Self-play: statistical significance

Heinz recently completed a comprehensive experiment in self-play using the FRITZ chess engine to establish the ‘decreasing returns’ hypothesis with specific levels of statistical confidence. This note revisits the results and recalculates the confidence levels of this and other hypotheses. These appear to be better than Heinz’ initial analysis suggests.

Statistical methods for examining genetic influences of resistance to anti-epileptic drugs

It is generally accepted that genetics may be an important factor in explaining the variation between patients’ responses to certain drugs. However, identification and confirmation of the responsible genetic variants is proving to be a challenge in many cases. A number of difficulties that maybe encountered in pursuit of these variants, such as non-replication of a true effect, population structure and selection bias, can be mitigated or at least reduced by appropriate statistical methodology. Another major statistical challenge facing pharmacogenetics studies is trying to detect possibly small polygenic effects using large volumes of genetic data, while controlling the number of false positive signals. Here we review statistical design and analysis options available for investigations of genetic resistance to anti-epileptic drugs.

Statistical downscaling of river flows

An extensive statistical ‘downscaling’ study is done to relate large-scale climate information from a general circulation model (GCM) to local-scale river flows in SW France for 51 gauging stations ranging from nival (snow-dominated) to pluvial (rainfall-dominated) river-systems. This study helps to select the appropriate statistical method at a given spatial and temporal scale to downscale hydrology for future climate change impact assessment of hydrological resources. The four proposed statistical downscaling models use large-scale predictors (derived from climate model outputs or reanalysis data) that characterize precipitation and evaporation processes in the hydrological cycle to estimate summary flow statistics. The four statistical models used are generalized linear (GLM) and additive (GAM) models, aggregated boosted trees (ABT) and multi-layer perceptron neural networks (ANN). These four models were each applied at two different spatial scales, namely at that of a single flow-gauging station (local downscaling) and that of a group of flow-gauging stations having the same hydrological behaviour (regional downscaling). For each statistical model and each spatial resolution, three temporal resolutions were considered, namely the daily mean flows, the summary statistics of fortnightly flows and a daily ‘integrated approach’. The results show that flow sensitivity to atmospheric factors is significantly different between nival and pluvial hydrological systems which are mainly influenced, respectively, by shortwave solar radiations and atmospheric temperature. The non-linear models (i.e. GAM, ABT and ANN) performed better than the linear GLM when simulating fortnightly flow percentiles. The aggregated boosted trees method showed higher and less variable R2 values to downscale the hydrological variability in both nival and pluvial regimes. Based on GCM cnrm-cm3 and scenarios A2 and A1B, future relative changes of fortnightly median flows were projected based on the regional downscaling approach. The results suggest a global decrease of flow in both pluvial and nival regimes, especially in spring, summer and autumn, whatever the considered scenario. The discussion considers the performance of each statistical method for downscaling flow at different spatial and temporal scales as well as the relationship between atmospheric processes and flow variability.

Statistical evaluation of an acute dermal toxicity test using the dermal fixed dose procedure

The conventional method for the assessment of acute dermal toxicity (OECD Test Guideline 402, 1987) uses death of animals as an endpoint to identify the median lethal dose (LD50). A new OECD Testing Guideline called the dermal fixed dose procedure (dermal FDP) is being prepared to provide an alternative to Test Guideline 402. In contrast to Test Guideline 402, the dermal FDP does not provide a point estimate of the LD50, but aims to identify that dose of the substance under investigation that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonised System of Classification and Labelling scheme (GHS). The dermal FDP has been validated using statistical modelling rather than by in vivo testing. The statistical modelling approach enables calculation of the probability of each GHS classification and the expected numbers of deaths and animals used in the test for imaginary substances with a range of LD50 values and dose-response curve slopes. This paper describes the dermal FDP and reports the results from the statistical evaluation. It is shown that the procedure will be completed with considerably less death and suffering than guideline 402, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LD50 value.