On the parametrization of lateral dose profiles in proton radiation therapy.

Abstract Purpose The accurate evaluation of the lateral dose profile is an important issue in the field of proton radiation therapy. The beam spread, due to Multiple Coulomb Scattering (MCS), is described by the Moliere's theory. To take into account also the contribution of nuclear interactions, modern Treatment Planning Systems (TPSs) generally approximate the dose profiles by a sum of Gaussian functions. In this paper we have compared different parametrizations for the lateral dose profile of protons in water for therapeutical energies: the goal is to improve the performances of the actual treatment planning. Methods We have simulated typical dose profiles at the CNAO (Centro Nazionale di Adroterapia Oncologica) beamline with the FLUKA code and validated them with data taken at CNAO considering different energies and depths. We then performed best fits of the lateral dose profiles for different functions using ROOT and MINUIT. Results The accuracy of the best fits was analyzed by evaluating the reduced χ2, the number of free parameters of the functions and the calculation time. The best results were obtained with the triple Gaussian and double Gaussian Lorentz–Cauchy functions which have 6 parameters, but good results were also obtained with the so called Gauss–Rutherford function which has only 4 parameters. Conclusions The comparison of the studied functions with accurate and validated Monte Carlo calculations and with experimental data from CNAO lead us to propose an original parametrization, the Gauss–Rutherford function, to describe the lateral dose profiles of proton beams

Exosporium Morphogenesis in Bacillus Cereus and Bacillus Anthracis

Bacillus cereus is a Gram-positive spore-forming bacteria that can cause food poisoning and its close relative, Bacillus anthracis is the etiological agent of anthrax. In both cases, the spore, a differentiated cell type in a dormant state, starts the infection process. Thus, the exosporium, which constitutes the surface of the spore, plays an important role during natural infection of both B. cereus and B. anthracis. Proteins from the exosporium of B. cereus ATCC 4342, a B. anthracis-like strain, were extracted with 2% β-mercaptoethanol under alkaline conditions and identified by liquid chromatography coupled with tandem mass spectrometry. A novel cell surface protein, reticulocyte binding protein (Rbp), was identified in this sample. Inactivation of rbp by insertional mutagenesis resulted in spores devoid of the hair-like nap typical of the exosporium, which suggests that Rbp could be a new component of the exosporium nap or could have a role in its assembly. GerQ, a protein that is crosslinked by transglutaminase in the spore coat of Bacillus subtilis, was also identified in the B. cereus ATCC 4342 exosporium.Absence of GerQ during sporulation resulted in a brittle exosporium in both B. cereus ATCC 4342 and B. anthracis ΔSterne spores. This suggests that transglutaminase participates in exosporium assembly and maturation by crosslinking small proteins and processed peptides, providing structural stability and resistance to degradation to the spore surface. In addition, a novel exosporium protein, ExsM, was characterized in this study. Subcellular localization of an ExsM-GFP fusion protein revealed a dynamic pattern of fluorescence that follows the site of formation of the exosporium around the forespore. Under scanning electron microscopy, exsM null mutants presented a tightly wrapped exosporium resulting in smaller and rounder spores than wild-type spores that have an extended exosporium. Thin-section electron microscopy revealed that exsM spores were encased by a double layer exosporium, both of which were composed of a basal layer and a hair-like nap. Compared to wild-type spores, exsM spores were more resistant to lysozyme treatment, germinated with a higher efficiency, and had a delay in outgrowth. Insertional mutagenesis of exsM in B. anthracis ΔSterne rendered spores with a partial second exosporium that were also smaller in size. These findings suggest that ExsM plays a critical role in the formation of the exosporium. B.cereus, but not B. anthracis, spores possess long appendages projecting from their surface. B. cereus ATCC 14579 appendages were isolated from spores by extraction with 2% β-mercaptoethanol under alkaline conditions, followed by CsCl gradient ultracentrifugation. Mass spectrometry analysis revealed that camelysin (CalY) and spore coat-associated protein N (CotN) were associated with the appendages sample. Both proteins are homologous to TasA, the main component of B. subtilis biofim extracellular matrix. TasA forms amyloids fibrils that hold the cells together and provide structure to the extracellular matrix. Therefore, spore appendages may have a role in biofilm formation, acting like a scaffold for the biofilm matrix and holding the spores together

IL PAESAGGIO LINGUISTICO PER LE COMPETENZE DIGITALI: UNA SPERIMENTAZIONE DIDATTICA IN CONTESTO UNIVERSITARIO

L’impiego e la valorizzazione del paesaggio linguistico come risorsa educativa offre l’opportunità di arricchire l’esperienza didattica, in quanto permette agli studenti di ottenere una prospettiva unica sulla complessità e la stratificazione della variazione linguistica e sociolinguistica, culturale e semiotica, caratteristiche della comunicazione pubblica nella società attuale. In questo studio è stato valutata l’efficacia di un approccio basato sull’esplorazione diretta e l’analisi del paesaggio linguistico da parte di studenti universitari sullo sviluppo di competenze digitali e in materia di cittadinanza. I risultati della sperimentazione, conclusasi con la realizzazione di un sito web, confermano la validità di un tale metodo per l’acquisizione di abilità di decodifica e di una maggiore consapevolezza linguistica critica, nonché per lo sviluppo di abilità espositive, multimodali e legate all’alfabetizzazione digitale. L’esperienza descritta si configura, dunque, come modello efficace per l’integrazione di competenze multiple nel contesto accademico. Le conclusioni cui si giunge delineano nuove prospettive didattiche e di ricerca, volte a preparare gli studenti a essere cittadini globali, consapevoli e competenti.   The linguistic landscape for digital competences: a didactic experiment in a university context   The implementation and enhancement of linguistic landscape as an educational resource offers the opportunity to enrich the learning experience. Indeed, it enables students to gain a unique perspective on the complexity and stratification of linguistic, sociolinguistic, cultural, and semiotic variation, characteristic of public communication in the contemporary society. This study aims to evaluate the effectiveness of an approach based on direct exploration and analysis of the linguistic landscape by university students in developing digital and citizenship competences. The results of the educational activity, culminating in the creation of a website, confirm the validity of such a method for acquiring decoding skills and increasing critical language awareness, as well as for the development of expressive, multimodal, and digital literacy skills. Therefore, the described experience emerges as an effective model for integrating multiple competences in the academic context. The conclusions outline new educational and research perspectives aimed at preparing students to be informed and competent global citizens

Development and implementation of a non Gaussian model for the lateral dose prediction in a proton therapy treatment planning system

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A non Gaussian model for the lateral dose evaluation in hadrontherapy

Challenging issues in Treatment Planning System for hadrontherapy are the accurate calculation of dose distribution, the reduction in Memory space required to store the dose kernel of individual pencil beams and the shortening of computation time for dose optimization and calculation. In this framework, the prediction of lateral dose distributions is a topic of great interest because currently, a Double Gaussian parametrization is typically used as approximation although other parametrizations are also available. The best accuracy for this kind of calculations can be obtained by Monte Carlo (MC) methods, at the expense of a long computing time. As alternative, we propose a flexible model based on the full Molière theory for Coulomb multiple scattering. The use of the original equations of the theory allows to remove free parameters for the electromagnetic interaction with the advantage of full accuracy with a reasonable increase in the computing time. The contribution of the nuclear interactions are also fully taken into account with a two-parameters fit on FLUKA simulation and this part is added to the electromagnetic core with a proper weight. The model has been validate with MC simulations and with Heidelberg Ion-Beam Therapy Center (HIT) experimental data. In a second step, the model has been inserted in a research Treatment Planning System CERR - A Computational Environment for Radiotherapy Research at the Ludwig-Maximilians-Universitat Munchen, to compare its result against the ones obtained with the currently used Double Gaussian parametrization to evaluate the lateral energy deposition. A quantitative comparison has been done to evaluate the difference between a treatment plan obtained using the Double Gaussian parametrization and a treatment plan obtained using the model calculation, in the cases of a single beam and a full treatment plan in homogeneous water phantom and also a plan is performed in presence of inhomogeneities.Eine der anspruchsvollsten Herausforderungen in der Bestrahlungsplanung von Ionenstrahltherapie ist die präzise Berechnung der Dosisverteilung im Patienten, die Reduktion des Speicherbedarfs der Dosiskernel von einzelnen Pencil-beams, sowie die Verkürzung der Rechenzeit fur Dosisoptimierung und -berechnung. In diesem Rahmen ist die Berechnung der lateralen Protonen-Dosisverteilungen ein Thema von großem Interesse, da momentan eine Double Gaussian Parametrisierung als Näherung verwendet wird, obwohl weitere Parametrisierungen existieren. Die größte Genauigkeit fur diese Art von Berechnungen kann mit Monte Carlo (MC) Simulationen erzielt werden, jedoch auf Kosten langer Laufzeiten. Als Alternative wird in dieser Arbeit ein flexibles Modell vorgeschlagen, welches auf der vollständigen Moliere-Theorie fur Multiples Coulomb Streuung basiert. Die Verwendung der originalen Gleichungen der Theorie erlaubt die Reduktion der freien Parameter für die elektromagnetischen Wechselwirkungen, was den Vorteil der vollen Genauigkeit mit einer moderaten Erhöhung der Rechenzeit vereint. Der Beitrag von nuklearen Wechselwirkungen wird mit einem zwei-Parameter Fit an FLUKA Simulationen berucksichtigt und dieser Anteil wird dann zu dem elektromagnetischen Core mit einer Gewichtung addiert. Das Modell wurde in das Forschungs-Bestrahlungsplanungssystem CERR A Computational Environment for Radiotherapy Research implementiert, um die Ergebnisse bei der lateralen Dosis-Deposition mit der momentan verwendeten Double Gaussian Parametrisierung zu vergleichen. Ein quantitativer Vergleich wurde durchgeführt zwischen den Bestrahlungsplänen die einmal mit der Double Gauss Parametrisierung und einmal mit dem vorgeschlagene Modell berechnet wurden. Das untersuchte Szenario beinhaltete Pläne die entweder für einzelne Strahlen verschiedener Energien in einem homogenen Wasserphantom, ein voller Bestrahlungsplan in einem homogenen Wasserphantom, sowie einzelne Strahlen verschiedener Energien für ein Phantom mit Inhomogenitäten berechnet wurden.Temi di grande interesse nell’ambito dello sviluppo dei Software per il calcolo di piani di trattamento per adroterapia (Treatment Planning System (TPS)), sono la riduzione dei tempi computazionali del calcolo e dell’ottimizzazione della dose, e la riduzione della memoria richiesta per l’archiviazione della dose di ogni singolo fascio (pencil beam). In questo contesto, la valutazione della distribuzione laterale della dose è un argomento di grande interesse in quanto attualmente viene utilizzata una funzione a doppia gaussiana come approssimazione, che risulta non completamente accurata. Altre parametrizzazioni sono disponibili; anch’esse rimangono però approssimazioni. La migliore accuratezza per questo tipo di calcolo della dose viene ottenuta utilizzando le tecniche Monte Carlo (MC)che richiedono però tempi computazionali molto lunghi. In alternativa, questo lavoro propone un modello flessibile e analitico basato sulla teoria completa di Moli`ere per la valutazione dello scattering multiplo di Coulomb. L’utilizzo delle equazioni originali di questa teoria permette di rimuovere ogni parametro libero per il calcolo delle interazioni elettromagnetiche, ottenendo così il vantaggio di un’accuratezza pari a quella del metodo MC ma con tempi di calcolo di molto inferiori. Il contributo delle interazioni nucleari è considerato tramite un fit, con soli due parametri, sulle simulazioni MC FLUKA. La funzione viene aggiunta alla parte analitica elettromagnetica assegnando ad entrambe un fattore di peso di senso fisico, calcolato appropriatamente. Il modello così ottenuto è stato validato con simulazioni MC e con dati sperimentali del centro di adroterapia di Heidelberg, Heidelberg Ion-Beam Therapy Center (HIT). Successivamente, il modello è stato inserito nel TPS di ricerca CERR - A Computational Environment for Radiotherapy Research presso l’Università di Monaco Ludwig-Maximilians-Universitat Munchen, per confrontare i risultati ottenuti valutando piani di trattamento che utilizzano l’approssimazione gaussiana per il calcolo della dose, con piani ditrattamento che utilizzano il modello per il calcolo della dose stessa. Uno studio quantitativo è stato svolto considerando i casi di: singoli fasci di energia fissata in un fantoccio di acqua omogeneo, un piano di trattamento completo (come caso reale della pratica clinica, che considera più fasci di diverse energie e posizioni) in un fantoccio di acqua omogeneo, e infine i casi di singoli fasci a energie fissate in fantocci che presentano disomogeneità

Lingue e culture aumentate.

As an emerging technology, Augmented Reality (AR) demonstrated several advantages in education. However, the implementation of AR for plurilingual and intercultural education is still at an early stage and more studies are needed. Therefore, the research presented here aims to evaluate the impact of the implementation of AR on the development of adolescent students’ plurilingual and intercultural competence, as well as on their motivation. To achieve the aims described, several educational activities centered on authentic stories of migrants were developed through a Game-Based Learning approach and implemented. The stories were drawn from the DiMMi project, which collects autobiographical testimonies related to the themes of migration. Results showed how the integration of AR in plurilingual and intercultural education consists of an effective strategy to bring adolescent students closer to contemporary migration issues. Moreover, it enables the development of citizen and cultural awareness, as well as plurilingual and digital skills and competences. Furthermore, the study demonstrated the potential of AR to stimulate students’ interest in the topics covered by the activities implemented

SECONDARY STUDENTS’ ATTITUDES TOWARDS LINGUISTIC DIVERSITY: AN INVESTIGATION ON INDIVIDUAL AND EDUCATIONAL ASPECTS IN ITALIAN SCHOOLS

This paper aims at investigating lower and upper secondary students’ attitudes towards linguistic diversity, here assumed as an extension of the language attitude construct. The research focuses on individual factors, as well as on aspects related to the educational context. Drawing from a larger study, data was gathered from a considerable number of informants in a representative number Italian regions, employing a Likert scale-based questionnaire and through the triangulation of different information from a variety of sources. Results showed that gender, school grade, number of languages known and the migratory background are all predictors of attitudes towards linguistic diversity. Moreover, the adoption of éveil aux langues and CLIL and the purposeful use of the schoolscape though specific activities promoting plurilingualism and intercultural reflection have a significant impact on students’ attitudes.   Gli atteggiamenti degli studenti della scuola secondaria verso la diversità linguistica: un’indagine sugli aspetti individuali ed educativi nelle scuole italiane Questo articolo mira a indagare gli atteggiamenti degli studenti della scuola secondaria inferiore e superiore verso la diversità linguistica, qui assunta come un’estensione del costrutto di attitudine linguistica. La ricerca si concentra sia su fattori individuali sia su aspetti legati al contesto educativo. Attingendo da uno studio più ampio, i dati sono stati raccolti da un numero considerevole di informatori rappresentativi di diverse regioni italiane, utilizzando un questionario basato sulla scala Likert e attraverso la correlazione di diverse informazioni tratte da una varietà di fonti. I risultati hanno mostrato che il genere, il grado scolastico, il numero di lingue conosciute e il background migratorio sono tutti indicatori di atteggiamenti verso la diversità linguistica. Inoltre hanno messo in evidenza che l’adozione di éveil aux langues, del CLIL e l’uso mirato dello schoolscape, attraverso attività specifiche che promuovono il plurilinguismo e la riflessione interculturale, hanno un impatto significativo sugli atteggiamenti degli studenti

