Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery

High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Structure and dynamics of the nucleocapsid-binding domain of the Sendai virus phosphoprotein in solution

AbstractThe RNA-dependent RNA polymerase of the Sendai virus (SeV) consists of the large protein (L) and the phosphoprotein (P). P plays a crucial role in the enzyme by positioning L (which carries the polymerase activity) onto the matrix for transcription and replication formed by the RNA and the nucleoprotein, the N-RNA. P has a modular structure with distinct functional domains: an N-terminal domain involved in binding to N° (N that is not yet bound to RNA) and a C-terminal domain that carries the oligomerisation domain, the N-RNA binding domain and the L binding domain and that, combined with L, is active in transcription. Structural data have previously been obtained on the N-terminal domain and on the oligomerisation domain of P, but not yet on its N-RNA binding domain (also-called the X protein). Here we present an NMR and a small angle neutron scattering study of the SeV X protein. We show that this molecule presents two subdomains linked by an 11-residue linker, with the N-subdomain lacking a well-defined conformation. The 3D structure of the C-subdomain consists of three α-helices revealing an asymmetric charge distribution that may be important for binding to RNA-bound nucleoprotein. The structure of the entire C-terminal domain of P is modelled from its constituent parts in combination with small angle scattering data on this domain

Anisotropic Flow in the Few Collisions Regime: Application to Bottomonia

Kersting N, Borghini N, Feld S. Anisotropic Flow in the Few Collisions Regime: Application to Bottomonia. In: Albacete J, Bielcikova J, Grelli A, et al., eds. Hot Quarks 2018 — Workshop for Young Scientists on the Physics of Ultrarelativistic Nucleus-Nucleus Collisions. Proceedings. Vol 10. Basel Switzerland: MDPI; 2019: 16.Considering the kinetic Boltzmann equation in the limit of very few collisions, we study the evolution of the phase space distribution of bottomonia interacting with an expanding gas of massless partons. We investigate the scaling of the anisotropic flow coefficients on the initial eccentricities and the inverse Knudsen number, and compute their transverse momentum dependence

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| &lt; 0.8) in the transverse momentum range 1 &lt; pt &lt; 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Developing Agreed and Accepted Understandings of Spirituality and Spiritual Care Concepts among Members of an Innovative Spirituality Interest Group in the Republic of Ireland

A Spirituality Interest Group (SIG) was set up in in the School of Nursing and Midwifery, Trinity College Dublin, Republic of Ireland (ROI), in March 2013. This paper reports on some of the journey and requirements involved in developing the group. It highlights the essential work of establishing agreed understandings in an objective way in order for the group to move forward with action. These agreed understandings have contributed to the group’s success. Outlining the group’s journey in arriving at agreements may be of use to others considering creating similar groups. One key action taken to determine the suitability of the group’s aims and terms of reference was the distribution of a Survey Monkey to group members (n = 28) in 2014. One early meeting of the group discussed future goals and direction using the responses of this anonymous survey. This paper reports on the results of the survey regarding the establishment of the SIG and the development of a shared understanding of spiritual care among the members. There is consensus in the group that the spiritual care required by clients receiving healthcare ought to be an integrated effort across the healthcare team. However, there is an acceptance that spirituality and spiritual care are not always clearly understood concepts in practice. By developing shared or at least accepted understandings of spirituality and spiritual care, SIG hopes to be able to underpin both research and practice with solid foundational conceptual understanding, and in the process also to meet essential prerequisites for achieving the group’s aims