The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

325GHz Single Layer Sub-Millimeter Wave FSS Based Split Ring Linear to Circular Polarisation Convertor

A single layer, frequency selective surface based, sub-millimeter wave transmission polarizer is presented that converts incident slant linear 45° polarization into circular polarization upon transmission. The polarization convertor consists of a 30 mm diameter 10 thick silicon reinforced metalized screen containing 2700 resonator cells and perforated with nested split ring slot apertures. The screen was designed and optimized using CST Microwave Studio and predictions were validated experimentally by transmission measurements over the 250-365 GHz frequency range. This frequency range is used for remote environmental monitoring and 325 GHz represents a molecular emission line for H2O. The results obtained show good agreement between measured and modeled predictions. The measured 3 dB axial ratio bandwidth was 11.75%, measured minimum Axial Ratio was 0.19 dB and the measured insertion loss of the single layer screen was 3.38 dB

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1-4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

Low-complexity iterative method of equalization for single carrier with cyclic prefix in doubly selective channels

Orthogonal frequency division multiplexing (OFDM) requires an expensive linear amplifier at the transmitter due to its high peak-to-average power ratio (PAPR). Single carrier with cyclic prefix (SC-CP) is a closely related transmission scheme that possesses most of the benefits of OFDM but does not have the PAPR problem. Although in a multipath environment, SC-CP is very robust to frequency-selective fading, it is sensitive to the time-selective fading characteristics of the wireless channel that disturbs the orthogonality of the channel matrix (CM) and increases the computational complexity of the receiver. In this paper, we propose a time-domain low-complexity iterative algorithm to compensate for the effects of time selectivity of the channel that exploits the sparsity present in the channel convolution matrix. Simulation results show the superior performance of the proposed algorithm over the standard linear minimum mean-square error (L-MMSE) equalizer for SC-CP.

Patterns of hospitalisation before and following initiation of haemodialysis: a 5 year single centre study

Background: The utilisation of healthcare resources by prevalent haemodialysis patients has been robustly evaluated with regard to the provision of outpatient haemodialysis; however, the impact of hospitalisation among such patients is poorly defined. Minimal information is available in the UK to estimate the health and economic burden associated with the inpatient management of prevalent haemodialysis patients. The aim of this study was to assess the pattern of hospitalisation among a cohort of haemodialysis patients, before and following their initiation of haemodialysis. In addition the study sought to assess the impact of their admissions on bed occupancy in a large tertiary referral hospital in a single region in the UK.

Methods: All admission episodes were reviewed and those receiving dialysis with the Belfast City Hospital Programme were identified over a 5 year period from January 2001 to December 2005. This tertiary referral centre provides dialysis services for a population of approximately 700?000 and additional specialist renal services for the remainder of Northern Ireland. The frequency and duration of hospitalisation, and contribution to bed day occupancy of haemodialysis patients, was determined and compared to other common conditions which are known to be associated with high bed occupancy. In addition, the pattern and timing of admissions in dialysis patients in relation to their dialysis initiation date was assessed.

Results: Over the 5 year study period, 798 haemodialysis patients were admitted a total of 2882 times. These accounted for 2.5% of all admissions episodes; the median number of admissions for these patients was 3 (2–5) which compared with 1 (1–2) for non-dialysis patients. The majority of first hospitalisations (54%) were within 100 days before or after commencement of maintenance dialysis therapy. In all clinical specialties the median length of stay for haemodialysis patients was significantly longer than for patients not on haemodialysis (p=0.004). In multivariate analysis with adjustment for age, gender, and other clinically relevant diagnostic codes, maintenance haemodialysis patients stayed on average 3.75 times longer than other patient groups (ratio of geometric means 3.75, IQR 3.46–4.06).

Conclusions: Maintenance haemodialysis therapy is an important risk factor for prolonged hospitalisation regardless of the primary reason for admission. Such patients require admission more frequently than the general hospital population, particularly within 100 days before and after initiation of their first dialysis treatment.

Low frequency rTMS effects on sensorimotor synchronization

Previous studies using low frequency (1 Hz) rTMS over the motor and premotor cortex have examined repetitive movements, but focused either on motor aspects of performance such as movement speed, or on variability of the produced intervals. A novel question is whether TMS affects the synchronization of repetitive movements with an external cue (sensorimotor synchronization). In the present study participants synchronized finger taps with the tones of an auditory metronome. The aim of the study was to examine whether motor and premotor cortical inhibition induced by rTMS affects timing aspects of synchronization performance such as the coupling between the tap and the tone and error correction after a metronome perturbation. Metronome sequences included perturbations corresponding to a change in the duration of a single interval (phase shifts) that were either small and below the threshold for conscious perception (10 ms) or large and perceivable (50 ms). Both premotor and motor cortex stimulation induced inhibition, as reflected in a lengthening of the silent period. Neither motor nor premotor cortex rTMS altered error correction after a phase shift. However, motor cortex stimulation made participants tap closer to the tone, yielding a decrease in tap-tone asynchrony. This provides the first neurophysiological demonstration of a dissociation between error correction and tap-tone asynchrony in sensorimotor synchronization. We discuss the results in terms of current theories of timing and error correction.

Single mating in orchid bees (Euglossa, Apinae): implications for mate choice and social evolution

Neotropical orchid bees (Euglossini) are conspicuously different from other corbiculate bees (Apinae) in their lack of advanced sociality and in male use of acquired odors (fragrances) as pheromone-analogues. In both contexts, orchid bee mating systems, in particular the number of males a female mates with, are of great interest but are currently unknown. To assess female mating frequency in the genus Euglossa, we obtained nests from three species in Mexico and Panama and genotyped mothers and their brood at microsatellite DNA loci. In 26 out of 29 nests, genotypes of female brood were fully consistent with being descended from a singly mated mother. In nests with more than one adult female present, those adult females were frequently related, with genotypes being consistent with full sister-sister (r = 0.75) or mother-daughter (r = 0.5) relationships. Thus, our genetic data support the notions of female philopatry and nest-reuse in the genus Euglossa. Theoretically, single mating should promote the evolution of eusociality by maximizing the relatedness among individuals in a nest. However, in Euglossini this genetic incentive has not led to the formation of eusocial colonies as in other corbiculate bees, presumably due to differing ecological or physiological selective regimes. Finally, monandry in orchid bees is in agreement with the theory that females select a single best mate based on the male fragrance phenotype, which may contain information on male age, cognitive ability, and competitive strength.

TEMPORALLY AND SPATIALLY-RESOLVED PLASMA PARAMETERS AND EEDF MEASUREMENTS IN A LOW-FREQUENCY DISCHARGE

A time-resolved Langmuir probe technique is used to measure the dependence of the electron density, electron temperature, plasma potential and electron energy distribution function (EEDF) on the phase of the driving voltage in a RF driven parallel plate discharge. The measurements were made in a low-frequency (100-500 kHz), symmetrically driven, radio frequency discharge operating in H-2, D-2 and Ar at gas pressures of a few hundred millitorr. The EEDFs could not be represented by a single Maxwellian distribution and resembled the time averaged EEDFs reported in 13.56 MHz discharges. The measured parameters showed structure in their spatial and temporal dependence, generally consistent with a simple oscillating sheath model. Electron temperatures of less than 0.1 eV were measured during the phase of the RF cycle when both electrodes are negative with respect to the plasma.

The UK Renal Registry Advanced CKD Study: frequency of incorrect reporting of date of start of RRT

Background: A preliminary review of the UK Renal Registry (UKRR) pre-RRT study data revealed results suggesting that, for some patients, the date of start of renal replacement therapy (RRT), as reported to the UKRR, was incorrect and often significantly later than the true date of start. A more detailed study then aimed to validate a set of criteria to identify patients with an incorrect start date. Methods: Pre-RRT laboratory data were electronically extracted from 8,810 incident RRT patients from 9 UK renal centres. Any patient with a low urea (<15 mmol/L) at the start of RRT or with a substantial improvement in kidney function (either a fall in urea >10 mmol/L or rise in eGFR >2 ml/min/1.73 m) within the two months prior to RRT were considered to potentially have an incorrect date of start. In 4
selected centres, the electronic patient records of all patients flagged were reviewed to validate these criteria.
Results: Of 8,810 patients, 1,616 (18.3%) were flagged by the identification criteria as having a potentially incorrect date of start of RRT, although a single centre accounted for 41% of the total flagged cohort. Of these flagged patients, 61.7% had been assigned an incorrect date of start of haemodialysis (HD), 5.7% had evidence of acute RRT being given before the reported date of start of HD
and 9.2% had evidence of starting peritoneal dialysis exchanges prior to the reported date of start. Of
those flagged, 10.7% had a correct date of start of RRT.
Conclusions: Accurate reporting of RRT episodes is vital for the analysis of time dependent studies such as survival or time to transplantation. A proportion of patients starting RRT were assigned an incorrect start date. In order to improve the accuracy of this reporting the UK Renal Registry
must work with renal centres and clinical staff on improving data input for the start of RRT.

Comparison of frequency-selective screen-based linear to circular split-ring polarisation convertors

This study presents the use of periodic arrays of freestanding slot frequency-selective screens (FSS) as a means for generating circularly polarised signals from an incident linearly polarised signal at normal incidence to the structure. Measured and simulated results for crossed, linear and various ring slot element shapes in single and double-layer polarisation convertor structures are presented for 10 GHz operation. It is shown that 3 dB axial ratio (AR) bandwidths of 21% can be achieved with the one-layer perforated screen design and that the rate of change is lower than the double-layer structures. An insertion loss of 0.34 dB can be achieved for the split circular ring double-layer periodic array, and of the three topologies presented the hexagonal split-ring polarisation convertor gives the lowest variation of AR with angle of incidence 1.8 dB/45° and 3.6 dB/45° for the single and double-screen FSS, respectively. In addition, their tolerance to angle of incidence variation is presented. The capability of the surfaces reported here as twist polariser or spatial isolator components has been demonstrated with up to -30 dB isolation between incident and re-reflected signals for the double-layer designs being measured. © 2010 The Institution of Engineering and Technology.

EEG decoding of semantic category reveals distributed representations for single concepts

Achieving a clearer picture of categorial distinctions in the brain is essential for our understanding of the conceptual lexicon, but much more fine-grained investigations are required in order for this evidence to contribute to lexical research. Here we present a collection of advanced data-mining techniques that allows the category of individual concepts to be decoded from single trials of EEG data. Neural activity was recorded while participants silently named images of mammals and tools, and category could be detected in single trials with an accuracy well above chance, both when considering data from single participants, and when group-training across participants. By aggregating across all trials, single concepts could be correctly assigned to their category with an accuracy of 98%. The pattern of classifications made by the algorithm confirmed that the neural patterns identified are due to conceptual category, and not any of a series of processing-related confounds. The time intervals, frequency bands and scalp locations that proved most informative for prediction permit physiological interpretation: the widespread activation shortly after appearance of the stimulus (from 100. ms) is consistent both with accounts of multi-pass processing, and distributed representations of categories. These methods provide an alternative to fMRI for fine-grained, large-scale investigations of the conceptual lexicon. © 2010 Elsevier Inc.

Power allocation strategies across N orthogonal channels for single-relay networks at both source and relay

We consider a wireless relay network with one source, one relay and one destination, where communications between nodes are preformed over N orthogonal channels. This, for example, is the case when orthogonal frequency division multiplexing is employed for data communications. Since the power available at the source and relay is limited, we study optimal power allocation strategies at the source and relay in order to maximize the overall source-destination capacity. Depending on the availability of the channel state information at both the source and relay or only at the relay, power allocation is performed at both the source and relay or only at the relay. Considering different setups for the problem, various optimization problems are formulated and solved. Some properties of the optimal solution are also proved.

Circular polarisation frequency selective surface operating in Ku and Ka band

Single and double layer frequency selective surfaces (FSS) for Circular polarization (CP) operation were designed. The designed FSS provide reflection in the Ku-band (11.7 – 12.75 GHz) and transmission in the Ka-band (17.3 – 20.2 GHz). CP is conserved in each of the bands. For the double layer design over the Ku-band the reflection loss was less than 0.05 dB for TE and TM polarizations while the axial ratio was below 0.2 dB. Over the Ka-band transmission loss and axial ratio were each less than 0.25 dB.

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.