Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Analysing admittance of obstacles in evanescent waveguide using the Imaginary Smith Chart

We present a technique, using the Imaginary Smith Chart, for determining the admittance of obstacles introduced into evanescent waveguide. The admittance of an inductive iris, capacitive iris, capacitive post, variable width strip and length of evanescent waveuide are investigated. © 2012 IEEE.

Increased Bandwidth Evanescent Open-Ended Waveguide Antenna Design Using the Imaginary Smith Chart

We present a novel antenna matching technique that uses the Imaginary Smith Chart to permit wideband matching of an evanescent open-ended waveguide antenna using a dielectric sheet air-spaced from the aperture. The fabricated antenna design is demonstrated to have a measured bandwidth of 24%, from 2.13–2.7 GHz, for reflection coefficient $qquad{<} -!!10~{rm dB}$ , with 2.725 GHz waveguide cutoff. The antenna's maximum aperture dimension is ${< 0.5}lambda_{0}$ at the upper frequency in the bandwidth and so it is suitable for use in a wide angle scanning phased array

Prevalence, phenomenology, aetiology and predictors of challenging behaviour in Smith-Magenis syndrome

Background

The prevalence, phenomenology aetiology and correlates of four forms of challenging behaviour in 32 children and adults with Smith-Magenis syndrome (SMS) were investigated.

Methods

Cognitive assessments, questionnaires and semi-structured interviews were used to gather data on intellectual disability, verbal and physical aggression, destructive behaviour and self-injury and on characteristics known to be associated with aggression.

Results

Aggression in SMS was more prevalent (87%), but not more severe than aggression in contrast groups. Aggressive behaviour was more frequently associated with environmental contingencies (e.g. attention, escape and access to tangibles) than self-injury and destructive behaviours. Severity of challenging behaviours was associated with high impulsivity.

Conclusion

Aggression is seen in the majority of people with SMS. Results suggest that behavioural disinhibition and operant social reinforcement are associated with the manifestation of aggression.

Causal Models of Clinically Significant Behaviors in Angelman, Cornelia de Lange, Prader-Willi and Smith-Magenis Syndromes

The operant learning theory account of behaviors of clinical significance in people with intellectual disability (ID) has dominated the field for nearly 50 years. However, in the last two decades, there has been a substantial increase in published research that describes the behavioral phenotypes of genetic disorders and shows that behaviors such as self-injury and aggression are more common in some syndromes than might be expected given group characteristics. These cross-syndrome differences in prevalence warrant explanation, not least because this observation challenges an exclusively operant learning theory account. To explore this possible conflict between theoretical account and empirical observation, we describe the genetic cause and physical, social, cognitive and behavioral phenotypes of four disorders associated with ID (Angleman, Cornelia de Lange, Prader-Willi and Smith-Magenis syndromes) and focus on the behaviors of clinical significance in each syndrome. For each syndrome we then describe a model of the interactions between physical characteristics, cognitive and motivational endophenotypes and environmental factors (including operant reinforcement) to account for the resultant behavioral phenotype. In each syndrome it is possible to identify pathways from gene to physical phenotype to cognitive or motivational endophenotype to behavior to environment and back to behavior. We identify the implications of these models for responsive and early intervention and the challenges for research in this area. We identify a pressing need for meaningful dialog between different disciplines to construct better informed models that can incorporate all relevant and robust empirical evidence.

Report of the workshop for life detection in samples from Mars

The question of whether there is or was life on Mars has been one of the most pivotal since Schiaparellis' telescopic observations of the red planet. With the advent of the space age, this question can be addressed directly by exploring the surface of Mars and by bringing samples to Earth for analysis. The latter, however, is not free of problems. Life can be found virtually everywhere on Earth. Hence the potential for contaminating the Mars samples and compromising their scientific integrity is not negligible. Conversely, if life is present in samples from Mars, this may represent a potential source of extraterrestrial biological contamination for Earth. A range of measures and policies, collectively termed ‘planetary protection’, are employed to minimise risks and thereby prevent undesirable consequences for the terrestrial biosphere. This report documents discussions and conclusions from a workshop held in 2012, which followed a public conference focused on current capabilities for performing life-detection studies on Mars samples. The workshop focused on the evaluation of Mars samples that would maximise scientific productivity and inform decision making in the context of planetary protection. Workshop participants developed a strong consensus that the same measurements could be employed to effectively inform both science and planetary protection, when applied in the context of two competing hypotheses: 1) that there is no detectable life in the samples; or 2) that there is martian life in the samples. Participants then outlined a sequence for sample processing and defined analytical methods that would test these hypotheses. They also identified critical developments to enable the analysis of samples from Mars.

Evidence Base

Natalie Doyle and Richard Henry outline the evidence around Charles Campion-Smith's article on primary care after cancer treatment.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.