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Rationale and Objectives: The new version of the Contrast Enhanced Mammography (CEM) Breast imaging Reporting and Data System (BIRADs) encourages investigations of a new enhancement descriptor: “Lesion Conspicuity” (LC). The study aims to assess the diagnostic performance and the relationship with the receptor profile of this new enhancement descriptor. Materials and Methods: Three hundred twenty-five patients with 381 breast lesions who underwent CEM before histological assessmentwere selected. Four radiologists, blinded to each other, categorized LC into the following levels: absent, low, moderate, and high. Considering moderate and high evaluations as predictive of malignancy, the diagnostic performance of CEM was calculated using histological results of the biopsy as the gold standard. The association between LC values and the receptor profile of the neoplasms was also evaluated. Results: The median age at the CEM examination was 50 years (IQR: 45-59). Considering the value of LC of the most experienced radiologist with the interpretation of Low Energy images (LE), we obtained a sensitivity (SE) of 91.9% (95% CI: 88.6%-95.2%) and a specificity (SP) of 67.2% (95% CI: 58.9%-75.5%). An association between “high” lesion conspicuity with ER/PgR not expressed (p = 0.025), with Ki-67>20% (p = 0.033), and with Grading G3 (p = 0.020) was observed. Conclusion: The new feature of enhancement, “Lesion Conspicuity”, demonstrated satisfactory performance in predicting the malignancy of lesions and significant correlation with the receptor profile of malignant breast neoplasms.

Gli ex voto dipinti sono un oggetto di culto dalla lunga storia. Esempi di questo tipo di ex-voto, largamente utilizzati fino alla fine dell'Ottocento nell'Italia meridionale e in altre regioni dell'Europa meridionale, sono infatti già attestati nel mondo classico (pinakes, tabellea pictae). Nel passaggio tra il mondo "pagano" e il mondo "cristiano", nel mutare dei referenti divini e delle teologie, si osserva una continuità dei simboli rituali e delle pratiche votive e, più in generale, una significativa persistenza di forme, funzioni e significati in campo religioso. The painted ex-votos are a cult object with a long history. Examples of this type of ex-voto, widely used up to the end of the 19th century in Southern Italy and in other regions of Southern Europe, are in fact already attested in the classical world (pinakes, tabellea pictae). In the passage between the "pagan" world and the "Christian" world, in the changing of the divine referents and theologies, we observe a continuity of the ritual symbols and votive practices and, more generally, a significant persistence of forms, functions and meanings in the religious field.

The Galactic magnetic field plays an important role in the evolution of the Galaxy, but its small-scale behaviour is still poorly known. It is not known whether the Galactic field permeates the halo of the Galaxy. By observing pulsars in the halo globular cluster 47 Tucanae, we have probed the Galactic magnetic field at arcsecond scales, discovering an unexpected large gradient in the component of the magnetic field parallel to the line of sight. This gradient is aligned with a direction perpendicular to the Galactic disk and could be explained by magnetic fields amplified to some 60 mu G within the globular cluster. Such a scenario supports the existence of a magnetized outflow that extends from the Galactic disk to the halo and interacts with 47 Tucanae. Observations of the Faraday rotation towards pulsars in the halo globular cluster 47 Tucanae have been used to constrain the magnetic field strength in the Galactic halo, finding that it is unexpectedly strong.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first reported from the Wuhan city of China in December 2019, swept the world in a few months and became a global health emergency of primary international concern continues to be a priority health problem. Recent studies suggest that subjects with autoimmune disorders (JIA, RA, SLE) do not have an increased risk to get Sars-Cov2. Juvenile Idiopathic Arthritis (JIA) is an inflammatory chronic disease concerning joints and others structures. According to International League of Association for Rheumatology (ILAR) seven subtypes of arthritis can be defined in relation with the number of joints and the extra-articular involvement occurring in the first six months of disease. NSAIDs and intra-articular steroids represent the first line treatment for JIA. Systemic steroids, disease modifying anti-rheumatic drugs (DMARDs) and biologic drugs are used in children with severe disease. Objectives: To evaluate the incidence and the impact on the disease course of Sars-cov2 infection in a group of children affected from juvenile idiopathic arthritis in treatment with Methotrexate and/or biological drugs. Methods: This study includes 77 children affected from JIA (55 females, 22 males). JIA diagnosis was made according to ILAR criteria and treatment was assigned with recommendations of the American College of Rheumatology. For each patient we recorded the type and the duration of pharmacological treatment, JIA subtype and relapses (defined according to Wallace criteria). During follow up visit from Nov 1st, 2020 to April 30th, 2021 we investigated in each patient history of Sars-Cov2 infection and related symptoms, diagnostic tests for Sars-Cov2. Results: The mean age at the last follow-up visit was 13.3±5.61 years. Thirteen out of 77 patients was affected Sars-Cov2 infection, none of them needed to be hospitalized. The most common symptom was headache (8 of 13 patients), followed by myalgia (6 of 13), fever (4 of 13), anosmia or dysgeusia (3 of 13), upper respiratory tract symptoms (3 of 13) and nausea (3 of 13). Five out of 13 patients were asymptomatic (38,5%). The mean duration of Sars-Cov2 infection was 12,5 days (confirmed with nose pharyngeal swab). In the group of patients with Sars-Cov2 infection 4 of 13 (30%) were in treatment with MTX, 2 of 13 (15%) with both MTX and biological drugs, 5 of 13(38%) with biological drugs, 2 of 13 (15%) with NSAIDs. In the group of patients without Sars-Cov2 infection 37 of 64 (48%) patients were in treatment with MTX, 32 of 64 (41,5%) with biological drugs, 18 of 64 (28%) with both MTX and biological drugs, 10 of 64 (15,6%) with NSAIDs. We didn’t find a higher risk to contract Sars-Cov2 infection in patients under MTX treatment (48% vs 46.15 %; p value 0.6416), in ones under MTX and biological drugs (28.1% vs 15.4%p value 0.543) or in ones under only biological therapy (50% vs 53.8% ; p value 0.231). We found that in patient with JIA the risk to get Sars-Cov2 infection is not related to the treatment. The percentage of JIA relapses was higher in patients with Sars-Cov2 infection than in the ones without infection (53,8% vs 9%; p value 0.0004). Conclusion: Treatment with MTX or biological drugs did not increase the risk to get Sars-Cov2 infection. The frequency of JIA relapses was higher in patients who got Sars-Cov2 infection than in ones who didn’t get it

La scoperta delle pulsar è stata rivoluzionaria per l’astronomia dando la possibilità di usare questi oggetti come orologi Galattici di alta precisione. Le pulsar emettono luce come un faro in una grande banda di frequenza e, grazie alla stabilità della loro rotazione, hanno le caratteristiche ideali per sondare il campo gravitazionale e il gas che le circondano. I densi ammassi globulari che circondano la Galassia sono tra i più prolifici luoghi di formazione delle pulsar veloci (conosciute come pulsar a millisecondo) e sono oggetti estremamente affascinanti. Nel loro centro si pensa contengano buchi neri di massa intermedia (IMBH), l’anello mancante tra i buchi neri stellari e quelli supermassicci che si trovano al centro delle galassie e la chiave per capire l’evoluzione buchi neri. Inoltre, grazie al gas ed al campo magnetico degli ammassi globulari si può campionare il campo magnetico a grande scala della Galassia, specialmente nell’alone galattico che è in gran parte sconosciuto. La presenza delle pulsar permette lo studio degli ammassi con una precisione senza precedenti. Possiamo calcolare l’accelerazione sentita dalla pulsar misurando la derivata del periodo rotazionale. Questo permette di analizzare il profilo di densità e di cercare deviazioni che potrebbero essere causate dalla presenza di un IMBH. Gli effetti di un buco nero centrale sono visibili anche nelle derivate dell’accelerazione che sono accessibili monitorando la pulsar per lunghi periodi. La grande banda di emissione delle pulsar permette l’analisi del contenuto di gas ionizzato e del campo magnetico tramite gli effetti della dispersione e della rotazione Faraday. In questa tesi ho applicato queste tecniche all’ammasso globulare 47 Tucanae che contiene 25 pulsar note per misurarne i parametri strutturali. Ho confermato la presenza di gas ionizzato trovando la migliore distribuzione spaziale e, per la prima volta, ho scoperto un campo magnetico nell’ammasso. Nessun campo magnetico era mai stato proposto in un ammasso globulare, ma le osservazioni confermano che è presente e che è circa un ordine di grandezza più forte di quanto si supporrebbe se fosse in equipartizione con il gas. Questo campo magnetico è originato dall’interazione dell’ammasso con un vento magnetizzato proveniente dal disco Galattico e che si propaga nell’alone. Questa analisi supporta la presenza di questo tipo di vento già introdotto in letteratura. L’ammasso globulare M62 ha tre pulsar vicino al centro le cui accelerazioni non sono compatibili con il profilo di densità. Nelle regioni centrali c’è un eccesso di massa di circa 3900 masse solari con un intervallo di confidenza al 68% di (1200,6000) masse solari. Questo eccesso ha un valore molto alto di rapporto massa-luminosità e potrebbe essere causato da un IMBH o da un sistema di buchi neri stellari. Per confermare la presenza di un IMBH sono necessarie ulteriori osservazioni e simulazioni specifiche. Nella mia tesi esploro inoltre la possibilità di usare quanto imparato dalle pulsar negli ammassi globulari per studiare la formazione dell’ammasso stellare che circonda il centro Galattico. Un possibile scenario di formazione propone come origine la distruzione mareale di ammassi stellari. Anche se nessuna pulsar a millisecondo è mai stata osservata in questa regione, ho mostrato, tramite simulazioni, quale dovrebbe essere la distribuzione delle pulsar e dove puntare per vederli. Le scoperte scientifiche possibili grazie alle pulsar negli ammassi globulari sono varie e possono riguardare l’intera Galassia. Il futuro di questo campo sarà dominato dai radio-telescopi di prossima generazione come il nuovo telescopio MeerKAT in Sudafrica. Questo strumento è descritto nel capitolo finale insieme con quello che sarà in grado di scoprire nel campo delle pulsar negli ammassi globulari. The discovery of pulsars has been revolutionary