Control and analysis of oriented thin films of lipid inverse bicontinuous cubic phases using grazing incidence small-angle X‑ray scattering

Lipid cubic phases are complex nanostructures that form naturally in a variety of biological systems, with applications including drug delivery and nanotemplating. Most X-ray scattering studies on lipid cubic phases have used unoriented polydomain samples as either bulk gels or suspensions of micrometer-sized cubosomes. We present a method of investigating cubic phases in a new form, as supported thin films that can be analyzed using grazing incidence small-angle X-ray scattering (GISAXS). We present GISAXS data on three lipid systems: phytantriol and two grades of monoolein (research and industrial). The use of thin films brings a number of advantages. First, the samples exhibit a high degree of uniaxial orientation about the substrate normal. Second, the new morphology allows precise control of the substrate mesophase geometry and lattice parameter using a controlled temperature and humidity environment, and we demonstrate the controllable formation of oriented diamond and gyroid inverse bicontinuous cubic along with lamellar phases. Finally, the thin film morphology allows the induction of reversible phase transitions between these mesophase structures by changes in humidity on subminute time scales, and we present timeresolved GISAXS data monitoring these transformations.

Resistance to the anticoagulant rodenticides – the deployment of the new molecular methodology to identify mutations of the VKORC1 ‘resistance gene’, and understanding their potential impact on treatment outcome

Anticoagulants rodenticides have already known for over half a century, as effective and safe method of rodent control. However, discovered in 1958 anticoagulant resistance has given us a very important problem for their future long-term use. Laboratory tests provide the main method for identification the different types of anticoagulant resistances, quantify the magnitude of their effect and help us to choose the best pest control strategy. The main important tests are lethal feeding period (LFP) and blood clotting response (BCR) tests. These tests can now be used to quantify the likely effect of the resistance on treatment outcome by providing an estimate of the ‘resistance factor’. In 2004 the gene responsible for anticoagulant resistance (VKORC1) was identified and sequenced. As a result, a new molecular resistance testing methodology has been developed, and a number of resistance mutations, particularly in Norway rats and house mice. Three mutations of the VKORC1 gene in Norway rats have been identified to date that confer a degree of resistance to bromadiolone and difenacoum, sufficient to affect treatment outcome in the field.

Experimental confirmation of transformation pathways between inverse double diamond and gyroid cubic phases

A macroscopically oriented double diamond inverse bicontinuous cubic phase (QIID) of the lipid glycerol monooleate is reversibly converted into a gyroid phase (QIIG). The initial QIID phase is prepared in the form of a film coating the inside of a capillary, deposited under flow, which produces a sample uniaxially oriented with a ⟨110⟩ axis parallel to the symmetry axis of the sample. A transformation is induced by replacing the water within the capillary tube with a solution of poly(ethylene glycol), which draws water out of the QIID sample by osmotic stress. This converts the QIID phase into a QIIG phase with two coexisting orientations, with the ⟨100⟩ and ⟨111⟩ axes parallel to the symmetry axis, as demonstrated by small-angle X-ray scattering. The process can then be reversed, to recover the initial orientation of QIID phase. The epitaxial relation between the two oriented mesophases is consistent with topologypreserving geometric pathways that have previously been hypothesized for the transformation. Furthermore, this has implications for the production of macroscopically oriented QIIG phases, in particular with applications as nanomaterial templates.

The greater whole: towards a synthesis of system dynamics and soft systems methodology

This paper makes a theoretical case for using these two systems approaches together. The theoretical and methodological assumptions of system dynamics (SD) and soft system methodology (SSM) are briefly described and a partial critique is presented. SSM generates and represents diverse perspectives on a problem situation and addresses the socio-political elements of an intervention. However, it is weak in ensuring `dynamic coherence'. consistency between the intuitive behaviour resulting from proposed changes and behaviour deduced from ideas on causal structure. Conversely, SD examines causal structures and dynamic behaviours. However, whilst emphasising the need for a clear issue focus, it has little theory for generating and representing diverse issues. Also, there is no theory for facilitating sensitivity to socio-political elements. A synthesis of the two called ‘Holon Dynamics' is proposed. After an SSM intervention, a second stage continues the socio-political analysis and also operates within a new perspective which values dynamic coherence of the mental construct - the holon - which is capable of expressing the proposed changes. A model of this holon is constructed using SD and the changes are thus rendered `systemically desirable' in the additional sense that dynamic consistency has been confirmed. The paper closes with reflections on the proposal and the need for theoretical consistency when mixing tools is emphasised.

Modelling as learning: a consultancy methodology for enhancing learning in management teams

This article reviews the experiences of a practising business consultancy division. It discusses the reasons for the failure of the traditional, expert consultancy approach and states the requirements for a more suitable consultancy methodology. An approach called ‘Modelling as Learning’ is introduced, its three defining aspects being: client ownership of all analytical work performed, consultant acting as facilitator and sensitivity to soft issues within and surrounding a problem. The goal of such an approach is set as the acceleration of the client's learning about the business. The tools that are used within this methodological framework are discussed and some case studies of the methodology are presented. It is argued that a learning experience was necessary before arriving at the new methodology but that it is now a valuable and significant component of the division's work.

An optimal inverse method using Doppler lidar measurements to estimate the surface sensible heat flux

Inverse methods are widely used in various fields of atmospheric science. However, such methods are not commonly used within the boundary-layer community, where robust observations of surface fluxes are a particular concern. We present a new technique for deriving surface sensible heat fluxes from boundary-layer turbulence observations using an inverse method. Doppler lidar observations of vertical velocity variance are combined with two well-known mixed-layer scaling forward models for a convective boundary layer (CBL). The inverse method is validated using large-eddy simulations of a CBL with increasing wind speed. The majority of the estimated heat fluxes agree within error with the proscribed heat flux, across all wind speeds tested. The method is then applied to Doppler lidar data from the Chilbolton Observatory, UK. Heat fluxes are compared with those from a mast-mounted sonic anemometer. Errors in estimated heat fluxes are on average 18 %, an improvement on previous techniques. However, a significant negative bias is observed (on average −63%) that is more pronounced in the morning. Results are improved for the fully-developed CBL later in the day, which suggests that the bias is largely related to the choice of forward model, which is kept deliberately simple for this study. Overall, the inverse method provided reasonable flux estimates for the simple case of a CBL. Results shown here demonstrate that this method has promise in utilizing ground-based remote sensing to derive surface fluxes. Extension of the method is relatively straight-forward, and could include more complex forward models, or other measurements.

The WFDEI meteorological forcing data set: WATCH Forcing Data methodology applied to ERA-Interim reanalysis data

The WFDEI meteorological forcing data set has been generated using the same methodology as the widely used WATCH Forcing Data (WFD) by making use of the ERA-Interim reanalysis data. We discuss the specifics of how changes in the reanalysis and processing have led to improvement over the WFD. We attribute improvements in precipitation and wind speed to the latest reanalysis basis data and improved downward shortwave fluxes to the changes in the aerosol corrections. Covering 1979–2012, the WFDEI will allow more thorough comparisons of hydrological and Earth System model outputs with hydrologically and phenologically relevant satellite products than using the WFD.

Probability functions to build composite indicators: a methodology to measure environmental impacts of genetically modified crops

There is an on-going debate on the environmental effects of genetically modified crops to which this paper aims to contribute. First, data on environmental impacts of genetically modified (GM) and conventional crops are collected from peer-reviewed journals, and secondly an analysis is conducted in order to examine which crop type is less harmful for the environment. Published data on environmental impacts are measured using an array of indicators, and their analysis requires their normalisation and aggregation. Taking advantage of composite indicators literature, this paper builds composite indicators to measure the impact of GM and conventional crops in three dimensions: (1) non-target key species richness, (2) pesticide use, and (3) aggregated environmental impact. The comparison between the three composite indicators for both crop types allows us to establish not only a ranking to elucidate which crop is more convenient for the environment but the probability that one crop type outperforms the other from an environmental perspective. Results show that GM crops tend to cause lower environmental impacts than conventional crops for the analysed indicators.

Sustainability assessment indicators and methodology for intelligent buildings

The sustainable intelligent building is a building that has the best combination of environmental, social, economic and technical values. And its sustainability assessment is related with system engineering methods and multi-criteria decision-making. Therefore firstly, the wireless monitoring system of sustainable parameters for intelligent buildings is achieved; secondly, the indicators and key issues based on the “whole life circle” for sustainability of intelligent buildings are researched; thirdly, the sustainable assessment model identified on the structure entropy and fuzzy analytic hierarchy process is proposed.

