Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States

Background and aims: Thiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. Methods: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan-Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the "noncontinuers," we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. Results: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ?18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. Conclusion: Most patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization

Chaotic scalar fields as models for dark energy

We consider stochastically quantized self-interacting scalar fields as suitable models to generate dark energy in the universe. Second quantization effects lead to new and unexpected phenomena is the self interaction strength is strong. The stochastically quantized dynamics can degenerate to a chaotic dynamics conjugated to a Bernoulli shift in fictitious time, and the right amount of vacuum energy density can be generated without fine tuning. It is numerically observed that the scalar field dynamics distinguishes fundamental parameters such as the electroweak and strong coupling constants as corresponding to local minima in the dark energy landscape. Chaotic fields can offer possible solutions to the cosmological coincidence problem, as well as to the problem of uniqueness of vacua.Comment: 30 pages, 3 figures. Replaced by final version accepted by Phys. Rev.

Collisions of particles in locally AdS spacetimes I. Local description and global examples

We investigate 3-dimensional globally hyperbolic AdS manifolds containing "particles", i.e., cone singularities along a graph $\Gamma$. We impose physically relevant conditions on the cone singularities, e.g. positivity of mass (angle less than $2\pi$ on time-like singular segments). We construct examples of such manifolds, describe the cone singularities that can arise and the way they can interact (the local geometry near the vertices of $\Gamma$). We then adapt to this setting some notions like global hyperbolicity which are natural for Lorentz manifolds, and construct some examples of globally hyperbolic AdS manifolds with interacting particles.Comment: This is a rewritten version of the first part of arxiv:0905.1823. That preprint was too long and contained two types of results, so we sliced it in two. This is the first part. Some sections have been completely rewritten so as to be more readable, at the cost of slightly less general statements. Others parts have been notably improved to increase readabilit

Dark Energy and Neutrino Mass Limits from Baryogenesis

In this brief report we consider couplings of the dark energy scalar, such as Quintessence to the neutrinos and discuss its implications in studies on the neutrino mass limits from Baryogenesis. During the evolution of the dark energy scalar, the neutrino masses vary, consequently the bounds on the neutrino masses we have here differ from those obtained before.Comment: 5 pages,3 figures. Version accepted for publication in Phys. Rev.

Area metric gravity and accelerating cosmology

Area metric manifolds emerge as effective classical backgrounds in quantum string theory and quantum gauge theory, and present a true generalization of metric geometry. Here, we consider area metric manifolds in their own right, and develop in detail the foundations of area metric differential geometry. Based on the construction of an area metric curvature scalar, which reduces in the metric-induced case to the Ricci scalar, we re-interpret the Einstein-Hilbert action as dynamics for an area metric spacetime. In contrast to modifications of general relativity based on metric geometry, no continuous deformation scale needs to be introduced; the extension to area geometry is purely structural and thus rigid. We present an intriguing prediction of area metric gravity: without dark energy or fine-tuning, the late universe exhibits a small acceleration.Comment: 52 pages, 1 figure, companion paper to hep-th/061213

Primordial Nucleosynthesis as a Test of the Friedmann Equation in the Early Universe

In the standard hot big bang model, the expansion of the early universe is given by the Friedmann equation with an energy density dominated by relativistic particles. Since in a variety of models this equation is altered, we introduce modifications in the Friedmann equation and show that we can constrain them using big bang nucleosynthesis data. When there is no neutrino/antineutrino asymmetry these modifications are tightly bounded but in presence of an asymmetry the bounds become much looser. As an illustration, we apply our results to a model where the second and third families couple to gravity differently than the first family (non-universal gravity).Comment: 6 figures. Revised version. Matches with the accepted one for publication in PR

Quintessence and variation of the fine structure constant in the CMBR

We study dependence of the CMB temperature anisotropy spectrum on the value of the fine structure constant $\alpha$ and the equation of state of the dark energy component of the total density of the universe. We find that bounds imposed on the variation of $\alpha$ from the analysis of currently available CMB data sets can be significantly relaxed if one also allows for a change in the equation of state.Comment: 5 pages, 3 figures. Several references added and a few minor typos corrected in the revised versio

Sub-millimeter Tests of the Gravitational Inverse-square Law

Motivated by a variety of theories that predict new effects, we tested the gravitational 1/r^2 law at separations between 10.77 mm and 137 microns using two different 10-fold azimuthally symmetric torsion pendulums and rotating 10-fold symmetric attractors. Our work improves upon other experiments by up to a factor of about 100. We found no deviation from Newtonian physics at the 95% confidence level and interpret these results as constraints on extensions of the Standard Model that predict Yukawa or power-law forces. We set a constraint on the largest single extra dimension (assuming toroidal compactification and that one extra dimension is significantly larger than all the others) of R <= 160 microns, and on two equal-sized large extra dimensions of R <= 130 microns. Yukawa interactions with |alpha| >= 1 are ruled out at 95% confidence for lambda >= 197 microns. Extra-dimensions scenarios stabilized by radions are restricted to unification masses M >= 3.0 TeV/c^2, regardless of the number of large extra dimensions. We also provide new constraints on power-law potentials V(r)\propto r^{-k} with k between 2 and 5 and on the gamma_5 couplings of pseudoscalars with m <= 10 meV/c^2.Comment: 34 pages, 38 figure

Quintessential Maldacena-Maoz Cosmologies

Maldacena and Maoz have proposed a new approach to holographic cosmology based on Euclidean manifolds with disconnected boundaries. This approach appears, however, to be in conflict with the known geometric results [the Witten-Yau theorem and its extensions] on spaces with boundaries of non-negative scalar curvature. We show precisely how the Maldacena-Maoz approach evades these theorems. We also exhibit Maldacena-Maoz cosmologies with [cosmologically] more natural matter content, namely quintessence instead of Yang-Mills fields, thereby demonstrating that these cosmologies do not depend on a special choice of matter to split the Euclidean boundary. We conclude that if our Universe is fundamentally anti-de Sitter-like [with the current acceleration being only temporary], then this may force us to confront the holography of spaces with a connected bulk but a disconnected boundary.Comment: Much improved exposition, exponent in Cai-Galloway theorem fixed, axionic interpretation of scalar explained, JHEP version. 33 pages, 3 eps figure

How does the electromagnetic field couple to gravity, in particular to metric, nonmetricity, torsion, and curvature?

The coupling of the electromagnetic field to gravity is an age-old problem. Presently, there is a resurgence of interest in it, mainly for two reasons: (i) Experimental investigations are under way with ever increasing precision, be it in the laboratory or by observing outer space. (ii) One desires to test out alternatives to Einstein's gravitational theory, in particular those of a gauge-theoretical nature, like Einstein-Cartan theory or metric-affine gravity. A clean discussion requires a reflection on the foundations of electrodynamics. If one bases electrodynamics on the conservation laws of electric charge and magnetic flux, one finds Maxwell's equations expressed in terms of the excitation H=(D,H) and the field strength F=(E,B) without any intervention of the metric or the linear connection of spacetime. In other words, there is still no coupling to gravity. Only the constitutive law H= functional(F) mediates such a coupling. We discuss the different ways of how metric, nonmetricity, torsion, and curvature can come into play here. Along the way, we touch on non-local laws (Mashhoon), non-linear ones (Born-Infeld, Heisenberg-Euler, Plebanski), linear ones, including the Abelian axion (Ni), and find a method for deriving the metric from linear electrodynamics (Toupin, Schoenberg). Finally, we discuss possible non-minimal coupling schemes.Comment: Latex2e, 26 pages. Contribution to "Testing Relativistic Gravity in Space: Gyroscopes, Clocks, Interferometers ...", Proceedings of the 220th Heraeus-Seminar, 22 - 27 August 1999 in Bad Honnef, C. Laemmerzahl et al. (eds.). Springer, Berlin (2000) to be published (Revised version uses Springer Latex macros; Sec. 6 substantially rewritten; appendices removed; the list of references updated