High Spin Gauge Fields and Two-Time Physics

All possible interactions of a point particle with background electromagnetic, gravitational and higher-spin fields is considered in the two-time physics worldline formalism in (d,2) dimensions. This system has a counterpart in a recent formulation of two-time physics in non-commutative field theory with local Sp(2) symmetry. In either the worldline or field theory formulation, a general Sp(2) algebraic constraint governs the interactions, and determines equations that the background fields of any spin must obey. The constraints are solved in the classical worldline formalism (h-bar=0 limit) as well as in the field theory formalism (all powers of h-bar). The solution in both cases coincide for a certain 2T to 1T holographic image which describes a relativistic particle interacting with background fields of any spin in (d-1,1) dimensions. Two disconnected branches of solutions exist, which seem to have a correspondence as massless states in string theory, one containing low spins in the zero Regge slope limit, and the other containing high spins in the infinite Regge slope limit.Comment: LaTeX 22 pages. Typos corrected in version

Marginal Deformations of Field Theories with AdS_4 Duals

We generate new AdS_4 solutions of D=11 supergravity starting from AdS_4 x X_7 solutions where X_7 has U(1)^3 isometry. We consider examples where X_7 is weak G_2, Sasaki-Einstein or tri-Sasakian, corresponding to d=3 SCFTs with N=1,2 or 3 supersymmetry, respectively, and where the deformed solutions preserve N=1,2 or 1 supersymmetry, respectively. For the special cases when X_7 is M(3,2), Q(1,1,1) or N(1,1)_I we identify the exactly marginal deformation in the dual field theory. We also show that the volume of supersymmetric 5-cycles of N(1,1)_I agrees with the conformal dimension predicted by the baryons of the dual field theory.Comment: 28 pages, 2 figures; v2. typos correcte

Marginal Deformations with U(1)^3 Global Symmetry

We generate new 11-dimensional supergravity solutions from deformations based on U(1)^3 symmetries. The initial geometries are of the form AdS_4 x Y_7, where Y_7 is a 7-dimensional Sasaki-Einstein space. We consider a general family of cohomogeneity one Sasaki-Einstein spaces, as well as the recently-constructed cohomogeneity three L^{p,q,r,s} spaces. For certain cases, such as when the Sasaki-Einstein space is S^7, Q^{1,1,1} or M^{1,1,1}, the deformed gravity solutions correspond to a marginal deformation of a known dual gauge theory.Comment: 28pp; Refs. added and to appear in JHE

Duality and Spontaneously Broken Supergravity in Flat Backgrounds

It is shown that the super Higgs mechanism that occurs in a wide class of models with vanishing cosmological constant (at the classical level) is obtained by the gauging of a flat group which must be an electric subgroup of the duality group. If the residual massive gravitinos which occur in the partial supersymmetry breaking are BPS saturated, then the flat group is non abelian. This is so for all the models obtained by a Scherk-Schwarz supersymmetry breaking mechanism. If gravitinos occur in long multiplets, then the flat groups may be abelian. This is the case of supersymmetry breaking by string compactifications on an orientifold T^6/Z_2 with non trivial brane fluxes.Comment: Version to appear on Nuclear Physics

Constrained Supermanifolds for AdS M-Theory Backgrounds

A long standing problem is the supergauge completion of AdS_4 x (G/H)_7 or AdS_5 x (G/H)_5 backgrounds which preserve less then maximal supersymmetry. In parallel with the supersolvable realization of the AdS_4 x S^7 background based on Kappa-symmetry, we develop a technique which amounts to solving the above-mentioned problem in a way useful for pure spinor quantization for supermembranes and superstrings. Instead of gauge fixing some of the superspace coordinates to zero, we impose an additional constraint on them reproducing the simplifications of the supersolvable representations. The constraints are quadratic, homogeneous, Sp(4,R)-covariant, and consistent from the quantum point of view in the pure spinor approach. Here we provide the geometrical solution which, in a subsequent work, will be applied to the membrane and the superstring sigma models.Comment: LaTex, 47 pages, no figure

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days. Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4–4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3–1.6) for placebo (HR = 0.64, 95% CI: 0.38–1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6–4.2) months for brivanib and 2.0 months (95% CI: 1.2–2.7) for placebo (HR: 0.56, 95% CI: 0.26–1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6–4.2) and was 2.0 months (95% CI: 1.2–2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25–1.17; p = 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib