Novel linkage to chromosome 20p using latent classes of psychotic illness in 270 Irish high-density families

Background: Several lines of evidence suggest that the clinical heterogeneity of schizophrenia is due to genetic heterogeneity. Genetic heterogeneity may decrease the signal-to-noise ratio in linkage and association studies. Therefore, linkage studies of clinically homogeneous classes of psychotic illness may result in greater power to detect at least some loci.

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O>=1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T>2,500K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

Distance limits to intermediate- and high-velocity clouds

We present optical spectra of 403 stars and quasi-stellar objects in order to obtain distance limits towards intermediate- and high-velocity clouds (IHVCs), including new Fibre-fed Extended Range Optical Spectrograph (FEROS) observations plus archival ELODIE, FEROS, High Resolution Echelle Spectrometer (HIRES) and Ultraviolet and Visual Echelle Spectrograph (UVES) data. The non-detection of Ca II K interstellar (IS) absorption at a velocity of −130 to −60 km s−1 towards HDE 248894 (d ∼ 3 kpc) and HDE 256725 (d ∼ 8 kpc) in data at signal-to-noise ratio (S/N) > 450 provides a new firm lower distance limit of 8 kpc for the anti-centre shell HVC. Similarly, the non-detection of Ca II K IS absorption towards HD 86248 at S/N ∼ 500 places a lower distance limit of 7.6 kpc for Complex EP, unsurprising since this feature is probably related to the Magellanic System. The lack of detection of Na I D at S/N = 35 towards Mrk 595 puts an improved upper limit for the Na I column density of log (NNaD <) 10.95 cm−2 towards this part of the Cohen Stream where Ca II was detected by Wakker et al. Absorption at ∼ −40 km s−1 is detected in Na I D towards the Galactic star PG 0039+049 at S/N = 75, placing a firm upper distance limit of 1 kpc for the intermediate-velocity cloud south (IVS), where a tentative detection had previously been obtained by Centurion et al. Ca ´ II K and Na I D absorption is detected at −53 km s−1 towards HD 93521, which confirms the upper distance limit of 2.4 kpc for part of the IV arch complex obtained using the International Ultraviolet Explorer (IUE) data by Danly. Towards HD 216411 in Complex H a non-detection in Na D towards gas with log(NH I) = 20.69 cm−2 puts a lower distance limit of 6.6 kpc towards this HVC complex. Additionally, Na I D absorption is detected at −43.7 km s−1 in the star HD 218915 at a distance of 5.0 kpc in gas in the same region of the sky as Complex H. Finally, the Na I/Ca II and Ca II/H I ratios of the current sample are found to lie in the range observed for previous studies of IHVCs.

Resonant Rayleigh light scattering response of individual Au nanoparticles to antigen--antibody interaction

A proof-of-concept study was reported on analysis of antigen–antibody recognition based on resonant Rayleigh scattering response of single Au nanoparticles in an imaging chamber. As benefited by a traditional dark-field microscope and a spectrograph, individual Au nanoparticles (30 nm) were observed with high signal-to-noise ratio and they were effectively utilized to monitor changes in refractive index induced by specific binding of the adsorbates. Using PSA antigen as a model, a LSPR ?max shift of about 2.85 nm was recorded for a molecular binding corresponding to 0.1 pg ml-1 of the protein biomarker. This result successfully demonstrates a non-labeling detection system for proteins as well as thousands of different chemical or biological species, and it possesses a great potential as a sensitive, on-chip and multiplexing detection.

Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F:T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F:T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F:T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F:T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F:T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F:T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F:T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F:T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.

Cognitive Single Carrier Systems: Joint Impact of Multiple Licensed Transceivers

In this paper, the impact of interference from multiple licensed transceivers on cognitive underlay single carrier systems is examined. Specifically, the situation is considered in which the secondary network is limited by three key parameters: 1) maximum transmit power at the secondary transmitter, 2) peak interference power at the primary receivers, and 3) interference power from the primary transmitters. For this cognitive underlay single carrier system, the signal-to-interference ratio (SIR) of the secondary network is obtained for transmission over frequency selective fading channels. Based on this, a new closedform expression for the cumulative distribution function of the SIR is evaluated, from which the outage probability and the ergodic capacity are derived. Further insights are established by analyzing the asymptotic outage probability and the asymptotic ergodic capacity in the high transmission power regime. In particular, it is corroborated that the asymptotic outage diversity gain is equal to the multipath gain of the frequency selective channel in the secondary network. The asymptotic ergodic capacity also gives new insight into the additional power cost for different network parameters while maintaining a specified target ergodic capacity. Illustrative numerical examples are presented to validate the outage probability and ergodic capacity under different interference power profiles.

Security Enhancement of Cooperative Single Carrier Systems

In this paper, the impact of multiple active eavesdroppers on cooperative single carrier systems with multiple relays and multiple destinations is examined. To achieve the secrecy diversity gains in the form of opportunistic selection, a two-stage scheme is proposed for joint relay and destination selection, in which, after the selection of the relay with the minimum effective maximum signal-to-noise ratio (SNR) to a cluster of eavesdroppers, the destination that has the maximum SNR from the chosen relay is selected. In order to accurately assess the secrecy performance, the exact and asymptotic expressions are obtained in closed-form for several security metrics including the secrecy outage probability, the probability of non-zero secrecy rate, and the ergodic secrecy rate in frequency selective fading. Based on the asymptotic analysis, key design parameters such as secrecy diversity gain, secrecy array gain, secrecy multiplexing gain, and power cost are characterized, from which new insights are drawn. Moreover, it is concluded that secrecy performance limits occur when the average received power at the eavesdropper is proportional to the counterpart at the destination. Specifically, for the secrecy outage probability, it is confirmed that the secrecy diversity gain collapses to zero with outage floor, whereas for the ergodic secrecy rate, it is confirmed confirm that its slope collapses to zero with capacity ceiling.

Design methodology for low power and arametric robustness through output-quality modulation:Application to color-interpolation filtering

Power dissipation and robustness to process variation have conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor upsizing for parametric-delay variation tolerance can be detrimental for power dissipation. However, for a class of signal-processing systems, effective tradeoff can be achieved between Vdd scaling, variation tolerance, and output quality. In this paper, we develop a novel low-power variation-tolerant algorithm/architecture for color interpolation that allows a graceful degradation in the peak-signal-to-noise ratio (PSNR) under aggressive voltage scaling as well as extreme process variations. This feature is achieved by exploiting the fact that all computations used in interpolating the pixel values do not equally contribute to PSNR improvement. In the presence of Vdd scaling and process variations, the architecture ensures that only the less important computations are affected by delay failures. We also propose a different sliding-window size than the conventional one to improve interpolation performance by a factor of two with negligible overhead. Simulation results show that, even at a scaled voltage of 77% of nominal value, our design provides reasonable image PSNR with 40% power savings. © 2006 IEEE.

Design methodology to trade off power, output quality and error resiliency: Application to color interpolation filtering

Power dissipation and tolerance to process variations pose conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor up-sizing for process tolerance can be detrimental for power dissipation. However, for certain signal processing systems such as those used in color image processing, we noted that effective trade-offs can be achieved between Vdd scaling, process tolerance and "output quality". In this paper we demonstrate how these tradeoffs can be effectively utilized in the development of novel low-power variation tolerant architectures for color interpolation. The proposed architecture supports a graceful degradation in the PSNR (Peak Signal to Noise Ratio) under aggressive voltage scaling as well as extreme process variations in. sub-70nm technologies. This is achieved by exploiting the fact that some computations are more important and contribute more to the PSNR improvement compared to the others. The computations are mapped to the hardware in such a way that only the less important computations are affected by Vdd-scaling and process variations. Simulation results show that even at a scaled voltage of 60% of nominal Vdd value, our design provides reasonable image PSNR with 69% power savings.

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.

Intelligent potentiostat for identification of heavy metals in situ

This article presents a low-cost portable electrochemical instrument capable of on-site identification of heavy metals. The instrument acquires metal-specific voltage and current signals by the application of differential pulse anodic stripping voltammetry. This technique enhances the analytical current and rejects the background current, resulting in a higher signal-to-noise ratio for a better detection limit. The identification of heavy metals is based on an intelligent machine-based method using a multilayer perceptron neural network consisting of three layers of neurons. The neural network is implemented using a 16 bit microcontroller. The system is developed for use in the field in order to avoid expensive and time-consuming procedures and can be used in a variety of situations to help environmental assessment and control. 

AgriSense: Multichannel disposable sensors for animal health disease diagnostics

Rapid and sensitive detection of viral infections associated with Bovine Respiratory Disease (BRD) in live animals is recognized as key to minimizing the impact of this disease. ELISA-based testing is limited as it typically relies on the detection of a single viral antibody subtype within an individual test sample and testing is relatively slow and expensive. We have recently initiated a new project entitled AgriSense to develop a novel low-cost and label-free, integrated bimodal electronic biosensor system for BRD. The biosensor system will consist of an integrated multichannel thin-film-transistor biosensor and an electrochemical impedance spectroscopy biosensor, interfaced with PDMS-based microfluidic sample delivery channels. By using both sensors in tandem, nonspecific binding biomolecules must have the same mass to charge ratio as the target analyte to elicit equivalent responses from both sensors. The system will target simultaneous multiplexed sensing of the four primary viral agents involved in the development of BRD: bovine herpesvirus-1 (BHV-1), bovine parainfluenza virus-3 (BPIV-3), bovine respiratory syncytial virus (BRSV), and bovine viral diarrhea (BVD). Optimized experimental conditions derived through model antigen-antibody studies will be applied to the detection of serological markers of BRD-related infections based on IgG interaction with a panel of sensor-immobilized viral proteins. This rapid, “cowside” multiplex sensor capability presents a major step forward in disease diagnosis, helping to ensure the integrity of the agri-food supply chain by reducing the risk of disease spread during animal movement and transport.

The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.

On Infinite Time Performance of Nonlinear Model Predictive Controllers

This paper addresses the problem of infinite time performance of model predictive controllers applied to constrained nonlinear systems. The total performance is compared with a finite horizon optimal cost to reveal performance limits of closed-loop model predictive control systems. Based on the Principle of Optimality, an upper and a lower bound of the ratio between the total performance and the finite horizon optimal cost are obtained explicitly expressed by the optimization horizon. The results also illustrate, from viewpoint of performance, how model predictive controllers approaches to infinite optimal controllers as the optimization horizon increases.

An invasive-native mammalian species replacement process captured by camera trap survey random encounter models

Camera traps are used to estimate densities or abundances using capture-recapture and, more recently, random encounter models (REMs). We deploy REMs to describe an invasive-native species replacement process, and to demonstrate their wider application beyond abundance estimation. The Irish hare Lepus timidus hibernicus is a high priority endemic of conservation concern. It is threatened by an expanding population of non-native, European hares L. europaeus, an invasive species of global importance. Camera traps were deployed in thirteen 1 km squares, wherein the ratio of invader to native densities were corroborated by night-driven line transect distance sampling throughout the study area of 1652 km2. Spatial patterns of invasive and native densities between the invader’s core and peripheral ranges, and native allopatry, were comparable between methods. Native densities in the peripheral range were comparable to those in native allopatry using REM, or marginally depressed using Distance Sampling. Numbers of the invader were substantially higher than the native in the core range, irrespective of method, with a 5:1 invader-to-native ratio indicating species replacement. We also describe a post hoc optimization protocol for REM which will inform subsequent (re-)surveys, allowing survey effort (camera hours) to be reduced by up to 57% without compromising the width of confidence intervals associated with density estimates. This approach will form the basis of a more cost-effective means of surveillance and monitoring for both the endemic and invasive species. The European hare undoubtedly represents a significant threat to the endemic Irish hare.