Xanthomatous Hypophysitis Mimicking a Pituitary Adenoma: Case Report and Review of the Literature

Background. Hypophysitis is an inflammatory disease of the pituitary gland that may mimic pituitary tumors clinically and radiologically. Case Description. We report a case of a xanthomatous hypophysitis initially diagnosed as pituitary adenoma. A 31-year-old woman presented with headache, diabetes insipidus, and amenorrhea. A head CT scan showed no intrasellar changes, while an MRI scan showed a sellar cystic mass. An endocrinological work up revealed mild hypocortisolism and diabetes insipidus (DI). Transsphenoidal surgery was performed. The intraoperative histological examination suggested a pituitary adenoma. The removed tissue showed central necrosis surrounded by accumulation of foamy cells and xanthomatous epithelioid cells. The patient made an uneventful postoperative recovery, Nevertheless, DI persisted and the adenohypophysis hypofunction did not recover. Conclusion. We describe an unusual inflammatory lesion of the pituitary gland mimicking an adenoma. A high level of clinical suspicion of inflammatory disorders is necessary for correct diagnosis and optimal management

The COVID-19 Pandemic Sparked off a Large-Scale Outbreak of Carbapenem-Resistant Acinetobacter baumannii from the Endemic Strains at an Italian Hospital

Acinetobacter baumannii is a nosocomial pathogen that poses a serious threat due to the rise of incidence of multidrug-resistant (MDR) strains. During the COVID-19 pandemic, MDR A. baumannii clones have caused several outbreaks worldwide. Here, we describe a detailed investigation of an MDR A. baumannii outbreak that occurred at Policlinico San Matteo (Pavia, Italy). A total of 96 A. baumannii strains, isolated between January and July 2020 from 41 inpatients (both SARS-CoV-2 positive and negative) in different wards, were characterized by phenotypic and genomic analyses combining Illumina and Nanopore sequencing. Antibiotic susceptibility testing revealed that all isolates were resistant to carbapenems, and the sequence analysis attributed this to the carbapenemase gene blaOXA-23. Virulence factor screening unveiled that all strains carried determinants for biofilm formation, while plasmid analysis revealed the presence of two plasmids, one of which was ~100 kbp long and encoded a phage sequence. A core genome-based phylogeny was inferred to integrate outbreak strain genomes with background genomes from public databases and the local surveillance program. All strains belonged to the globally disseminated sequence type 2 (ST2) clone and were mainly divided into two clades. Isolates from the outbreak clustered with surveillance isolates from 2019, suggesting that the outbreak was caused by two strains that were already circulating in the hospital before the start of the pandemic. The intensive spread of A. baumannii in the hospital was enhanced by the extreme emergency situation of the first COVID-19 pandemic wave that resulted in reduced attention to infection prevention and control practices. IMPORTANCE: The COVID-19 pandemic, especially during the first wave, posed a great challenge to the hospital management and generally promoted nosocomial pathogen dissemination. MDR A. baumannii can easily spread and persist for a long time on surfaces, causing outbreaks in health care settings. Infection prevention and control practices, epidemiological surveillance, and microbiological screening are fundamental in order to control such outbreaks. Here, we sequenced the genomes of 96 isolates from an outbreak of MDR A. baumannii strains using both short- and long-read technology in order to reconstruct the outbreak events in fine detail. The sequence data demonstrated that two endemic clones of MDR A. baumannii were the source of this large hospital outbreak during the first COVID-19 pandemic wave, confirming the effect of COVID-19 emergency disrupting the protection provided by the use of the standard prevention procedures