Clinical and molecular characterisation of KCNT1-related severe early onset epilepsy

Objective: To characterise the phenotypic spectrum, molecular genetic findings and functional consequences of pathogenic variants in early onset KCNT1-epilepsy. Methods: We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple gene next generation sequencing panel and whole exome sequencing. Additional patients with non-EIMFS early onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. Where possible, we performed homology modelling to predict putative effects of variants on protein structure and function. We undertook electrophysiological assessment of mutant KCNT1 channels in a Xenopus oocyte model system. Results: We identified pathogenic variants in KCNT1 in 12 patients, four of which are novel. Most variants occurred de novo. Ten had a clinical diagnosis of EIMFS and the other two presented with early onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in one. Computational modelling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain-of-function, with significantly increased channel amplitude and variable blockade by quinidine. Conclusions: Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, though clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy

The Big Five in Context: Personality, Diversity and Attitudes toward Equal Opportunities for Immigrants in Switzerland

The paper analyzes the link between personality traits and attitudes of Swiss citizens toward equal opportunities for immigrants. In particular, we examine the extent to which this relationship is moderated by the socio-structural context. We test the assumption that the direct links between personality traits and attitudes toward equal opportunities are strengthened by perceived ethnic diversity. Based on our empirical analyses, we are able to replicate central findings of the research on personality traits and attitudes toward immigrants for the Swiss context. While openness toward experience and agreeableness are positively related to a preference for equal opportunities, conscientiousness is negatively linked to these attitudes. Furthermore, our results reveal that the link between conscientiousness and attitudes toward equal opportunities is significantly moderated by the perceived share of foreigners in the neighborhood. This finding is especially relevant for future research on the effects of personality traits

Opting for an Open Society? Personality Traits and Attitudes toward the Openness of Switzerland

The tension between openness and closedness is one of the most important cleavages in Swiss political debates. In the present article, we study the psychological foundations of attitudes regarding this issue. More precisely, we examine the link between personality and attitudes toward the degree of openness of Switzerland as a general stance toward the cultural, economic and political alignment of the country. Personality is understood as a complex and multifaceted concept that forms the basis for consistent patterns of attitudes and behavior. We build on the Five-Factor Theory to explain the link between personality traits, contextual factors and political attitudes. Analyzing survey data from a random sample of Swiss citizens, we find clear evidence that personality traits affect political attitudes. Furthermore, we are able to demonstrate that the relationship between personality and attitudes toward the degree of openness of Switzerland is moderated by perceived ethnic diversity in the neighborhood

The Personality of Stealth Democrats: How traits shape attitudes towards expert-based governments

While some scholars call for mechanisms to give citizens a greater voice in politics, others critically question the demand for more citizen participation. Rather, they find that the people do not want to be involved in politics and prefer independent experts to make political decisions. This perspective is captured by Hibbing and Theiss-Morse in their concept of stealth democracy. They describe stealth democrats as people who think that political debates are unnecessary or who naturally avoid all sorts of conflict. Especially the latter argument points to a potential psychological underpinning of stealth attitudes, which forms the starting point of the investigation here. This article evaluates the personality of stealth democrats and makes use of a well-known concept to capture personality traits, the ‘Big Five’ model. Analysing unique survey data from Switzerland, the results reveal significant relationships between personality traits such as conscientiousness, agreeableness, and neuroticism and stealth attitudes

What Actually Matters? Understanding Attitudes toward Immigration in Switzerland

On 9 February 2014, the Swiss people accepted the popular initiative “against mass immigration” launched by the national-conservative Swiss People’s Party (SVP). This voting outcome has triggered wide-ranging debates about both the policy on immigrants as well as the future of Switzerland within the European context. Against this background, we evaluate attitudes toward immigration in Switzerland. Using hitherto unexplored survey data of MOSAiCH, our empirical analyses show that already in the year 2013, before the debate about the initiative on mass immigration was in full swing, roughly 53 percent of the 1011 interviewed Swiss citizens stated that immigration should be reduced. Moreover, our estimations indicate that the threats and fears induced by immigration and the will to maintain sovereignty and autonomy are particularly relevant for attitudes toward immigration. By contrast, education and national or personal economic conditions are only weakly related to the immigration issue.Die am 9. Februar 2014 angenommene Volksinitiative über die Masseneinwanderung bewirkt eine tiefgreifende Debatte über den zukünftigen Weg der Schweiz im europäischen Umfeld und in der Einwanderungspolitik. Vor diesem Hintergrund widmen wir uns in diesem Beitrag den Einstellungen der Schweizerinnen und Schweizer gegenüber der Immigration. Unsere Auswertungen des Datensatzes MOSAiCH 2013 zeigen, dass sich bereits ein Jahr vor der Abstimmung die Hälfte der Schweizer für eine Verringerung der Zuwanderung aussprach. Darüber hinaus deuten unsere Ergebnisse darauf hin, dass insbesondere die durch die Immigration induzierten Ängste in der Bevölkerung massgebend für die Haltung gegenüber der Zuwanderung sind. Wer sich um die Schweizer Kultur sorgt, seinen Arbeitsplatz gefährdet sieht und sich vor zunehmender Kriminalität fürchtet, spricht sich für eine Begrenzung der Immigration aus. Ähnliches gilt für die Wahrung nationaler Eigenständigkeit. Wer gegen die politische Einmischung von aussen ist, lehnt die Zuwanderung ebenfalls ab. Der Bildungstand und Einschätzungen zur allgemeinen wie persönlichen wirtschaftlichen Lage spielen hingegen keine oder nur eine untergeordnete Rolle, wenn es um die Meinung der Schweizer zur Immigration geht

Freiwilligen-Monitor Schweiz 2016

Rund ein Viertel der Personen über 15 Jahren engagiert sich in der Schweiz unentgeltlich in einer Organisation, zehn Prozent besetzen ein gewähltes Ehrenamt. Und fast 40 Prozent wirken als Freiwillige ausserhalb von Vereinen. Insgesamt leisten die Menschen in der Schweiz etwa 700 Millionen Stunden Freiwilligenarbeit pro Jahr. Dies entspricht etwa neun Prozent der geleisteten 7700 Millionen Stunden Erwerbsarbeit. Die Bewohnerinnen und Bewohner der Schweiz sind aber je nach Geschlecht, Alter, Region, Grösse des Wohnorts, Religionszugehörigkeit, Bildungsniveau, Einkommen, Zivilstand und beruflicher Stellung unterschiedlich stark freiwillig engagiert. Nach 2007 und 2010 wurde das freiwillige Engagement in der Schweiz mit diesem Monitor zum dritten Mal erforscht. Neben Analysen zum Verlauf und zu den Beweggründen wie möglichen Anreizen unbezahlter Arbeit liefert die Studie auch erstmalig Informationen zum freiwilligen Engagement im Internet und untersucht spezifisch die Situation junger Erwachsener und Menschen mit Migrationshintergrund. Zudem werden Einsichten zum Persönlichkeitsprofil von Freiwilligen und deren politischen und sozialen Einstellungen präsentiert