Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

BACKGROUND/AIMS: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. METHODS: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. RESULTS: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. CONCLUSION: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate

Direct Emission of multiple strange baryons in ultrarelativistic heavy-ion collisions from the phase boundary

We discuss a model for the space-time evolution of ultrarelativistic heavy-ion collisions which employs relativistic hydrodynamics within one region of the forward light-cone, and microscopic transport theory (i.e. UrQMD) in the complement. Our initial condition consists of a quark-gluon plasma which expands hydrodynamically and hadronizes. After hadronization the solution eventually changes from expansion in local equilibrium to free streaming, as determined selfconsistently by the interaction rates between the hadrons and the local expansion rate. We show that in such a scenario the inverse slopes of the $m_T$-spectra of multiple strange baryons ($\Xi$, $\Omega$) are practically unaffected by the purely hadronic stage of the reaction, while the flow of $p$'s and $\Lambda$'s increases. Moreover, we find that the rather ``soft'' transverse expansion at RHIC energies (due to a first-order phase transition) is not washed out by strong rescattering in the hadronic stage. The earlier kinetic freeze-out as compared to SPS-energies results in similar inverse slopes (of the $m_T$-spectra of the hadrons in the final state) at RHIC and SPS energies.Comment: 4 pages, 3 figures, statistics for Omegas improved, slight revision of the manuscript (expansion of hadronization volume more emphasized, pi-Omega scattering is discussed very briefly

Nonequilibrium evolution in scalar O(N) models with spontaneous symmetry breaking

We consider the out-of-equilibrium evolution of a classical condensate field and its quantum fluctuations for a scalar O(N) model with spontaneously broken symmetry. In contrast to previous studies we do not consider the large N limit, but the case of finite N, including N=1, i.e., plain $\lambda \phi^ 4$ theory. The instabilities encountered in the one-loop approximation are prevented, as in the large-N limit, by back reaction of the fluctuations on themselves, or, equivalently, by including a resummation of bubble diagrams. For this resummation and its renormalization we use formulations developed recently based on the effective action formalism of Cornwall, Jackiw and Tomboulis. The formulation of renormalized equations for finite N derived here represents a useful tool for simulations with realistic models. Here we concentrate on the phase structure of such models. We observe the transition between the spontaneously broken and the symmetric phase at low and high energy densities, respectively. This shows that the typical structures expected in thermal equilibrium are encountered in nonequilibrium dynamics even at early times, i.e., before an efficient rescattering can lead to thermalization.Comment: 31 pages, 19 Figures, LaTeX; extended discussion on the basis of: fluctuations, eff. potential, correlations, analytic calculation of parametric resonance for "pion"_and_ "sigma" field

Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans

Quantum field dynamics of the slow rollover in the linear delta expansion

We show how the linear delta expansion, as applied to the slow-roll transition in quantum mechanics, can be recast in the closed time-path formalism. This results in simpler, explicit expressions than were obtained in the Schr\"odinger formulation and allows for a straightforward generalization to higher dimensions. Motivated by the success of the method in the quantum-mechanical problem, where it has been shown to give more accurate results for longer than existing alternatives, we apply the linear delta expansion to four-dimensional field theory. At small times all methods agree. At later times, the first-order linear delta expansion is consistently higher that Hartree-Fock, but does not show any sign of a turnover. A turnover emerges in second-order of the method, but the value of $$at the turnover is larger that that given by the Hartree-Fock approximation. Based on this calculation, and our experience in the corresponding quantum-mechanical problem, we believe that the Hartree-Fock approximation does indeed underestimate the value of$$ at the turnover. In subsequent applications of the method we hope to implement the calculation in the context of an expanding universe, following the line of earlier calculations by Boyanovsky {\sl et al.}, who used the Hartree-Fock and large-N methods. It seems clear, however, that the method will become unreliable as the system enters the reheating stage.Comment: 17 pages, 9 figures, revised version with extra section 4.2 including second order calculatio

Signatures of Electronic Nematic Phase at Isotropic-Nematic Phase Transition

The electronic nematic phase occurs when the point-group symmetry of the lattice structure is broken, due to electron-electron interactions. We study a model for the nematic phase on a square lattice with emphasis on the phase transition between isotropic and nematic phases within mean field theory. We find the transition to be first order, with dramatic changes in the Fermi surface topology accompanying the transition. Furthermore, we study the conductivity tensor and Hall constant as probes of the nematic phase and its transition. The relevance of our findings to Hall resistivity experiments in the high-$T_c$ cuprates is discussed.Comment: 5 pages, 3 figure

Microwave pyrolysis of Laminaria digitata to produce unique seaweed-derived bio-oils

Microwave pyrolysis has become an attractive form of processing technology to generate bio-oil, bio-char and syngas from different biomass feedstocks. In this study, microwave pyrolysis was performed on the UK native seaweed Laminaria digitata and its extract residue from a bio-refinery process. Pyrolysis of these two feedstocks was successfully achieved without the requirement of microwave susceptors, as pelletizing the biomass was sufficient to allow microwave pyrolysis to occur. It was found that average energy requirements as low as 1.84–2.83 kJ g−1 were required to pyrolyse 55–70% of both feedstocks and bio-oil yields of 5–8% and 10–14% for native and extraction residue L. digitata were produced, respectively. Maximum microwave pyrolysis processing times were in the order of 200 s. The bio-oil generated from both feedstocks contained no phenolic based compounds, but a greater number of nitrogen-containing compounds and compounds derived from macroalgal polysaccharides. Yields of certain compounds differed in bio-oils generated from the two L. digitata feedstocks, however it was observed that specific energy did not have a direct influence on bio-oil compound yield. Furthermore, the identification of a particular nitrogen-containing compound L-Proline, 1-methyl-5-oxo-, methylester is thought to be a unique product of microwave pyrolysis when carbon-based additives are avoided

Open-label, cluster randomised controlled trial and economic evaluation of a brief letter from a GP on unscheduled medical contacts associated with the start of the school year: the PLEASANT trial

BACKGROUND: Asthma is seasonal with peaks in exacerbation rates in school-age children associated with the return to school following the summer vacation. A drop in prescription collection in August is associated with an increase in the number of unscheduled contacts after the school return. OBJECTIVE: To assess whether a public health intervention delivered in general practice reduced unscheduled medical contacts in children with asthma. DESIGN: Cluster randomised trial with trial-based economic evaluation. Randomisation was at general practice level, stratified by size of practice. The intervention group received a letter from their general practitioner (GP) in late July outlining the importance of (re)taking asthma medication before the return to school. The control group was usual care. SETTING: General practices in England and Wales. PARTICIPANTS: 12 179 school-age children in 142 general practices (70 randomised to intervention). MAIN OUTCOME: Proportion of children aged 5-16 years who had an unscheduled contact in September. Secondary endpoints included collection of prescriptions in August and medical contacts over 12 months (September-August). Economic endpoints were quality-adjusted life-years gained and health service costs. RESULTS: There was no evidence of effect (OR 1.09; 95% CI 0.96 to 1.25 against treatment) on unscheduled contacts in September. The intervention increased the proportion of children collecting a prescription in August by 4% (OR 1.43; 95% CI 1.24 to 1.64). The intervention also reduced the total number of medical contacts between September-August by 5% (incidence ratio 0.95; 95% CI 0.91 to 0.99).The mean reduction in medical contacts informed the health economics analyses. The intervention was estimated to save £36.07 per patient, with a high probability (96.3%) of being cost-saving. CONCLUSIONS: The intervention succeeded in increasing children collecting prescriptions. It did not reduce unscheduled care in September (the primary outcome), but in the year following the intervention, it reduced the total number of medical contacts. TRIAL REGISTRATION NUMBER: ISRCTN03000938; Results