for astronomy and opened the possibility of performing extremely high precision timekeeping in our Galaxy. The pulsars, with their broadband lighthouse-like emission and stability of their rotation, have the perfect characteristics to probe the potential well and the gaseous environments around them. The dense globular clusters that surround the Galaxy are some of the most efficient factories of fast pulsars (known as millisecond pulsars) and are extremely fascinating objects to study. In their very centres they are thought to contain intermediate mass black holes (IMBHs), the missing links between the stellar black holes and the supermassive ones that inhabit the centres of galaxies, and the key to understanding the black hole population and evolution. Furthermore, the gas content and magnetic field of the globular clusters is able to probe the large scale magnetic field of the Galaxy, especially in the largely unknown Galactic halo. The presence of pulsars allows us to study the clusters with unprecedented precision. We can estimate the acceleration felt by the pulsar by measuring the derivative of the rotation period. This allows us to study the mass density profile of the cluster and look for deviations that might be caused by the presence of an IMBH. The effects of a central black hole are visible also in the derivatives of the acceleration that can be measured by timing the pulsar for long periods. The broadband nature of the pulsar emission enables the study of the ionized gas content and the magnetic field through the effects of dispersion and Faraday rotation. I apply these techniques to globular cluster 47 Tucanae that contains 25 known pulsars and measure the structural parameters of the cluster. I confirm the presence of ionized gas, test different distribution models, and discover, for the first time, a magnetic field in the cluster. No magnetic field has ever been proposed in a globular cluster, but the observations suggest that it is present and is about one order of magnitude stronger than what energy equipartition with the gas would imply. In this thesis I claim that the magnetic field is caused by an interaction of the cluster with a magnetized outflow from the Galactic disk that extends in the halo. Such an outflow has been previously proposed and here finds confirmation. No IMBH is found in 47 Tucanae with mass higher than 4000 Solar masses. However, the study of another cluster returned more exciting results. The globular cluster M62 has three known pulsars close to the centre which have accelerations that are not compatible with the published density profile. An excess of ~3900 Solar masses with a 68% confidence interval of (1200,6000) Solar masses is found in the central region. This excess has a very high mass to light ratio and could be due to an IMBH or a system of stellar mass black holes. Only with more observations and simulations tailored to this cluster, the IMBH can be confirmed. In my thesis I further explore the possibility of using the knowledge gained from the globular cluster pulsars to probe the formation history of the stellar cluster that surrounds the Galactic centre. One possible formation scenario points towards the tidal disruption of stellar clusters. Although no millisecond pulsars have been found in the region, using simulations, I show what the distribution of pulsars should be and where we should look to find them. The scientific discoveries possible with globular cluster pulsars are diverse and can extend out of the clusters into the entire Galaxy. The future of this field will be dominated by the next generation radio-telescopes like the new MeerKAT radio telescope in South Africa which promises to revolutionize our knowledge of pulsars. In the final chapter I describe this facility and what it will be able to achieve in the field of globular cluster pulsars.

Theoretical models suggest that intermediate mass black holes (IMBHs) may form and reside in the centers of globular clusters. IMBHs are still elusive to observations, but the accelerations of pulsars may bring along a unique fingerprint of their presence. In this work, we focus on the pulsars in the globular cluster M62. Using the new distance of M62 obtained from Gaia observations, we find that the measured pulsars' accelerations suggest a central excess of mass in the range [1200, 6000]$M_{\odot}$, corresponding to [0.2, 1] percent of the current total mass of the cluster. Our analysis can not unambiguously discriminate between an IMBH or a system of stellar mass dark remnants of comparable total mass., Comment: 7 pages, 5 figures. Accepted for publication in Astrophysical Journal Letters

Despite considerations of mass loss from stellar evolution suggesting otherwise, the content of gas in globular clusters seems poor and hence its measurement very elusive. One way of constraining the presence of ionized gas in a globular cluster is through its dispersive effects on the radiation of the millisecond pulsars included in the cluster. This effect led Freire et al. in 2001 to the first detection of any kind of gas in a globular cluster in the case of 47 Tucanae. By exploiting the results of 12 additional years of timing, as well as the observation of new millisecond pulsars in 47 Tucanae, we revisited this measurement: we first used the entire set of available timing parameters in order to measure the dynamical properties of the cluster and the three-dimensional position of the pulsars. Then we applied and tested various gas distribution models: assuming a constant gas density, we confirmed the detection of ionized gas with a number density of $n= 0.23\pm 0.05$ cm$^{-3}$, larger than the previous determination (at 2$\sigma$ uncertainty). Models predicting a decreasing density or following the stellar distribution density are highly disfavoured. We are also able to investigate the presence of an intermediate mass black hole in the centre of the cluster, showing that is not required by the available data, with an upper limit for the mass at $\sim 4000$ M$_{\odot}$., Comment: 14 pages, 10 figures, accepted for publication in MNRAS

Purpose: A morphological and morphometric study of the adult zebrafish ocular surface was performed to provide a comprehensive description of its parts and to evaluate its similarity to the human. Materials and Methods: The eyes of adult zebrafish were processed for light, transmission and scanning electron microscopy, and for immunohistochemical stain of corneal nerves; a morphometric analysis was also performed on several morphological parameters. Results: The corneal epithelium was formed by five layers of cells. No Bowman’s layer could be demonstrated. The stroma consisted of lamellae of different thickness with few keratocytes. The Descemet’s membrane was absent as the flat and polygonal endothelial cells directly adhered to the deepest corneal lamella. The immunohistochemical stain of neurofilaments failed to demonstrate corneal nerve fibers. The conjunctival epithelium was stratified, overlying the stroma formed by a subepithelial and a deep layer, this latter connected to the scleral cartilage. In the peripheral cornea and in the conjunctiva, many goblet and rodlet cells were observed. The morphometric analysis showed that the peripheral cornea epithelium was thicker when compared to the other parts of the ocular surface, with smaller superficial cells. Desmosomes and hemidesmosomes in the conjunctiva were significantly fewer in number than the other parts of the ocular surface. The stroma was thinner in the conjunctiva than in the cornea, while corneal lamellae were thicker in the intermediate stroma. Conclusions: The zebrafish ocular surface showed significant differences compared to the human, such as the absence of Bowman’s layer, Descemet’s membrane and corneal nerve fibers, the reduced stromal thickness, and the presence of rodlet cells. On the basis of these original findings, it is suggested that the use of the zebrafish as a model for studying normal or pathological human corneas should be undertaken with particular caution.

The origin of the Nuclear Star Cluster in the centre of our Galaxy is still unknown. One possibility is that it formed after the disruption of stellar clusters that spiralled into the Galactic Centre due to dynamical friction. We trace the formation of the Nuclear Star Cluster around the central black hole, using state-of-the-art N-body simulations, and follow the dynamics of the neutron stars born in the clusters. We then estimate the number of Millisecond Pulsars (MSPs) that are released in the Nuclear Star Cluster, during its formation. The assembly and tidal dismemberment of globular clusters lead to a population of MSPs distributed over a radius of about 20 pc, with a peak near 3 pc. No clustering is found on the sub-parsec scale. We simulate the detectability of this population with future radio telescopes like the MeerKAT radio telescope and SKA1, and find that about of order ten MSPs can be observed over this large volume, with a paucity of MSPs within the central parsec. This helps discriminating this scenario from the in-situ formation model for the Nuclear Star Cluster that would predict an over abundance of MSPs closer to the black hole. We then discuss the potential contribution of our MSP population to the gamma-ray excess at the Galactic Centre., Comment: 11 pages, 8 figures, accepted for publication in MNRAS