Kraichnan–Leith–Batchelor similarity theory and two-dimensional inverse cascades

We study the scaling properties and Kraichnan–Leith–Batchelor (KLB) theory of forced inverse cascades in generalized two-dimensional (2D) fluids (α-turbulence models) simulated at resolution 8192x8192. We consider α=1 (surface quasigeostrophic flow), α=2 (2D Euler flow) and α=3. The forcing scale is well resolved, a direct cascade is present and there is no large-scale dissipation. Coherent vortices spanning a range of sizes, most larger than the forcing scale, are present for both α=1 and α=2. The active scalar field for α=3 contains comparatively few and small vortices. The energy spectral slopes in the inverse cascade are steeper than the KLB prediction −(7−α)/3 in all three systems. Since we stop the simulations well before the cascades have reached the domain scale, vortex formation and spectral steepening are not due to condensation effects; nor are they caused by large-scale dissipation, which is absent. One- and two-point p.d.f.s, hyperflatness factors and structure functions indicate that the inverse cascades are intermittent and non-Gaussian over much of the inertial range for α=1 and α=2, while the α=3 inverse cascade is much closer to Gaussian and non-intermittent. For α=3 the steep spectrum is close to that associated with enstrophy equipartition. Continuous wavelet analysis shows approximate KLB scaling ℰ(k)∝k−2 (α=1) and ℰ(k)∝k−5/3 (α=2) in the interstitial regions between the coherent vortices. Our results demonstrate that coherent vortex formation (α=1 and α=2) and non-realizability (α=3) cause 2D inverse cascades to deviate from the KLB predictions, but that the flow between the vortices exhibits KLB scaling and non-intermittent statistics for α=1 and α=2.

Validation of Canopy Height Profile methodology for small-footprint full-waveform airborne LiDAR data in a discontinuous canopy environment

A Canopy Height Profile (CHP) procedure presented in Harding et al. (2001) for large footprint LiDAR data was tested in a closed canopy environment as a way of extracting vertical foliage profiles from LiDAR raw-waveform. In this study, an adaptation of this method to small-footprint data has been shown, tested and validated in an Australian sparse canopy forest at plot- and site-level. Further, the methodology itself has been enhanced by implementing a dataset-adjusted reflectance ratio calculation according to Armston et al. (2013) in the processing chain, and tested against a fixed ratio of 0.5 estimated for the laser wavelength of 1550nm. As a by-product of the methodology, effective leaf area index (LAIe) estimates were derived and compared to hemispherical photography-derived values. To assess the influence of LiDAR aggregation area size on the estimates in a sparse canopy environment, LiDAR CHPs and LAIes were generated by aggregating waveforms to plot- and site-level footprints (plot/site-aggregated) as well as in 5m grids (grid-processed). LiDAR profiles were then compared to leaf biomass field profiles generated based on field tree measurements. The correlation between field and LiDAR profiles was very high, with a mean R2 of 0.75 at plot-level and 0.86 at site-level for 55 plots and the corresponding 11 sites. Gridding had almost no impact on the correlation between LiDAR and field profiles (only marginally improvement), nor did the dataset-adjusted reflectance ratio. However, gridding and the dataset-adjusted reflectance ratio were found to improve the correlation between raw-waveform LiDAR and hemispherical photography LAIe estimates, yielding the highest correlations of 0.61 at plot-level and of 0.83 at site-level. This proved the validity of the approach and superiority of dataset-adjusted reflectance ratio of Armston et al. (2013) over a fixed ratio of 0.5 for LAIe estimation, as well as showed the adequacy of small-footprint LiDAR data for LAIe estimation in discontinuous canopy forests.

Inverse modeling of the 14C bomb pulse in stalagmites to constrain the dynamics of soil carbon cycling at selected European cave sites

The decomposition of soil organic matter (SOM) is temperature dependent, but its response to a future warmer climate remains equivocal. Enhanced rates of decomposition of SOM under increased global temperatures might cause higher CO2 emissions to the atmosphere, and could therefore constitute a strong positive feedback. The magnitude of this feedback however remains poorly understood, primarily because of the difficulty in quantifying the temperature sensitivity of stored, recalcitrant carbon that comprises the bulk (>90%) of SOM in most soils. In this study we investigated the effects of climatic conditions on soil carbon dynamics using the attenuation of the 14C ‘bomb’ pulse as recorded in selected modern European speleothems. These new data were combined with published results to further examine soil carbon dynamics, and to explore the sensitivity of labile and recalcitrant organic matter decomposition to different climatic conditions. Temporal changes in 14C activity inferred from each speleothem was modelled using a three pool soil carbon inverse model (applying a Monte Carlo method) to constrain soil carbon turnover rates at each site. Speleothems from sites that are characterised by semi-arid conditions, sparse vegetation, thin soil cover and high mean annual air temperatures (MAATs), exhibit weak attenuation of atmospheric 14C ‘bomb’ peak (a low damping effect, D in the range: 55–77%) and low modelled mean respired carbon ages (MRCA), indicating that decomposition is dominated by young, recently fixed soil carbon. By contrast, humid and high MAAT sites that are characterised by a thick soil cover and dense, well developed vegetation, display the highest damping effect (D = c. 90%), and the highest MRCA values (in the range from 350 ± 126 years to 571 ± 128 years). This suggests that carbon incorporated into these stalagmites originates predominantly from decomposition of old, recalcitrant organic matter. SOM turnover rates cannot be ascribed to a single climate variable, e.g. (MAAT) but instead reflect a complex interplay of climate (e.g. MAAT and moisture budget) and vegetation development.

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes.