Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

It is premature to include non-CO2 effects of aviation in emission trading schemes

The recent G8 Gleneagles climate statement signed on 8 July 2005 specifically mentions a determination to lessen the impact of aviation on climate [Gleneagles, 2005. The Gleneagles communique: climate change, energy and sustainable development. http://www.fco.gov.uk/Files/kfile/PostG8_Gleneagles_Communique.pdf]. In January 2005 the European Union Emission Trading Scheme (ETS) commenced operation as the largest multi-country, multi-sector ETS in the world, albeit currently limited only to CO2 emissions. At present the scheme makes no provision for aircraft emissions. However, the UK Government would like to see aircraft included in the ETS and plans to use its Presidencies of both the EU and G8 in 2005 to implement these schemes within the EU and perhaps internationally. Non-CO2 effects have been included in some policy-orientated studies of the impact of aviation but we argue that the inclusion of such effects in any such ETS scheme is premature; we specifically argue that use of the Radiative Forcing Index for comparing emissions from different sources is inappropriate and that there is currently no metric for such a purpose that is likely to enable their inclusion in the near future. (c) 2005 Elsevier Ltd. All rights reserved.

Hitting emissions targets with (statistical) confidence in multi-instrument Emissions Trading Schemes

A means of assessing, monitoring and controlling aggregate emissions from multi-instrument Emissions Trading Schemes is proposed. The approach allows contributions from different instruments with different forms of emissions targets to be integrated. Where Emissions Trading Schemes are helping meet specific national targets, the approach allows the entry requirements of new participants to be calculated and set at a level that will achieve these targets. The approach is multi-levelled, and may be extended downwards to support pooling of participants within instruments, or upwards to embed Emissions Trading Schemes within a wider suite of policies and measures with hard and soft targets. Aggregate emissions from each instrument are treated stochastically. Emissions from the scheme as a whole are then the joint probability distribution formed by integrating the emissions from its instruments. Because a Bayesian approach is adopted, qualitative and semi-qualitative data from expert opinion can be used where quantitative data is not currently available, or is incomplete. This approach helps government retain sufficient control over emissions trading scheme targets to allow them to meet their emissions reduction obligations, while minimising the need for retrospectively adjusting existing participants’ conditions of entry. This maintains participant confidence, while providing the necessary policy levers for good governance.

Under-investigation of older people with abnormal chest radiographs

Background: Whilst many authors have previously suggested that older people are under-represented in the investigation and management of lung cancer, few data are available as to the effect of age on the subsequent investigation and management of a patient with an abnormal chest radiograph. Methods: During a 3-month period in a university teaching hospital, all abnormal chest radiographs suggestive of a possible diagnosis of lung cancer were identified, and patients subsequently followed to determine investigation, management and date of death over a 5-year period. Results: Thirty-seven younger (less than or equal to69 years, median age 62 years) and 43 older patients ( 670 years, median age 80 years) were identified. Of the 80 patients with a possible bronchial carcinoma only 59% had a further chest radiograph performed. Bronchoscopy was performed in 34% of patients, but a biopsy of the lesion was undertaken in only 24% of patients. Sixteen of the 80 patients, irrespective of what investigations had been undertaken, were referred for an oncological or surgical opinion. During the study period ( 3 months), 24% of the patients died. At 6, 24 and 60 months, respectively, the total deaths were 40, 78 and 88%. Conclusion: Older patients compared with those aged less than 70 years were less likely to be investigated, further, were more likely to be managed differently (i.e., less aggressively) and more likely to die within each time interval. In more of the older group a presumed death certificate diagnosis of pneumonia was made. When an abnormal chest radiograph raises the possibility of an underlying bronchial carcinoma, the finding of this study suggests that an ageist attitude influences the subsequent management of some patients. Copyright (C) 2005 S. Karger AG, Basel.

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

Background: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. Method: 2 7 children who had a sibling with AS were administered the children's version of the 'Eyes Test'(Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. Results: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. Discussion: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

A three-regime model of speculative behaviour: modelling the evolution of the S&P 500 composite index

We examine whether a three-regime model that allows for dormant, explosive and collapsing speculative behaviour can explain the dynamics of the S&P 500. We extend existing models of speculative behaviour by including a third regime that allows a bubble to grow at a steady rate, and propose abnormal volume as an indicator of the probable time of bubble collapse. We also examine the financial usefulness of the three-regime model by studying a trading rule formed using inferences from it, whose use leads to higher Sharpe ratios and end of period wealth than from employing existing models or a buy-and-hold strategy.

The Clean Development Mechanism as ethical development? Reconciling emissions trading and local development

This paper examines the ethics of the Clean Development Mechanism (CDM) in its architecture, processes and outcomes and its potential to allocate resources to the poor as ‘ethical development’. Two specific examples of CDM projects help us to explore some of the quandaries that seem to be quickly defining operating procedure for the CDM in its efforts to bring entitlementsto the poor. The paper concludes with reflections on the normative and social complications of the CDM and closes with three key areas of further investigation.