Common variant at 16p11.2 conferring risk of psychosis

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence

Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis

Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

De bankencrisis van de jaren twintig

Lessen uit een lang vergeten crisis voor hedendaagse beleidsmakers en banken.

Book Review - An Architecture of Parts: Architects, Building Workers and Industrialisation in Britain 1940–1970 by Christine Wall and Architecture and the Welfare State, edited by Mark Swenarton, Tom Avermaete and Dirk van den Heuvel.

Distributed Sounding Art – Practices in Distributing Sound (eds. Barry Truax, Marcel Cobussen and Vincent Meelberg)

This chapter examines distributed sounding art by focusing on three key aspects that we consider essentially tied to the notion of distribution: assignment, transport and sharing. These aspects aid us in navigating through a number of nodes in a history of sounding art practices where sound becomes assigned, transported and shared between places and people. Sound or data become distributed, and in the process of distribution, meanings become assigned and altered through differing socio-cultural contexts of places and people. We have selected several works, commencing in the 1960’s as we consider this period as having produced some of the seminal works that address distribution.
We draw on works by composers, performers and sound artists and thus present a history of sounding art, which is amongst the many histories of sounding art in the 20th and 21st century.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers.

Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals.

Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk.

Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

SATCOM Retrodirective Array

We present an in depth look at the challenges involved in using analogue retrodirective arrays for satellite communications. The main technical issues surrounding the development of a retrodirective (self-steering) Satellite Communications (SATCOM) system are given and techniques for mitigating these issues provided. Detailed results are given for a prototype high performance circularly polarized retrodirective array architecture suitable for mounting on an un-stabilized mobile platform. The paper concludes with practical retrodirective L-band array results with the array used to acquire actual broadband satellite data signals from a commercial L-band satellite system. Received satellite signals as low as -130dBm at the antenna elements are tracked. Accurate self-tracking occurs over the azimuth range of up to +/- 40 degrees.

De triomf van de tiran: Triumphi als kritiekmiddel in Romeinse literatuur

Of all the rituals of ancient Rome none was more spectacular than the triumph. Scholarly attention has long been devoted to the origins and circumstances of this ritual, but lately the role of the triumph in moral discourse has also come into focus. Emperors could gain great military prestige from celebrating a triumphus, yet this prestige could (posthumously) be undermined by hostile historians and biographers who used descriptions of triumphal processions to cast unpopular emperors in a negative light. Discussing in particular the ‘bad triumphs’ of Nero, Elagabalus, and Gallienus, but also considering many other cases, this article explores how triumphal descriptions could be employed as literary weapons. Ancient authors did not hesitate to emphasize, distort, or invent certain aspects of the ritual to suit their purposes. In fact, the triumphal idiom proved such a powerful tool for the delegitimation of emperors that it was even employed to situations which did not constitute triumphal celebrations at all. Hence the cultural elite sought to control the meaning of the ritual and to establish whether emperors counted as benign rulers or tyrants.