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 response to high magnetic fields of the vacuum phototriodes for the compact muon solenoid endcap electromagnetic calorimeter

The endcap electromagnetic calorimeter of the Compact Muon Solenoid (CMS) detects particles with the dense fast scintillator lead tungstate (PbWO4). Due to the low light yield of this scintillator photodetectors with internal gain are required. Silicon avalanche photodiodes cannot be used in the endcap region due to the intense neutron flux. Following an extensive R&D programme 26 mm diameter single-stage photomultipliers (vacuum phototriodes) have been chosen as the photodetector in the endcap region. The first 1400 production devices are currently being evaluated following recent tests of a pre-production batch of 500 tubes. Tubes passing our acceptance tests have responses, averaged over the angular acceptance of the endcap calorimeter, corresponding to the range 20 to 55 electrons per MeV deposited in PbWO4. These phototriodes operate, with a typical gain of 10, in magnetic fields up to 4T.PPARC, EC(INTAS-CERN scheme 99-424

Grid-based simulation of soil moisture in the UK: future changes in extremes and wetting and drying dates

Soil moisture, typically defined as the amount of water in the unsaturated soil layer, is a central component of the hydrological cycle. The potential impacts of climate change on soil moisture have been less specifically studied than those on river flows, despite soil moisture deficits/excesses being a factor in a range of natural hazards, as well as having obvious importance for agriculture. Here, 1 km grids of monthly mean soil moisture content are simulated using a national-scale grid-based hydrological model, more typically applied to look at changes in river flows across Britain. A comparison of the soil moisture estimates from an observation-based simulation, with soil moisture deficit data from an operational system developed by the UK Met Office (Meteorological Office Rainfall and Evaporation Calculation System; MORECS), shows relatively good correspondence in soil drying and wetting dates, and in the month when soils are driest. The UK Climate Projections 2018 Regional projections are then used to drive the hydrological model, to investigate changes in occurrence of indicative soil moisture extremes and changes in typical wetting and drying dates of soils across the country. Analyses comparing baseline (December 1981–November 2011) and future (December 2050–November 2080) time-slices suggest large increases in the spatial occurrence of low soil moisture levels, along with later soil wetting dates, although changes to soil drying dates are less clear. Such information on potential future changes in soil moisture is important to enable the development of appropriate adaptation strategies for a range of sectors vulnerable to soil moisture levels

An assessment of the possible impacts of climate change on snow and peak river flows across Britain

A temperature-based snow module has been coupled with a grid-based distributed hydrological model, to improve simulations of river flows in upland areas of Britain subject to snowfall and snowmelt. The coupled model has been driven with data from an 11-member perturbed-parameter climate model ensemble, for two time-slices (1960-1990 and 2069-2099), to investigate the potential impacts of climate change. The analysis indicates large reductions in the ensemble mean of the number of lying snow days across the country. This in turn affects the seasonality of peak river flows in some parts of the country; for northerly regions, annual maxima tend to occur earlier in the water year in future. For more southerly regions the changes are less straightforward, and likely driven by changes in rainfall patterns rather than snow. The modelled percentage changes in peak flows illustrate high spatial variability in hydrological response to projected climate change, and large differences between ensemble members. When changes in projected future peak flows are compared to an estimate of current natural variability, more changes fall outside the range of natural variability in southern Britain than in the north

Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study.

We investigated long-term (to 25 years) seizure prognosis and survival in people with newly diagnosed epilepsy in the community. We explored whether prognosis is different in those with epilepsy (>2 unprovoked seizures) and those with a single seizure at presentation. This is a prospective observational cohort study of people with newly diagnosed seizures. We investigated seizure outcome and survival in people presenting with a single seizure and in those presenting with >2 seizures (epilepsy). 695 people (median follow-up 23.6 years) had unprovoked epileptic seizures. For seizure analysis we excluded 38 people with missing data leaving 657 (309 male, and 249 aged <18 years). Seizures recurred in 67%. The 354 people with epilepsy were only slightly more likely to have further seizure recurrence than the 302 people with a single seizure at presentation (HR 1.32, 95% CI 1.09 to 1.59). In 327 people with complete follow-up, 268 (82%, 95% CI 77% to 86%) were in terminal remission; (80%, (95% CI 73% to 85%) in those with epilepsy at presentation). Premature mortality was increased in people with epilepsy (standardised mortality ratio 1.67; 95% CI 1.40 to 1.99) and those with a single seizure at presentation (standardised mortality ratio 2.65; 95% CI 2.23 to 3.15). It is also high in those with early remission. People with epilepsy and with single seizures at presentation in the community generally have good prognosis for seizure control with prolonged follow-up. The risk of premature mortality is significantly increased in both groups

National-scale analysis of low flow frequency: historical trends and potential future changes

The potential impact of climate change on hydrological extremes is of increasing concern across the globe. Here, a national-scale grid-based hydrological model is used to investigate historical trends and potential future changes in low flow frequency across Great Britain. The historical analyses use both observational data (1891–2015) and ensemble data from a regional climate model (1900–2006). The results show relatively few significant trends in historical low flows (2- or 20-year return period), whether based on 7- or 30-day annual minima. Significant negative trends seen in some limited parts of the country when using observational data are generally not seen when using climate model data. The future analyses use climate model ensemble data for both near future and far future time periods (2020–2049 and 2070–2099 respectively), which are compared to a baseline sub-period from the historical ensemble (1975–2004). The results show future reductions in low flows, which are generally larger in the south of the country, at the higher (20-year) return period, and for the later time period. Reductions are more limited if the estimates of future potential evaporation include the effect of increased carbon dioxide concentrations on stomatal resistance. Such reductions in river flow could have significant impacts on the aquatic environment and on agriculture, and present a challenge for water managers, especially as reductions in water supply are likely to occur alongside increases in demand

An assessment of the potential for natural flood management to offset climate change impacts

Natural Flood Management (NFM) aims to work with natural processes to reduce flood risk, and can potentially contribute to integrated flood risk management (alongside engineering solutions) by providing landscape-based resilience to climate change impacts. Here, two approaches are used to assess the extent to which NFM could offset the impacts of climate change on floods in Great Britain. The first looks at specific catchments where there is quantitative evidence for the effect of NFM measures on peak flows. The second takes a broad-brush national view, assuming two potential levels of NFM reductions in peak flows. Both approaches use flood impacts derived from climate change projections for a range of future time-slices and emissions scenarios. The results show that NFM measures are much less likely to be able to offset the impacts of climate change for later time-slices and for higher emissions scenarios, but also that the chance of offsetting the impacts of climate change in any individual catchment will depend on its type (how sensitive it is to climatic changes) and its location (due to spatial variation in climatic changes). Confounding factors in the analysis include any time lag associated with the NFM reduction in peak flows, and different effects of NFM on peak flows of different return periods. It is also unclear whether there is any relationship between a catchment's type and its practical potential for implementing NFM, or the level of peak flow reduction that NFM could achieve; any such relationship could be critical in determining the overall potential for NFM to offset climate change impacts in different catchments. Although the focus here is Great Britain, a similar approach could be applied internationally

Connections between Deep-Inelastic and Annihilation Processes at Next-to-Next-to-Leading Order and Beyond

We have discovered 7 intimate connections between the published results for the radiative corrections, \Ck, to the Gross--Llewellyn Smith (GLS) sum rule, in deep-inelastic lepton scattering, and the radiative corrections, \Cr, to the Adler function of the flavour-singlet vector current, in \ee annihilation. These include a surprising relation between the scheme-independent single-electron-loop contributions to the 4-loop QED $\beta$\/-function and the zero-fermion-loop abelian terms in the 3-loop GLS sum rule. The combined effect of all 7 relations is to give the factorization of the 2-loop $\beta$\/-function in \Ds\equiv\Ck\Cr-1=\frac{\Be}{\Aq}\left\{S_1\Cf\Aq+\left[S_2\Tf\Nf +\Sa\Ca+\Sf\Cf\right]\Cf\Aq^2\right\}+O(\Aq^4)\,, where \Aq=\al(\mu^2=Q^2)/4\pi is the \MS coupling of an arbitrary colour gauge theory, and S_1=-\Df{21}{2}+12\Ze3\,;\quad S_2=\Df{326}{3}-\Df{304}{3}\Ze3\,;\quad \Sa=-\Df{629}{2}+\Df{884}{3}\Ze3\,;\quad \Sf=\Df{397}{6}+136\Ze3-240\Ze5 specify the sole content of \Ck that is not already encoded in \Cr and \Be=Q^2\rd\Aq/\rd Q^2 at O(\Aq^3). The same result is obtained by combining the radiative corrections to Bjorken's polarized sum rule with those for the Adler function of the non-singlet axial current. We suggest possible origins of $\beta$ in the `Crewther discrepancy', \Ds, and determine \Ds/(\Be/\Aq), to all orders in \Nf\Aq, in the large-\Nf limit, obtaining the {\em entire\/} series of coefficients of which $S_1$ and $S_2$ are merely the first two members.Comment: 11 pages, LATEX, preprint INR-820/93, OUT-4102-45; In memoriam Sergei Grogorievich Corishny, 1958-198

Role of the Coulomb and the vector-isovector ρ\rho potentials in the isospin asymmetry of nuclear pseudospin

We investigate the role of the Coulomb and the vector-isovector $\rho$ potentials in the asymmetry of the neutron and proton pseudospin splittings in nuclei. To this end, we solve the Dirac equation for the nucleons using central vector and scalar potentials with Woods-Saxon shape and $Z$ and $N-Z$ dependent Coulomb and $\rho$ potentials added to the vector potential. We study the effect of these potentials on the energy splittings of proton and neutron pseudospin partners along a Sn isotopic chain. We use an energy decomposition proposed in a previous work to assess the effect of a pseudospin-orbit potential on those splittings. We conclude that the effect of the Coulomb potential is quite small and the $\rho$ potential gives the main contribution to the observed isospin asymmetry of the pseudospin splittings. This isospin asymmetry results from a cancellation of the various energy terms and cannot be attributed only to the pseudospin-orbit term, confirming the dynamical character of this symmetry pointed out in previous works.Comment: 9 pages, 11 figures, uses revtex4; title was changed and several small corrections were made throughout the tex

Continuous loading of a magnetic trap

We have realized a scheme for continuous loading of a magnetic trap (MT). ^{52}Cr atoms are continuously captured and cooled in a magneto-optical trap (MOT). Optical pumping to a metastable state decouples atoms from the cooling light. Due to their high magnetic moment (6 Bohr magnetons), low-field seeking metastable atoms are trapped in the magnetic quadrupole field provided by the MOT. Limited by inelastic collisions between atoms in the MOT and in the MT, we load 10^8 metastable atoms at a rate of 10^8 atoms/s below 100 microkelvin into the MT. After loading we can perform optical repumping to realize a MT of ground state chromium atoms.Comment: 4 pages, 4 figures, version 2, modified references, included additional detailed information, minor changes in figure 3 and in tex