Internal structure and tectonic evolution of an underthrust tectonic m\ue9lange: the Sestola-Vidiciatico tectonic unit of the Northern Apennines, Italy

The Sestola-Vidiciatico Tectonic Unit (SVTU) in the Northern Apennines is an underthrust tectonic melange presently sandwiched between the Tuscan-Umbrian foredeep units and the overlying Ligurian/Subligurian thrust-nappe. The SVTU has been generated during the collision between the European and the Adria plates and now it separates the former oceanic accretionary wedge -Ligurian/Subligurian thrust nappe-from the underlying fold-and-thrust belt formed by Adria sedimentary units. The collision caused an eastward migrating foredeep basin and the overthrusting of the frontal part of the Ligurian/Subligurian thrust-nappe on the subducting Adria margin. Part of the inner lower-slope sediments of the migrating foredeep basin have been unconformably deposited on a frontal prism formed by material already accreted in the Ligurian/Subligurian prism gravitationally and tectonically reworked. The frontal prism and its sedimentary cover have been progressively dragged down along the plate boundary zone generating the SVTU. The lower-slope sediments have been incorporated in the melange as they were not completely lithified, and they show a long deformation history ranging from continuous and pervasive soft-sediment deformation to discontinuous brittle deformation concentrated along faults and mainly controlled by cycles of fluid pressure as testified by the presence of crack-and-seal texture and implosion breccia in the veins

Italian tax incentives for film industry: the impact on the domestic sector and on the State

The national approach to public funding of the film industry has been subject to a shift in recent years, at an international level, moving from a grant and subsidy scheme towards more automatic form of supports, including tax incentives. The paper aims at analysing the impact of the new tax credit measures for the Italian film industry, introduced in 2008, within the framework of the 2007 financial law, and in force since the third quarter of 2009. The impact is evaluated on both the domestic film production companies and on the State accounts level. The measure of tax credit for film with cultural requirements provides the film production company with the possibility of offsetting its tax debt (national and regional income tax, VAT, social contribution and costs) during the production, within a cap of 15% of total eligible costs. Starting from the data collected and processed by the Ministry of Culture since the beginning of the implementation phase, the paper aims at demonstrating the positive balance for the State determined by the increase of private investments on film with cultural requirements and, consequently, of the induced direct and indirect tax return. A brief description of the measure will be followed by a comparison of the incremental value produced by the film sector throughout the year following the enforcement of the tax credit measures.The national approach to public funding of the film industry has been subject to a shift in recent years, at an international level, moving from a grant and subsidy scheme towards more automatic form of supports, including tax incentives. The paper aims at analysing the impact of the new tax credit measures for the Italian film industry, introduced in 2008, within the framework of the 2007 financial law, and in force since the third quarter of 2009. The impact is evaluated on both the domestic film production companies and on the State accounts level. The measure of tax credit for film with cultural requirements provides the film production company with the possibility of offsetting its tax debt (national and regional income tax, VAT, social contribution and costs) during the production, within a cap of 15% of total eligible costs. Starting from the data collected and processed by the Ministry of Culture since the beginning of the implementation phase, the paper aims at demonstrating the positive balance for the State determined by the increase of private investments on film with cultural requirements and, consequently, of the induced direct and indirect tax return. A brief description of the measure will be followed by a comparison of the incremental value produced by the film sector throughout the year following the enforcement of the tax credit measures.Invited Submission

San Vincenzo, Isola di Stromboli (Lipari, Prov. Di Messina) - Campagna 2014

Presentazione sintetica dei risultati della campagne di scavo effettuate nel 2014 nel sito archeologico di San Vincenzo a Strombol

Allelic Variation Investigation of the Estrogen Receptor Within an Australian Multiple Sclerosis Population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9-14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ-producing and IL2-producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients

Identification and validation of diagnostic cut-offs of the ELISpot assay for the diagnosis of invasive aspergillosis in high-risk patients

Objective: We investigated the performance of enzyme linked immunospot (ELISpot) assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematologic malignancies. Methods: We prospectively enrolled two cohorts of patients undergoing intensive myelosuppressive or immunosuppressive treatments at high risk for IA. ELISpot was performed to detect Aspergillus-specific T cells producing Interleukin-10. Results: In the discovery cohort, a derived cut-off of 40 spot forming cells (SFCs)/106 PBMCs has shown to correctly classify IA cases with a sensitivity and specificity of 89.5% and 88.6%, respectively. This cut-off is lowered to 25 SFC when considering the subset of possible IA patients, with sensitivity and specificity of 76% and 93%, respectively. The application of the 40 SFCs cut-off to the validation cohort resulted in a positivity rate of 83.3% in proven/probable cases and a negativity rate of 92.5% in possible/non-IA cases. Adopting the 25 SCFs cut-off, the assay resulted positive in 83.3% of proven/probable cases while it resulted negative in 66.7% of possible/non-IA cases. Conclusions: ELISpot shows promises in the diagnosis of IA and the possibility to use two distinct cut-offs with similar diagnostic performances according to patients' different pre-test probability of infection can widen its use in patients at risk

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies

: Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies