Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

The nutritional profile of baby and toddler food products sold in Australian supermarkets

Background/Aims To examine the nutritional profile of baby and toddler foods sold in Australia. Methods Nutrient information for baby and toddler foods available at Australian supermarkets was collected between August and December 2013. Levels of declared energy, total fat, saturated fat, total sugar, sodium and estimated added sugar were examined, as well as the presence of additional micronutrients on the label. The Health Star Rating (HSR) system was used to determine nutritional quality. The range of products on offer was also examined by product type and by the age category for which the product was marketed. Results Of the 309 products included, 29 % were fortified. On a per 100 g basis, these 309 products provided a mean (±SD) of 476 ± 486 kJ, 1.6 ± 2.4 g total fat, 10.7 ± 12.2 g total sugar, 2.7 ± 7.4 g added sugar, and 33.5 ± 66.5 mg sodium. Fruit-based products or products with fruit listed as an ingredient (58 %) were the predominant product type. On the nutrition label, 42 % displayed at least one additional micronutrient while 37 % did not display saturated fat. The most common HSR was four stars (45 %) and 6? months was the most commonly identified targeted age group (36 %). Conclusions The majority of baby and toddler foods sold in Australian supermarkets are ready-made fruit-based products aimed at children under 12 months of age. Baby and toddler foods are overlooked in public policy discussions pertaining to population nutrient intake but their relatively high sugar content deriving from fruits requires close attention to ensure these foods do not replace other more nutrient dense foods, given children have an innate preference for sweet tastes.

Provisioning a 3.3 MW PhotoVoltaic generation system onto a distribution authority’s 11 kV rural feeder

This paper describes part of an engineering study that was undertaken to demonstrate that a multi-megawatt Photovoltaic (PV) generation system could be connected to a rural 11 kV feeder without creating power quality issues for other consumers. The paper concentrates solely on the voltage regulation aspect of the study as this was the most innovative part of the study. The study was carried out using the time-domain software package, PSCAD/EMTDC. The software model included real time data input of actual measured load and scaled PV generation data, along with real-time substation voltage regulator and PV inverter reactive power control. The outputs from the model plot real-time voltage, current and power variations throughout the daily load and PV generation variations. Other aspects of the study not described in the paper include the analysis of harmonics, voltage flicker, power factor, voltage unbalance and system losses.

Financially optimized scheduling of electric energy storage in presence of renewable energy resources

The increasing integration of Renewable Energy Resources (RER) and the role of Electric Energy Storage (EES) in distribution systems has created interest in using energy management strategies. EES has become a suitable resource to manage energy consumption and generation in smart grid. Optimize scheduling of EES can also maximize retailer’s profit by introducing energy time-shift opportunities. This paper proposes a new strategy for scheduling EES in order to reduce the impact of electricity market price and load uncertainty on retailers’ profit. The proposed strategy optimizes the cost of purchasing energy with the objective of minimizing surplus energy cost in hedging contract. A case study is provided to demonstrate the impact of the proposed strategy on retailers’ financial benefit.

Impact of electric energy storage scheduling on reliability of distribution system

The development of Electric Energy Storage (EES) integrated with Renewable Energy Resources (RER) has increased use of optimum scheduling strategy in distribution systems. Optimum scheduling of EES can reduce cost of purchased energy by retailers while improve the reliability of customers in distribution system. This paper proposes an optimum scheduling strategy for EES and the evaluation of its impact on reliability of distribution system. Case study shows the impact of the proposed strategy on reliability indices of a distribution system.

Effectiveness of electrocardiographic guidance in CVAD tip placement

Background International standard practice for the correct confirmation of the central venous access device is the chest X-ray. The intracavitary electrocardiogram-based insertion method is radiation-free, and allows real-time placement verification, providing immediate treatment and reduced requirement for post-procedural repositioning. Methods Relevant databases were searched for prospective randomised controlled trials (RCTs) or quasi RCTs that compared the effectiveness of electrocardiogram-guided catheter tip positioning with placement using surface-anatomy-guided insertion plus chest X-ray confirmation. The primary outcome was accurate catheter tip placement. Secondary outcomes included complications, patient satisfaction and costs. Results Five studies involving 729 participants were included. Electrocardiogram-guided insertion was more accurate than surface anatomy guided insertion (odds ratio: 8.3; 95% confidence interval (CI) 1.38; 50.07; p=0.02). There was a lack of reporting on complications, patient satisfaction and costs. Conclusion The evidence suggests that intracavitary electrocardiogram-based positioning is superior to surface-anatomy-guided positioning of central venous access devices, leading to significantly more successful placements. This technique could potentially remove the requirement for post-procedural chest X-ray, especially during peripherally inserted central catheter (PICC) line insertion.

Multilingualism and speech-language competence in early childhood: Impact on academic and social-emotional outcomes at school

This large-scale longitudinal population study provided a rare opportunity to consider the interface between multilingualism and speech-language competence on children’s academic and social-emotional outcomes and to determine whether differences between groups at 4 to 5 years persist, deepen, or disappear with time and schooling. Four distinct groups were identified from the Kindergarten cohort of the Longitudinal Study of Australian Children (LSAC) (1) English-only + typical speech and language (n = 2,012); (2) multilingual + typical speech and language (n = 476); (3) English-only + speech and language concern (n = 643); and (4) multilingual + speech and language concern (n = 109). Two analytic approaches were used to compare these groups. First, a matched case-control design was used to randomly match multilingual children with speech and language concern (group 4, n = 109) to children in groups 1, 2, and 3 on gender, age, and family socio-economic position in a cross-sectional comparison of vocabulary, school readiness, and behavioral adjustment. Next, analyses were applied to the whole sample to determine longitudinal effects of group membership on teachers’ ratings of literacy, numeracy, and behavioral adjustment at ages 6 to 7 and 8 to 9 years. At 4 to 5 years, multilingual children with speech and language concern did equally well or better than English-only children (with or without speech and language concern) on school readiness tests but performed more poorly on measures of English vocabulary and behavior. At ages 6 to 7 and 8 to 9, the early gap between English-only and multilingual children had closed. Multilingualism was not found to contribute to differences in literacy and numeracy outcomes at school; instead, outcomes were more related to concerns about children’s speech and language in early childhood. There were no group differences for socio-emotional outcomes. Early evidence for the combined risks of multilingualism plus speech and language concern was not upheld into the school years.

Development of a switch mode assisted linear amplifier for use as a high fidelity voltage source

Frequency Domain Spectroscopy (FDS) is one of the major techniques used for determining the condition of the cellulose based paper and pressboard components in large oil/paper insulated power transformers. This technique typically makes use of a sinusoidal voltage source swept from 0.1 mHz to 1 kHz. The excitation test voltage source used must meet certain characteristics, such as high output voltage, high fidelity, low noise and low harmonic content. The amplifier used; in the test voltage source; must be able to drive highly capacitive loads. This paper proposes that a switch-mode assisted linear amplifier (SMALA) can be used in the test voltage source to meet these criteria. A three level SMALA prototype amplifier was built to experimentally demonstrate the effectiveness of this proposal. The developed SMALA prototype shows no discernable harmonic distortion in the output voltage waveform, or the need for output filters, and is therefore seen as a preferable option to pulse width modulated digital amplifiers. The lack of harmonic distortion and high frequency switching noise in the output voltage of this SMALA prototype demonstrates its feasibility for applications in FDS, particularly on highly capacitive test objects such as transformer insulation systems.

Real time maximum power conversion tracking and resonant frequency modification for high power piezoelectric ultrasound transducer

Piezoelectric ultrasound transducers are commonly used to convert mechanical energy to electrical energy and vice versa. The transducer performance is highly affected by the frequency at which it is excited. If excitation frequency and main resonant frequency match, transducers can deliver maximum power. However, the problem is that main resonant frequency changes in real time operation resulting in low power conversion. To achieve the maximum possible power conversion, the transducer should be excited at its resonant frequency estimated in real time. This paper proposes a method to first estimate the resonant frequency of the transducer and then tunes the excitation frequency accordingly in real time. The measurement showed a significant difference between the offline and real time resonant frequencies. Also, it was shown that the maximum power was achieved at the resonant frequency estimated in real time compare to the one measured offline.

Early mathematical learning: Number processing skills and executive function at 5 and 8 years of age

This research investigated differences and associations in performance in number processing and executive function for children attending primary school in a large Australian metropolitan city. In a cross-sectional study, performance of 25 children in the first full-time year of school, (Prep; mean age = 5.5 years) and 21 children in Year 3 (mean age = 8.5 years) completed three number processing tasks and three executive function tasks. Year 3 children consistently outperformed the Prep year children on measures of accuracy and reaction time, on the tasks of number comparison, calculation, shifting, and inhibition but not on number line estimation. The components of executive function (shifting, inhibition, and working memory) showed different patterns of correlation to performance on number processing tasks across the early years of school. Findings could be used to enhance teachers’ understanding about the role of the cognitive processes employed by children in numeracy learning, and so inform teachers’ classroom practices.

Final report of Working Group 2: Traffic psychology [A COST Action TU1101 / HOPE collaboration]

BACKGROUND The workgroup of Traffic Psychology is concerned with the social, behavioral, and perceptual aspects that are associated with use and non-use of bicycle helmets, in their various forms and under various cycling conditions. OBJECTIVES The objectives of WG2 are to (1) share current knowledge among the people already working in the field, (2) suggest new ideas for research on and evaluation of the design of bicycle helmets, and (3) discuss options for funding of such research within the individual frameworks of the participants. Areas for research include 3.1. The patterns of use of helmets among different users: children, adults, and sports enthusiasts. 3.2. The use of helmets in different environments: rural roads, urban streets, and bike trails. 3.3. Concerns bicyclists have relative to their safety and convenience and the perceived impact of using helmets on comfort and convenience. 3.4. The benefit of helmets for enhancing visibility, and how variations in helmet design and colors affect daytime, nighttime, and dusktime visibility. 3.5. The role of helmets in the acceptance of city-wide pickup-and-drop-off bicycles. 3.6. The impact of helmets on visual search behaviour of bicyclists.

Evaluation of the relationship between Chlamydia pecorum sequence types and disease using a species-specific multi-locus sequence typing scheme (MLST)

Chlamydia pecorum is globally associated with several ovine diseases including keratoconjunctivitis and polyarthritis. The exact relationship between the variety of C. pecorum strains reported and the diseases described in sheep remains unclear, challenging efforts to accurately diagnose and manage infected flocks. In the present study, we applied C. pecorum multi-locus sequence typing (MLST) to C. pecorum positive samples collected from sympatric flocks of Australian sheep presenting with conjunctivitis, conjunctivitis with polyarthritis, or polyarthritis only and with no clinical disease (NCD) in order to elucidate the exact relationships between the infecting strains and the range of diseases. Using Bayesian phylogenetic and cluster analyses on 62 C. pecorum positive ocular, vaginal and rectal swab samples from sheep presenting with a range of diseases and in a comparison to C. pecorum sequence types (STs) from other hosts, one ST (ST 23) was recognised as a globally distributed strain associated with ovine and bovine diseases such as polyarthritis and encephalomyelitis. A second ST (ST 69) presently only described in Australian animals, was detected in association with ovine as well as koala chlamydial infections. The majority of vaginal and rectal C. pecorum STs from animals with NCD and/or anatomical sites with no clinical signs of disease in diseased animals, clustered together in a separate group, by both analyses. Furthermore, 8/13 detected STs were novel. This study provides a platform for strain selection for further research into the pathogenic potential of C. pecorum in animals and highlights targets for potential strain-specific diagnostic test development.

A directed continuous time random walk model with jump length depending on waiting time

In continuum one-dimensional space, a coupled directed continuous time random walk model is proposed, where the random walker jumps toward one direction and the waiting time between jumps affects the subsequent jump. In the proposed model, the Laplace-Laplace transform of the probability density function P(x,t) of finding the walker at position at time is completely determined by the Laplace transform of the probability density function φ(t) of the waiting time. In terms of the probability density function of the waiting time in the Laplace domain, the limit distribution of the random process and the corresponding evolving equations are derived.

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer

Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10-5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10-4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10-9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.