Overview of the design of the ITER heating neutral beam injectors

The heating neutral beam injectors (HNBs) of ITER are designed to deliver 16.7MWof 1 MeVD0 or 0.87 MeVH0 to the ITER plasma for up to 3600 s. They will be the most powerful neutral beam\uf0a0(NB) injectors ever, delivering higher energy NBs to the plasma in a tokamak for longer than any previous systems have done. The design of the HNBs is based on the acceleration and neutralisation of negative ions as the efficiency of conversion of accelerated positive ions is so low at the required energy that a realistic design is not possible, whereas the neutralisation ofH 12 andD 12 remains acceptable ( 4856%). The design of a long pulse negative ion based injector is inherently more complicated than that of short pulse positive ion based injectors because: \u2022 negative ions are harder to create so that they can be extracted and accelerated from the ion source; \u2022 electrons can be co-extracted from the ion source along with the negative ions, and their acceleration must be minimised to maintain an acceptable overall accelerator efficiency; \u2022 negative ions are easily lost by collisions with the background gas in the accelerator; \u2022 electrons created in the extractor and accelerator can impinge on the extraction and acceleration grids, leading to high power loads on the grids; \u2022 positive ions are created in the accelerator by ionisation of the background gas by the accelerated negative ions and the positive ions are back-accelerated into the ion source creating a massive power load to the ion source; \u2022 electrons that are co-accelerated with the negative ions can exit the accelerator and deposit power on various downstream beamline components. The design of the ITER HNBs is further complicated because ITER is a nuclear installation which will generate very large fluxes of neutrons and gamma rays. Consequently all the injector components have to survive in that harsh environment. Additionally the beamline components and theNBcell, where the beams are housed, will be activated and all maintenance will have to be performed remotely. This paper describes the design of theHNBinjectors, but not the associated power supplies, cooling system, cryogenic system etc, or the high voltage bushingwhich separates the vacuum of the beamline fromthehighpressureSF6 of the high voltage (1MV) transmission line, through which the power, gas and coolingwater are supplied to the beam source. Also themagnetic field reduction system is not described

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

Background: The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies. Methods: The PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients. Results: First, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16− cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between Í14+PD-L1+ and Í8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells. Conclusions: Our data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment

DEDALO: PHASE II STUDY OF DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION

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Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

Competency-based (CanMEDS) residency training programme in radiology: systematic design procedure, curriculum and success factors

Based on the CanMEDS framework and the European Training Charter for Clinical Radiology a new radiology curriculum was designed in the Netherlands. Both the development process and the resulting new curriculum are presented in this paper. The new curriculum was developed according to four systematic design principles: discursiveness, hierarchical decomposition, systematic variation and satisficing (satisficing is different from satisfying; in this context, satisficing means searching for an acceptable solution instead of searching for an optimal solution). The new curriculum is organ based with integration of radiological diagnostic techniques, comprises a uniform national common trunk followed by a 2-year subspecialisation, is competency outcome based with appropriate assessment tools and techniques, and is based on regional collaboration among radiology departments. The application of the systematic design principles proved successful in producing a new curriculum approved by all authorities. The principles led to a structured, yet flexible, development process in which creative solutions could be generated and adopters (programme directors, supervisors and residents) were highly involved. Further research is needed to empirically test the components of the new curriculum

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

<p>Abstract</p> <p>Background</p> <p>Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.</p> <p>Aim</p> <p>To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.</p> <p>Materials and methods</p> <p>315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.</p> <p>Results</p> <p>Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.</p> <p>Discussion</p> <p>Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.</p

Could the Fermi-LAT detect gamma-rays from dark matter annihilation in the dwarf galaxies of the Local Group?

The detection of gamma-rays from dark matter (DM) annihilation is among the scientific goals of the Fermi Large Area Telescope (formerly known as GLAST) and Cherenkov telescopes. In this paper we investigate the existence of realistic chances of such a discovery selecting some nearby dwarf spheroidal galaxies (dSph) as a target. We study the detectability with the Fermi-LAT of the gamma-ray flux from DM annihilation in Draco, Ursa Minor, Carina, and Sextans, for which the state-of-art DM density profiles were available. We assume the DM is made of Weakly Interacting Massive Particles such as the Lightest Supersymmetric Particle (LSP) and compute the expected gamma-ray flux for optimistic choices of the unknown underlying particle physics parameters. We then compute the boost factors due to the presence of DM clumps and of a central supermassive black hole. Finally, we compare our predictions with the Fermi-LAT sensitivity maps. We find that the dSph galaxies shine above the Galactic smooth halo: e.g., the Galactic halo is brighter than the Draco dSph only for angles smaller than 2.3 degrees above the Galactic Center. We also find that the presence of a cusp or a constant density core in the DM mass density profile does not produce any relevant effect in the gamma-ray flux due to the fortunate combination of the geometrical acceptance of the Fermi-LAT detector and the distance of the galaxies and that no significant enhancement is given by the presence of a central black hole or a population of sub-subhalos. We conclude that, even for the most optimistic scenario of particle physics, the gamma-ray flux from DM annihilation in the dSph galaxies of the LG would be too low to be detected with the Fermi-LAT.Comment: 11 pages, 11 figures, accepted for publication in A&