Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children

BackgroundCombination therapies are frequently recommended as maintenance therapy for people with asthma, whose disease is not adequately controlled with inhaled steroids. Fluticasone/salmeterol (FP/SAL) and budesonide/formoterol (BUD/F) have been assessed against their respective monocomponents, but there is a need to compare these two therapies on a head-to-head basis.ObjectivesTo estimate the relative effects of fluticasone/salmeterol and budesonide/formoterol in terms of asthma control, safety and lung function.Search strategyWe searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Searches are current to May 2008.Selection criteriaRandomised studies comparing fixed dose FP/SAL and BUD/ F were eligible, for a minimum of 12 weeks. Crossover studies were excluded. Our primary outcomes were: i) exacerbations requiring oral steroid bursts, ii) hospital admission and iii) serious adverse events.Data collection and analysisTwo authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR).Main resultsFive studies met the review entry criteria (5537 participants). Primary outcomes: The odds of an exacerbation requiring oral steroids did not differ significantly between treatments (OR 0.89; 95% CI 0.73 to 1.09, three studies, 4515 participants). The odds of an exacerbation leading hospital admission were also not significantly different (OR 1.29; 95% CI 0.68 to 2.47, four studies, 4879 participants). The odds of serious adverse events did not differ significantly between treatments (OR 1.47; 95% CI 0.75, 2.86, three studies, 4054 participants). Secondary outcomes: Lung function outcomes, symptoms, rescue medication, exacerbations leading ED visit/hospital admission and adverse events were not significantly different between treatments.Authors' conclusionsThe evidence in this review indicates that differences in the requirement for oral steroids and hospital admission between BUD/F and FP/SAL do not reach statistical significance. However, the confidence intervals do not exclude clinically important differences between treatments in reducing exacerbations or causing adverse events. The width of the confidence intervals for the primary outcomes justify further trials in order to better determine the relative effects of these drug combinations. Although this review sought to assess the effects of these drugs in both adults and children, no trials were identified in the under-12s and research in this area is of a high priority

Combined analysis of solar neutrino and solar irradiance data: further evidence for variability of the solar neutrino flux and its implications concerning the solar core

A search for any particular feature in any single solar neutrino dataset is unlikely to establish variability of the solar neutrino flux since the count rates are very low. It helps to combine datasets, and in this article we examine data from both the Homestake and GALLEX experiments. These show evidence of modulation with a frequency of 11.85 yr-1, which could be indicative of rotational modulation originating in the solar core. We find that precisely the same frequency is prominent in power spectrum analyses of the ACRIM irradiance data for both the Homestake and GALLEX time intervals. These results suggest that the solar core is inhomogeneous and rotates with sidereal frequency 12.85 yr-1. We find, by Monte Carlo calculations, that the probability that the neutrino data would by chance match the irradiance data in this way is only 2 parts in 10,000. This rotation rate is significantly lower than that of the inner radiative zone (13.97 yr-1) as recently inferred from analysis of Super-Kamiokande data, suggesting that there may be a second, inner tachocline separating the core from the radiative zone. This opens up the possibility that there may be an inner dynamo that could produce a strong internal magnetic field and a second solar cycle.Comment: 22 pages, 9 tables, 10 figure

Power Spectrum Analysis of Physikalisch-Technische Bundesanstalt Decay-Rate Data: Evidence for Solar Rotational Modulation

Evidence for an anomalous annual periodicity in certain nuclear decay data has led to speculation concerning a possible solar influence on nuclear processes. We have recently analyzed data concerning the decay rates of Cl-36 and Si-32, acquired at the Brookhaven National Laboratory (BNL), to search for evidence that might be indicative of a process involving solar rotation. Smoothing of the power spectrum by weighted-running-mean analysis leads to a significant peak at frequency 11.18/yr, which is lower than the equatorial synodic rotation rates of the convection and radiative zones. This article concerns measurements of the decay rates of Ra-226 acquired at the Physikalisch-Technische Bundesanstalt (PTB) in Germany. We find that a similar (but not identical) analysis yields a significant peak in the PTB dataset at frequency 11.21/yr, and a peak in the BNL dataset at 11.25/yr. The change in the BNL result is not significant since the uncertainties in the BNL and PTB analyses are estimated to be 0.13/yr and 0.07/yr, respectively. Combining the two running means by forming the joint power statistic leads to a highly significant peak at frequency 11.23/yr. We comment briefly on the possible implications of these results for solar physics and for particle physics.Comment: 15 pages, 13 figure

Analysis and packaging of radiochemical solar neutrino data. 1. Bayesian approach

According to current practice, the results of each run of a radiochemical solar neutrino experiment comprise an estimate of the flux and upper and lower error estimates. These estimates are derived by a maximum-likelihood procedure from the times of decay events in the analysis chamber. This procedure has the following shortcomings: (a) Published results sometimes include negative flux estimates. (b) Even if the flux estimate is non-negative, the probability distribution function implied by the flux and error estimates will extend into negative territory; and (c) The overall flux estimate derived from the results of a sequence of runs may differ substantially from an estimate made by a global analysis of all of the timing data taken together. These defects indicate that the usual packaging of data in radiochemical solar neutrino experiments provides an inadequate summary of the data, which implies a loss of information. This article reviews this problem from a Bayesian perspective, and suggests an alternative scheme for the packaging of radiochemical solar neutrino data, which is we believe free from the above objections.Comment: 8 page

Ground-state properties of rutile: electron-correlation effects

Electron-correlation effects on cohesive energy, lattice constant and bulk compressibility of rutile are calculated using an ab-initio scheme. A competition between the two groups of partially covalent Ti-O bonds is the reason that the correlation energy does not change linearly with deviations from the equilibrium geometry, but is dominated by quadratic terms instead. As a consequence, the Hartree-Fock lattice constants are close to the experimental ones, while the compressibility is strongly renormalized by electronic correlations.Comment: 1 figure to appear in Phys. Rev.

Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic.

Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic-industry co-development pathway from identification and assay development to validation for clinical use.I recieved an honorarium from Roche Diagnostics for my participation in the advisory panel meeting leading to this pape

Correlation effects in ionic crystals: I. The cohesive energy of MgO

High-level quantum-chemical calculations, using the coupled-cluster approach and extended one-particle basis sets, have been performed for (Mg2+)n (O2-)m clusters embedded in a Madelung potential. The results of these calculations are used for setting up an incremental expansion for the correlation energy of bulk MgO. This way, 96% of the experimental cohesive energy of the MgO crystal is recovered. It is shown that only 60% of the correlation contribution to the cohesive energy is of intra-ionic origin, the remaining part being caused by van der Waals-like inter-ionic excitations.Comment: LaTeX, 20 pages, no figure

VEP oscillation solutions to the solar neutrino problem

We study the solar neutrino problem within the framework of a parametrized post-Newtonian formulation for the gravitational interaction of the neutrinos, which incorporates a violation to the equivalence principle (VEP). Using the current data on the rates and the energy spectrum we find two possible oscillation solutions, both for a large mixing angle. One of them involves the MSW effect in matter and the other corresponds to vacuum oscillations. An interesting characteristic of this mechanism is that it predicts a semi-annual variation of the neutrino flux. Our analysis provides new constraints for some VEP parameters.Comment: revtex, 18 pages, 11 figure

Measurement of the solar neutrino capture rate with gallium metal

The solar neutrino capture rate measured by the Russian-American Gallium Experiment (SAGE) on metallic gallium during the period January 1990 through December 1997 is 67.2 (+7.2-7.0) (+3.5-3.0) SNU, where the uncertainties are statistical and systematic, respectively. This represents only about half of the predicted Standard Solar Model rate of 129 SNU. All the experimental procedures, including extraction of germanium from gallium, counting of 71Ge, and data analysis are discussed in detail.Comment: 34 pages including 14 figures, Revtex, slightly shortene