A protocol for Italian validation of DEMQoL-Proxy Scale: assessing the Quality of Life of people with moderate or mild dementia

In this paper, we propose an adaptation of a protocol for a tool's validation. We have utilized this phases-theory to validate in Italian language an instrument to assess Quality of Life for people with moderate or mild dementia. We will explain the example of our Italian validation of DEMQoL-Proxy considering each De Vellis's phase. We will explain our application of De Vellis's model to Italian example described. For the first three phases, we reproduced the original validating study in which authors (Smith et al., 2005) defined what to measure, how generate a set of items and the structure of the scale. Indeed, for the last five phases we explained the adaptation of De Vellis's model to Italian validation. We hope that this model could be effective to validating goals, for researchers and in particular for all professionals who deal with caregivers and patients with moderate and mild dementia. Furthermore, the measurement of the Quality of Life makes the scale widely useful within the various professional specialties and setting. Finally, thanks to the methodological assumptions adopted following the De Vellis's eight-phase model, we can affirm that this first Italian pre-validation of the DEMQoL-Proxy seems to be an excellent forerunner for its effective validation in the Italian context

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

High-frequency cyclicity in the latest Messinian Adriatic foreland basin: Insight into palaeoclimate and palaeoenvironments of the Mediterranean Lago-Mare episode

Late Messinian Lago-Mare deposits show high-frequency cyclicity in the whole Mediterranean Basin. Both millimeter- and centimeter-scale cyclicities have been observed in several ODP sites as well as in stratigraphic sections from the Mediterranean borderland. We have analyzed a well-exposed late Messinian Lago-Mare section from the Adriatic side of the central Apennines (Italy). At the Fonte dei Pulcini section (SE Majella Mts.), millimeter- and centimeter-scale white-and-dark couplets have been observed in the field. A 50 cm regular-spaced sampling has been performed in the uppermost 53 m of the late Messinian Lago- Mare clays. On the 107 collected samples, geochemical (CaCO3 content), mineralogical (XRD analyses), and micropalaeontological investigations have been performed. In addition, SEM and microprobe investigations as well as mineralogical and micropalaeontological analyses have been carried out on single lamina from a 34-cm-thick interval of millimeter-scale laminites. Besides the 103 cycles/m and 102 cycles/m frequencies observed in the field, spectral analyses performed on the CaCO3 data set indicated other high-frequency cyclicities: 0.47 cycles/m, 0.35 cycles/m, and 0.17 cycles/m. Taking into account the estimated sedimentation rate, these frequencies correspond, respectively, to periodicities of: 1 year, 10 years, 2.1 kyr, 2.8 kyr, and 5.6 kyr. These sub-Milankovitch cyclicities have been related to annual and sunspot solar activity. The millimeter-scale couplets are interpreted as varves sedimented in an ephemeral water environment marginal to a perennial brackish water lagoonal basin. These varved sediments reflect a marked seasonality characterized by the alternation of arid and more humid climatic phases. The presence of high values of smectite (60–80%) in the clay minerals of the analyzed samples could be a consequence of these climatic oscillations from drier to moister conditions. The climatic scenario suggested in this paper for the late Messinian Lago-Mare episode is in agreement with the monsoon system that, according to some authors, starting from 5.8 Ma developed in the Mediterranean area