Assessment of alternative divertor configurations as an exhaust solution for DEMO

Plasma exhaust has been identified as a major challenge towards the realisation of magnetic confinement fusion. To mitigate the risk that the single null divertor (SND) with a high radiation fraction in the scrape-of-layer (SOL) adopted for ITER will not extrapolate to a DEMO reactor, the EUROfusion consortium is assessing potential benefits and engineering challenges of alternative divertor configurations. Alternative configurations that could be readily adopted in a DEMO design include the X divertor (XD), the Super-X divertor (SXD), the Snowflake divertor (SFD) and the double null divertor (DND). The flux flaring towards the divertor target of the XD is limited by the minimum grazing angle at the target set by gaps and misalignments. The characteristic increase of the target radius in the SXD is a trade-off with the increased TF coil volume, but, ultimately, also limited by forces onto coils. Engineering constraints also limit XD and SXD characteristics to the outer divertor leg with a solution for the inner leg requiring up-down symmetric configurations. Capital cost increases with respect to a SND configuration are largest for SXD and SFD, which require both significantly more poloidal field coil conductors and in the case of the SXD also more toroidal field coil conductors. Boundary models with increasing degrees of complexity have been used to predict the beneficial effect of the alternative configurations on exhaust performance. While all alternative configurations should decrease the power that must be radiated in the outer divertor, only the DND and possibly the SFD also ease the radiation requirements in the inner divertor. These decreases of the radiation requirements are however expected to be small making the ability of alternative divertors to increase divertor radiation without excessive core performance degradation their main advantage. Initial 2D fluid modeling of argon seeding in XD and SFD configurations indicate such advantages over the SND, while results for SXD and DND are still pending. Additional improvements, expected from increased turbulence in the low poloidal field region of the SFD also remain to be verified. A more precise comparison with the SND as well as absolute quantitative predictions for all configurations requires more complete physics models that are currently only being developed

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Improved comprehensibility and reliability of explanations via restricted halfspace discretization

Abstract. A number of two-class classification methods first discretize each attribute of two given training sets and then construct a propositional DNF formula that evaluates to True for one of the two discretized training sets and to False for the other one. The formula is not just a classification tool but constitutes a useful explanation for the differences between the two underlying populations if it can be comprehended by humans and is reliable. This paper shows that comprehensibility as well as reliability of the formulas can sometimes be improved using a discretization scheme where linear combinations of a small number of attributes are discretized

CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells

CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin's lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME

Treatment After Anterior Cruciate Ligament Injury: Panther Symposium ACL Treatment Consensus Group

© The Author(s) 2020. Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury