Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Blastomycosis in Ontario, 1994–2003

Clinicians in Ontario should be aware of symptoms and areas where disease is endemic

Study of Charmless Hadronic B Meson Decays to Pseudoscalar-Vector Final States

We report results of searches for charmless hadronic B meson decays to pseudoscalar(pi^+-,K^+-,Pi^0 or Ks^0)-vector(Rho, K* or Omega) final states. Using 9.7 million BBbar pairs collected with the CLEO detector, we report first observation of B^- --> Pi^-Rho^0, B^0 --> Pi^+-Rho^-+ and B^- --> Pi^-Omega, which are expected to be dominated by hadronic b --> u transitions. The measured branching fractions are (10.4+3.3-3.4+-2.1)x10^-6, (27.6+8.4-7.4+-4.2)x10^-6 and (11.3+3.3-2.9+-1.4)x10^-6, respectively. Branching fraction upper limits are set for all the other decay modes investigated.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Further Search for the Two-Photon Production of the Glueball Candidate fJ(2220)f_{J}(2220)

The CLEOII detector at the Cornell e+ e- storage ring CESR has been used to search for the two-photon production of the $f_J(2220)$ decaying into pi+ pi-. No evidence for a signal is found in data corresponding to an integrated luminosity of 4.77/fb and a 95% CL upper limit on $\Gamma_{two-photon} * BR{pi+ pi-}$ of 2.5 eV is set. If this result is combined with the BES Collaboration's measurement of $f_J(2220) -> pi+ pi-$ in radiative $J/\psi$ decay, a 95% CL lower limit on the stickiness of the $f_J(2220)$ of 73 is obtained. If the recent CLEO result for \Gamma_{two-photon} * BR{\K_S K_S} is combined with the present result, the stickiness of the $f_J(2220)$ is found to be larger than 102 at the 95% CL. These results for the stickiness (the ratio of the probabilities for two-gluon coupling and two-photon coupling) provide further support for a substantial neutral parton content in the $f_J(2220)$.Comment: 8 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Observation of Radiative Leptonic Decay of the Tau Lepton

Using 4.68 fb^{-1} of e^+e^- annihilation data collected with the CLEO II detector at the Cornell Electron Storage Ring (CESR) we have studied tau radiative decays tau -> mu nu nu gamma and tau -> e nu nu gamma. For a 10 MeV minimum photon energy in the tau rest frame, the branching fraction of radiative tau decay to a muon or electron is measured to be (3.61+-0.16+-0.35)*10^{-3} or (1.75+-0.06+-0.17)*10^{-2}, respectively. The branching fractions are in agreement with the Standard Model theoretical predictions.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Hadronic Structure in the Decay τ−→π−π0ντ\tau^{-}\to \pi^{-}\pi^{0}\nu_{\tau}

We report on a study of the invariant mass spectrum of the hadronic system in the decay tau- -> pi- pi0 nu_tau. This study was performed with data obtained with the CLEO II detector operating at the CESR e+ e- collider. We present fits to phenomenological models in which resonance parameters associated with the rho(770) and rho(1450) mesons are determined. The pi- pi0 spectral function inferred from the invariant mass spectrum is compared with data on e+ e- -> pi+ pi- as a test of the Conserved Vector Current theorem. We also discuss the implications of our data with regard to estimates of the hadronic contribution to the muon anomalous magnetic moment.Comment: 39 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

First Observation of Υ(1S)→γππ\Upsilon(1S)\to \gamma\pi\pi

We report on a study of exclusive radiative decays of the Upsilon(1S) resonance collected with the CLEO-II detector operating at CESR. We present the first observation of the radiative decays Upsilon(1S)->gamma pi+pi- and Upsilon(1S)->gamma pi0pi0. For the dipion mass regime m(pipi)>1.0 GeV, we obtain Br(Upsilon(1S)->gamma pi+pi-=(6.3+/-1.2+/-1.3) x 10^(-5), and Br(Upsilon(1S)->gamma pi0pi0=(1.7+/-0.6+/-0.3) x 10^(-5). The observed gamma pipi events are consistent with the hypothesis Upsilon(1S)->gamma f2(1270).Comment: 9 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Study of 3-prong Hadronic τ\tau Decays with Charged Kaons

Using a sample of 4.7/fb integrated luminosity accumulated with the CLEO-II detector at the Cornell Electron Storage Ring (CESR), we have measured the branching fractions of the tau lepton into $K^- h^+ \pi^- \nu_\tau$ and $K^- K^+ \pi^- \nu_\tau$ relative to $h^- h^+ h^- \nu_\tau; K^- h^+ \pi^- \pi^0\nu_\tau$ and $K^- K^+ \pi^- \pi^0\nu_\tau$ relative to $h^- h^+ h^- \pi^0 \nu_\tau$. The relative branching fractions are: (5.16+-0.20+-0.50)*$10^{-2}$, (1.52+-0.14+-0.29)*$10^{-2}$, (2.54+-0.44+-0.39)*$10^{-2}$ and $<0.0154$ at 95% C.L., respectively. Coupled with additional experimental information, we use our results to extract information on the structure of three-prong tau decays to charged kaons.Comment: 16 pages postscript file also available through http://w4.lns.cornell.edu/public/CLN

A Measurement of the Decay Asymmetry Parameters in \Xi_{c}^{0}\to \X^{-}\pi^{+}

Using the CLEO II detector at the Cornell Electron Storage Ring we have measured the $\Xi_c^{0}$ decay asymmetry parameter in the decay $\Xi_c^{0} \to \Xi^{-} \pi^+$. We find $\alpha_{\Xi_c^{0}} \alpha_{\Xi} = 0.26 \pm 0.18{(stat)}^{+0.05}_{-0.04}{(syst)}$, using the world average value of $\alpha_{\Xi} = -0.456 \pm 0.014$ we obtain $\alpha_{\Xi_c^{0}} = -0.56 \pm 0.39{(stat)}^{+0.10}_{-0.09}{(syst)}$. The physically allowed range of a decay asymmetry parameter is $-1<\alpha<+1$. Our result prefers a negative value: $\alpha_{\Xi_c^{0}}$ is $<0.1$ at the 90% CL. The central value occupies the middle of the theoretically expected range but is not yet precise enough to choose between models.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN