Integrazione della riduzione della mobilità respiratoria nel trattamento radiante esterno conformazionale

Several methods to reduce respiratory-induced motion have been described in literature, with the goal of increasing accuracy of treatment to minimize normal tissue toxicity or increase dose to the target volume. We analyzed two different techniques of respiratory gating: the deep inspiration breath hold technique and the respiratory gating using the Real-time Position Management (RPM) system. The first method is a self-gating technique in which radiation treatment take place during a phase of breath-holding. The second technique use a reflective marker placed on the patient’s anterior surface. The motion of the marker is tracked using a camera interfaced to a computer. The gating thresholds are set when the tumor is in the desired portion of the respiratory cycle. These thresholds determine when the gating system turns the treatment beam on and off. We compared both techniques with a standard external radiation treatment. The dosimetric analysis has led to considerable advantage of these methods compared to the external radiation treatment, particularly in reducing the dose to the lung.

Restauro e rifunzionalizzazione ex deposito S.I.T.A. mcmxxxv - Forlì

La mia tesi propone un progetto di restauro e rifunzionalizzazione dell’Ex Stabilimento SITA di Forli costruito nel 1935. Attualmente l’edificio, al confine fra centro storico e tessuto urbano moderno, crea un grande vuoto urbano. L’obiettivo principale del progetto è il restauro e il consolidamento del manufatto, nonché una sua successiva rifunzionalizzazione. L’obbiettivo è la creazione di un centro culturale pubblico, di aggregazione e di incontro, che stimoli un nuovo impulso vitale ed economico nella zona circostante. La nuova funzione è quella di un centro culturale polifunzionale, gestito da una fondazione che fornisca spazi di utilizzo ampi, flessibili ed intercambiabili. Nello specifico si intende: spazi per conferenze cittadine, spettacoli teatrali temporanei, fiere, mercatini, mostre con particolari esigenze di dimensioni, concerti e festival organizzati sia dal privato che dalla pubblica amministrazione. Concludendo la parola chiave e il fine di questa tesi sono il restauro e la conservazione, e gli strumenti che si utilizzeranno per raggiungerli sono il consolidamento e la rifunzionalizzazione. Per questo motivo gli spazi e la struttura subiscono i minimi cambiamenti necessari per le nuove funzioni, seppur nei limiti imposti dal preesistente.

Pondicherry, India. riqualificazione di un isolato urbano

Il progetto di riqualificazione all'interno del nucleo urbano di Pondicherry, ho come principale obiettivo quello di inserirsi nel territorio seguendo i caratteri locali. Dopo un approfondito studio storico e funzionale, ho scelto di allacciarmi all'elemento che da sempre contraddistingue questa città: il Grand Canal, un canale artificiale che taglia in due parti la città (indiana e francese). A esso si affacciano, nella parte occidentale, una scuola di arti e mestieri e un complesso di abitazioni. La prima ha come obiettivo quella di riunire le più diverse attività artigianali, da offrire come possibilità di crescita economica del paese stesso (sia a livello di offerta lavorativa, che come attrazione turistica). Le abitazioni, su lotti lunghi e stretti in analogia alla tipologia a schiera, sono state studiate secondo i temi culturali caratteristici di questa zona, con variazioni legate alle dimensioni dei lotti e alla diversa composizione delle famiglie.

Percezione e paesaggio: un percorso di reastauro tra le rovine di Castelnuovo

Questo progetto tratta di un Luogo, composto di vari elementi, che concorrono a tracciarne l'identità. Partendo dal principio che non solo il restauro di tali oggetti ne garantirebbe la sopravvivenza, la storia del restauro ci insegna che prendersi cura dei monumenti non significa solo preservarne l'integrità materica, ma anche gestire il loro valore d'uso, garantendone una adeguata fruizione. Questa tesi, quindi, non si occuperà solo della conservazione materiale dei manufatti nel tempo ma anche del trattamento del loro intorno, al fine di creare un sistema fruibile, basato sulle dinamiche percettive del Luogo.

Riqualificazione del bastione miralfiore a Pesaro

Oggetto di lavoro della tesi, è un programma di riqualificazione dell’area urbana riguardante il bastione Miralfiore a Pesaro, situato in un punto strategico, poiché compreso tra la stazione ferroviaria, l’accesso sud alla città da via Miralfiore, e il Teatro Rossini, che affaccia su Piazza Lazzarini. L’obiettivo principale del programma, è la creazione di un polo culturale, che possa valorizzare le caratteristiche storiche e morfologiche dell’area, ridando vita alle antiche mura del bastione, e riportando in auge il nome del teatro cittadino, il Teatro Rossini. Il bastione, attualmente ospita la sede dell’Azienda Ospedaliera San Salvatore, per la quale è in sede di discussione, la proposta della realizzazione di un nuovo polo ospedaliero tra Pesaro e Fano, che di fatto porterebbe alla graduale liberazione di un vuoto urbano all’interno del centro storico. L’intervento, prevede la creazione di due musei, il primo dei quali dedicato all’esposizione permanente, che ospiterà apparati di produzione, di scena, di pubblicistica e didattici riguardanti Rossini e l’opera. L’altro museo è adibito all’esposizione temporanea, pensata per ospitare mostre e rappresentazioni, sia durante l’Opera Rossini Festival, in parallelo al Museo Permanente, che durante il restante periodo dell’anno. Al teatro originario è stato affiancato un Auditorium, dotato di una sala da 1200 posti, che permetterà alla città di ospitare spettacoli e rappresentazioni di portata maggiore. Sono stati predisposti inoltre degli edifici per uffici, insieme all’edificio dell’ex ospedale, che assume così una nuova funzione, i quali ospiteranno oltre agli uffici di pertinenza dei due musei, la Fondazione Rossini ed altre istituzioni, A completare il progetto, abbiamo previsto una stecca di edifici residenziali che affacciano su via Oberdan, ed un Presidio Sanitario Territoriale, conforme alle nuove norme sanitarie nazionali, che garantisce una presenza medica costante. L’intero complesso è immerso nel verde, in parte privato, adibito ad area espositiva esterna del Museo Temporaneo, ed in parte pubblico, che oltre ad avvolgere l’area del bastione, continua sulla fascia di via della Liberazione, fino a congiungersi con il bastione degli Orti Giulii.

Genetic and environmental factors associated with the risk of cognitive decline and dementia

AD is the most common age related neurodegenerative disease in the industrialized world. Clinically AD is defined as a progressing decline of cognitive functions. Neuropathologically, AD is characterized by the aggregation of b-amyloid (Ab) peptide in the form of extracellular senile plaques, and hyperphosphorlylated tau protein in the form of intracellular neurofibrillary tangles. These neuropathological hallmarks are often accompanied by abundant microvascular damage and pronounced inflammation of the affected brain regions. In this thesis we investigated several aspects of AD focusing on the genetic aspect. We confirmed that Alpha 1 antichymotrypsin (ACT), an acute phase protein, was associated to AD subjects, being plasma levels higher in AD cases than controls. In addition, in a GWA study we demonstrated that two different gene, Clusterin and CR1 were strongly associated to AD. A single gene association not explain such a complex disease like AD. The goal should be to created a network of genetic, phenotypic and clinical data associated to AD. We used a new algorithm, the ANNs, aimed to map variables and search for connectivity among variables. We found specific variables associated to AD like cholesterol levels, the presence of variation in HMGCR enzyme and the age. Other factors such as the BMI, the amount of HDL and blood folate levels were also associated with AD. Pathogen infections, above all viral infections, have been previously associated to AD. The hypothesis suggests that virus and in particular herpes virus could enter the brain when an individual becomes older, perhaps because of a decline in the immune system. Our new hypothesis is that the presence of SNPs in our GWA gene study results in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging.

New insight on a Group A Streptococcus protective antigen contributing to bacterial cell division

Bioinformatic analysis of Group A Streptococcus (GAS) genomes aiming at the identification of new vaccine antigens, revealed the presence of a gene coding for a putative surface-associated protein, named GAS40, inducing protective antibodies in an animal model of sepsis. The aim of our study was to unravel the involvement of GAS40 in cell division processes and to identify the putative interactor. Firstly, bioinformatic analysis showed that gas40 shares homology with ezrA, a gene coding for a negative regulator of Z-ring formation during cell division process. Both scanning and transmission electron microscopy indicated morphological differences between wild-type and the GAS40 knock-out mutant strain, with the latter showing an impaired capacity to divide resulting in the formation of very long chains. Moreover, when the localization of the antigen on the bacterial surface was analyzed, we found that in bacteria grown at exponential phase GAS40 specifically localized at septum, indicating a possible role in cell division. Furthermore, by ELISA and co-sedimentation assays, we found that GAS40 is able to interact with FtsZ, a protein involved in Z-ring formation during cell division process. These data together with the co-localization of GAS40/FtsZ at bacterial septum demonstrated by by confocal microscopy, strongly support the hypothesis for a key role of GAS40 in bacterial cell division.

New polymeric materials for vascular surgery

The dramatic impact that vascular diseases have on human life quality and expectancy nowadays is the reason why both medical and scientific communities put great effort in discovering new and effective ways to fight vascular pathologies. Among the many different treatments, endovascular surgery is a minimally-invasive technique that makes use of X-ray fluoroscopy to obtain real-time images of the patient during interventions. In this context radiopaque biomaterials, i.e. materials able to absorb X-ray radiation, play a fundamental role as they are employed both to enhance visibility of devices during interventions and to protect medical staff and patients from X-ray radiations. Organic-inorganic hybrids are materials that combine characteristics of organic polymers with those of inorganic metal oxides. These materials can be synthesized via the sol-gel process and can be easily applied as thin coatings on different kinds of substrates. Good radiopacity of organic-inorganic hybrids has been recently reported suggesting that these materials might find applications in medical fields where X-ray absorption and visibility is required. The present PhD thesis aimed at developing and characterizing new radiopaque organic-inorganic hybrid materials that can find application in the vascular surgery field as coatings for the improvement of medical devices traceability as well as for the production of X-ray shielding objects and garments. Novel organic-inorganic hybrids based on different polyesters (poly-lactic acid and poly-ε-caprolactone) and polycarbonate (poly-trimethylene carbonate) as the polymeric phase and on titanium oxide as the inorganic phase were synthesized. Study of the phase interactions in these materials allowed to demonstrate that Class II hybrids (where covalent bonds exists between the two phases) can be obtained starting from any kind of polyester or polycarbonate, without the need of polymer pre-functionalization, thanks to the occurrence of transesterification reactions operated by inorganic molecules on ester and carbonate moieties. Polyester based hybrids were successfully coated via dip coating on different kinds of textiles. Coated textiles showed improved radiopacity with respect to the plain fabric while remaining soft to the touch. The hybrid was able to coat single fibers of the yarn rather than coating the yarn as a whole. Openings between yarns were maintained and therefore fabric breathability was preserved. Such coatings are promising for the production of light-weight garments for X-ray protection of medical staff during interventional fluoroscopy, which will help preventing pathologies that stem from chronic X-ray exposure. A means to increase the protection capacity of hybrid-coated fabrics was also investigated and implemented in this thesis. By synthesizing the hybrid in the presence of a suspension of radiopaque tantalum nanoparticles, PDMS-titania hybrid materials with tunable radiopacity were developed and were successfully applied as coatings. A solution for enhancing medical device radiopacity was also successfully investigated. High metal radiopacity was associated with good mechanical and protective properties of organic-inorganic hybrids in the form of a double-layer coating. Tantalum was employed as the constituent of the first layer deposited on sample substrates by means of a sputtering technique. The second layer was composed of a hybrid whose constituents are well-known biocompatible organic and inorganic components, such as the two polymers PCL and PDMS, and titanium oxide, respectively. The metallic layer conferred to the substrate good X-ray visibility. A correlation between radiopacity and coating thickness derived during this study allows to tailor radiopacity simply by controlling the metal layer sputtering deposition time. The applied metal deposition technique also permits easy shaping of the radiopaque layer, allowing production of radiopaque markers for medical devices that can be unambiguously identified by surgeons during implantation and in subsequent radiological investigations. Synthesized PCL-titania and PDMS-titania hybrids strongly adhered to substrates and show good biocompatibility as highlighted by cytotoxicity tests. The PDMS-titania hybrid coating was also characterized by high flexibility that allows it to stand large substrate deformations without detaching nor cracking, thus being suitable for application on flexible medical devices.

Mastocitosi cutanee: il mastocitoma in età pediatrica

Background: Mastocytosis is a rare disease involving mast cells (MC) and their CD34+ progenitors. According to the WHO consensus classification, cutaneous mastocytosis (CM) is considered a benign disease confined to the skin, preferentially seen in young children with a marked tendency to regress spontaneously. Aim of our study was the long-term assessment of the outcome of solitary (SM) and multiple (MM) mastocytomas in a pediatric population. Materials and methods: From January 1996 to December 2010, 241 pediatric patients with a diagnosis of CM were followed-up at the outpatient division of pediatric dermatology of the University of Bologna. We focused our retrospective evaluation on patients affected by SM or MM. We collected, through the analysis of medical records and with a telephone questionnaire for patients and their families, information on clinical aspects of the disease evolution and on the efficacy of topical steroid therapy. Results: Over the 241 considered patients we recorded: SM or MM in 176 (73%) pts., urticaria pigmentosa in 53 (22%) pts., telangiectasia macularis eruptiva perstans in 9 (4%) pts., diffuse CM in 2 (0,9%) pts. and polymorph CM in 1 (0,4%) pt. On 176 children affected by SM or MM (97 M vs. 79 F), 130 (74%) patients were followed-up with a mean of 56,3 (r. 4-142) months. A satisfactory outcome was recorded in 99 (76%) cases of whom 52 (53%) treated with topic steroids. Mean time to complete regression was 16.4 m. on treated patients vs. 34.7 m. on non treated patients (p=0,001). Conclusions: From our study emerged that resolution of the disease is independent from therapy, but the time to regression and to complete recovery of the coetaneous lesions is faster and favored by the application of topic steroid with an improvement of the quality of life for children and their families.