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Superficial spreading melanoma (SSM) and nodular melanoma (NM) are the most common melanoma histologic subtypes and are characterized by different biological features. We retrospectively analyzed all consecutive patients with advanced melanoma, treated with anti-PD-1 and/or anti-CTLA-4 at our center, with data available on primary tumor subtype. The primary objective was to assess the association between histologic subtype and patients' outcomes. In addition, we analyzed whole-exome and whole-transcriptome sequencing data of a cohort of advanced melanoma to identify genes and related pathways, characterized by significant differences between NMs and SSMs. Twenty-one patients with NM and 39 with SSM, treated with anti-PD-1(53/60) as monotherapy or combined with anti-CTLA-4 (7/60), were analyzed. All known clinical-pathologic prognostic factors were well balanced between NM and SSM groups, except for the ECOG-PS score. The overall response rate was 52.4% (95% confidence interval, 29.8-74.3) in the NMs group versus 20.5% (9.3-36.5) in the SSMs group (P-value=0.02). The median progression-free survival and overall survival were, respectively, 13.9 and 44.5 months in the NMs group versus only 3.2 and 12 months in SSMs group (progression-free survival P-value=0.032; overall survival P-value=0.002). Multivariable analysis adjusting for the ECOG-PS, confirmed similar results. Whole-exome and whole-transcriptome data of 28 NMs and 21 SSMs were analyzed. No significant differences were observed in terms of both TMB and frequency of mutation in any gene. A total of 266 genes were overexpressed in NMs as compared with SSMs, and enrichment-analysis revealed a significant enrichment (false discovery rate

L’impatto di un forte terremoto su una comunità urbana può essere ridotto con una azione tempestiva e ben pianificata da parte degli organi di Protezione Civile preposti. In tale prospettiva è di fondamentale importanza che gli organi preposti alla sorveglianza sismica del territorio nazionale si dotino di strumenti di osservazione puntuale in grado di fornire nell’immediato terremoto informazioni utilissime per la gestione ottimale delle emergenze. Ciò può essere fatto oggi mediante la realizzazione reti sismiche urbane, con funzionamento in tempo reale (OSU Osservatori Sismici Urbani), in grado di fornire in maniera tempestiva ai centri per la gestione delle emergenze, la distribuzione dell'intensità dello scuotimento a seguito di un terremoto. Le mappe di scuotimento potrebbero consentire agli organi preposti, un’ottimale gestione delle priorità e la ripartizione delle risorse in modo da ottenere una significativa riduzione del numero di vittime a seguito di un forte terremoto. Le verifiche del grado di danneggiamento e di agibilità degli edifici potrebbero così essere effettuate secondo una logica prioritaria sulla base dei massimi scuotimenti misurati dalla rete sismica urbana. La realizzazione di OSU per le finalità su preposte è l’obiettivo principale del progetto MEMS finanziato dal MIUR nell’ambito del programma SIR (Scientific Independence of young Researchers). La prima sfida affrontata nell’ambito del progetto MEMS è stata la progettazione e sviluppo di una stazione accelerometrica idonea agli scopi del progetto. Il presente lavoro ha lo scopo di descrivere nel dettaglio, la stazione accelerometrica basata su tecnologia MEMS (Micro ElectroMechanical Systems), implementata nell’abito dell’omonimo progetto. Ciò che stato realizzato è una stazione accelerometrica dalle ottime performance, estremamente versatile e a bassissimo costo. The impact of a strong earthqauke onto an urban community can be reduced taking timely actions managed by the authority in charge for the civil protection. In this view, it is of fundamental importance that the authority in charge for the seismic surveillance is provided with the appropriate monitoring tools able to give the most useful information for the best emergency management in the immediate post-event. Today this goal can be reached realizing urban-scale, real-time seismic monitoring networks (Osservatori Sismici Urbani, OSU, in Italian). The real-time OSU networks are able to promptly provide information to the emergency authority about the ground shaking at each node after an earthquake. Maps showing the spatial distribution of the ground shaking could help in the optimization of the priorities and a good management of the rescue resources in order to reduce the number of victims. Also the assessment of the damage of the buildings could be carried out according to the logic of priority given by the shakings measured by the OSU. The realisation of OSUs is the main objective of the MEMS project. This project is funded by the MIUR under the SIR program (Scientific Independence of young Researchers). The first challenge of the MEMS project was the design and the development of a devoted accelerometric stations. This work illustrates in detail the accelerometric station based on MEMS technology (Micro Electro-Mechanical Systems). The final product is a low-cost accelerometric station with high performance and great versatility.

We present the first application of a time reverse location method in a volcanic setting, for a family of long-period events recorded on Mt Etna. Results are compared with locations determined using a full moment tensor grid search inversion and cross-correlation method. From June 18th to July 3rd, 2008, 50 broadband seismic stations were deployed on Mt Etna, Italy, in close proximity to the summit. Two families of long-period events were detected with dominant spectral peaks around 0.9 Hz. The large number of stations close to the summit allowed us to locate all events in both families using a time reversal location method. The method involves taking the seismic signal, reversing it in time, and using it as a seismic source in a numerical seismic wave simulator where the reversed signals propagate through the numerical model, interfere constructively and destructively, and focus on the original source location. The source location is the computational cell with the largest displacement magnitude at the time of maximum energy current density inside the grid. Before we located the two long-period families we first applied the method to two synthetic datasets and found a good fit between the time reverse location and true synthetic location for a known velocity model. The time reverse location results of the two families show a shallow seismic region close to the summit in agreement with the locations using a moment tensor full waveform inversion method and a cross-correlation location method. AD 25/02/2014

A small L-shaped short-period seismic array was set up at Etna Volcano to measure the wave velocity and the incoming azimuth of the volcanic tremor generated by the volcanic activity at Etna in non eruptive-conditions. Cross-correlation techniques were used to measure the phase-shifts between the array stations. An approximately N-S direction of the propagation direction was estimated, coincident with the azimuth of the crater area of Etna. An apparent velocity of less than 500 m/s was estimated, suggesting a surface propagation of the tremor waves. Spectral analysis, confirming previous results, shows velocity spectra peaked at approximately 2 Hz. A localized source, coincident with the crater area, agrees with our data and could generate the volcanic tremor at Etna in non-eruptive stages.

Background: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. Methods: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian–Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. Results: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04–0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05–0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23–0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02–0.95). Conclusion: MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients.

We study the dynamics of open quantum many-body systems driven across a critical point by quenching an Hamiltonian parameter at a certain velocity. General scaling laws are derived for the density of excitations and energy produced during the quench as a function of quench velocity and bath temperature. The scaling laws and their regimes of validity are verified for the XY spin chain locally coupled to bosonic baths. A detailed derivation and analysis of the kinetic equation of the problem is presented., Comment: 15 pages, 13 figures