New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Är skiljeklausulen "unconscionable"? - En komparativ studie av Sverige och USA gällande oskäliga skiljeklausuler i kommersiella avtalsrelationer

Den svenska affärsjuridiken har utvecklats under de senaste decennierna. Influenser har med största sannolikhet hämtats från den internationella arenan och det syns en tydlig tendens mot en utveckling i samma riktning som den amerikanska avtalsrätten. Syftet med denna uppsats är att göra en jämförelse mellan det svenska och det amerikanska rättssystemet och att beskriva möjligheter att jämka eller åsidosätta en skiljeklausul med hänvisning till dess oskälighet. För att möjliggöra detta kommer jag presentera viktiga juridiska principer inom avtalsrätten, tolkningsprinciper och viktigast av allt generalklausulerna om oskälighet i de svenska och amerikanska rättssystemen. År 1976 introducerades 36 § avtalslagen, vilken är att se som en inskränkning av avtalsfriheten. Denna princip har en stark förankring i både det svenska och amerikanska rättssystemet och är högt värdesatt. 36§ avtalslagen gör det möjligt att åsidosätta eller jämka oskäliga (eller unconscionable) avtalsvillkor. Huvudsyftet med bestämmelsen är att skydda den svagare parten i en avtalsrelation, men regeln kan också tillämpas på kommersiella avtalsrelationer där parterna är jämbördiga. Även i det amerikanska rättssystemet är avtalsfriheten en av de viktigaste avtalsrättsliga principerna och domstolarna är därför restriktiva i sitt beslutande om begränsningar. Likväl uppställer unconscionability-doktrinen i UCC 2-302 ett juridiskt verktyg för att åsidosätta vissa avtalsvillkor. Denna framställning fokuserar därför på 36§ avtalslagen i förhållande till UCC 2-302. När det gäller tolkning skiljer sig reglerna till viss del åt mellan länderna. I Sverige är det viktigaste att fastslå den gemensamma partsavsikten, medan det amerikanska rättssystemet lägger större vikt vid avtalets skrivna ord. På så sätt är den amerikanska four corners rule på många sätt den totala motsatsen till den svenska gemensamma partavsikten. Skiljeklausuler förs ofta in i avtal och upprätthålls i de flesta fall. När parter kommer överens om att lösa eventuella framtida tvister genom skiljeförfarande frånsäger de sig sin rätt till domstolsprövning och måste istället få tvisten prövad av en skiljedomstol. Skiljedomarens beslut binder parterna och kan endast under vissa omständigheter bli upphävd av en allmän domstol. Trots detta, och trots att det amerikanska och det svenska rättssystemet härstammar från två olika rättsfamiljer, är det tydligt att båda systemen är ovilliga att åsidosätta skiljeklausuler i kommersiella avtal, med hänvisning till avtalsfriheten. Det finns en omfattande praxis som talar för skiljeklausuler, framförallt baserad på det faktum att skiljeförfarande ofta är ett mer effektivt och mindre kostsamt sätt att lösa en tvist på.The Swedish business law have developed during the past decades, especially through impressions from the international arena, and it can be seen that influences have been taken from the American traditions of contracting. The aim of this thesis is to make a comparison between the Swedish and the American legal system and describe the possibilities to invalidate an arbitration agreement or an arbitration clause due to unreasonableness or unconscionability. In order to conduct this study, I will present important legal principles of contract law, interpretation principles, and most important the general clauses of unconscionability in the both legal systems. In 1976 the article 36 of the Swedish act of contracts was introduced, which can be seen as a limitation of the freedom of contract. In both the Swedish and American regulation, freedom of contract is highly valued. Art 36 makes it possible to set aside or adjust unfair (or unconscionable) contract terms. The main purpose of the article is to protect the weaker party in a contract relation, but it can also be applicable to commercial contract relations were the parties is to be seen as equal. In the American system as well, the freedom of contract is one of the most important contract principles and most courts are careful in their deciding of limitations. Nevertheless, the doctrine of unconscionability is providing a legal tool through UCC 2-302 to set aside certain clauses in contracts. In this thesis, the main focus will be on art 36 Swedish act of contracts compared to the American UCC 2-302. When it comes to interpretation, the rules differ between the two countries. In Sweden, the most important is to find out the shared intention of the contract parties, but in the US emphasis is given to the written word in the contract. The American four corner rule is in many ways the complete opposite to the Swedish “gemensam partsavsikt” (shared intention). Arbitration clauses are included in many contracts and are generally upheld. When parties agree to arbitrate any dispute arising out of their contract, they forgo their right to litigate disputes in court and must instead have the dispute resolved by arbitration. The arbitrator’s decision binds the parties and can only on certain limited grounds be reviewed by a court. Therefore, by entering an arbitration agreement, a party abandons her fundamental right to have a court resolve a dispute arising out of the contract relation. Despite this, and despite the fact that American and Swedish law comes from two different legal families, it is evident that both systems are unwilling to set aside arbitration clauses in commercial contracts, with regards to the freedom of contract. There is an extensive policy in favor of arbitration, mostly based on the fact that arbitration is often a more efficient and less expensive way to settle a dispute

Walking Time Is associated With Hippocampal Volume in Overweight and Obese Office Workers

Objectives: To investigate the long-term effects on cognition and brain function after installing treadmill workstations in offices for 13 months. Methods: Eighty healthy overweight or obese office workers aged 40–67 years were individually randomized to an intervention group, receiving a treadmill workstation and encouraging emails, or to a control group, continuing to work as usual. Effects on cognitive function, hippocampal volume, prefrontal cortex (PFC) thickness, and circulating brain-derived neurotrophic factor (BDNF) were analyzed. Further, mediation analyses between changes in walking time and light-intensity physical activity (LPA) on changes in BDNF and hippocampal volume between baseline and 13 months, and multivariate analyses of the baseline data with percentage sitting time as the response variable, were performed. Results: No group by time interactions were observed for any of the outcomes. In the mediation analyses, positive associations between changes in walking time and LPA on changes in hippocampal volume were observed, although not mediated by changes in BDNF levels. In the multivariate analyses, a negative association between percentage sitting time and hippocampal volume was observed, however only among those older than 51 years of age. Conclusion: Although no group by time interactions were observed, our analyses suggest that increased walking and LPA may have positive effects on hippocampal volume and that sedentary behavior is associated with brain structures of importance for memory functions. Trial Registration: www.ClinicalTrials.gov as NCT01997970