Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity

Real-Time Terahertz Absorption Spectroscopy of Methanol and Deuterated-Methanol Vapour, using a TeraFET Detector Array

Here we have demonstrated the potential of terahertz (THz) spectroscopy using a THz-frequency quantum cascade lasers coupled with a THz field-effect-transistors detector as a tool for probing chemical reactions, by observing distinct transitions in methanol and deuterated methanol (CH 3 OD) in the 3.35, 3.4 and 3.45 THz region

Implementation of a multi-element detector consisting of an 8x8 network of patch-antenna-coupled TeraFETs for gas spectroscopy with THz-QCLs

Monolithically integrated, antenna-coupled field-effect transistors (TeraFETs) are known as sensitive detectors, which can be designed to work properly over the entire THz range (0.1-10 THz). In this work, we present a new multi-element THz detector design. It employs 8×8 monolithically integrated patch-antenna-coupled TeraFETs fabricated in a commercial 65-nm CMOS process. In contrast to conventional detector matrices, where each TeraFET represents a pixel, here the entire TeraFET network serves as a single pixel, combining the output signals of all elements in a parallel read-out circuit. The matrix approach offers two advantages: A larger effective detector area, which makes beam alignment easier, and a significantly reduced electrical resistance down to approx. 300 at the working bias point, leading not only to a reduction in detector noise but also to an increase in achievable modulation bandwidth, which improves the time resolution of measurements of dynamical processes. We demonstrate applicability of the detector for laboratory methanol vapor gas spectroscopy at 3.4 THz with a quantum cascade laser (QCL) applied as a radiation source

Amplitude Stabilization of a THz Quantum-Cascade Laser using a Photonic Integrated Circuit

We demonstrate a method to stabilize the output power of a ∼3.3-THz quantum-cascade laser (QCL) using a photonic integrated circuit, consisting of a racetrack resonator (RTR) coupled to a QCL ridge waveguide. Amplitude stabilization was achieved for >300 seconds, without perturbation to the emission spectrum, by dynamically adjusting the electrical bias to the RTR, and hence the coupling between the QCL and RTR

Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosis : a pooled analysis of EVA-3S, SPACE and ICSS

Recent randomised controlled trials comparing carotid artery stenting (CAS) with endarterectomy (CEA) for the treatment of symptomatic carotid stenosis were not powered to investigate differences in risks in specific patient subgroups. We therefore performed a pooled analysis of individual patient data from the Symptomatic Severe Carotid Stenosis trial (EVA-3S), the Stent-Protected Angioplasty versus Carotid Endarterectomy trial (SPACE), and the International Carotid Stenting Study (ICSS)