Improved Survival After Acute Graft-Versus-Host Disease Diagnosis in the Modern Era

Acute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft-versus-host disease (n=497 for 1999–2001, n=962 for 2002–2005, n=1,446 for 2006–2010). The median (range) follow-up was 144 (4–174), 97 (4–147) and 60 (8–99) months for 1999–2001, 2002–2005, and 2006–2010, respectively. Among the cohort with grade II-IV acute graft-versus-host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999–2001, 2002–2005, and 2006–2012, respectively (P\u3c0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease

Kasner and Mixmaster behavior in universes with equation of state w \ge 1

We consider cosmological models with a scalar field with equation of state $w\ge 1$ that contract towards a big crunch singularity, as in recent cyclic and ekpyrotic scenarios. We show that chaotic mixmaster oscillations due to anisotropy and curvature are suppressed, and the contraction is described by a homogeneous and isotropic Friedmann equation if $w>1$. We generalize the results to theories where the scalar field couples to p-forms and show that there exists a finite value of $w$, depending on the p-forms, such that chaotic oscillations are suppressed. We show that $Z_2$ orbifold compactification also contributes to suppressing chaotic behavior. In particular, chaos is avoided in contracting heterotic M-theory models if $w>1$ at the crunch.Comment: 25 pages, 2 figures, minor changes, references adde

Effective field theory analysis of the self-interacting chameleon

We analyse the phenomenology of a self-interacting scalar field in the context of the chameleon scenario originally proposed by Khoury and Weltman. In the absence of self-interactions, this type of scalar field can mediate long range interactions and simultaneously evade constraints from violation of the weak equivalence principle. By applying to such a scalar field the effective field theory method proposed for Einstein gravity by Goldberger and Rothstein, we give a thorough perturbative evaluation of the importance of non-derivative self-interactions in determining the strength of the chameleon mediated force in the case of orbital motion. The self-interactions are potentially dangerous as they can change the long range behaviour of the field. Nevertheless, we show that they do not lead to any dramatic phenomenological consequence with respect to the linear case and solar system constraints are fulfilled.Comment: 15 pages, 2 figures. Final version accepted for publication on General Relativity and Gravitatio

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

The Equivalence Principle and the Constants of Nature

We briefly review the various contexts within which one might address the issue of ``why'' the dimensionless constants of Nature have the particular values that they are observed to have. Both the general historical trend, in physics, of replacing a-priori-given, absolute structures by dynamical entities, and anthropic considerations, suggest that coupling ``constants'' have a dynamical nature. This hints at the existence of observable violations of the Equivalence Principle at some level, and motivates the need for improved tests of the Equivalence Principle.Comment: 12 pages; invited talk at the ISSI Workshop on the Nature of Gravity: Confronting Theory and Experiment in Space, Bern, Switzerland, 6-10 October 2008; to appear in Space Science Review

Cosmological Evolution of Brane World Moduli

We study cosmological consequences of non-constant brane world moduli in five dimensional brane world models with bulk scalars and two boundary branes. We focus on the case where the brane tension is an exponential function of the bulk scalar field, $U_b \propto \exp{(\alpha \phi)}$. In the limit $\alpha \to 0$, the model reduces to the two-brane model of Randall-Sundrum, whereas larger values of $\alpha$ allow for a less warped bulk geometry. Using the moduli space approximation, we derive the four-dimensional low-energy effective action from a supergravity-inspired five-dimensional theory. For arbitrary values of $\alpha$, the resulting theory has the form of a bi-scalar-tensor theory. We show that, in order to be consistent with local gravitational observations, $\alpha$ has to be small (less than $10^{-2}$) and the separation of the branes must be large. We study the cosmological evolution of the interbrane distance and the bulk scalar field for different matter contents on each branes. Our findings indicate that attractor solutions exist which drive the moduli fields towards values consistent with observations. The efficiency of the attractor mechanism crucially depends on the matter content on each branes. In the five-dimensional description, the attractors correspond to the motion of the negative tension brane towards a bulk singularity, which signals the eventual breakdown of the four-dimensional description and the necessity of a better understanding of the bulk singularity.Comment: 18 pages, 10 figures, typos and factor of 2 corrected, version to appear in Physical Review

Metric Expansion from Microscopic Dynamics in an Inhomogeneous Universe

Theories with ingredients like the Higgs mechanism, gravitons, and inflaton fields rejuvenate the idea that relativistic kinematics is dynamically emergent. Eternal inflation treats the Hubble constant H as depending on location. Microscopic dynamics implies that H is over much smaller lengths than pocket universes to be understood as a local space reproduction rate. We illustrate this via discussing that even exponential inflation in TeV-gravity is slow on the relevant time scale. In our on small scales inhomogeneous cosmos, a reproduction rate H depends on position. We therefore discuss Einstein-Straus vacuoles and a Lindquist-Wheeler like lattice to connect the local rate properly with the scaling of an expanding cosmos. Consistency allows H to locally depend on Weyl curvature similar to vacuum polarization. We derive a proportionality constant known from Kepler's third law and discuss the implications for the finiteness of the cosmological constant.Comment: 23 pages, no figure

Effective theory for close limit of two branes

We discuss the effective theory for the close limit of two branes in a covariant way. To do so we solve the five dimensional Einstein equation along the direction of the extra dimension. Using the Taylor expansion we solve the bulk spacetimes and derive the effective theory describing the close limit. We also discuss the radion dynamics and braneworld black holes for the close limit in our formulation.Comment: 6 pages, a version to be published in Phy.Rev.

Cosmological perturbations from varying masses and couplings

We study the evolution of perturbations during the domination and decay of a massive particle species whose mass and decay rate are allowed to depend on the expectation value of a light scalar field. We specialize in the case where the light field is slow-rolling, showing that during a phase of inhomogeneous mass-domination and decay the isocurvature perturbation of the light field is converted into a curvature perturbation with an efficiency which is nine times larger than when the mass is fixed. We derive a condition on the annihilation cross section and on the decay rate for the domination of the massive particles and we show that standard model particles cannot dominate the universe before nucleosynthesis. We also compare this mechanism with the curvaton model. Finally, observational signatures are discussed. A cold dark matter isocurvature mode can be generated if the dark matter is produced out of equilibrium by both the inflaton and the massive particle species decay. Non-Gaussianities are present: they are chi-square deviations. However, they might be too small to be observable.Comment: 21 pages, 4 figures, published versio

Cosmic Density Perturbations from Late-Decaying Scalar Condensations

We study the cosmic density perturbations induced from fluctuation of the amplitude of late-decaying scalar condensations (called \phi) in the scenario where the scalar field \phi once dominates the universe. In such a scenario, the cosmic microwave background (CMB) radiation originates to decay products of the scalar condensation and hence its anisotropy is affected by the fluctuation of \phi. It is shown that the present cosmic density perturbations can be dominantly induced from the primordial fluctuation of \phi, not from the fluctuation of the inflaton field. This scenario may change constraints on the source of the density perturbations, like inflation. In addition, a correlated mixture of adiabatic and isocurvature perturbations may arise in such a scenario; possible signals in the CMB power spectrum are discussed. We also show that the simplest scenario of generating the cosmic density perturbations only from the primordial fluctuation of \phi (i.e., so-called ``curvaton'' scenario) is severely constrained by the current measurements of the CMB angular power spectrum if correlated mixture of the adiabatic and isocurvature perturbations are generated.Comment: 31pages, 14figure