous system regulates autonomously from the central nervous system all the reflex pathways that control blood flow, motility, water and electrolyte transport and acid secretion. The ability of the gut to function in isolation is one of the most intriguing phenomenons in neurogastroenterology. This requires coding of sensory stimuli by cells in the gut wall. Enteric neurons are prominent candidates to relay mechanosensitivity. Surprisingly, the identity of mechanosensitive neurons in the enteric nervous system as well as the appropriate stimulus modality is unknown despite the evidence that enteric neurons respond to sustained distension. Objectives: The aim of our study was to record from mechanosensitive neurons using physiological stimulus modalities. Identification of sensory neurons is of central importance to understand sensory transmission under normal conditions and in gut diseases associated with sensorimotor dysfunctions, such as Irritable Bowel Syndrome. Only then it will be possible to identify novel targets that help to normalise sensory functions. Methods: We used guinea-pig ileum myenteric plexus preparations and recorded responses of all neurons in a given ganglion with a fast neuroimaging technique based on voltage sensitive dyes. To evoke a mechanical response we used two different kinds of stimuli: firstly we applied a local mechanical distortion of the ganglion surface with von Frey hair. Secondarily we mimic the ganglia deformation during physiological movements of myenteric ganglia in a freely contracting ileal preparation. We were able to reliably and reproducibly mimic this distortion by intraganglionic injections of small volumes of oxygenated and buffered Krebs solution using stimulus parameters that correspond to single contractions. We also performed in every ganglion tested, electrical stimulations to evoke fast excitatory postsynaptic potentials. Immunohistochemistry reactions were done with antibodies against Calbindin and NeuN, considered markers for sensory neurons. Results: Recordings were performed in 46 ganglia from 31 guinea pigs. In every ganglion tested we found from 1 to 21 (from 3% to 62%) responding cells with a median value of 7 (24% of the total number of neurons). The response consisted of an almost instantaneous spike discharge that showed adaptation. The median value of the action potential frequency in the responding neurons was 2.0 Hz, with a recording time of 1255 ms. The spike discharge lasted for 302 ± 231 ms and occurred only during the initial deformation phase. During sustained deformation no spike discharge was observed. The response was reproducible and was a direct activation of the enteric neurons since it remained after synaptic blockade with hexamethonium or ω-conotoxin and after long time perfusion with capsaicin. Muscle tone appears not to be required for activation of mechanosensory neurons. Mechanosensory neurons showed a response to mechanical stimulation related to the stimulus strength. All mechanosensory neurons received fast synaptic inputs. There was no correlation between mechanosensitivity and Calbindin-IR and NeuN-IR (44% of mechanosensitive neurones Calb-IR-/NeuN-IR-). Conclusions: We identified mechanosensitive neurons in the myenteric plexus of the guinea pig ileum which responded to brief deformation. These cells appear to be rapidly accommodating neurons which respond to dynamic change. All mechanosensitive neurons received fast synaptic input suggesting that their activity can be highly modulated by other neurons and hence there is a low stimulus fidelity which allows adjusting the gain in a sensory network. Mechanosensitivity appears to be a common feature of many enteric neurons belonging to different functional classes. This supports the existence of multifunctional enteric neurons which may fulfil sensory, integrative and motor functions.

Molluscs of the marine protected area "Secche di Tor Paterno"

The thesis describes the molluscan biodiversity of the infralittoral off-shore reefs in the "Secche di Tor Paterno" marine protected area lying in the Central Tyrrhenian Sea off the coasts of Lazio south of Roma. Data originate from underwater sampling activities carried out by SCUBA diving in four biocoenoses: Posidonia oceanica leaves and rhizomes, coralligenous concretions and detritic pools. The representativeness of molluscs as descriptors of biocoenoses is evaluated by preliminary comparisons with data about Polychaeta, Pleocyemata (Crustacea) and Brachiopoda obtained in the same survey. The malacocoenoses of the four biocoenoses are treated in detail. Then data are compared with other data sets to assess differences and similarities with other communities. The agreement between death and living assemblages in the reefs is evaluated for the Posidonia oceanica and the coralligenous biocoenosis and was carried out by a set of standard metrics and some benthic ecology methods. Molluscs perform very well as descriptors of biocoenoses, better than the other phyla. The molluscan assemblages of the reefs are very rich in species despite richness is mainly concentrated in the coralligenous and in the rhizomes of Posidonia oceanica. The leaves of Posidonia oceanica host a rather poor assemblage. Detritic pools host a poor but peculiar species assemblage. The dead-live agreement showed that death assemblages are highly representative of sediments of nearby biocoenoses as a result of low bottom transport. Fidelity metrics suggest a good agreement between the living and death assemblages when species richness and taxonomic composition are considered. The study suggests that fidelity is lower when considering the species dominance. These differences could be associated to the trophism of species and possibly to the species life span.

La traduction des textes de théatre. Analyse comparée des réalités contemporaines française et italienne

The aim of the present study is to address contemporary drama translation by comparing two different scenarios, namely France and Italy. For each country, the following areas are described: publications of translated drama texts, their promotion and dissemination, the legal framework concerning copyright in publication and performance contracts. Moreover, the analysis highlights that the translation process of drama texts is part of a working cycle networking different professional figures, such as dramatic authors, directors, actors and publishers. Within this cycle, the translator is in a middle and central position at the same time, a sort of border zone between different contexts, i.e. the source language and culture and the target language and culture. As regards translation-related issues, on the basis of theoretical approaches that can be applied to drama translation, a number of translators’ opinions, statements, positions and practices are compared, thus highlighting an idea of drama translation wavering between translation and adaptation. Drama translators seem to follow these two orientations simultaneously, in compliance with translation ethics and the functional needs of target texts. Such ambivalence is due to the desire and difficulty of translating the specific nature of drama texts, i.e. translating textual elements that are linked, eventually, to stage performance. Indeed, the notion of text or form fidelity is replaced by the notion of fidelity to the theatrical value of a text, in terms of fidelity to its theatrical nature and rhythmical tension. The analysis reveals that drama translators work together with theatre operators, and that in many cases translators are authors, directors or actors themselves. These drama skills enable translators to apply relevant strategies when translating elements that generate rhythm, thus choosing from deleting, reproducing or recreating.

Identification of the N-Linked Glycosylation Sites of the Transcription Factor Rest and Effect of Glycosylation on DNA Binding and Transcriptional Activity

REST is a zinc-finger transcription factor implicated in several processes such as maintenance of embryonic stem cell pluripotency and regulation of mitotic fidelity in non-neuronal cells [Chong et al., 1995]. The gene encodes for a 116-kDa protein that acts as a molecular platform for co-repressors recruitment and promotes modifications of DNA and histones [Ballas, 2005]. REST showed different apparent molecular weights, consistent with the possible presence of post-translational modifications [Lee et al., 2000]. Among these the most common is glycosylation, the covalent attachment of carbohydrates during or after protein synthesis [Apweiler et al., 1999] My thesis has ascertained, for the first time, the presence of glycan chians in the transcription factor REST. Through enzymatic deglycosylation and MS, oligosaccharide composition of glycan chains was evaluated: a complex mixture of glycans, composed of N-acetylgalactosamine, galactose and mannose, was observed thus confirming the presence of O- and N-linked glycan chains. Glycosylation site mapping was done using a 18O-labeling method and MS/MS and twelve potential N-glycosylation sites were identified. The most probable glycosylation target residues were mutated through site-directed mutagenesis and REST mutants were expressed in different cell lines. Variations in the protein molecular weight and mutant REST ability to bind the RE-1 sequence were analyzed. Gene reporter assays showed that, altogether, removal of N-linked glycan chains causes loss of transcriptional repressor function, except for mutant N59 which showed a slight residual repressor activity in presence of IGF-I. Taken togheter these results demonstrate the presence of complex glycan chians in the transcription factor REST: I have depicted their composition, started defining their position on the protein backbone and identified their possible role in the transcription factor functioning. Considering the crucial role of glycosylation and transcription factors activity in the aetiology of many diseases, any further knowledge could find important and interesting pharmacological application.

Towards Centrifugal Compressor Stages Virtual Testing

Flow features inside centrifugal compressor stages are very complicated to simulate with numerical tools due to the highly complex geometry and varying gas conditions all across the machine. For this reason, a big effort is currently being made to increase the fidelity of the numerical models during the design and validation phases. Computational Fluid Dynamics (CFD) plays an increasing role in the assessment of the performance prediction of centrifugal compressor stages. Historically, CFD was considered reliable for performance prediction on a qualitatively level, whereas tests were necessary to predict compressors performance on a quantitatively basis. In fact "standard" CFD with only the flow-path and blades included into the computational domain is known to be weak in capturing efficiency level and operating range accurately due to the under-estimation of losses and the lack of secondary flows modeling. This research project aims to fill the gap in accuracy between "standard" CFD and tests data by including a high fidelity reproduction of the gas domain and the use of advanced numerical models and tools introduced in the author's OEM in-house CFD code. In other words, this thesis describes a methodology by which virtual tests can be conducted on single stages and multistage centrifugal compressors in a similar fashion to a typical rig test that guarantee end users to operate machines with a confidence level not achievable before. Furthermore, the new "high fidelity" approach allowed understanding flow phenomena not fully captured before, increasing aerodynamicists capability and confidence in designing high efficiency and high reliable centrifugal compressor stages.

Simulations for Gravitational Lensing of 21 cm Radiation at EoR and Post-EoR Redshifts

21 cm cosmology opens an observational window to previously unexplored cosmological epochs such as the Epoch of Reionization (EoR), the Cosmic Dawn and the Dark Ages using powerful radio interferometers such as the planned Square Kilometer Array (SKA). Among all the other applications which can potentially improve the understanding of standard cosmology, we study the promising opportunity given by measuring the weak gravitational lensing sourced by 21 cm radiation. We performed this study in two different cosmological epochs, at a typical EoR redshift and successively at a post-EoR redshift. We will show how the lensing signal can be reconstructed using a three dimensional optimal quadratic lensing estimator in Fourier space, using single frequency band or combining multiple frequency band measurements. To this purpose, we implemented a simulation pipeline capable of dealing with issues that can not be treated analytically. Considering the current SKA plans, we studied the performance of the quadratic estimator at typical EoR redshifts, for different survey strategies and comparing two thermal noise models for the SKA-Low array. The simulation we performed takes into account the beam of the telescope and the discreteness of visibility measurements. We found that an SKA-Low interferometer should obtain high-fidelity images of the underlying mass distribution in its phase 1 only if several bands are stacked together, covering a redshift range that goes from z=7 to z=11.5. The SKA-Low phase 2, modeled in order to improve the sensitivity of the instrument by almost an order of magnitude, should be capable of providing images with good quality even when the signal is detected within a single frequency band. Considering also the serious effect that foregrounds could have on this detections, we discussed the limits of these results and also the possibility provided by these models of measuring an accurate lensing power spectrum.