Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

We present a simulation-based method designed to establish that software developed to fit a specific Bayesian model works properly, capitalizing on properties of Bayesian posterior distributions. We illustrate the validation technique with two examples. The validation method is shown to find errors in software when they exist and, moreover, the validation output can be informative about the nature and location of such errors.

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This study reports evidence that schizophrenia patients are significantly impaired in both spatial and object (shape) working memory. A 3-s delay between exposure and recall of targets was used and Bayesian item-response theory was applied to compensate for the tasks' differential difficulty while simultaneously taking account of missing data from participant attrition. Weaker evidence was found that in schizophrenia both domains are equally impaired on average, that spatial and object working memory appear to be more highly correlated with each other in the schizophrenia population than in the normal population, and that schizophrenia patients show greater variability in spatial than object working memory performance.

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In genetic association studies, tests for Hardy-Weinberg proportions are often employed as a quality control checking procedure. Missing genotypes are typically discarded prior to testing. In this paper we show that inference for Hardy-Weinberg proportions can be biased when missing values are discarded. We propose to use multiple imputation of missing values in order to improve inference for Hardy-Weinberg proportions. For imputation we employ a multinomial logit model that uses information from allele intensities and/or neighbouring markers. Analysis of an empirical data set of single nucleotide polymorphisms possibly related to colon cancer reveals that missing genotypes are not missing completely at random. Deviation from Hardy-Weinberg proportions is mostly due to a lack of heterozygotes. Inbreeding coefficients estimated by multiple imputation of the missings are typically lowered with respect to inbreeding coefficients estimated by discarding the missings. Accounting for missings by multiple imputation qualitatively changed the results of 10 to 17% of the statistical tests performed. Estimates of inbreeding coefficients obtained by multiple imputation showed high correlation with estimates obtained by single imputation using an external reference panel. Our conclusion is that imputation of missing data leads to improved statistical inference for Hardy-Weinberg proportions.

Microfossils recovered from chalk tesserae in mosaics from the Roman town Calleva Atrebatum, modern Silchester, southern England, are used to suggest a provenance for the source-rock. The microfossils include foraminifera characteristic of late Cretaceous (Campanian) foraminiferal biozone BGS20 (quadrata macrofaunal biozone) and subzone BGS21i (basal mucronata macrofaunal biozone). Calcareous nannofossil assemblages from the same tesserae are poorly preserved, preventing precise age determination, but confirm an age of Santonian to Campanian. As indurated chalk beds of this age are not present in the chalks of southern England, it is probable that calcretized chalk, formed by secondary calcification beneath Palaeogene rock cover, was used to manufacture the tesserae. This suggestion is supported by a comparative analysis of chalk tesserae from the Norden Roman site in Dorset.Although the provenance of the chalk in some of the Silchester tesserae can be placed only within a broad geographical area of downland in southern England, others apparently originated in the Dorchester-Swanage-Portsdown area, some 100 km to the

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