4Specialist Children's Services, North West Wales NHS Trust, Bangor, UK Clock gene anomalies have been suggested as causative factors in autism. We screened eleven clock/clock-related genes in a predominantly high-functioning Autism Genetic Resource Exchange sample of strictly diagnosed autistic disorder progeny and their parents (110 trios) for association of clock gene variants with autistic disorder. We found significant association (P < 0.05) for two single-nucleotide polymorphisms in per1 and two in npas2. Analysis of all possible combinations of two-marker haplotypes for each gene showed that in npas2 40 out of the 136 possible two-marker combinations were significant at the P < 0.05 level, with the best result between markers rs1811399 and rs2117714, P = 0.001. Haplotype analysis within per1 gave a single significant result: a global P = 0.027 for the markers rs2253820-rs885747. No two-marker haplotype was significant in any of the other genes, despite the large number of tests performed. Our findings support the hypothesis that these epistatic clock genes may be involved in the etiology of autistic disorder. Problems in sleep, memory and timing are all characteristics of autistic disorder and aspects of sleep, memory and timing are each clock-gene-regulated in other species. We identify how our findings may be relevant to theories of autism that focus on the amygdala, cerebellum, memory and temporal deficits. We outline possible implications of these findings for developmental models of autism involving temporal synchrony/social timing.

We suggest that anomalies in clock genes operating as timing genes in high frequency oscillator systems may underlie the timing deficits of autism. We outline how anomalies in methylation-related genes may also be implicated.

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Airport and airspace planners need a reliable method for quantifying the effects of nighttime operations on communities. Research has shown that cumulative metrics such as Lnight, Ldn and Lden show little or no correlation with aircraft noise event (ANE) produced awakenings. What is needed is a reliable method for quantifying the likely awakenings that will result from a full night of aircraft operations. This paper reports the results of an update of the analysis reported previously in Noise Control Engineering, 55(2). The objective of this present analysis is to refine the awakening dose-response relationships to be broadly applicable across airports and communities and it does that by adding European awakening data from Schiphol to the original data from three U.S. airports. It derives new regression coefficients and then tests two aspects of the results: whether the populations around the four airports are significantly different in their probability of awakening; whether coefficients that reflect subject "sensitivity" to awakening are real or a result of the random nature of awakenings.

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