Immunogenity of the pneumococcal polysaccharide vaccine in COPD patients. The effect of systemic steroids

AbstractRationale: To investigate if systemic steroids influence the antibody response to the 23-valent pneumococcal polysaccaride vaccine (23-PPV) in COPD patients.Patients and methods: COPD patients on: (a)⩾10mg of prednisolone/day (SS, n=30); (b) inhalative steroids (IS, n=30); (c) controls without COPD (CG, n=29) were vaccinated with 23-PPV. The concentration (μg/ml) of capsular specific anti-pneumococcal IgG antibodies (AB) for the serotypes (PNC) 4,6B,9V,14,18C,19F,23F were measured by Elisa technique before, 3 and 12 months (m) after vaccination. Non-responders were defined when AB-concentrations did neither doubled nor reach ⩾1μg/ml.Results: N=24 (CG), n=29 (IS), n=18 (SS) patients completed the study (mean age 64yrs.). Serious adverse events were not observed. Geometric mean (GM) AB-concentration of all serotypes increased significantly (CG, IS, SS) 3 and 12m after vaccination (P<0.05). The percentage of non-responders ranged between 16% (PNC 19F, IS) and 65% (PNC 4, SS) after 3m and 21% (PNC 19F, IS) and 82% (PNC 4, CG) after 12m. Neither post-vaccine AB-concentrations (3 and 12m) nor the rate of non-responders differed significantly between patients on systemic steroids and the other groups (IS, CG).Conclusions: Systemic steroids did not influence the AB-response. In all groups mean AB-concentration increased significantly after vaccination but an important percentage of subjects of all three groups were non-responders

Rotating solenoidal perfect fluids of Petrov type D

We prove that aligned Petrov type D perfect fluids for which the vorticity vector is not orthogonal to the plane of repeated principal null directions and for which the magnetic part of the Weyl tensor with respect to the fluid velocity has vanishing divergence, are necessarily purely electric or locally rotationally symmetric. The LRS metrics are presented explicitly.Comment: 6 pages, no figure

Silent universes with a cosmological constant

We study non-degenerate (Petrov type I) silent universes in the presence of a non-vanishing cosmological constant L. In contrast to the L=0 case, for which the orthogonally spatially homogeneous Bianchi type I metrics most likely are the only admissible metrics, solutions are shown to exist when L is positive. The general solution is presented for the case where one of the eigenvalues of the expansion tensor is 0.Comment: 11 pages; several typos corrected which were still present in CGQ version; minor change

Dynamical mean-field theory for bosons

We discuss the recently developed bosonic dynamical mean-field (B-DMFT) framework, which maps a bosonic lattice model onto the selfconsistent solution of a bosonic impurity model with coupling to a reservoir of normal and condensed bosons. The effective impurity action is derived in several ways: (i) as an approximation to the kinetic energy functional of the lattice problem, (ii) using a cavity approach, and (iii) by using an effective medium approach based on adding a one-loop correction to the selfconsistently defined condensate. To solve the impurity problem, we use a continuous-time Monte Carlo algorithm based on a sampling of a perturbation expansion in the hybridization functions and the condensate wave function. As applications of the formalism we present finite temperature B-DMFT phase diagrams for the bosonic Hubbard model on a 3d cubic and 2d square lattice, the condensate order parameter as a function of chemical potential, critical exponents for the condensate, the approach to the weakly interacting Bose gas regime for weak repulsions, and the kinetic energy as a function of temperature.Comment: 26 pages, 19 figure

Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12

Cytokine-modified tumour cells have been used in clinical trials for immunotherapy of neuroblastoma, but primary tumour cells from surgical biopsies are difficult to culture. Autologous fibroblasts, however, are straightforward to manipulate in culture and easy to transfect using nonviral or viral vectors. Here we have compared the antitumour effect of fibroblasts and tumour cells transfected ex vivo to coexpress interleukin-2 (IL-2) and IL-12 in a syngeneic mouse model of neuroblastoma. Coinjection of cytokine-modified fibroblasts with Neuro-2A tumour cells abolished their in vivo tumorigenicity. Treatment of established tumours with three intratumoral doses of transfected fibroblasts showed a significant therapeutic effect with reduced growth or complete eradication of tumours in 90% of mice, associated with extensive leukocyte infiltration. Splenocytes recovered from vaccinated mice showed enhanced IL-2 production following Neuro-2A coculture, and increased cytotoxicity against Neuro-2A targets compared with controls. Furthermore, 100% of the tumour-free mice exhibited immune memory against tumour cells when rechallenged three months later. The potency of transfected fibroblasts was equivalent to that of tumour cells in all experiments. We conclude that syngeneic fibroblasts cotransfected with IL-2 and IL-12 mediate therapeutic effects against established disease, and are capable of generating immunological memory. Furthermore, as they are easier to recover and manipulate than autologous tumour cells, fibroblasts provide an attractive alternative immunotherapeutic strategy for the treatment of neuroblastoma

Minimal tensors and purely electric or magnetic spacetimes of arbitrary dimension

