The Challenge of Early Crossover in Oncology Trials

This paper provides preparatory reading, to facilitate discussion during the meeting on “The Challenge of Early Crossover in Oncology Trials” to be held in Adelaide, Australia, in October 2014. The paper is not exhaustive, and does not cover every issue associated with treatment crossover (also called treatment switching) in detail. However it aims to provide an overview of the key issues associated with treatment crossover in the context of oncology randomised controlled trials (RCTs). In Section 2 of this paper we will define what we mean by treatment switching. In Section 3 we will describe why treatment switching causes a problem for the analysis of trials, from the perspective of a range of stakeholders. This will take into account clinical development programmes and the challenges of designing these in the face of international variations in clinical, regulatory and coverage practice with respect to evidence requirements and expectations. In Section 4 we will introduce approaches that may be taken to adjust for treatment switching and in Section 5 we will summarise the performance of these methods in simulation studies. This paper is supplemented by five additional papers: Background Paper 2 provides details on case studies submitted by Workshop participants; Background Papers 3-5 provide relevant guidance and recommendations on the use of switching adjustment methods made by regulatory and reimbursement agencies from around the world. Brief background and introduction to these papers are provided in Sections 6 and 7 of this paper. Background Paper 6 presents the proposed confidentiality rules for the Workshop. In the final section of the current paper, we highlight areas that have not been addressed by currently available guidance documents

Two-Photon Beatings Using Biphotons Generated from a Two-Level System

We propose a two-photon beating experiment based upon biphotons generated from a resonant pumping two-level system operating in a backward geometry. On the one hand, the linear optical-response leads biphotons produced from two sidebands in the Mollow triplet to propagate with tunable refractive indices, while the central-component propagates with unity refractive index. The relative phase difference due to different refractive indices is analogous to the pathway-length difference between long-long and short-short in the original Franson interferometer. By subtracting the linear Rayleigh scattering of the pump, the visibility in the center part of the two-photon beating interference can be ideally manipulated among [0, 100%] by varying the pump power, the material length, and the atomic density, which indicates a Bell-type inequality violation. On the other hand, the proposed experiment may be an interesting way of probing the quantum nature of the detection process. The interference will disappear when the separation of the Mollow peaks approaches the fundamental timescales for photon absorption in the detector.Comment: to appear in Phys. Rev. A (2008

Electromagnetic Magic: The Relativistically Rotating Disk

A closed form analytic solution is found for the electromagnetic field of the charged uniformly rotating conducting disk for all values of the tip speed $v$ up to $c$. For $v=c$ it becomes the Magic field of the Kerr-Newman black hole with $G$ set to zero. The field energy, field angular momentum and gyromagnetic ratio are calculated and compared with those of the electron. A new mathematical expression that sums products of 3 Legendre functions each of a different argument, is demonstrated.Comment: 10 pages, one figur

The stellar mass-accretion rate relation in T Tauri stars and brown dwarfs

Recent observations show a strong correlation between stellar mass and accretion rate in young stellar and sub-stellar objects, with the scaling $\dot{M}_{acc} \propto M_*^2$ holding over more than four orders of magnitude in accretion rate. We explore the consequences of this correlation in the context of disk evolution models. We note that such a correlation is not expected to arise from variations in disk angular momentum transport efficiency with stellar mass, and suggest that it may reflect a systematic trend in disk initial conditions. In this case we find that brown dwarf disks initially have rather larger radii than those around more massive objects. By considering disk evolution, and invoking a simple parametrization for a shut-off in accretion at the end of the disk lifetime, we show that such models predict that the scatter in the stellar mass-accretion rate relationship should increase with increasing stellar mass, in rough agreement with current observations.Comment: 4 pages, 2 figures. Accepted for publication in ApJ Letter

Bell inequality and the locality loophole: Active versus passive switches

All experimental tests of the violation of Bell's inequality suffer from some loopholes. We show that the locality loophole is not independent of the detection loophole: in experiments using low efficient detectors, the locality loophole can be closed equivalently using active or passive switches.Comment: 6 pages, 1 figur

From Bell's Theorem to Secure Quantum Key Distribution

Any Quantum Key Distribution (QKD) protocol consists first of sequences of measurements that produce some correlation between classical data. We show that these correlation data must violate some Bell inequality in order to contain distillable secrecy, if not they could be produced by quantum measurements performed on a separable state of larger dimension. We introduce a new QKD protocol and prove its security against any individual attack by an adversary only limited by the no-signaling condition.Comment: 5 pages, 2 figures, REVTEX

Non-local two-photon correlations using interferometers physically separated by 35 meters

An experimental demonstration of quantum correlations is presented. Energy and time entangled photons at wavelengths of 704 and 1310 nm are produced by parametric downconversion in KNbO3 and are sent through optical fibers into a bulk-optical (704 nm) and an all-fiber Michelson-interferometer (1310 nm), respectively. The two interferometers are located 35 meters aside from one another. Using Faraday-mirrors in the fiber-interferometer, all birefringence effects in the fibers are automatically compensated. We obtained two-photon fringe visibilities of up to 95 % from which one can project a violation of Bell's inequality by 8 standard deviations. The good performance and the auto-aligning feature of Faraday-mirror interferometers show their potential for a future test of Bell's inequalities in order to examine quantum-correlations over long distances.Comment: 9 pages including 3 postscript figures, to be published in Europhys. Let

Atom-photon, atom-atom and photon-photon entanglement preparation via fractional adiabatic passage

We propose a relatively robust scheme to generate maximally entangled states of (i) an atom and a cavity photon, (ii) two atoms in their ground states, and (iii) two photons in two spatially separate high-Q cavities. It is based on the interaction via fractional adiabatic passage of a three-level atom traveling through a cavity mode and a laser beam. The presence of optical phases is emphasized.Comment: 6 pages, 7 figures. We have changed the title, the abstract and the text. The references have been updated. (Accepted by Phys. Rev. A

Thermodynamic fluctuation relation for temperature and energy

The present work extends the well-known thermodynamic relation $C=\beta ^{2}< \delta {E^{2}}>$ for the canonical ensemble. We start from the general situation of the thermodynamic equilibrium between a large but finite system of interest and a generalized thermostat, which we define in the course of the paper. The resulting identity $=1+< \delta {E^{2}}> \partial ^{2}S(E) /\partial {E^{2}}$ can account for thermodynamic states with a negative heat capacity $C<0$; at the same time, it represents a thermodynamic fluctuation relation that imposes some restrictions on the determination of the microcanonical caloric curve $\beta (E) =\partial S(E) /\partial E$. Finally, we comment briefly on the implications of the present result for the development of new Monte Carlo methods and an apparent analogy with quantum mechanics.Comment: Version accepted for publication in J. Phys. A: Math and The