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

Performance of sugarcane varieties with contrasting growth habit in different row spacings and configurations

Controlled traffic (matching wheel and row spacing) is being widely adopted in the Australian sugar industry to minimise the adverse effect of soil compaction caused by heavy machinery such as cane harvesters and haul-outs. In this study, the performance of current cane varieties with contrasting growth habits in differing row spacings and planting arrangements designed to achieve controlled traffic outcomes is reported. The study was conducted on an irrigated site in the Farnsfield district of the Isis mill area. Cane varieties Q138, Q188A, Q205A and Q222A were planted with whole stick, conventional mouldboard opener planters in 1.5 m and 1.8 m single rows and in dual rows on 1.8 m or 2.0 m centres, as well as by billet planting in a 1.8 m wide throat system. Shoot counts and biomass samples were collected at intervals during the growing season. There were no significant differences in cane yields, ccs or sugar yields between row spacings at harvest, and nor was there any significant interaction between varieties and row spacings for any parameter. This was despite there being significantly fewer harvested stalks in 1.8 m single rows (8.2/m2) and 1.8 m wide throat (9.3/m2) than in standard 1.5 m single rows (10.2/m2) or the 1.8 m (10.6/m2) and 2.0 m (10.3/m2) dual row spacings. Much heavier individual stalk weights recorded in the 1.8 m single and wide throat billet plantings were able to compensate for lower stalk numbers. Results confirm the relative insensitivity of cane yields to crop row spacing and suggest considerable flexibility in developing row spacings to suit controlled traffic farming systems. There were significant differences between varieties in cane yields, ccs and sugar yields. Cane yields for Q205A and Q222A (124 t/ha and 121 t/ha) were significantly higher than Q188A (115 t/ha) and Q138 (112 t/ha). However, in terms of sugar yield, these cane yield differences were modified to some extent by variation in ccs, with Q222A and Q188A (13.8% and 13.5%, respectively) having higher CCS than Q205A (12.9%) and Q138 (11.1%). The combined effects resulted in the highest sugar yields in Q222A (16.8 t/ha), with Q205A and Q188A (15.8 and 15.5 t/ha, respectively) out yielding Q138 (12.7 t/ha). Varieties used different strategies to achieve final cane yields, with high final stalk numbers in Q138 (10.5/m2) and low stalk numbers in Q188A (9.0/m2) compensated for by differences in individual stalk weights

Managing yield decline in sugarcane cropping systems

This paper summarises the results from ten years of yield decline research carried out by the Sugar Yield Decline Joint Venture in the Australian sugar industry. The research concludes that, although the ultimate expression of yield decline may be through adverse effects of pathogens on sugarcane root systems, yield decline is a complex issue caused by a number of factors being out of balance in the sugarcane cropping system. Soil degradation has been the result of the long-term sugarcane monoculture and how it has been practiced. Specific research has shown that the long-term monoculture, uncontrolled traffic from heavy machinery and excessive tillage along with practices that deplete organic matter all contribute to yield decline. It is argued that changes to the cropping system that will conserve organic matter, break the monoculture, control traffic and minimize tillage are the most appropriate ways to combat yield decline. The technology is now available to incorporate these changes into the cropping system and a more sustainable, profitable and environmentally responsible cropping system is proposed. The proposed system is not prescriptive and many acceptable variations will be just as suitable providing the basic principles of organic matter conservation, breaking the monoculture, controlling traffic and minimizing tillage are no compromised

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