Guidance for using pilot studies to inform the design of intervention trials with continuous outcomes

Background: A pilot study can be an important step in the assessment of an intervention by providing information to design the future definitive trial. Pilot studies can be used to estimate the recruitment and retention rates and population variance and to provide preliminary evidence of efficacy potential. However, estimation is poor because pilot studies are small, so sensitivity analyses for the main trial's sample size calculations should be undertaken. Methods: We demonstrate how to carry out easy-to-perform sensitivity analysis for designing trials based on pilot data using an example. Furthermore, we introduce rules of thumb for the size of the pilot study so that the overall sample size, for both pilot and main trials, is minimized. Results: The example illustrates how sample size estimates for the main trial can alter dramatically by plausibly varying assumptions. Required sample size for 90% power varied from 392 to 692 depending on assumptions. Some scenarios were not feasible based on the pilot study recruitment and retention rates. Conclusion: Pilot studies can be used to help design the main trial, but caution should be exercised. We recommend the use of sensitivity analyses to assess the robustness of the design assumptions for a main trial

The Baryon-Dark Matter Ratio Via Moduli Decay After Affleck-Dine Baryogenesis

Low-scale supersymmetry breaking in string motivated theories implies the presence of O(100) TeV scale moduli, which generically lead to a significant modification of the history of the universe prior to Big Bang Nucleosynthesis. Such an approach implies a non-thermal origin for dark matter resulting from scalar decay, where the lightest supersymmetric particle can account for the observed dark matter relic density. We study the further effect of the decay on the baryon asymmetry of the universe, and find that this can satisfactorily address the problem of the over-production of the baryon asymmetry by the Affleck-Dine mechanism in the MSSM. Remarkably, there is a natural connection between the baryon and dark matter abundances today, which leads to a solution of the `Cosmic Coincidence Problem'.Comment: 12 pages, no figure. v2: references adde

Quartic Gauge Couplings and the Radiation Zero in pp to l nu gamma gamma events at the LHC

We report a study of the process pp to l nu gamma gamma at CERN's Large Hadron Collider, using a leading order partonic-level event generator interfaced to the Pythia program for showering and hadronisation and a with a generic detector simulation. The process is sensitive to possible anomalous quartic gauge boson couplings of the form W W gamma gamma. It is shown how unitarity-safe limits may be placed on these anomalous couplings by applying a binned maximum likelihood fit to the distribution of the two-photon invariant mass, M(gamma gamma), below a cutoff of 1TeV. Assuming 30fb-1 of integrated luminosity, the expected limits are two orders of magnitude tighter than those available from LEP. It is also demonstrated how the Standard Model radiation zero feature of the qq to W gamma gamma process may be observed in the difference between the two-photon and charged lepton pseudo-rapidities.Comment: 9 pages, 7 figure

Relations between entanglement, Bell-inequality violation and teleportation fidelity for the two-qubit X states

Based on the assumption that the receiver Bob can apply any unitary transformation, Horodecki {\it et al.} [Phys. Lett. A {\bf 222}, 21 (1996)] proved that any mixed two spin-1/2 state which violates the Bell-CHSH inequality is useful for teleportation. Here, we further show that any X state which violates the Bell-CHSH inequality can also be used for nonclassical teleportation even if Bob can only perform the identity or the Pauli rotation operations. Moreover, we showed that the maximal difference between the two average fidelities achievable via Bob's arbitrary transformations and via the sole identity or the Pauli rotation is 1/9.Comment: 5 pages, to be published in "Quantum Information Processing

The Point of Origin of the Radio Radiation from the Unresolved Cores of Radio-Loud Quasars

Locating the exact point of origin of the core radiation in active galactic nuclei (AGN) would represent important progress in our understanding of physical processes in the central engine of these objects. However, due to our inability to resolve the region containing both the central compact object and the jet base, this has so far been difficult. Here, using an analysis in which the lack of resolution does not play a significant role, we demonstrate that it may be impossible even in most radio loud sources for more than a small percentage of the core radiation at radio wavelengths to come from the jet base. We find for 3C279 that $\sim85$ percent of the core flux at 15 GHz must come from a separate, reasonably stable, region that is not part of the jet base, and that then likely radiates at least quasi-isotropically and is centered on the black hole. The long-term stability of this component also suggests that it may originate in a region that extends over many Schwarzschild radii.Comment: 7 pages with 3 figures, accepted for publication in Astrophysics and Space Scienc

Measurement of liver iron by magnetic resonance imaging in the UK Biobank population

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan™. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p=0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment

Partial Description of Quantum States

One of the most central and controversial element of quantum mechanics is the use of non zero vectors of a Hilbert space (or, more generally, of one dimension subspaces) for representing the state of a quantum system. In particular, the question whether such a representation is complete has been debated since almost the early days of quantum mechanics. In this article, we develop an alternate way to formalize knowledge about the state of quantum systems, based solely on experimentally accessible elements, namely on outcomes of finite measurements. We introduce what we call partial description which, given a feasible measurement, indicates some outcomes which are known to be impossible (i.e. known to have a probability equal to 0 to occur) and hence have to be discarded. Then, we introduce partial states (which are partial descriptions providing as much information as possible) and compare this way to describe quantum states to the orthodox one, using vector rays. Finally, we show that partial states allow to describe quantum states in a strictly more expressive way that the orthodox description does

Molecular dynamics simulation of the order-disorder phase transition in solid NaNO2_2

We present molecular dynamics simulations of solid NaNO$_2$ using pair potentials with the rigid-ion model. The crystal potential surface is calculated by using an \emph{a priori} method which integrates the \emph{ab initio} calculations with the Gordon-Kim electron gas theory. This approach is carefully examined by using different population analysis methods and comparing the intermolecular interactions resulting from this approach with those from the \emph{ab initio} Hartree-Fock calculations. Our numerics shows that the ferroelectric-paraelectric phase transition in solid NaNO$_2$ is triggered by rotation of the nitrite ions around the crystallographical c axis, in agreement with recent X-ray experiments [Gohda \textit{et al.}, Phys. Rev. B \textbf{63}, 14101 (2000)]. The crystal-field effects on the nitrite ion are also addressed. Remarkable internal charge-transfer effect is found.Comment: RevTeX 4.0, 11 figure

Anharmonic force fields of perchloric acid, HClO4_4, and perchloric anhydride, Cl2_2O7_7. An extreme case of inner polarization

DFT (density functional theory) anharmonic force fields with basis sets near the Kohn-Sham limit have been obtained for perchloric acid, HClO$_4$, and perchloric anhydride, Cl$_2$O$_7$. Calculated fundamental frequencies are in very good agreement with available experimental data. Some reassignments in the vibrational spectra of Cl$_2$O$_7$ are proposed based on our calculations. HClO$_4$ and Cl$_2$O$_7$ are particularly severe examples of the `inner polarization' phenomenon. The polarization consistent basis sets pc-1 and pc-2 (as well as their augmented counterparts) should be supplemented with two (preferably three) and one (preferably two) high-exponent $d$ functions, respectively, on second-row atoms. Complete anharmonic force fields are available as electronic supporting information.Comment: J. Mol. Struct., in press (special issue); Electronic Supporting Information at http://theochem.weizmann.ac.il/web/papers/Cl2O7.htm

Integrin activation - the importance of a positive feedback

Integrins mediate cell adhesion and are essential receptors for the development and functioning of multicellular organisms. Integrin activation is known to require both ligand and talin binding and to correlate with cluster formation but the activation mechanism and precise roles of these processes are not yet resolved. Here mathematical modeling, with known experimental parameters, is used to show that the binding of a stabilizing factor, such as talin, is alone insufficient to enable ligand-dependent integrin activation for all observed conditions; an additional positive feedback is required.Comment: in press in Bulletin of Mathematical Biolog