1,721,146 research outputs found
The fluid dynamics of climate: General Circulation Models and applications to past, present and future climatic changes
Full text linkLa presente tesi di ricerca riguarda l'ottimizzazione e l'utilizzo di modelli climatici globali, ed in modo particolare del modello climatico globale ad alta risoluzione EC-Earth, per affrontare una serie di problemi di interesse nel contesto della dinamica del clima e del cambiamento climatico. In particolare, l'attività di ricerca ha riguardato il lavoro di ottimizzazione, ovvero di tuning, del modello climatico globale EC-Earth, appartenente alla categoria degli Earth System Models, e nello specifico della componente atmosferica del modello. Lo studio del cosiddetto "Equable Climate" dell'Eocene, un periodo caldo verificatosi circa 50 milioni di anni fa caratterizzato da una bassa differenza di temperatura tra equatore e poli e ridotto ciclo annuale alle alte latitudini. Gli "Equable Climates" sono un problema tutt'ora irrisolto nelle scienze del clima e la loro comprensione potrebbe avere importanti implicazioni circa la nostra comprensione ed interpretazione dei cambiamenti climatici in corso. L'analisi delle caratteristiche della precipitazione invernale nella regione montuosa dell'Hindu-Kush Karakoram, nell'Himalaya occidentale, e delle sue teleconnessioni, con particolare riferimento all'Oscillazione Nord Atlantica. Lo studio é stato condotto mediante l'utilizzo congiunto di dati osservativi, rianalisi atmosferiche e simulazioni climatiche realizzate con il modello EC-Earth. Lo studio del cambiamento climatico nelle regioni montane, ed in particolare della dipendenza dalla quota dell'aumento delle temperature superficiali terrestri registrato durante il corso del XX secolo e previsto per le prossime decadi (Elevation-Dependent Warming, EDW). Lo studio si é focalizzato principalmente sulla regione montuosa dell'Himalaya- Tibetan Plateau ed é stato condotto mediante l'utilizzo di un ensemble di modelli climatici globali che hanno partecipato al Coupled Model Intercomparison Project Phase 5 (CMIP5) e all'analisi dei dati osservativi disponibil
Il paesaggio agrario italiano. Tecnologia e racconto
Full text linkLa tesi indaga attraverso l’opera di tre autori classici del riformismo agrario italiano – Simonde de Sismondi, Carlo Cattaneo, Emilio Sereni – una specifica forma di racconto geografico agrario del territorio. Un racconto declinato, nei tre autori, in tre differenti stili di analisi che condividono una centralità dell’approccio morfologico: la lettura elementarista e sistemica di Sismondi, la lettura stratigrafica di Cattaneo, lo sguardo paesaggistico e strutturalista di Sereni. La tesi decostruisce queste tre strategie analitiche e discorsive rintracciando in esse una medesima ipotesi di ricerca: indagare nelle forme della costruzione materiale e sociale del territorio il dispiegarsi di un determinato paradigma economico politico di sviluppo delle campagne. Paradigmi, ancora oggi centrali nel progetto e nella riflessione sullo sviluppo rurale, che i tre autori contribuiscono in maniera determinante a codificare attraverso la loro lettura ravvicinata di tre laboratori regionali: Toscana, Lombardia, Emilia.
Accanto a questa marcata capacità di lettura delle forme della costruzione materiale e sociale dello spazio, emerge in questa tradizione analitica una specifica tensione alla figurazione in grado di produrre pervasive immagini della ruralità. Uno sforzo visivo che contribuisce a riflettere e veicolare precisi valori e temi ideologici agganciati al pensiero economico politico dei tre autori e conferisce una dimensione progettuale alla loro lettura territoriale. Un asse di questi racconti che la tesi indaga attraverso una analogia con la tradizione pittorica coeva decostruendo tre potenti e paradigmatiche immagini della ruralità – pervasive anche al di fuori della cultura italiana – che possono essere lette come fondative di una genealogia, tutta interna alla tradizione del riformismo agrario, della spessa iconografia del paesaggio agrario italiano.
La tesi avanza infine alcune conclusioni circa l’attualità di questa caratteristica forma del racconto di territorio mettendola a confronto con le due opposte narrazioni che alimentano oggi la riflessione intorno alla transizione ecologica delle tecnologie e dei sistemi agrari: da un lato, una nuova ruralità contadina che recupera e aggiorna tecniche colturali e paesaggi storici, dall’altro lato, una inedita modernità ecologica che integra sviluppo tecnologico intensivo ed estesa rinaturalizzazione. Emerge in questo confronto una rimozione profonda di quella capacità del riformismo agrario di leggere nella materialità e spazialità di un determinato sistema agrario, nei rapporti sociali che ne governano la costruzione e riproduzione, nella dialettica storica e conflittuale di cui è esito, un complesso progetto insieme tecnologico, sociale ed estetico
A safety review of drugs used for the treatment of retinopathy of prematurity
Full text linkRetinopathy of Prematurity (ROP) is a sight-threatening disease representing one of the main disabling diseases affecting premature newborns. Presently, ROP is treated by surgical interventions and drug therapies are limited to the off-label use of a little amount of molecules approved for other pathologies
Targeting the Beta-Adrenergic System to Treat retinopathy of Prematurity: A New Therapeutic Approach?
No full textRetinopathy of prematurity (ROP) is a hypoxia-induced neovascular retinal disease representing the major cause of blindness and visual impairment in children. Currently, surgical approaches (i.e. vitrectomy and laser photocoagulation) are the treatments of choice for ROP although they may result in a variety of complications, and new therapeutic strategies are eagerly required. In general, intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents represent the most promising form of therapy to treat neovascular retinal disorders and there is expectancy for the use of these drugs to also treat ROP. However, for the use of these substances in ROP, the optimal choice of agent and dose remain unknown, while the possibility that the treatment may interfere with serum VEGF levels, and therefore affect normal vessel growth in developing tissues, remains to be considered. The serendipitous demonstration that a non-selective β-adrenergic receptor (β-AR) antagonist, propranolol, promotes the regression of infantile hemangiomas, the most common vascular tumor of infancy, aroused an interest around the involvement of the β-adrenergic system in angiogenic processes in humans. In particular, accumulating evidence indicates that the β-adrenergic system is involved in the hypoxia-induced neo-angiogenesis that is typically observed in ROP. In this respect, animal studies carried out in the mouse model of oxygen-induced retinopathy (OIR), which replicates the main features of ROP, have shown that β-AR blockade is effective in reducing pathological angiogenesis. For instance, propranolol has been demonstrated to inhibit hypoxia-induced VEGF expression and neo-angiogenesis when administered to OIR mice. Consequent to the encouraging results obtained in the animal model, a pilot clinical trial has shown that propranolol administered orally protects newborns from ROP progression. Indeed, compared to newborns with ROP stage 2 receiving standard treatment, the newborns with ROP stage 2 treated with oral propranolol showed a reduced progression to stage 3 or stage 3 plus and no newborns progressed to stage 4. However, some serious adverse effects of oral propranolol have been also reported. Therefore, this pilot study on the one hand has established the efficacy of propranolol treatment to counteract the progression of ROP, but on the other has indicated that the safety is a concern. Recent studies performed in rabbits have reported that the administration of propranolol through eye drops induces retinal concentrations of propranolol similar to those measured after oral administration, but with significantly lower plasma concentration. In addition, propranolol eye drops have been shown to reduce VEGF levels and retinal neovascularization in the mouse OIR model. These findings have opened the perspective of possible topical treatment with propranolol in newborns with ROP, and an ongoing study is indeed exploring the possibility of administering propranolol to newborns with ROP through eye drops with the objective to significantly reduce the side effects observed after oral propranolol administrations
99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications
No full textBackground: In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography (PET), utilizing FAP inhibitors (FAPi) labeled with positron emitters, has gained traction as a powerful imaging approach in both cancer and inflammation. However, PET represents a high-cost technology, and its widespread adoption is still limited compared to the availability of gamma cameras. To address this issue, several efforts have been made to explore the potential of [99mTc]Tc-FAPi tracers as molecular probes for imaging with gamma cameras and single photon emission computed tomography (SPECT). Main body: Several approaches have been investigated for labeling FAPi-based compounds with 99mTc. Specifically, the mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies have been applied to produce [99mTc]Tc-FAPi tracers, which have been tested in vitro and in animal models. Overall, these labeling approaches have demonstrated high efficiency and strong binding. The resulting [99mTc]Tc-FAPi tracers have shown high specificity for FAP-positive cells and xenografts in both in vitro and animal model studies, respectively. However, the majority of [99mTc]Tc-FAPi tracers have exhibited variable levels of lipophilicity, leading to preferential excretion through the hepatobiliary route and undesirable binding to lipoproteins. Consequently, efforts have been made to synthesize more hydrophilic FAPi-based compounds to improve pharmacokinetic properties and achieve a more favorable biodistribution, particularly in the abdominal region. SPECT imaging with [99mTc]Tc-FAPi has yielded promising results in patients with gastrointestinal tumors, demonstrating comparable or superior diagnostic performance compared to other imaging modalities. Similarly, encouraging outcomes have been observed in subjects with gliomas, lung cancer, breast cancer, and cervical cancer. Beyond oncological applications, [99mTc]Tc-FAPi-based imaging has been successfully employed in myocardial and idiopathic pulmonary fibrosis. Conclusions: This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation
The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective
No full textIntroductionTriple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. It predominantly affects younger women and is associated with a poor prognosis. This systematic review aims to evaluate the current role of positron emission tomography (PET) in the management of TNBC patients and to identify future research directions.MethodsWe systematically searched the PubMed, Scopus, and Web of Science databases up to February 2024. A team of five researchers conducted data extraction and analysis. The quality of the selected studies was assessed using a specific evaluation form.ResultsTwenty-eight studies involving 2870 TNBC patients were included in the review. Key clinical applications of PET in TNBC included predicting pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC), assessing the prognostic value of baseline PET, and initial disease staging. Two studies utilized PSMA-ligand agents, while the majority used [18F]FDG-based PET. Significant associations were found between baseline [18F]FDG uptake and molecular biomarkers such as PDL-1, androgen receptor, and Ki67. Baseline [18F]FDG PET led to the upstaging of patients from stage IIB to stage IV, influencing treatment decisions and survival outcomes. In the NAC setting, serial PET scans measuring changes in [18F]FDG uptake, indicated by maximum standardized uptake value (SUVmax), predicted pCR with varying cut-off values correlated with different response rates. Semiquantitative parameters such as metabolic tumor volume (MTV) and PET lung index were prognostic for metastatic disease.ConclusionsIn TNBC patients, [18F]FDG PET is essential for initial disease staging in both localized and metastatic settings. It is also useful for assessing treatment response to NAC. The ability of PET to correlate metabolic activity with molecular markers and predict treatment outcomes highlights its potential in TNBC management. Further prospective studies are needed to refine these clinical indications and establish its definitive role
Radiolabeled FAPI in pancreatic cancer: can it be an additional value in the management of patients?
No full textIntroduction: To discuss the current evidence about radiolabeled-FAPI in patients affected by pancreatic cancer by underlying the advantages, disadvantages, and the future perspectives also in the theragnostic field. Areas covered: A literature search up until February 2023 was performed in PubMed, EBSCO, and EMBASE databases. Clinical reports, conference abstracts, editorials, and letters-to-the-editor were excluded. The results were presented according to the PRISMA guidelines. The quality of studies was evaluated by using the Critical Appraisal Skill Program checklist. Expert opinion: From the initial 139 studies, 21 papers were selected for the final analysis. Ten papers were related to FAPI-uptake in health/benign/malignant pancreas, eight studies were focalized on the utility of radiolabeled-FAPI for the identification of premalignant and malignant pancreatic lesions and only three papers were related to the the theragnostic approach. Only two papers enrolled exclusively patients with pancreatic cancer undergoing FAPI-PET. In total, 55 patients underwent FAPI-PET for the identification of the suspicious mass/primary tumor (n = 43) and recurrent disease (n = 12). In both the studies, FAPI-PET detected more lesions than 2-[18F]FDG. Preliminary data about the FAPI-based theragnostic approach in patients with pancreatic cancer (n = 9 patients, totally) are now available. Radiolabeled-FAPI is a promising agent for the identification of pancreatic malignant lesions, but further prospective studies are still necessary
Role of host β1- and β2-adrenergic receptors in a murine model of B16 melanoma: functional involvement of β3-adrenergic receptors
No full textComplex interactions between tumor cells and their surrounding compartment are strongly influenced by the host in which the tumor grows. In melanoma, for instance, stress associated norephinephrine (NE), acting at β-adrenergic receptors (β-ARs), stimulates melanoma cell proliferation and tumor angiogenesis. Among β-ARs, β3-ARs play a role acting not only at tumor cells but also at non-neoplastic stromal cells within the melanoma. In the present study, we used a murine model of B16 melanoma to evaluate the role of the host β1- and β2-ARs in melanoma growth and we determined whether the role of β3-ARs can be influenced by the absence of stromal β1- and β2-ARs. As compared to wild type mice, β1/2-AR knockout mice displayed i. increased intratumoral levels of both NE and β3-ARs, as evidentiated at both messenger and protein levels, ii. increased tumor vascularization, iii. decreased tumor cell proliferation but increased tumor cell apoptosis and iv. increased responsiveness to intratumoral injection of the β3-AR blocker L-748,337 in terms of decrease in tumor growth, tumor vascular response, tumor cell proliferation and increase in tumor cell death. These findings together validate the role of β-AR signalling in melanoma microenvironment suggesting that non-neoplastic stromal cells may be targeted by β-AR-related drugs. The additional fact that β3-ARs play an important role in melanoma growth suggest selective β3-AR antagonists as important proapoptotic agents
Synthetic imaging for research and education in nuclear medicine: Who’s afraid of the black box?
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Phosphorus-32 microparticles for locally advanced pancreatic cancer: how and when?
No full textPhosphorus-32 microparticles for locally advanced pancreatic cancer: how and
when
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