We consider time reversal transformations to obtain twofold orthogonal splittings of any tensor on a Lorentzian space of arbitrary dimension n. Applied to the Weyl tensor of a spacetime, this leads to a definition of its electric and magnetic parts relative to an observer (i.e., a unit timelike vector field u), in any n. We study the cases where one of these parts vanishes in particular, i.e., purely electric (PE) or magnetic (PM) spacetimes. We generalize several results from four to higher dimensions and discuss new features of higher dimensions. We prove that the only permitted Weyl types are G, I_i and D, and discuss the possible relation of u with the WANDs; we provide invariant conditions that characterize PE/PM spacetimes, such as Bel-Debever criteria, or constraints on scalar invariants, and connect the PE/PM parts to the kinematic quantities of u; we present conditions under which direct product spacetimes (and certain warps) are PE/PM, which enables us to construct explicit examples. In particular, it is also shown that all static spacetimes are necessarily PE, while stationary spacetimes (e.g., spinning black holes) are in general neither PE nor PM. Ample classes of PE spacetimes exist, but PM solutions are elusive, and we prove that PM Einstein spacetimes of type D do not exist, for any n. Finally, we derive corresponding results for the electric/magnetic parts of the Riemann tensor. This also leads to first examples of PM spacetimes in higher dimensions. We also note in passing that PE/PM Weyl tensors provide examples of minimal tensors, and we make the connection hereof with the recently proved alignment theorem. This in turn sheds new light on classification of the Weyl tensors based on null alignment, providing a further invariant characterization that distinguishes the types G/I/D from the types II/III/N.Comment: 43 pages. v2: new proposition 4.10; some text reshuffled (former sec. 2 is now an appendix); references added; some footnotes cancelled, others incorporated into the main text; some typos fixed and a few more minor changes mad

GD2-directed bispecific trifunctional antibody outperforms dinutuximab beta in a murine model for aggressive metastasized neuroblastoma

Background: Neuroblastoma is the most common extracranial solid tumor of childhood. Patients with high-risk disease undergo extremely aggressive therapy and nonetheless have cure rates below 50%. Treatment with the ch14.18 monoclonal antibody (dinutuximab beta), directed against the GD2 disialoganglioside, improved 5-year event-free survival in high-risk patients when administered in postconsolidation therapy and was recently implemented in standard therapy. Relapse still occurred in 57% of these patients, necessitating new therapeutic options. Bispecific trifunctional antibodies (trAbs) are IgG-like molecules directed against T cells and cancer surface antigens, redirecting T cells (via their CD3 specificity) and accessory immune cells (via their functioning Fc-fragment) toward tumor cells. We sought proof-of-concept for GD2/CD3-directed trAb efficacy against neuroblastoma. Methods: We used two GD2-specific trAbs differing only in their CD3-binding specificity: EKTOMUN (GD2/human CD3) and SUREK (GD2/mouse Cd3). This allowed trAb evaluation in human and murine experimental settings. Tumor-blind trAb and the ch14.18 antibody were used as controls. A coculture model of human peripheral blood mononuclear cells (PBMCs) and neuroblastoma cell lines was established to evaluate trAb antitumor efficacy by assessing expression of T-cell surface markers for activation, proinflammatory cytokine release and cytotoxicity assays. Characteristics of tumor-infiltrating T cells and response of neuroblastoma metastases to SUREK treatment were investigated in a syngeneic immunocompetent neuroblastoma mouse model mimicking minimal residual disease. Results: We show that EKTOMUN treatment caused effector cell activation and release of proinflammatory cytokines in coculture with neuroblastoma cell lines. Furthermore, EKTOMUN mediated GD2-dependent cytotoxic effects in human neuroblastoma cell lines in coculture with PBMCs, irrespective of the level of target antigen expression. This effect was dependent on the presence of accessory immune cells. Treatment with SUREK reduced the intratumor Cd4/Cd8 ratio and activated tumor infiltrating T cells in vivo. In a minimal residual disease model for neuroblastoma, we demonstrated that single-agent treatment with SUREK strongly reduced or eliminated neuroblastoma metastases in vivo. SUREK as well as EKTOMUN demonstrated superior tumor control compared with the anti-GD2 antibody, ch14.18. Conclusions: Here we provide proof-of-concept for EKTOMUN preclinical efficacy against neuroblastoma, presenting this bispecific trAb as a promising new agent to fight neuroblastoma

Beta-decay in odd-A and even-even proton-rich Kr isotopes

Beta-decay properties of proton-rich odd-A and even-even Krypton isotopes are studied in the framework of a deformed selfconsistent Hartree-Fock calculation with density-dependent Skyrme forces, including pairing correlations between like nucleons in BCS approximation. Residual spin-isospin interactions are consistently included in the particle-hole and particle-particle channels and treated in Quasiparticle Random Phase Approximation. The similarities and differences in the treatment of even-even and odd-A nuclei are stressed. Comparison to available experimental information is done for Gamow-Teller strength distributions, summed strengths, and half-lives. The dependence of these observables on deformation is particularly emphasized in a search for signatures of the shape of the parent nucleus.Comment: 29 pages, 16 figure

Resident burnout:evaluating the role of the learning environment

Background: Although burnout is viewed as a syndrome rooted in the working environment and organizational culture, the role of the learning environment in the development of resident burnout remains unclear. We aimed to evaluate the association between burnout and the learning environment in a cohort of Belgian residents. Methods: We conducted a cross-sectional online survey among residents in a large university hospital in Belgium. We used the Dutch version of the Maslach Burnout Inventory (UBOS-C) to assess burnout and the Dutch Residency Educational Climate Test (D-RECT) to assess the learning environment. Results: A total of 236 residents (29 specialties) completed the survey (response rate 34.6%), of which 98 (41.5%) met standard criteria for burnout. After multivariate regression analysis adjusting for hours worked per week, quality of life and satisfaction with work-life balance, we found an inverse association between D-RECT scores and the risk of burnout (adjusted odds ratio; 0.47 for each point increase in D-RECT score; 95% CI, 0.23 - 0.95; p = 0.01). Conclusions: Resident burnout is highly prevalent in our cohort of Belgian residents. Our results suggest that the learning environment plays an important role in reducing the risk of burnout among residents