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SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.
We review the performance of the PollyVote, which combined forecasts from polls, prediction markets, experts’ judgment, political economy models, and index models to predict the two-party popular vote in the 2012 US presidential election. Throughout the election year the PollyVote provided highly accurate forecasts, outperforming each of its component methods, as well as the forecasts from FiveThirtyEight.com. Gains in accuracy were particularly large early in the campaign, when uncertainty about the election outcome is typically high. The results confirm prior research showing that combining is one of the most effective approaches to generating accurate forecasts.
Commission 53 on Extrasolar Planets was created at the 2006 Prague General Assembly of the IAU, in recognition of the outburst of astronomical progress in the field of extrasolar planet discovery, characterization, and theoretical work that has occurred since the discovery of the pulsar planets in 1992 and the discovery of the first planet in orbit around a solar-type star in 1995. Commission 53 is the logical successor to the IAU Working Group on Extrasolar Planets WG-ESP, which ended its six years of existence in August 2006. The founding president of Commission 53 is Michael Mayor, in honor of his seminal contributions to this new field of astronomy. The vice-president is Alan Boss, the former chair of the WG-ESP, and the members of the Commission 53 Organizing Committee are the other former members of the WG-ESP.
Cones composed of noble metals with dimensions of the order of 100 nm, especially gold cones, are extremely well suited for optical near-field investigations using visible light. Their plasmon resonance frequency lies within the range of visible light frequencies, and upon illumination, strong electric field enhancement can be observed in the direct vicinity of the cone tip. For this purpose, a method to fabricate well-controlled nanocones with sharp tips is required. We present a top-down process in which arrays of cones are dry-etched from a metal stack on silicon. During the ion milling step, patterned hydrogen silsesquioxane resist is used as an etch mask. The resulting cones have tunable base diameters around 150 nm and tip radii down to less than 10 nm. Their optical characteristics are investigated by means of apertureless optical near-field microscopy, in which field enhancement at the cone tip is observed.
The Working Group on Extrasolar Planets (hereafter the WGESP) was created at a meeting of the IAU Executive Council in 1999 as a Working Group of IAU Division III and was renewed for three more years at the IAU General Assembly in 2003. The charge of the WGESP is to act as a focal point for international research on extrasolar planets. The membership of the WGESP has remained unchanged for the last three years.
Jacques de Vitry's Historia Occidentalis is one of the more remarkable and informative studies of contemporary western Christendom to come out of the thirteenth century. As numerous commentators have pointed out, it is unmistakably the product of the spiritual-intellectual school of Master Peter the Chanter of Paris, who inspired a generation of scholars and churchmen to marry popular preaching with the theology of the schools. Written early in the third decade of the thirteenth century, the Historia Occidentalis analyzes the moral state of the western church and juxtaposes in full relief the modes of both degeneracy and religious renewal within that society. Its thesis is that despite all the evils of the day, God is still working in and through the various elements of Christian society to sanctify his people; and these Christian people, for all of their failings, continue to share in the spiritual regeneration of Providence. The Historia Occidentalis has been characterized by one modern historian as “pulpit history.”