Dynamical dimensional reduction in toy models of 4D causal quantum gravity

In recent years several approaches to quantum gravity have found evidence for a scale dependent spectral dimension of space-time varying from four at large scales to two at small scales of order of the Planck length. The first evidence came from numerical results on four-dimensional causal dynamical triangulations (CDT) [Ambjorn et al., Phys. Rev. Lett. 95 (2005) 171]. Since then little progress has been made in analytically understanding the numerical results coming from the CDT approach and showing that they remain valid when taking the continuum limit. Here we argue that the spectral dimension can be determined from a model with fewer degrees of freedom obtained from the CDTs by "radial reduction". In the resulting "toy" model we can take the continuum limit analytically and obtain a scale dependent spectral dimension varying from four to two with scale and having functional behaviour exactly of the form which was conjectured on the basis of the numerical results.Comment: 12 pages, 2 figures, v3: improved discussion, results unchanged, as publishe

Aspects of dynamical dimensional reduction in multigraph ensembles of CDT

We study the continuum limit of a "radially reduced" approximation of Causal Dynamical Triangulations (CDT), so-called multigraph ensembles, and explain why they serve as realistic toy models to study the dimensional reduction observed in numerical simulations of four-dimensional CDT. We present properties of this approximation in two, three and four dimensions comparing them with the numerical simulations and pointing out some common features with 2+1 dimensional Horava-Lifshitz gravity.Comment: 4 pages, 1 figure, Presented at "Gravity, Quantum, and Black Holes" session of IC-MSQUARE 2012, Budapest, to appear in the proceedings, IOP Conference Serie

Spectral dimension flow on continuum random multigraph

We review a recently introduced effective graph approximation of causal dynamical triangulations (CDT), the multigraph ensemble. We argue that it is well suited for analytical computations and that it captures the physical degrees of freedom which are important for the reduction of the spectral dimension as observed in numerical simulations of CDT. In addition multigraph models allow us to study the relationship between the spectral dimension and the Hausdorff dimension, thus establishing a link to other approaches to quantum gravityComment: 6 pages, 1 figure, to appear in the Proceedings of Sixth International School on Field Theory and Gravitation 2012 (Petropolis, Brazil

Multigraph models for causal quantum gravity and scale dependent spectral dimension

We study random walks on ensembles of a specific class of random multigraphs which provide an "effective graph ensemble" for the causal dynamical triangulation (CDT) model of quantum gravity. In particular, we investigate the spectral dimension of the multigraph ensemble for recurrent as well as transient walks. We investigate the circumstances in which the spectral dimension and Hausdorff dimension are equal and show that this occurs when rho, the exponent for anomalous behaviour of the resistance to infinity, is zero. The concept of scale dependent spectral dimension in these models is introduced. We apply this notion to a multigraph ensemble with a measure induced by a size biased critical Galton-Watson process which has a scale dependent spectral dimension of two at large scales and one at small scales. We conclude by discussing a specific model related to four dimensional CDT which has a spectral dimension of four at large scales and two at small scales.Comment: 30 pages, 3 figures, references added, minor changes in the abstract to match the published versio

A tight Tsirelson inequality for infinitely many outcomes

We present a novel tight bound on the quantum violations of the CGLMP inequality in the case of infinitely many outcomes. Like in the case of Tsirelson's inequality the proof of our new inequality does not require any assumptions on the dimension of the Hilbert space or kinds of operators involved. However, it is seen that the maximal violation is obtained by the conjectured best measurements and a pure, but not maximally entangled, state. We give an approximate state which, in the limit where the number of outcomes tends to infinity, goes to the optimal state for this setting. This state might be potentially relevant for experimental verifications of Bell inequalities through multi-dimenisonal entangled photon pairs.Comment: 5 pages, 2 figures; improved presentation, change in title, as published

Sum over topologies and double-scaling limit in 2D Lorentzian quantum gravity

We construct a combined non-perturbative path integral over geometries and topologies for two-dimensional Lorentzian quantum gravity. The Lorentzian structure is used in an essential way to exclude geometries with unacceptably large causality violations. The remaining sum can be performed analytically and possesses a unique and well-defined double-scaling limit, a property which has eluded similar models of Euclidean quantum gravity in the past.Comment: 9 pages, 3 Postscript figures; added comments on strip versus bulk partition functio

Bendamustine in patients with relapsed or refractory multiple myeloma

<p>Abstract</p> <p>Objective</p> <p>In patients with multiple myeloma, bendamustine monotherapy is effective as 1^stand 2^ndline therapy. However, data for patients with advanced multiple myeloma is rare.</p> <p>Methods</p> <p>In this retrospective analysis we have identified 39 patients with relapsed or refractory multiple myeloma by means of case research, who have been treated at our institution with bendamustine as salvage therapy. After in median 2 lines of prior therapy (range:1-5) patients received in median 3 (range: 1-10) cycles of bendamustine. Bendamustine dosage was 80-150 mg on day 1+2 of a monthly cycle. Bendamustine was administered as monotherapy in 39% of patients, whereas 61% received concomitant steroids.</p> <p>Results</p> <p>Toxicity was mild to moderate. Response rates were as follows: 3% vgPR, 33% PR, 18% MR, 26% SD and 20% PD. The median event-free and overall survival were 7 and 17 months, respectively.</p> <p>Conclusions</p> <p>In conclusion, in patients with advanced multiple myeloma bendamustine is effective and associated with mild toxicity. Therefore, the role of bendamustine in patients with multiple myeloma should be investigated in further clinical trials.</p

Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study

BACKGROUND: Most patients with ovarian cancer will relapse after receiving frontline platinum-based chemotherapy and eventually develop platinum-resistant or platinum-refractory disease. We report results of avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) compared with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer. METHODS: JAVELIN Ovarian 200 was an open-label, parallel-group, three-arm, randomised, phase 3 trial, done at 149 hospitals and cancer treatment centres in 24 countries. Eligible patients were aged 18 years or older with epithelial ovarian, fallopian tube, or peritoneal cancer (maximum of three previous lines for platinum-sensitive disease, none for platinum-resistant disease) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m2 intravenously every 4 weeks), or PLD and stratified by disease platinum status, number of previous anticancer regimens, and bulky disease. Primary endpoints were progression-free survival by blinded independent central review and overall survival in all randomly assigned patients, with the objective to show whether avelumab alone or avelumab plus PLD is superior to PLD. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02580058. The trial is no longer enrolling patients and this is the final analysis of both primary endpoints. FINDINGS: Between Jan 5, 2016, and May 16, 2017, 566 patients were enrolled and randomly assigned (combination n=188; PLD n=190, avelumab n=188). At data cutoff (Sept 19, 2018), median duration of follow-up for overall survival was 18·4 months (IQR 15·6-21·9) for the combination group, 17·4 months (15·2-21·3) for the PLD group, and 18·2 months (15·8-21·2) for the avelumab group. Median progression-free survival by blinded independent central review was 3·7 months (95% CI 3·3-5·1) in the combination group, 3·5 months (2·1-4·0) in the PLD group, and 1·9 months (1·8-1·9) in the avelumab group (combination vs PLD: stratified HR 0·78 [repeated 93·1% CI 0·59-1·24], one-sided p=0·030; avelumab vs PLD: 1·68 [1·32-2·60], one-sided p>0·99). Median overall survival was 15·7 months (95% CI 12·7-18·7) in the combination group, 13·1 months (11·8-15·5) in the PLD group, and 11·8 months (8·9-14·1) in the avelumab group (combination vs PLD: stratified HR 0·89 [repeated 88·85% CI 0·74-1·24], one-sided p=0·21; avelumab vs PLD: 1·14 [0·95-1·58], one-sided p=0·83]). The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysesthesia syndrome (18 [10%] in the combination group vs nine [5%] in the PLD group vs none in the avelumab group), rash (11 [6%] vs three [2%] vs none), fatigue (ten [5%] vs three [2%] vs none), stomatitis (ten [5%] vs five [3%] vs none), anaemia (six [3%] vs nine [5%] vs three [2%]), neutropenia (nine [5%] vs nine [5%] vs none), and neutrophil count decreased (eight [5%] vs seven [4%] vs none). Serious treatment-related adverse events occurred in 32 (18%) patients in the combination group, 19 (11%) in the PLD group, and 14 (7%) in the avelumab group. Treatment-related adverse events resulted in death in one patient each in the PLD group (sepsis) and avelumab group (intestinal obstruction). INTERPRETATION: Neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival versus PLD. These results provide insights for patient selection in future studies of immune checkpoint inhibitors in platinum-resistant or platinum-refractory ovarian cancer. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany

Signature change events: A challenge for quantum gravity?

Within the framework of either Euclidian (functional-integral) quantum gravity or canonical general relativity the signature of the manifold is a priori unconstrained. Furthermore, recent developments in the emergent spacetime programme have led to a physically feasible implementation of signature change events. This suggests that it is time to revisit the sometimes controversial topic of signature change in general relativity. Specifically, we shall focus on the behaviour of a quantum field subjected to a manifold containing regions of different signature. We emphasise that, regardless of the underlying classical theory, there are severe problems associated with any quantum field theory residing on a signature-changing background. (Such as the production of what is naively an infinite number of particles, with an infinite energy density.) From the viewpoint of quantum gravity phenomenology, we discuss possible consequences of an effective Lorentz symmetry breaking scale. To more fully understand the physics of quantum fields exposed to finite regions of Euclidean-signature (Riemannian) geometry, we show its similarities with the quantum barrier penetration problem, and the super-Hubble horizon modes encountered in cosmology. Finally we raise the question as to whether signature change transitions could be fully understood and dynamically generated within (modified) classical general relativity, or whether they require the knowledge of a full theory of quantum gravity.Comment: 33 pages. 4 figures; V2: 3 references added, no physics changes; V3: now 24 pages - significantly shortened - argument simplified and more focused - no physics changes - this version accepted for publication in Classical and Quantum Gravit