Responsiveness of PROMIS® to change in chronic obstructive pulmonary disease.

BackgroundChronic obstructive pulmonary disease (COPD) is a progressive chronic disease characterized by airflow obstruction that leads to shortness of breath and substantial negative impacts on health-related quality of life (HRQL). The course of COPD includes periodic acute exacerbations that require changes in treatment and/or hospitalizations. This study was designed to examine the responsiveness of Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures to changes associated with COPD exacerbation recovery.MethodsA longitudinal analysis using mixed-effects models was conducted of people who were enrolled while stable (n = 100) and those who experienced an acute exacerbation (n = 85). PROMIS (physical function, pain interference, pain behavior, fatigue, anxiety, depression, anger, social roles, discretionary social activities, Global Health, dyspnea severity and dyspnea functional limitations) and COPD-targeted HRQL measures were completed at baseline and at 12 weeks.ResultsWe administered PROMIS measures using computer adaptive testing (CAT), followed by administration of any remaining short form (SF) items that had not yet been administered by CAT. Examination of the difference between group differences from baseline to 12 weeks in the stable and exacerbation groups revealed that the exacerbation group changed (improved) significantly more than the stable group in anxiety (p < .001 to p < .01; f2 effect size [ES] = 0.023/0.021), fatigue (p < .0001; ES = 0.036/0.047) and social roles (p < .001 to p < .05; ES = 0.035/0.024). All effect sizes were small in magnitude and smaller than hypothesized. Depression was also statistically significant (p < .05, SF only) but the ES was trivial. For all other PROMIS domains, the differences were not significant and ES were trivial.ConclusionsThis longitudinal study provides some support for the validity of the PROMIS fatigue, anxiety, and social roles domains in COPD, but further evaluation of responsiveness is warranted

Genetic Correlates of Brain Aging on MRI and Cognitive Test Measures: A Genome-Wide Association and Linkage Analysis in the Framingham Study

BACKGROUND: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. METHODS: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. RESULTS: The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). CONCLUSION: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.National Institutes of Health National Center for Research Resources Shared Instrumentation grant (ISI0RR163736-01A1); National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institute of Aging (5R01-AG08122, 5R01-AG16495); National Institute of Neurological Disorders and Stroke (5R01-NS17950

Three Numerical Puzzles and the Top Quark's Chiral Weak-Moment

Versus the standard model's t --> W b decay helicity amplitudes, three numerical puzzles occur at the 0.1 % level when one considers the amplitudes in the case of an additional (f_M + f_E) coupling of relative strength 53 GeV. The puzzles are theoretical ones which involve the t --> W b decay helicity amplitudes in the two cases, the relative strength of this additional coupling, and the observed masses of these three particles. A deeper analytic realization is obtained for two of them. Equivalent realizations are given for the remaining one. An empirical consequence of these analytic realizations is that it is important to search for effects of a large chiral weak-moment of the top-quark, the effective mass-scale is about 53 GeV. A full theoretical resolution would include relating the origin of such a chiral weak-moment and the mass generation of the top-quark, the W-boson, and probably the b-quark.Comment: 18 pages, 1 postscript table (revised to better explain notation, model #1, add a little material...

Taming the Penguin in the B0(t) -> Pi+Pi- CP-asymmetry: Observables and Minimal Theoretical Input

Penguin contributions, being not negligible in general, can hide the information on the CKM angle alpha coming from the measurement of the time-dependent B0(t) -> pi+pi- CP-asymmetry. Nevertheless, we show that this information can be summarized in a set of simple equations, expressing alpha as a multi-valued function of a single theoretically unknown parameter, which conveniently can be chosen as a well-defined ratio of penguin to tree amplitudes. Using these exact analytic expressions, free of any assumption besides the Standard Model, and some reasonable hypotheses to constrain the modulus of the penguin amplitude, we derive several new upper bounds on the penguin-induced shift |2alpha-2alpha_eff|, generalizing the recent result of Grossman and Quinn. These bounds depend on the averaged branching ratios of some decays (pi0pi0, K0K0bar, K+-pi-+) particularly sensitive to the penguin. On the other hand, with further and less conservative approximations, we show that the knowledge of the B+- -> Kpi+- branching ratio alone gives sufficient information to extract the free parameter without the need of other measurements, and without knowing |V_td| or |V_ub|. More generally, knowing the modulus of the penguin amplitude with an accuracy of ~30% might result in an extraction of alpha competitive with the experimentally more difficult isospin analysis. We also show that our framework allows to recover most of the previous approaches in a transparent and simple way, and in some cases to improve them. In addition we discuss in detail the problem of the various kinds of discrete ambiguities.Comment: LaTeX2e, 44 pages, 9 figures (from 18 postscript files) included with epsf. Minor changes, references updated. New CLEO results from ICHEP'98 are taken into account. To appear in Phys. Rev.

A new CP violating observable for the LHC

We study a new type of CP violating observable that arises in three body decays that are dominated by an intermediate resonance. If two interfering diagrams exist with different orderings of final state particles, the required CP-even phase arises due to the different virtualities of the resonance in each of the two diagrams. This method can be an important tool for accessing new CP phases at the LHC and future colliders.Comment: 22 pages, v2: discussion of charged particle decays and a few references added v3: typos corrected, matches published versio

Charm multiplicity and the branching ratios of inclusive charmless b quark decays in the general two-Higgs-doublet models

In the framework of general two-Higgs-doublet models, we calculate the branching ratios of various inclusive charmless b decays by using the low energy effective Hamiltonian including next-to-leading order QCD corrections, and examine the current status and the new physics effects on the determination of the charm multiplicity $n_c$ and semileptonic branching ratio $B_{SL}$. Within the considered parameter space, the enhancement to the ratio $BR(b \to s g)$ due to the charged-Higgs penguins can be as large as a factor of 8 (3) in the model III (II), while the ratio $BR(b \to no charm)$ can be increased from the standard model prediction of 2.49% to 4.91% (2.99%) in the model III (II). Consequently, the value of $B_{SL}$ and $n_c$ can be decreased simultaneously in the model III. The central value of $B_{SL}$ will be lowered slightly by about 0.003, but the ratio $n_c$ can be reduced significantly from the theoretical prediction of $n_c= 1.28 \pm 0.05$ in the SM to $n_c= 1.23 \pm 0.05$, $1.18 \pm 0.05$ for $m_{H^+}=200, 100$ GeV, respectively. We find that the predicted $n_c$ and the measured $n_c$ now agree within roughly one standard deviation after taking into account the effects of gluonic charged Higgs penguins in the model III with a relatively light charged Higgs boson.Comment: 25 pages, Latex file, axodraw.sty, 6 figures. Final version to be published in Phys.Rev.

On leptonic models for blazars in the Fermi era

Some questions raised by Fermi-LAT data about blazars are summarized, along with attempts at solutions within the context of leptonic models. These include both spectral and statistical questions, including the origin of the GeV breaks in low-synchrotron peaked blazars, the location of the gamma-ray emission sites, the correlations in the spectral energy distributions with luminosity, and the difficulty of synchrotron/SSC models to fit the spectra of some TeV blazars.Comment: 9 pages, 1 figure, in "Beamed and Unbeamed Gamma Rays from Galaxies," Muonio, Finland, 11-15 April, 2011, ed. R. Wagner, L. Maraschi, A. Sillanpaa, to appear in Journal of Physics: Conference Serie

B-Decay CP Asymmetries, Discrete Ambiguities and New Physics

The first measurements of CP violation in the $B$ system will likely probe $\sin 2\alpha$, $\sin 2\beta$ and $\cos 2\gamma$. Assuming that the CP angles $\alpha$, $\beta$ and $\gamma$ are the interior angles of the unitarity triangle, these measurements determine the angle set $(\alpha,\beta,\gamma)$ except for a twofold discrete ambiguity. If one allows for the possibility of new physics, the presence of this discrete ambiguity can make its discovery difficult: if only one of the two candidate solutions is consistent with constraints from other measurements in the $B$ and $K$ systems, one is not sure whether new physics is present or not. We review the methods used to resolve the discrete ambiguity and show that, even in the presence of new physics, they can usually be used to uncover this new physics. There are some exceptions, which we describe in detail. We systematically scan the parameter space and present examples of values of $(\alpha,\beta,\gamma)$ and the new-physics parameters which correspond to all possibilities. Finally, we show that if one relaxes the assumption that the bag parameters \BBd and \BK are positive, one can no longer definitively establish the presence of new physics.Comment: 29 pages, LaTeX, 1 figures, presentation substantially reworked, physics conclusions unchanged. This version will be published in Phys. Rev.

Exploring CP Violation with B_d -> D K_s Decays

We (re)examine CP violation in the decays B_d -> D K_s, where D represents D^0, D(bar), or one of their excited states. The quantity $\sin^2(2\beta + \gamma)$ can be extracted from the time-dependent rates for $B_d(t) -> {\bar D}^{**0} K_s$ and $B_d(t) -> D^{**0} K_s$, where the $D^{**0}$ decays to $D^{(*)+}\pi^-$. If one considers a non-CP-eigenstate hadronic final state to which both D(bar) and D^0 can decay (e.g. $K^+\pi^-$), then one can obtain two of the angles of the unitarity triangle from measurements of the time-dependent rates for $B_d(t) -> (K^+\pi^-)_{D K_s}$ and $B_d(t) -> (K^-\pi^+)_{D K_s}$. There are no penguin contributions to these decays, so all measurements are theoretically clean.Comment: 15 pages, LaTeX, no figure