Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, Pmeta = 2.5 × 10−9, OR[T] = 0.81) and 17q21.32 (rs72823592, Pmeta = 9.3 × 10−9, OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, Pmeta = 9.1 × 10−9, OR[T] = 0.68) and at 1q43 for JME (rs12059546, Pmeta = 4.1 × 10−8, OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, Pmeta = 4.0 × 10−6) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndrome

Without consent: Principles of justified acquisition and duty-imposing powers

A controversy in political philosophy and applied ethics concerns the validity of duty-imposing powers, that is, rights entitling one person to impose new duties on others without their consent. Many philosophers have criticized as unplausible any such moral right, in particular that of appropriating private property unilaterally. Some, finding duty-imposing powers weird, unfamiliar or baseless, have argued that principles of justified acquisition should be rejected; others have required them to satisfy exacting criteria. I investigate the many ways in which we regularly impose duties on one another without prior consent. I show that doing so is not weird, and I offer criteria which demarcate the reasonable from the worrisome aspects of duty-imposing powers

Building on Weber to understand governance: exploring the links between identity, democracy and 'inner distance'

The paper builds up a conceptual picture of two types of governance - network and organic. In this process it highlights the legitimacies of co-ordination (interior authority and democracy) that lie outside Weber's typology of domination and are relatively neglected in governance literature. The exploration of interior authority, through discussion of identity and substantive liberty, reflects a perspective on human agency that acknowledges the interconnection of the social and non-social and links sociological understanding of agency with political philosophy. It is suggested that this theoretical work gives some necessary content to Weber's concept of inner distance. In turn, this also has implications for our understanding of what is involved in democratizing governance

What's valued most? Similarities and differences between the organizational values of the public and private sector

In recent administrative and organizational literature much attention has been paid to values that guide organizational and managerial behaviour in the public and private domain. Comparative empirical research efforts, however, are sparse. This article reports the results of a comparative empirical survey of 382 managers from a variety of public and private sector organizations in The Netherlands. Contrary to much recent literature that presupposes the intermixing or convergence of value systems guiding governance in different kinds of organizations, the results of this study show two distinct and relatively classical value systems for government and business as well as a 'common core' of important organizational qualities. These are accountability, expertise, reliability, efficiency and effectiveness, all of which are considered crucial in both public and private sector organizations. Additional analysis shows that value preferences are primarily attached to sector rather than to age, gender, working experience, or previous employment in the other sector. © 2008 The Author. Journal compilation © 2008 Blackwell Publishing Ltd