Retrieval of noise-limited minor atmospheric constituents from satellite emission measurements and determination of atmospheric trends

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) is a limb Fourier transform spectrometer that operated onboard the polar-orbiting ESA ENVIronmental SATellite from July 2002 to April 2012. MIPAS measured the atmospheric limb emission in the middle/upper atmosphere in the spectral range from 4.15 to 14.6 μm. The MIPAS instrument was designed to improve the knowledge of the distribution of some key chemical components and the dynamics of the middle atmosphere. The main target of this PhD thesis is the retrieval and the study of minor constituents of the middle atmosphere using MIPAS measurements. These molecules give a minor contribution to the MIPAS spectra but their retrieval is fundamental to improve the general knowledge of the chemistry of the middle atmosphere. In the first part of this PhD project, we focused on the retrieval of carbonyl chloride (COCl2) and on the study of its distribution in the UTLS region. COCl2 is a gas used in the insecticides, pharmaceuticals and herbicides preparation. Due to its high toxicity, its usage has been reduced over the years. COCl2 has been retrieved for the first time using MIPAS measurements. The main features and the seasonality of its distribution have been studied and compared with ACE-FTS measurements. In the second part, we studied the carbon tetrachloride (CCl4) lifetime, its global distribution and its seasonality in the UTLS region using the ESA official Level 2 Version 7 products. CCl4 is a strong ozone-depleting substance, banned by the Montreal protocol starting from 1996. MIPAS CCl4 measurements have been compared with independent measurements from ACE-FTS, MIPAS-Balloon and data from the EMAC model. CCl4 trends as a function of latitude and altitude have been evaluated and compared with other satellite trend estimates and other surface global network measurements

The molecular landscape of colitis-associated carcinogenesis

In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-\u3b1, IL-6, IL-10, IFN-\u3b3), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-\u3baB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapie

La valutazione del patrimonio museale:il caso del Museo di Storia Naturale di Firenze

Il presente lavoro mira ad individuare le prassi per la valutazione dei beni culturali di proprietà delle pubbliche amministrazioni attraverso lo studio del caso del Museo di Storia Naturale di Firenze. Dopo aver esaminato le principali indicazioni della prassi e della dottrina in tema di valutazione dei beni culturali, gli autori affrontano un caso di studio nel quale è stato adottato, per l’inventariazione dell’intero patrimonio museale, uno dei metodi in precedenza discussi, ossia la stima degli esperti, quale proxy del valore di mercato delle collezioni. Con riferimento al caso di studio si indicano le motivazioni a supporto del metodo adottato e le difficoltà incontrate nella conduzione del processo valutativo. Dall’indagine condotta emergono alcuni limiti ed alcuni potenziali sviluppi della ricerca, evidenziati nelle conclusioni, sui criteri di valutazione del patrimonio museale

Phosgene in the UTLS: seasonal and latitudinal variations from MIPAS observations

Abstract. The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) is a Fourier transform spectrometer that measured mid-infrared atmospheric limb emission spectra from July 2002 to April 2012 on board the polar-orbiting satellite ENVISAT. We have used MIPAS data to study the latitudinal variations of phosgene (COCl2 or carbonyl chloride) and, for the first time, its seasonal variation in the upper troposphere/lower stratosphere region (UTLS). Retrievals of phosgene were made using the 830–860 cm−1 region, corresponding to the ν5 bands of COCl2. Unfortunately, in that region, the ν4 band of CFC-11, which is much stronger than COCl2 ν5, hides the phosgene emission. In order to evaluate seasonality and latitudinal distribution of phosgene we have analysed all the measurements made by MIPAS on days 18 and 20 of each month of 2008 with the optimized retrieval model (ORM) recently upgraded with the multi-target retrieval technique and with the optimal estimation functionality to apply external constraints to the state vector. Average seasonal profiles of phosgene show an evident latitudinal variability with the largest values observed in the tropical regions (maximum  ≈  35 parts per trillion by volume (pptv) at about 300 hPa). In the midlatitude and polar regions, the volume mixing ratio (VMR) values do not exceed 30 pptv and the vertical distributions are less peaked. Our analysis highlights that COCl2 seasonal variability is fairly low, apart from the polar regions

Lesioni non palpabili della mammella: la Mammotome-biopsy nella gestione preoperatoria del cancro della mammella

Premessa: Il tumore del seno è nei paesi occidentali al primo posto per frequenza nelle donne e la sua incidenza è in costante crescita. Grazie soprattutto alla diffusione dello screening mammografico e ad una maggiore consapevolezza del problema, negli ultimi anni è aumentata la diagnosi delle cosiddette lesioni “non palpabili”; parimenti si è assistito ad un importante sviluppo delle metodiche diagnostiche di tipo mininvasivo. Alla tradizionale citologia con ago sottile si sono affiancate infatti varie procedure bioptiche percutanee; tali metodiche microistologiche hanno quasi del tutto sostituito la biopsia chirurgica escissionale e l’esame intra-operatorio al congelatore. Pazienti e metodo: Nella nostra Divisione di Chirurgia Generale, Vascolare e Mininvasiva, dal dicembre 1999 al settembre 2004 abbiamo eseguito, in collaborazione con il servizio di Radiologia, 214 biopsie su guida ecografia utilizzando la vacuum-assisted biopsy (Mammotome® ) con ago 11-Gauge. I risultati ottenuti per ciò che concerne l’accuratezza diagnostica, la quantità e qualità delle informazioni ottenute, il significato delle stesse nella eventuale gestione chirurgica, il discomfort globale per la paziente sono stati analizzati e discussi nel presente lavoro. Risultati: Delle 214 biopsie eseguite con tecnica Mammotome, nell’89,3% dei casi si è trattato di lesioni clinicamente non palpabili, con un diametro medio di 8 mm. L’età media delle pazienti era di 57,6 anni (range 31-88). La positività per patologia maligna è stata di 90 casi (42%). Nei casi di iperplasia duttale atipica e radial scar (6%) è stata effettuata l’exeresi chirurgica della lesione che ha confermato nel 100% dei casi la precedente diagnosi bioptica. Il 19% delle pazienti sottoposte a biopsia Mammotome era stato precedentemente sottoposto ad un prelievo citologico con ago sottile. Confrontando i risultati delle due metodiche, l’attendibilità diagnostica della seconda risulta essere significativamente superiore (p<0,05) come pure il numero di informazioni ottenute (istotipo, invasività, grading, recettori ormonali, etc.); il discomfort legato alla procedura, valutato in termini di dolore (VAS), è risultato inferiore a quello del prelievo con ago sottile (p<0,05). L’unica complicanza della biopsia Mammotome è rappresentata dall’ematoma nella sede del prelievo (8% dei casi). Il numero dei falsi negativi è stato di un caso, dovuto ad un non corretto centraggio del bersaglio. Conclusioni: Allo stato attuale in presenza di una lesione non palpabile della mammella la scelta della metodica diagnostica (agobiopsia o Mammotome) è legata al sospetto radiologico nella prospettiva di un eventuale intervento chirurgico. La biopsia con Mammotome nelle lesioni non palpabil

Using a Newly Developed Computer-Based Program to Evaluate Learning of Visuomotor Procedures in Children with Autism: A Pilot Study

Inspired by the recent literature, we designed a computer-based program that allows, with the aid of a digital tablet, to evaluate learning of visuomotor procedures, similar to the ones involved in handwriting. After extensive trials on children with typical development, we conducted a preliminary study to assess the effectiveness of this program in evaluating these abilities in children with ASD

Characterisation of the immune-related transcriptome in resected biliary tract cancers

Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906

Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature

SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors