Improving Prediction Strategies in Rheumatoid Arthritis: Additional Predictive Ability of Synovial Pathotype over Clinical, Laboratory and Imaging Findings

PhDRheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin affecting approximately 1% of adult population worldwide. The clinical course of RA is highly variable, ranging from self-­‐limiting to severe disease, with considerable individual and socio-­‐economic implications. It is now well acknowledged that early diagnosis and treatment equates to better long-­‐term outcomes. However, despite major therapeutic advances in recent decades, the management of RA remains challenging as a significant proportion of patients presents with active disease despite maximization of therapy. It is also difficult to predict which patients will respond adequately to various treatment regimens. The identification of biomarkers of clinical outcome capable of stratifying patients into accurate prognostic categories and guide pharmacological intervention is therefore urgently needed. Notably, along with clinical variability, RA is characterised by high biological heterogeneity at the tissue level. The cellular infiltrate of the RA synovium can be distinguished into at least three main patterns according to the degree and organisation of the immune cells: the ‘Lymphoid’ pattern characterised by predominant B and T lymphocytes which tend to cluster in discrete aggregates resembling ectopic lymphoid structures; the ‘Myeloid’ pattern characterised by absence of lymphocytic aggregates but significant expression of sublining macrophages; the ‘Pauci-­‐immune’ pattern, that hardly shows any infiltrating immune cells. The hypothesis of this thesis was to determine whether these distinct synovial pathotypes may define specific disease subsets and predict response to therapy in patients with RA. Specifically, this work aims at: 1. evaluating whether the synovial pathotype associates with the presence of specific clinical, serological, radiological and ultrasonographic findings in an early RA cohort (< 1 year onset); 2. exploring the potential role of the synovial pathotype as a predictor of response to conventional synthetic disease-­‐modifying antirheumatic drugs (csDMARD) after 6 months in an early RA cohort; 3. exploring the potential role of the synovial pathotype as a predictor of response to anti-­‐TNFα treatment after 3 months in a csDMARD-­‐failure established RA cohort

LEAN SIX SIGMA E STRUMENTI DI SIMULAZIONE PER L'OTTIMIZZAZIONE DEI PERCORSI DI CURA. IL CASO DEGLI INDICATORI DI EFFICACIA DI UN DIPARTIMENTO DI EMERGENZA OSPEDALIERO.

Ogni giorno, all’interno del Pronto Soccorso (PS), vengono accolti, presi in carico e curati numerosissimi pazienti. In questo contesto, la gestione del tempo è un fattore di primaria importanza. Il tempo deve infatti essere impiegato in maniera razionale poiché pochi minuti potrebbero mettere in pericolo la vita di una persona. Il PS, uno dei reparti più rilevanti per la società, è chiamato a gestire ingenti flussi di pazienti in tempi estremamente ristretti. Inoltre, tali aree sono state storicamente caratterizzate da fenomeni di congestionamento e da conseguenti lunghi tempi di attesa e trattamento per i pazienti in ingresso. Gli strumenti tipici del Lean Six Sigma (LSS), approccio che sarà ampiamente discusso nel corso del presente lavoro di tesi, trovano ottima applicabilità in tale contesto. Al fine di affrontare le criticità sopra enunciate ed impattare sulla variabile tempo, le finalità che si possono perseguire nella gestione del PS sono le seguenti: •Incrementare il valore per il cliente, dove il valore è sostanzialmente misurato dal tempo che un paziente trascorre all’interno del PS ricevendo cure; •Migliorare i processi che contribuiscono alla creazione di valore e facilitare il flusso dei pazienti attraverso le vaie fasi di trattamento sanitario; •Eliminare i colli di bottiglia, nonché tutte le attività generatrici di spreco; •Standardizzare le procedure operative; •Aumentare la “produttività” delle postazioni di lavoro. Il PS è un’area ottimale in cui adottare una strategia LSS: è richiesta per definizione una certa dinamicità sia nelle azioni che vengono compiute sia nella mente dei professionisti che vi lavorano; le unità di misura utilizzate sono le ore o i minuti, il lead time dei processi si aggira intorno a qualche ora. Diversamente, in un reparto di ricovero si parla di degenze che si sviluppano su più giornate. Queste caratteristiche permettono di realizzare un progetto pilota in breve tempo con impatti anche notevoli garantiti dai grossi volumi di pazienti in ingresso

Mortality in relation to smoking: the British Doctors Study

The British doctors study: the first strong statistical proof of association between smoking and many diseases

Robots for Exploration, Digital Preservation and Visualization of Archeological Sites

Monitoring and conservation of archaeological sites are important activities necessary to prevent damage or to perform restoration on cultural heritage. Standard techniques, like mapping and digitizing, are typically used to document the status of such sites. While these task are normally accomplished manually by humans, this is not possible when dealing with hard-to-access areas. For example, due to the possibility of structural collapses, underground tunnels like catacombs are considered highly unstable environments. Moreover, they are full of radioactive gas radon that limits the presence of people only for few minutes. The progress recently made in the artificial intelligence and robotics field opened new possibilities for mobile robots to be used in locations where humans are not allowed to enter. The ROVINA project aims at developing autonomous mobile robots to make faster, cheaper and safer the monitoring of archaeological sites. ROVINA will be evaluated on the catacombs of Priscilla (in Rome) and S. Gennaro (in Naples)

Potential effects of E-cigarettes and vaping in pediatric asthma

Asthma is the most common chronic disease in childhood and exposure to tobacco smoke has been long recognized as a risk factor for its onset as well as for exacerbations and poor disease control. Since the early 2000s, electronic cigarettes have been marketed worldwide as a non-harmful electronic alternative to combustible cigarettes and as a device likely to help stop smoking, and their use is continuously rising, particularly among adolescents. However, several studies have shown that vape contains many different well-known toxicants, causing significant cytotoxic and pro-inflammatory effects on the airways in-vitro and in animal models. In humans, a variety of harmful lung effects related to vaping, ranging from bronchoconstriction to severe respiratory distress has been already reported

Linking Hydrogeology and Ecology in Karst Landscapes: The Response of Epigean and Obligate Groundwater Copepods (Crustacea: Copepoda)

Groundwater invertebrate communities in karst landscapes are known to vary in response to multiple environmental factors. This study aims to explore the invertebrate assemblages' composition of an Apennine karst system in Italy mainly described by the Rio Gamberale surface stream and the Stiffe Cave. The stream sinks into the carbonate rock and predominantly feeds the saturated karst into the cave. For a minor portion, groundwater flows from the epikarst and the perched aquifer within it. The spatial distribution of the species belonging to the selected target group of the Crustacea Copepoda between the surface stream and the groundwater habitats inside the cave highlighted a different response of surface-water species and obligate groundwater dwellers to the hydrogeological traits of the karst unit. Our results suggest that fast endorheic infiltration routes promoted the drift of epigean species from the surface to groundwater via the sinking stream while most of the obligate groundwater dwellers come from the perched aquifer in the epikarst from diffuse infiltration pathways

Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome

Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences

Cyanidiophyceae (Rhodophyta) Tolerance to Precious Metals: Metabolic Response to Palladium and Gold

Polyextremophilic red algae, which belong to the class Cyanidiophyceae, are adapted to live in geothermal and volcanic sites. These sites often have very high concentrations of heavy and precious metals. In this study, we assessed the capacity of three strains of Galdieria (G. maxima, G. sulphuraria, and G. phlegrea) and one strain of Cyanidium caldarium to tolerate different concentrations of precious metals, such as palladium (Cl4K2Pd) and gold (AuCl4K) by monitoring algal growths in cultures exposed to metals, and we investigated the algae potential oxidative stress induced by the metals. This work provides further understanding of metals responses in the Cyanidiophyceae, as this taxonomic class is developed as a biological refinement tool

Cyanidiophyceae (Rhodophyta) Tolerance to Precious Metals: Metabolic Response to Palladium and Gold

Polyextremophilic red algae, which belong to the class Cyanidiophyceae, are adapted to live in geothermal and volcanic sites. These sites often have very high concentrations of heavy and precious metals. In this study, we assessed the capacity of three strains of Galdieria (G. maxima, G. sulphuraria, and G. phlegrea) and one strain of Cyanidium caldarium to tolerate different concentrations of precious metals, such as palladium (Cl4K2Pd) and gold (AuCl4K) by monitoring algal growths in cultures exposed to metals, and we investigated the algae potential oxidative stress induced by the metals. This work provides further understanding of metals responses in the Cyanidiophyceae, as this taxonomic class is developed as a biological refinement tool