Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout.

ObjectiveLesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.MethodsSafety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).ResultsIn the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.ConclusionAt the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified

The time delay of the quadruple quasar RX J0911.4+0551

We present optical lightcurves of the gravitationally lensed components A (=A1+A2+A3) and B of the quadruple quasar RX J0911.4+0551 (z = 2.80). The observations were primarily obtained at the Nordic Optical Telescope between 1997 March and 2001 April and consist of 74 I-band data points for each component. The data allow the measurement of a time delay of 146 +- 8 days (2 sigma) between A and B, with B as the leading component. This value is significantly shorter than that predicted from simple models and indicates a very large external shear. Mass models including the main lens galaxy and the surrounding massive cluster of galaxies at z = 0.77, responsible for the external shear, yield H_0 = 71 +- 4 (random, 2 sigma) +- 8 (systematic) km/s/Mpc. The systematic model uncertainty is governed by the surface-mass density (convergence) at the location of the multiple images.Comment: 12 pages, 3 figures, ApJL, in press (June 20, 2002

Linking the chiral and deconfinement phase transitions

We show that the electric glueball becomes critical at the end-point of the deconfinement phase transition in finite temperature QCD. Based on this observation and existing lattice data, we argue that the chiral phase transition at a zero quark mass and the deconfinement phase transition at an infinite quark mass are continuously connected by the glueball-sigma mixing.Comment: 4 pages, terminology corrected. To appear in Phys. Rev.

On the Quantitative Impact of the Schechter-Valle Theorem

We evaluate the Schechter-Valle (Black Box) theorem quantitatively by considering the most general Lorentz invariant Lagrangian consisting of point-like operators for neutrinoless double beta decay. It is well known that the Black Box operators induce Majorana neutrino masses at four-loop level. This warrants the statement that an observation of neutrinoless double beta decay guarantees the Majorana nature of neutrinos. We calculate these radiatively generated masses and find that they are many orders of magnitude smaller than the observed neutrino masses and splittings. Thus, some lepton number violating New Physics (which may at tree-level not be related to neutrino masses) may induce Black Box operators which can explain an observed rate of neutrinoless double beta decay. Although these operators guarantee finite Majorana neutrino masses, the smallness of the Black Box contributions implies that other neutrino mass terms (Dirac or Majorana) must exist. If neutrino masses have a significant Majorana contribution then this will become the dominant part of the Black Box operator. However, neutrinos might also be predominantly Dirac particles, while other lepton number violating New Physics dominates neutrinoless double beta decay. Translating an observed rate of neutrinoless double beta decay into neutrino masses would then be completely misleading. Although the principal statement of the Schechter-Valle theorem remains valid, we conclude that the Black Box diagram itself generates radiatively only mass terms which are many orders of magnitude too small to explain neutrino masses. Therefore, other operators must give the leading contributions to neutrino masses, which could be of Dirac or Majorana nature.Comment: 18 pages, 4 figures; v2: minor corrections, reference added, matches journal version; v3: typo corrected, physics result and conclusions unchange

Effective chiral Lagrangians for spin-1 mesons

The commonly used types of effective theory for vector mesons are reviewed and their relationships clarified. They are shown to correspond to different choices of field for spin-1 particles and the rules for transforming between them are described. The importance of respecting chiral symmetry is stressed. The choice of fields that transform homogeneously under the nonlinear realisation of chiral symmetry imposes no preconceptions about the types of coupling for the mesons. This representation thus provides a convenient framework for relating different theories. It is also used to elucidate the nature of the assumptions in specific hidden-gauge and massive Yang-Mills models that have been widely used.Comment: 46 pages (RevTeX