Idiopathic pulmonary fibrosis: evaluation of progression and prognosis after the ATS/ERS/JRS/ALAT statement 2011

Objectives The prediction of usual interstitial pneumonia (UIP) progression and prognosis by the a application of HRCT criteria pattern recommended by ATS/ERS/JALAT guidelines 2011 Materials and methods Two radiologists after assessing the baseline HRCT have distributed 70 patients affected by fibrotic idiopathic interstitial pneumonia (IIP) in three groups (UIP type= group 1, possible-UIP=group 2, inconsistence UIP=group 3) on the basis of 2011 guidelines. The different abnormalities (honeycombing, reticulation, ground-glass, bronchiectasis) were visually scored at baseline and during the follow-up (total HRCT 179). Overall CT score and fibrotic score (honeycombing plus reticulation) were calculated. The progression of the abnormalities and the correlation with mortality rate were assessed (Kaplan-Mayer survival estimates). Results The inter-observed agreement was substantial or almost perfect (k=0.73-0.85). Forty-four patients were classified into group 1, 13 into group 2 and 13 into group 3. After a mean follow-up of 1386 days (DS 915), the mortality rate was significantly greater in the group 1 (18 died) versus group 2 and 3 (1 died each). In the group 1 patients whom showed at baseline a honeycombing rate greater than 25%, fibrotic score greater than 30, overall CT score greater than 45 and bronchiectasis in more than 4 lobes obtained the better prognostic value and significantly predicted mortality risk. A significant increment of fibrotic score and honeycombing rate was demonstrated in the group 1 and 3 but not in the group 2. Honeycombing progression was quantified in 3 points/year for UIP type. Conclusion In our study HRCT criteria for UIP pattern on the basis of 2011 guidelines showed high accuracy in the risk stratification of patients with idiopathic pulmonary fibrosis (IPF)

Individual differences in alpha frequency drive crossmodal illusory perception

Perception routinely integrates inputs from different senses. Stimulus temporal proximity critically determines whether or not these inputs are bound together. Despite the temporal window of integration being a widely accepted notion, its neurophysiological substrate remains unclear. Many types of common audio-visual interactions occur within a time window of -100ms [1-5]. For example, in the sound- induced double-flash illusion, when two beeps are presented within -100ms together with one flash, a second illusory flash is often perceived [2]. Due to their intrinsic rhythmic nature, brain oscillations are one candidate mechanism for gating the temporal window of integration. Interestingly, occipital alpha-band oscillations cycle on average every -100ms with peak frequencies ranging between 8-14Hz (i.e. 120-60ms cycle). Moreover, presenting a brief tone can phase-reset such oscillations in visual cortex [6, 7]. Based on these observations, we hypothesized that the duration of each alpha cycle might provide the temporal unit to bind audio-visual events. Here we first recorded EEG while participants performed the sound-induced double-flash illusion task [4] and found positive correlation between individual alpha-frequency (IAF) peak and the size of the temporal window of the illusion. Participants then performed the same task while receiving occipital transcranial alternating current stimulation (tACS), to modulate oscillatory activity [8] either at their IAF or at off-peak alpha-frequencies (IAF±2Hz). Compared to IAF tACS, IAF-2Hz and IAF+2Hz tACS respectively enlarged and shrunk the temporal window of illusion, suggesting that alpha oscillations might represent the temporal unit of visual processing that cyclically gates perception and the neurophysiological substrate promoting audio-visual interactions

Influenza dei Media sui comportamenti e gli stati di salute degli adolescenti

L’adolescenza è una fase della vita che è andata caratterizzandosi negli ultimi due secoli quando con la rivoluzione industriale e l’urbanizzazione si è creato uno strato di popolazione che, con le nuove abitudini sociali, ha avuto un periodo di istruzione più prolungato prima di raggiungere l’autonomia sociale. Contemporaneamente alla delineazione di questa nuova fase della crescita è emersa l’evidenza che gli adolescenti, in passato considerati fondamentalmente sani, presentano invece sempre maggiori e specifici bisogni assistenziali, diversi sia da quelli degli adulti che da quelli dei bambini. In questa fase della vita segnata da profondi cambiamenti, di ordine fisico, comportamentale e psicologico, la famiglia, la scuola e le istituzioni stanno assumendo un ruolo sempre più marginale e i ragazzi crescono costruendo la propria identità sui deleteri modelli di vita che sempre di più si discostano dalla realtà e fanno parte di un mondo “costruito” e fittizio come quello della televisione e di internet. Lo scopo di questo studio è quello di valutare in un campione di 1200 adolescenti tra gli 11 e i 14 anni, la prevalenza dell’uso dei media e l’esistenza di una eventuale relazione tra l’uso dei mezzi di comunicazione, i loro comportamenti e gli stati di salute. I risultati ottenuti permettono di affermare che molte patologie, come l’obesità, i disturbi della condotta alimentare e molti comportamenti dannosi per la salute, come l’abuso di sostanze (alcol, fumo, ecc..), le anomalie del comportamento sessuale, il comportamento aggressivo e l’uso della violenza sono largamente influenzati dal mondo mediatico. L’obiettivo è inoltre quello di proporre quelle che possono essere le linee di prevenzione con il coinvolgimento di tutte le figure professionali e non (scuola, famiglia, istituzioni…)

Essays in macroeconomics of debt deleveraging

This dissertation analyzes, in two chapters, how monetary and fiscal authorities can optimally manage debt reduction episodes. In the first chapter I show how public debt deleveraging leads to a recession with different effects on real interest rates according to the fiscal instruments the government is using to reduce the debt. The fiscal authority should not depress much consumption of the agents who hold savings to improve the welfare of the ones who do not have access to financial markets. Moreover speed and timing of public deleveraging depend crucially on the type of instrument the fiscal authority uses to enforce it. Nominal rigidities, in this context, seem to be beneficial for the agents who cannot insure themselves through financial markets. In the second chapter, written together with Prof. Pierpaolo Benigno, we show how deleveraging from high debt can provoke deep recession with significant international side effects. Due the debt reduction process, real and nominal variables can be subject to high uctuations. All these movements are inefficient and interesting trade-offs emerge from the perspective of global welfare. Counterintuitively, we show that the optimal adjustment to global imbalances should not necessarily require large movements in the nominal exchange rate. Moreover we show that, whenever countries have an high degree of openness to trade, Central Banks needs to create a global liquidity trap to face the deleveraging shock

Physiological role of PRRT2 and its involvement in the pathogenesis of paroxysmal disorders

Mutations in the PRoline-Rich Transmembrane protein 2 gene (PRRT2) underlie a heterogeneous group of paroxysmal disorders encompassing infantile epilepsy, paroxysmal kinesigenic dyskinesia, a combination of these phenotypes and migraine. For the majority of the pathogenic PRRT2 variants, the mutant proteins are not expressed or not correctly targeted to the plasma membrane, resulting in a loss-of function mechanism for PRRT2-related diseases. PRRT2 is a neuron-specific, type II transmembrane protein of 340 amino acids with an important functional role in synapse formation and maintenance, as well as in the regulation of fast neurotransmitter release at both glutamatergic and GABAergic terminals. The PRRT2 knock-out (PRRT2-KO) mouse, in which PRRT2 has been constitutively inactivated, displays alterations in brain structure and a sharp paroxysmal phenotype, reminiscent of the most common clinical manifestations of the human PRRT2-linked diseases. To gain further insights on the pathogenic role of PRRT2 deficiency, I used Multi-Electrode Arrays (MEAs) to characterize neuronal activity generated by primary hippocampal cultures obtained from the PRRT2-KO mouse embryos and to assess the epileptic propensity of cortico-hippocampal slices obtained from the same animal model. This experimental approach revealed a state of heightened spontaneous activity, hyper-synchronization in population bursts of action potentials (APs) and enhanced responsiveness to external stimuli in mutant networks. A complex interplay between (i) a synaptic phenotype, with weakened spontaneous transmission and increased short-term facilitation, and (ii) a marked increase in intrinsic excitability of excitatory neurons as assessed by single-cell electrophysiology, upholds this network phenotype. Furthermore, our group has generated cortical neurons from induced pluripotent stem cells (iPSCs) derived from heterozygous and homozygous siblings carrying the most common C.649dupC mutation. Patch-clamp recordings in neurons from homozygous patients showed an increased Na+ current that was fully rescued by expression of exogenous wild-type PRRT2. A strikingly similar electrophysiological phenotype was observed in excitatory primary cortical neurons from the PRRT2-KO mouse, which was accompanied by an increased length of the axon initial segment (AIS). At the network level, mutant cortical neurons grown on MEAs also displayed a state of spontaneous and evoked hyper-excitability and elevated propensity to synchronize their activity in network bursting events

Pulsed plasma thruster ignition system: investigation, test design and results

Fra i sistemi di propulsione elettrica per satelliti, il Pulsed Plasma Thruster, PPT, è quello dal design più semplice. È anche il primo sistema di propulsione elettrica utilizzato in un satellite artificiale, ossia ZOND-2 lanciato nel 1964 dall’Unione Sovietica. Tuttavia, dopo circa 50 anni di ricerca, la comprensione teorica e sperimentale di questo dispositivo rimane limitata. Questo elaborato di tesi magistrale indaga sul sottosistema di accensione del PPT, cercando di mettere in luce alcuni aspetti legati al lifetime della spark plug, SP. Tale SP, o candela, è l’attuatore del sottosistema di accensione. Questa produce una scintilla sulla sua superficie, la quale permette la realizzazione della scarica elettrica principale fra i due elettrodi del motore. Questa scarica crea una sottile parete di plasma che, per mezzo della forza elettromagnetica di Lorentz, produce la spinta del PPT. Poiché la SP si trova all’interno del catodo del motore e si affaccia nella camera di scarica, questa soffre di fenomeni di corrosione e di deposizione carbonacea proveniente dal propellente. Questi fenomeni possono limitare notevolmente il lifetime della SP. I parametri connessi alla vita operativa della SP sono numerosi. In questo elaborato si è analizzata la possibilità di utilizzare una elettronica di accensione della candela alternativa alla classica soluzione che utilizza un trasformatore. Il sottosistema di accensione classico e quello nuovo sono stati realizzati e testati, per metterne in luce le differenze ed i possibili vantaggi/svantaggi

On topological defect formation in the process of symmetry breaking phase transitions

By resorting to some results in quantum field theories with spontaneous breakdown of symmetry we show that an explanation based on microscopic dynamics can be given of the fact that topological defect formation is observed during the process of non-equilibrium phase transitions characterized by a non-zero order parameter. We show that the Nambu-Goldstone particle acquires an effective non-zero mass due to the boundary (finite volume) effects and this is related with the size of the defect. We also relate such volume effect with temperature effect.Comment: 12 pages, no figure

Individual Differences in Alpha Frequency Drive Crossmodal Illusory Perception

Perception routinely integrates inputs from different senses. Stimulus temporal proximity critically determines whether or not these inputs are bound together. Despite the temporal window of integration being a widely accepted notion, its neurophysiological substrate remains unclear. Many types of common audio-visual interactions occur within a time window of ∼100 ms [1-5]. For example, in the sound-induced double-flash illusion, when two beeps are presented within ∼100 ms together with one flash, a second illusory flash is often perceived [2]. Due to their intrinsic rhythmic nature, brain oscillations are one candidate mechanism for gating the temporal window of integration. Interestingly, occipital alpha band oscillations cycle on average every ∼100 ms, with peak frequencies ranging between 8 and 14 Hz (i.e., 120-60 ms cycle). Moreover, presenting a brief tone can phase-reset such oscillations in visual cortex [6, 7]. Based on these observations, we hypothesized that the duration of each alpha cycle might provide the temporal unit to bind audio-visual events. Here, we first recorded EEG while participants performed the sound-induced double-flash illusion task [4] and found positive correlation between individual alpha frequency (IAF) peak and the size of the temporal window of the illusion. Participants then performed the same task while receiving occipital transcranial alternating current stimulation (tACS), to modulate oscillatory activity [8] either at their IAF or at off-peak alpha frequencies (IAF±2 Hz). Compared to IAF tACS, IAF-2 Hz and IAF+2 Hz tACS, respectively, enlarged and shrunk the temporal window of illusion, suggesting that alpha oscillations might represent the temporal unit of visual processing that cyclically gates perception and the neurophysiological substrate promoting audio-visual interactions

RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the expression level of the thyroid differentiation genes was observed. Recently, a diagnostic role of RET/PTC rearrangements has been proposed. It can be searched for in the mRNA extracted from cytological sample especially in case with indeterminate cytology. However, both the fact that it can be present in a not negligible percentage of benign cases and the technical challenge in extracting mRNA from cytological material makes this procedure not applicable at routine level, at least for the moment