The CUORE Cryostat: A 1-Ton Scale Setup for Bolometric Detectors

The cryogenic underground observatory for rare events (CUORE) is a 1-ton scale bolometric experiment whose detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers. This will be the largest bolometric mass ever operated. The experiment will work at a temperature around or below 10 mK. CUORE cryostat consists of a cryogen-free system based on pulse tubes and a custom high power dilution refrigerator, designed to match these specifications. The cryostat has been commissioned in 2014 at the Gran Sasso National Laboratories and reached a record temperature of 6 mK on a cubic meter scale. In this paper, we present results of CUORE commissioning runs. Details on the thermal characteristics and cryogenic performances of the system will be also given.Comment: 7 pages, 2 figures, LTD16 conference proceedin

Jupiter's X-ray Emission 2007 Part 2:Comparisons with UV and Radio Emissions and In-Situ Solar Wind Measurements

We compare Chandra and XMM‐Newton X‐ray observations of Jupiter during 2007 with a rich multi‐instrument dataset including: upstream in‐situ solar wind measurements from the New Horizons spacecraft, radio emissions from the Nançay Decametric Array and Wind/Waves, and UV observations from the Hubble Space Telescope. New Horizons data revealed two corotating interaction regions (CIRs) impacted Jupiter during these observations. Non‐Io decametric bursts and UV emissions brightened together and varied in phase with the CIRs. We characterise 3 types of X‐ray aurorae: hard X‐ray bremsstrahlung main emission, pulsed/flared soft X‐ray emissions and a newly identified dim flickering (varying on short‐timescales, but quasi‐continuously present) aurora. For most observations, the X‐ray aurorae were dominated by pulsed/flaring emissions, with ion spectral lines that were best fit by Iogenic plasma. However, the brightest X‐ray aurora was coincident with a magnetosphere expansion. For this observation, the aurorae were produced by both flickering emission and erratic pulses/flares. Auroral spectral models for this observation required the addition of solar wind ions to attain good fits, suggesting solar wind entry into the outer magnetosphere or directly into the pole for this particularly bright observation. X‐ray bremsstrahlung from high energy electrons was only bright for one observation, which was during a forward shock. This bremsstrahlung was spatially coincident with bright UV main emission (power> 1TW) and X‐ray ion spectral line dusk emission, suggesting closening of upward and downward current systems during the shock. Otherwise, the bremsstrahlung was dim and UV main emission power was also lower(<700 GW), suggesting their power scaled together

Jupiter’s auroras during the Juno approach phase as observed by the Hubble Space Telescope

We present movies of the Hubble Space Telescope (HST) observations of Jupiter’s FUV auroras observed during the Juno approach phase and first capture orbit, and compare with Juno observations of the interplanetary medium near Jupiter and inside the magnetosphere. Jupiter’s FUV auroras indicate the nature of the dynamic processes occurring in Jupiter’s magnetosphere, and the approach phase provided a unique opportunity to obtain a full set of interplanetary data near to Jupiter at the time of a program of HST observations, along with the first simultaneous with Juno observations inside the magnetosphere. The overall goal was to determine the nature of the solar wind effect on Jupiter’s magnetosphere. HST observations were obtained with typically 1 orbit per day over three intervals: 16 May – 7 June, 22-30 June and 11-18 July, i.e. while Juno was in the solar wind, around the bow shock and magnetosphere crossings, and in the mid-latitude middle-outer magnetospheres. We show that these intervals are characterised by particularly dynamic polar auroras, and significant variations in the auroral power output caused by e.g. dawn storms, intense main emission and poleward forms. We compare the variation of these features with Juno observations of interplanetary compression regions and the magnetospheric environment during the intervals of these observations

Future Sea Level Change Under Coupled Model Intercomparison Project Phase 5 and Phase 6 Scenarios From the Greenland and Antarctic Ice Sheets

Projections of the sea level contribution from the Greenland and Antarctic ice sheets (GrIS and AIS) rely on atmospheric and oceanic drivers obtained from climate models. The Earth System Models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) generally project greater future warming compared with the previous Coupled Model Intercomparison Project phase 5 (CMIP5) effort. Here we use four CMIP6 models and a selection of CMIP5 models to force multiple ice sheet models as part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We find that the projected sea level contribution at 2100 from the ice sheet model ensemble under the CMIP6 scenarios falls within the CMIP5 range for the Antarctic ice sheet but is significantly increased for Greenland. Warmer atmosphere in CMIP6 models results in higher Greenland mass loss due to surface melt. For Antarctica, CMIP6 forcing is similar to CMIP5 and mass gain from increased snowfall counteracts increased loss due to ocean warming

Association between i.v. thrombolysis volume and door-to-needle times in acute ischemic stroke

Centralization of intravenous thrombolysis (IVT) for acute ischemic stroke in high-volume centers is believed to improve the door-to-needle times (DNT), but limited data support this assumption. We examined the association between DNT and IVT volume in a large Dutch province. We identified consecutive patients treated with IVT between January 2009 and 2013. Based on annualized IVT volume, hospitals were categorized as low-volume (≤ 24), medium-volume (25-49) or high-volume (≥ 50). In logistic regression analysis, low-volume hospitals were used as reference category. Of 17,332 stroke patients from 11 participating hospitals, 1962 received IVT (11.3 %). We excluded 140 patients because of unknown DNT (n = 86) or in-hospital stroke (n = 54). There were two low-volume (total 101 patients), five medium-volume (747 patients) and four high-volume hospitals (974 patients). Median DNT was shorter in high-volume hospitals (30 min) than in medium-volume (42 min, p < 0.001) and low-volume hospitals (38 min, p < 0.001). Patients admitted to high-volume hospitals had a higher chance of DNT < 30 min (adjusted OR 3.13, 95 % CI 1.70-5.75), lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.39, 95 % CI 0.16-0.92), and a lower mortality risk (adjusted OR 0.45, 95 % CI 0.21-1.01), compared to low-volume centers. There was no difference in DNT between low- and medium-volume hospitals. Onset-to-needle times (ONT) did not differ between the groups. Hospitals in this Dutch province generally achieved short DNTs. Despite this overall good performance, higher IVT volumes were associated with shorter DNTs and lower complication risks. The ONT was not associated with IVT volum

Insights on the vulnerability of Antarctic glaciers from the ISMIP6 ice sheet model ensemble and associated uncertainty

The Antarctic Ice Sheet represents the largest source of uncertainty in future sea level rise projections, with a contribution to sea level by 2100 ranging from −5 to 43 cm of sea level equivalent under high carbon emission scenarios estimated by the recent Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). ISMIP6 highlighted the different behaviors of the East and West Antarctic ice sheets, as well as the possible role of increased surface mass balance in offsetting the dynamic ice loss in response to changing oceanic conditions in ice shelf cavities. However, the detailed contribution of individual glaciers, as well as the partitioning of uncertainty associated with this ensemble, have not yet been investigated. Here, we analyze the ISMIP6 results for high carbon emission scenarios, focusing on key glaciers around the Antarctic Ice Sheet, and we quantify their projected dynamic mass loss, defined here as mass loss through increased ice discharge into the ocean in response to changing oceanic conditions. We highlight glaciers contributing the most to sea level rise, as well as their vulnerability to changes in oceanic conditions. We then investigate the different sources of uncertainty and their relative role in projections, for the entire continent and for key individual glaciers. We show that, in addition to Thwaites and Pine Island glaciers in West Antarctica, Totten and Moscow University glaciers in East Antarctica present comparable future dynamic mass loss and high sensitivity to ice shelf basal melt. The overall uncertainty in additional dynamic mass loss in response to changing oceanic conditions, compared to a scenario with constant oceanic conditions, is dominated by the choice of ice sheet model, accounting for 52 % of the total uncertainty of the Antarctic dynamic mass loss in 2100. Its relative role for the most dynamic glaciers varies between 14 % for MacAyeal and Whillans ice streams and 56 % for Pine Island Glacier at the end of the century. The uncertainty associated with the choice of climate model increases over time and reaches 13 % of the uncertainty by 2100 for the Antarctic Ice Sheet but varies between 4 % for Thwaites Glacier and 53 % for Whillans Ice Stream. The uncertainty associated with the ice–climate interaction, which captures different treatments of oceanic forcings such as the choice of melt parameterization, its calibration, and simulated ice shelf geometries, accounts for 22 % of the uncertainty at the ice sheet scale but reaches 36 % and 39 % for Institute Ice Stream and Thwaites Glacier, respectively, by 2100. Overall, this study helps inform future research by highlighting the sectors of the ice sheet most vulnerable to oceanic warming over the 21st century and by quantifying the main sources of uncertainty

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

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