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

Effects of sea temperature and stratification changes on seabird breeding success

As apex predators in marine ecosystems, seabirds may primarily experience climate change impacts indirectly, via changes to their food webs. Observed seabird population declines have been linked to climate-driven oceanographic and food web changes. However, relationships have often been derived from relatively few colonies and consider only sea surface temperature (SST), so important drivers, and spatial variation in drivers, could remain undetected. Further, explicit climate change projections have rarely been made, so longer-term risks remain unclear. Here, we use tracking data to estimate foraging areas for eleven black-legged kittiwake (Rissa tridactyla) colonies in the UK and Ireland, thus reducing reliance on single colonies and allowing calculation of colony-specific oceanographic conditions. We use mixed models to consider how SST, the potential energy anomaly (indicating density stratification strength) and the timing of seasonal stratification influence kittiwake productivity. Across all colonies, higher breeding success was associated with weaker stratification before breeding and lower SSTs during the breeding season. Eight colonies with sufficient data were modelled individually: higher productivity was associated with later stratification at three colonies, weaker stratification at two, and lower SSTs at one, whilst two colonies showed no significant relationships. Hence, key drivers of productivity varied among colonies. Climate change projections, made using fitted models, indicated that breeding success could decline by 21 – 43% between 1961-90 and 2070-99. Climate change therefore poses a longer-term threat to kittiwakes, but as this will be mediated via availability of key prey species, other marine apex predators could also face similar threats

Phantom Divide Crossing with General Non-minimal Kinetic Coupling

We propose a model of dark energy consists of a single scalar field with a general non-minimal kinetic couplings to itself and to the curvature. We study the cosmological dynamics of the equation of state in this setup. The coupling terms have the form $\xi_{1} R f(\phi)\partial_{\mu}\phi\partial^{\mu}\phi$ and $\xi_{2} R_{\mu\nu}f(\phi)\partial^{\mu}\phi\partial^{\nu}\phi$ where $\xi_{1}$ and $\xi_{2}$ are coupling parameters and their dimensions depend on the type of function $f(\phi)$. We obtain the conditions required for phantom divide crossing and show numerically that a cosmological model with general non-minimal derivative coupling to the scalar and Ricci curvatures can realize such a crossing.Comment: 12 pages, 4 figures. Accepted for publication in Gen. Rel. Grav. arXiv admin note: substantial text overlap with arXiv:1105.4967, arXiv:1201.1627, and with arXiv:astro-ph/0610092 by other author

Filtering out the cosmological constant in the Palatini formalism of modified gravity

According to theoretical physics the cosmological constant (CC) is expected to be much larger in magnitude than other energy densities in the universe, which is in stark contrast to the observed Big Bang evolution. We address this old CC problem not by introducing an extremely fine-tuned counterterm, but in the context of modified gravity in the Palatini formalism. In our model the large CC term is filtered out, and it does not prevent a standard cosmological evolution. We discuss the filter effect in the epochs of radiation and matter domination as well as in the asymptotic de Sitter future. The final expansion rate can be much lower than inferred from the large CC without using a fine-tuned counterterm. Finally, we show that the CC filter works also in the Kottler (Schwarzschild-de Sitter) metric describing a black hole environment with a CC compatible to the future de Sitter cosmos.Comment: 22 pages, 1 figure, discussion extended, references added, accepted by Gen.Rel.Gra

Probing interaction and spatial curvature in the holographic dark energy model

In this paper we place observational constraints on the interaction and spatial curvature in the holographic dark energy model. We consider three kinds of phenomenological interactions between holographic dark energy and matter, i.e., the interaction term $Q$ is proportional to the energy densities of dark energy ($\rho_{\Lambda}$), matter ($\rho_{m}$), and matter plus dark energy ($\rho_m+\rho_{\Lambda}$). For probing the interaction and spatial curvature in the holographic dark energy model, we use the latest observational data including the type Ia supernovae (SNIa) Constitution data, the shift parameter of the cosmic microwave background (CMB) given by the five-year Wilkinson Microwave Anisotropy Probe (WMAP5) observations, and the baryon acoustic oscillation (BAO) measurement from the Sloan Digital Sky Survey (SDSS). Our results show that the interaction and spatial curvature in the holographic dark energy model are both rather small. Besides, it is interesting to find that there exists significant degeneracy between the phenomenological interaction and the spatial curvature in the holographic dark energy model.Comment: 11 pages, 5 figures; to appear in JCA

Coherent QCD phenomena in the Coherent Pion-Nucleon and Pion-Nucleus Production of Two Jets at High Relative Momenta

We use QCD to compute the cross section for coherent production of a di-jet (treated as a $q\bar q$ moving at high relative transverse momentum,$\kappa_t$). In the target rest frame,the space-time evolution of this reaction is dominated by the process in which the high $\kappa_t$ $q\bar q$ component of the pion wave function is formed before reaching the target. It then interacts through two gluon exchange. In the approximation of keeping the leading order in powers of $\alpha_s$ and all orders in $\alpha_{s}\ln(\kappa_{t}^2/k_{0}^2),$ the amplitudes for other processes are shown to be smaller at least by a power of $\alpha_{s}$. The resulting dominant amplitude is proportional to $z(1-z) \kappa_t^{-4}$ ($z$ is the fraction light-cone(+)momentum carried by the quark in the final state) times the skewed gluon distribution of the target. For the pion scattering by a nuclear target, this means that at fixed $x_{N}= 2\kappa_{t}^2/s$ (but $\kappa_{t}^2\to \infty$) the nuclear process in which there is only a single interaction is the most important one to contribute to the reaction. Thus in this limit color transparency phenomena should occur.These findings are in accord with E971 experiment at FNAL. We also re-examine a potentially important nuclear multiple scattering correction which is positive and $\propto A^{1/3}/\kappa_t^4$. The meaning of the signal obtained from the experimental measurement of pion diffraction into two jets is also critically examined and significant corrections are identified.We show also that for values of $\kappa_t$ achieved at fixed target energies, di-jet production by the e.m. field of the nucleus leads to an insignificant correction which gets more important as $\kappa_t$ increases.Comment: 23 pages, 9 figure

Thermal leptogenesis in a model with mass varying neutrinos

In this paper we consider the possibility of neutrino mass varying during the evolution of the Universe and study its implications on leptogenesis. Specifically, we take the minimal seesaw model of neutrino masses and introduce a coupling between the right-handed neutrinos and the dark energy scalar field, the Quintessence. In our model, the right-handed neutrino masses change as the Quintessence scalar evolves. We then examine in detail the parameter space of this model allowed by the observed baryon number asymmetry. Our results show that it is possible to lower the reheating temperature in this scenario in comparison with the case that the neutrino masses are unchanged, which helps solve the gravitino problem. Furthermore, a degenerate neutrino mass patten with $m_i$ larger than the upper limit given in the minimal leptogenesis scenario is permitted.Comment: 18 pages, 7 figures, version to appear in PR

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe