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

Design Optimization, Cabling and Stability of Large-Diameter High Jc Nb3Sn Wires

In the framework of the High Field Magnets (HFM) program, CERN is developing and qualifying Nb 3 Sn Rutherford cables to support magnet development towards the requirements of a future energy-frontier collider, using both state-of-the-art commercial wires and experimental wires under development with industrial partners. The trend towards higher current density and larger diameter wires imposes challenges for magneto-thermal stability. In this study, rolling trials and Rutherford cabling have been performed at CERN for two designs of a 1 mm diameter distributed tin Nb 3 Sn wire produced by KAT, and for 1 mm and 1.1 mm diameter RRP® Nb 3 Sn wires procured from Bruker OST, and the self-field stability and cabling degradation have been analyzed. The 1 mm RRP® wire shows significant degradation in Ic and stability on cabling. Although the latter is not expected to impact the performance of research magnets, the potential of heat treatment optimization to improve stability has also been quantified. The distributed tin wire shows substantially poorer stability, but promising indications of low cabling degradation. The influence of wire design characteristics on cabling behavior and stability have been assessed, and the implications for future wire optimization towards high field accelerator magnet applications have been discussed

Mechanical properties of friction induced nanocrystalline pearlitic steel

Nanocrystalline structured variants of commercially available alloys have shown potential for boosting the mechanical properties of these materials, leading to a reduction in waste and thereby retaining feasible supply chains. One approach towards achieving these nanostructures resides in frictional treatments on manufactured parts, leading to differential refinement of the surface structure as compared to the bulk material. In this work the machining method is considered to be a testing platform for the formation and study of frictional nanostructured steel, assembly of which is stabilized by fast cooling of the produced chip. Analysis of the mechanical properties has shown extraordinary results at the surface, over 2000 MPa of strength on AISI1045 steel, more than three times the strength of the base material, demonstrating at the same time a reduction of 15% in the elastic modulus. The microscopic analysis suggests a reassembly of the elements in a new lattice of carbon supersaturated nano-ferrite

Influence of the heat treatment on the layer J_C of internal-Sn Nb₃Sn wires with internally oxidized nanoparticles

We evaluated various heat treatments (HT) for maximizing the Nb 3 Sn layer thickness while retaining a refined grain microstructure in low filament count internal-Sn Nb 3 Sn Rod-In-Tube wires with internally oxidized nanoparticles. These wires were manufactured in our laboratory using SnO 2 as oxygen source and Nb alloys containing Ta and Zr or Hf. By reacting the wires at 650 °C for 200 hours we obtained relatively thin reaction layers but high layer critical current densities (layer J C ) of ∼3000 A/mm 2 for Hf-containing wires and ∼2700 A/mm 2 for Zr-containing wires, both at 4.2 K and 16 T. Notably, both of these values are over the layer J C threshold of 2500 A/mm 2 , which is estimated to be necessary for attaining the corresponding Future Circular Collider (FCC) target non-Cu J C of 1500 A/mm 2 . Following this heat treatment, the fine-grained Nb 3 Sn area occupies only ∼35% of the filament area for Hf-containing wires and ∼20% for Zr-containing wires. After heat treatments with a reaction step at 700 °C these values increase to 70–80% and ∼60%, respectively, with only a minor increase of the grain size. However, we observed a noticeable decrease in the layer J C for these HT. Magnetic measurements show that the high J C wires exhibit a point defect contribution from precipitates to the pinning force, which is missing in wires with depressed J C values. The higher heat treatment temperatures may have caused excessive coarsening of the oxide precipitates, to sizes unsuitable for flux pinning. Reaction heat treatment temperatures in the range of 650 °C to 700 °C and durations between 50 and 200 hours may provide a better compromise between the Nb 3 Sn layer thickness, its grain size and nanoparticle size.</p

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P &lt; 0.01), had lower American Society of Anesthesiology score (ASA) grade (P &lt; 0.01) and less comorbidity (P &lt; 0.01), but were more likely to be current smokers (P &lt; 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P &lt; 0.01) and frequently underwent ileocecal resection (P &lt; 0.01) with higher rate of de-functioning/primary stoma construction (P &lt; 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P &lt; 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups

The relationship between people and lizards in Patagonia

Abstract: Understanding how human beings perceive and interact with the local herpetofauna is fundamental for its conservation. In this chapter, we propose looking forward to the local ecological knowledge (LEK) of the Patagonian lizards, especially the "matuasto". The preliminary analysis of ethnohistorical sources points out the relevant role of "matuastos" in the cosmologies of the original people from Patagonia, often considered as immortal, selfish and harmful beings. Field reports agree on the warning not to disturb these territorial lizards, otherwise they would react aggressively with bites. The recorded stories account for frequent biting events on sheep. The local perception on "matuastos" as harmful beings would provoke an attitude of caution and rejection towards them. This work provides a first overview on the relationship of lizards and the people from Patagonia while constituting an initial step for future research.Fil: Aigo, Juana del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Ladio, Ana Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Boretto, Jorgelina Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Cabezas Cartes, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Ibarguengoytía, Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin