Statistical evaluation of the fixed concentration procedure for acute inhalation toxicity assessment

The conventional method for the assessment of acute inhalation toxicity (OECD Test Guideline 403, 1981) uses death of animals as an endpoint to identify the median lethal concentration (LC50). A new OECD Testing Guideline called the Fixed Concentration Procedure (FCP) is being prepared to provide an alternative to Test Guideline 403. Unlike Test Guideline 403, the FCP does not provide a point estimate of the LC50, but aims to identify an airborne exposure level that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonized System of Classification and Labelling scheme (GHS). The FCP has been validated using statistical simulation rather than byin vivo testing. The statistical simulation approach predicts the GHS classification outcome and the numbers of deaths and animals used in the test for imaginary substances with a range of LC50 values and dose response curve slopes. This paper describes the FCP and reports the results from the statistical simulation study assessing its properties. It is shown that the procedure will be completed with considerably less death and suffering than Test Guideline 403, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LC50 value.

An observing system simulation experiment for climate monitoring with GNSS radio occulation data: setup and testbed study

The long-term stability, high accuracy, all-weather capability, high vertical resolution, and global coverage of Global Navigation Satellite System (GNSS) radio occultation (RO) suggests it as a promising tool for global monitoring of atmospheric temperature change. With the aim to investigate and quantify how well a GNSS RO observing system is able to detect climate trends, we are currently performing an (climate) observing system simulation experiment over the 25-year period 2001 to 2025, which involves quasi-realistic modeling of the neutral atmosphere and the ionosphere. We carried out two climate simulations with the general circulation model MAECHAM5 (Middle Atmosphere European Centre/Hamburg Model Version 5) of the MPI-M Hamburg, covering the period 2001–2025: One control run with natural variability only and one run also including anthropogenic forcings due to greenhouse gases, sulfate aerosols, and tropospheric ozone. On the basis of this, we perform quasi-realistic simulations of RO observables for a small GNSS receiver constellation (six satellites), state-of-the-art data processing for atmospheric profiles retrieval, and a statistical analysis of temperature trends in both the “observed” climatology and the “true” climatology. Here we describe the setup of the experiment and results from a test bed study conducted to obtain a basic set of realistic estimates of observational errors (instrument- and retrieval processing-related errors) and sampling errors (due to spatial-temporal undersampling). The test bed results, obtained for a typical summer season and compared to the climatic 2001–2025 trends from the MAECHAM5 simulation including anthropogenic forcing, were found encouraging for performing the full 25-year experiment. They indicated that observational and sampling errors (both contributing about 0.2 K) are consistent with recent estimates of these errors from real RO data and that they should be sufficiently small for monitoring expected temperature trends in the global atmosphere over the next 10 to 20 years in most regions of the upper troposphere and lower stratosphere (UTLS). Inspection of the MAECHAM5 trends in different RO-accessible atmospheric parameters (microwave refractivity and pressure/geopotential height in addition to temperature) indicates complementary climate change sensitivity in different regions of the UTLS so that optimized climate monitoring shall combine information from all climatic key variables retrievable from GNSS RO data.

Statistical properties of cloud lifecycles in cloud-resolving models

A new technique is described for the analysis of cloud-resolving model simulations, which allows one to investigate the statistics of the lifecycles of cumulus clouds. Clouds are tracked from timestep-to-timestep within the model run. This allows for a very simple method of tracking, but one which is both comprehensive and robust. An approach for handling cloud splits and mergers is described which allows clouds with simple and complicated time histories to be compared within a single framework. This is found to be important for the analysis of an idealized simulation of radiative-convective equilibrium, in which the moist, buoyant, updrafts (i.e., the convective cores) were tracked. Around half of all such cores were subject to splits and mergers during their lifecycles. For cores without any such events, the average lifetime is 30min, but events can lengthen the typical lifetime considerably.

New insights on growth mechanisms of protein clusters at surfaces: an AFM and simulation study

Despite its relevance to a wide range of technological and fundamental areas, a quantitative understanding of protein surface clustering dynamics is often lacking. In inorganic crystal growth, surface clustering of adatoms is well described by diffusion-aggregation models. In such models, the statistical properties of the aggregate arrays often reveal the molecular scale aggregation processes. We investigate the potential of these theories to reveal hitherto hidden facets of protein clustering by carrying out concomitant observations of lysozyme adsorption onto mica surfaces, using atomic force microscopy. and Monte Carlo simulations of cluster nucleation and growth. We find that lysozyme clusters diffuse across the substrate at a rate that varies inversely with size. This result suggests which molecular scale mechanisms are responsible for the mobility of the proteins on the substrate. In addition the surface diffusion coefficient of the monomer can also be extracted from the comparison between experiments and simulations. While concentrating on a model system of lysozyme-on-mica, this 'proof of concept' study successfully demonstrates the potential of our approach to understand and influence more biomedically applicable protein-substrate couples.

Statistical inferences in phylogeography

In conventional phylogeographic studies, historical demographic processes are elucidated from the geographical distribution of individuals represented on an inferred gene tree. However, the interpretation of gene trees in this context can be difficult as the same demographic/geographical process can randomly lead to multiple different genealogies. Likewise, the same gene trees can arise under different demographic models. This problem has led to the emergence of many statistical methods for making phylogeographic inferences. A popular phylogeographic approach based on nested clade analysis is challenged by the fact that a certain amount of the interpretation of the data is left to the subjective choices of the user, and it has been argued that the method performs poorly in simulation studies. More rigorous statistical methods based on coalescence theory have been developed. However, these methods may also be challenged by computational problems or poor model choice. In this review, we will describe the development of statistical methods in phylogeographic analysis, and discuss some of the challenges facing these methods.

Effect of internal partitioning on room air quality with mixing ventilation-statistical analysis

In designing modern office buildings, building spaces are frequently zoned by introducing internal partitioning, which may have a significant influence on the room air environment. This internal partitioning was studied by means of model test, numerical simulation, and statistical analysis as the final stage. In this paper, the results produced from the statistical analysis are summarized and presented.

A micro-level simulation for the prediction of intention and behaviour

In this contribution we aim at anchoring Agent-Based Modeling (ABM) simulations in actual models of human psychology. More specifically, we apply unidirectional ABM to social psychological models using low level agents (i.e., intra-individual) to examine whether they generate better predictions, in comparison to standard statistical approaches, concerning the intentions of performing a behavior and the behavior. Moreover, this contribution tests to what extent the predictive validity of models of attitude such as the Theory of Planned Behavior (TPB) or Model of Goal-directed Behavior (MGB) depends on the assumption that peoples’ decisions and actions are purely rational. Simulations were therefore run by considering different deviations from rationality of the agents with a trembling hand method. Two data sets concerning respectively the consumption of soft drinks and physical activity were used. Three key findings emerged from the simulations. First, compared to standard statistical approach the agent-based simulation generally improves the prediction of behavior from intention. Second, the improvement in prediction is inversely proportional to the complexity of the underlying theoretical model. Finally, the introduction of varying degrees of deviation from rationality in agents’ behavior can lead to an improvement in the goodness of fit of the simulations. By demonstrating the potential of ABM as a complementary perspective to evaluating social psychological models, this contribution underlines the necessity of better defining agents in terms of psychological processes before examining higher levels such as the interactions between individuals.

A combined engineering and statistical model of UK domestic appliance electrical load profiles

The development of a combined engineering and statistical Artificial Neural Network model of UK domestic appliance load profiles is presented. The model uses diary-style appliance use data and a survey questionnaire collected from 51 suburban households and 46 rural households during the summer of 2010 and2011 respectively. It also incorporates measured energy data and is sensitive to socioeconomic, physical dwelling and temperature variables. A prototype model is constructed in MATLAB using a two layer feed forward network with back propagation training which has a 12:10:24 architecture. Model outputs include appliance load profiles which can be applied to the fields of energy planning (microrenewables and smart grids), building simulation tools and energy policy.

Influence of probabilistic climate projections on building energy simulation

The Chartered Institute of Building Service Engineers (CIBSE) produced a technical memorandum (TM36) presenting research on future climate impacting building energy use and thermal comfort. One climate projection for each of four CO2 emissions scenario were used in TM36, so providing a deterministic outlook. As part of the UK Climate Impacts Programme (UKCIP) probabilistic climate projections are being studied in relation to building energy simulation techniques. Including uncertainty in climate projections is considered an important advance to climate impacts modelling and is included in the latest UKCIP data (UKCP09). Incorporating the stochastic nature of these new climate projections in building energy modelling requires a significant increase in data handling and careful statistical interpretation of the results to provide meaningful conclusions. This paper compares the results from building energy simulations when applying deterministic and probabilistic climate data. This is based on two case study buildings: (i) a mixed-mode office building with exposed thermal mass and (ii) a mechanically ventilated, light-weight office building. Building (i) represents an energy efficient building design that provides passive and active measures to maintain thermal comfort. Building (ii) relies entirely on mechanical means for heating and cooling, with its light-weight construction raising concern over increased cooling loads in a warmer climate. Devising an effective probabilistic approach highlighted greater uncertainty in predicting building performance, depending on the type of building modelled and the performance factors under consideration. Results indicate that the range of calculated quantities depends not only on the building type but is strongly dependent on the performance parameters that are of interest. Uncertainty is likely to be particularly marked with regard to thermal comfort in naturally ventilated buildings.

Assimilation of sea-ice concentration in a global climate model — physical and statistical aspects

We investigate the initialisation of Northern Hemisphere sea ice in the global climate model ECHAM5/MPI-OM by assimilating sea-ice concentration data. The analysis updates for concentration are given by Newtonian relaxation, and we discuss different ways of specifying the analysis updates for mean thickness. Because the conservation of mean ice thickness or actual ice thickness in the analysis updates leads to poor assimilation performance, we introduce a proportional dependence between concentration and mean thickness analysis updates. Assimilation with these proportional mean-thickness analysis updates leads to good assimilation performance for sea-ice concentration and thickness, both in identical-twin experiments and when assimilating sea-ice observations. The simulation of other Arctic surface fields in the coupled model is, however, not significantly improved by the assimilation. To understand the physical aspects of assimilation errors, we construct a simple prognostic model of the sea-ice thermodynamics, and analyse its response to the assimilation. We find that an adjustment of mean ice thickness in the analysis update is essential to arrive at plausible state estimates. To understand the statistical aspects of assimilation errors, we study the model background error covariance between ice concentration and ice thickness. We find that the spatial structure of covariances is best represented by the proportional mean-thickness analysis updates. Both physical and statistical evidence supports the experimental finding that assimilation with proportional mean-thickness updates outperforms the other two methods considered. The method described here is very simple to implement, and gives results that are sufficiently good to be used for initialising sea ice in a global climate model for seasonal to decadal predictions.

The DYMECS project: a statistical approach for the evaluation of convective storms in high-resolution NWP models

A new frontier in weather forecasting is emerging by operational forecast models now being run at convection-permitting resolutions at many national weather services. However, this is not a panacea; significant systematic errors remain in the character of convective storms and rainfall distributions. The DYMECS project (Dynamical and Microphysical Evolution of Convective Storms) is taking a fundamentally new approach to evaluate and improve such models: rather than relying on a limited number of cases, which may not be representative, we have gathered a large database of 3D storm structures on 40 convective days using the Chilbolton radar in southern England. We have related these structures to storm life-cycles derived by tracking features in the rainfall from the UK radar network, and compared them statistically to storm structures in the Met Office model, which we ran at horizontal grid length between 1.5 km and 100 m, including simulations with different subgrid mixing length. We also evaluated the scale and intensity of convective updrafts using a new radar technique. We find that the horizontal size of simulated convective storms and the updrafts within them is much too large at 1.5-km resolution, such that the convective mass flux of individual updrafts can be too large by an order of magnitude. The scale of precipitation cores and updrafts decreases steadily with decreasing grid lengths, as does the typical storm lifetime. The 200-m grid-length simulation with standard mixing length performs best over all diagnostics, although a greater mixing length improves the representation of deep convective storms.

On the ability of statistical wind-wave models to capture the variability and long-term trends of the North Atlantic winter wave climate

A dynamical wind-wave climate simulation covering the North Atlantic Ocean and spanning the whole 21st century under the A1B scenario has been compared with a set of statistical projections using atmospheric variables or large scale climate indices as predictors. As a first step, the performance of all statistical models has been evaluated for the present-day climate; namely they have been compared with a dynamical wind-wave hindcast in terms of winter Significant Wave Height (SWH) trends and variance as well as with altimetry data. For the projections, it has been found that statistical models that use wind speed as independent variable predictor are able to capture a larger fraction of the winter SWH inter-annual variability (68% on average) and of the long term changes projected by the dynamical simulation. Conversely, regression models using climate indices, sea level pressure and/or pressure gradient as predictors, account for a smaller SWH variance (from 2.8% to 33%) and do not reproduce the dynamically projected long term trends over the North Atlantic. Investigating the wind-sea and swell components separately, we have found that the combination of two regression models, one for wind-sea waves and another one for the swell component, can improve significantly the wave field projections obtained from single regression models over the North Atlantic.