Mind what you say-general and specific mechanisms for monitoring in speech production

For most people, speech production is relatively effortless and error-free. Yet it has long been recognized that we need some type of control over what we are currently saying and what we plan to say. Precisely how we monitor our internal and external speech has been a topic of research interest for several decades. The predominant approach in psycholinguistics has assumed monitoring of both is accomplished via systems responsible for comprehending others' speech. This special topic aimed to broaden the field, firstly by examining proposals that speech production might also engage more general systems, such as those involved in action monitoring. A second aim was to examine proposals for a production-specific, internal monitor. Both aims require that we also specify the nature of the representations subject to monitoring.

Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27- 1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.

Exhaustive search of the SNP-sNP interactome identifies epistatic effects on brain volume in two cohorts

The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting approximately 10(11) pairwise statistical tests. However, recent advances in machine learning, specifically the iterative sure independence screening (SIS) method, have enabled the analysis of datasets where the number of predictors is much larger than the number of observations. Using an implementation of the SIS algorithm (called EPISIS), we used exhaustive search of the genome-wide, SNP-SNP interactome to identify and prioritize SNPs for interaction analysis. We identified a significant SNP pair, rs1345203 and rs1213205, associated with temporal lobe volume. We further examined the full-brain, voxelwise effects of the interaction in the ADNI dataset and separately in an independent dataset of healthy twins (QTIM). We found that each additional loading in the epistatic effect was associated with approximately 5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples.

Common genetic variants influence human subcortical brain structures

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08×10 -33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects

Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (PMA = 4. 79 × 10-8). This commonly-carried genetic variant accounted for 2. 68 % and 0. 84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.

The contribution of genes to cortical thickness and volume

We analyzed brain MRI data from 372 young adult twins toidentify cortical regions in which gray matter thickness and volume are influenced by genetics. This was achieved using an A/C/E structural equation model that divides the variance of these traits, at each point on the cortex, into additive genetic (A), shared (C), and unique environmental (E) components. A strong genetic influencewas found in frontal and parietal regions. Inaddition, we correlated cortical thickness with full-scale intelligence quotient for comparison with the A/C/E maps, and several regions where cortical structure was correlated with intelligence quotient are under genetic control. These cortical measures may be useful phenotypes to narrow the searchfor quantitative trait lociinfluencing brain structure.

A new combined surface and volume registration

3D registration of brain MRI data is vital for many medical imaging applications. However, purely intensitybased approaches for inter-subject matching of brain structure are generally inaccurate in cortical regions, due to the highly complex network of sulci and gyri, which vary widely across subjects. Here we combine a surfacebased cortical registration with a 3D fluid one for the first time, enabling precise matching of cortical folds, but allowing large deformations in the enclosed brain volume, which guarantee diffeomorphisms. This greatly improves the matching of anatomy in cortical areas. The cortices are segmented and registered with the software Freesurfer. The deformation field is initially extended to the full 3D brain volume using a 3D harmonic mapping that preserves the matching between cortical surfaces. Finally, these deformation fields are used to initialize a 3D Riemannian fluid registration algorithm, that improves the alignment of subcortical brain regions. We validate this method on an MRI dataset from 92 healthy adult twins. Results are compared to those based on volumetric registration without surface constraints; the resulting mean templates resolve consistent anatomical features both subcortically and at the cortex, suggesting that the approach is well-suited for cross-subject integration of functional and anatomic data.

No specific role for the manual motor system in processing the meanings of words related to the hand

The present study explored whether semantic and motor systems are functionally interwoven via the use of a dual-task paradigm. According to embodied language accounts that propose an automatic and necessary involvement of the motor system in conceptual processing, concurrent processing of hand-related information should interfere more with hand movements than processing of unrelated body-part (i.e., foot, mouth) information. Across three experiments, 100 right-handed participants performed left- or right-hand tapping movements while repeatedly reading action words related to different body-parts, or different body-part names, in both aloud and silent conditions. Concurrent reading of single words related to specific body-parts, or the same words embedded in sentences differing in syntactic and phonological complexity (to manipulate context-relevant processing), and reading while viewing videos of the actions and body-parts described by the target words (to elicit visuomotor associations) all interfered with right-hand but not left-hand tapping rate. However, this motor interference was not affected differentially by hand-related stimuli. Thus, the results provide no support for proposals that body-part specific resources in cortical motor systems are shared between overt manual movements and meaning-related processing of words related to the hand.

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

Origins of Australian Football: Victoria's Early History. Volume 3: Covert 'Professionalism': The Power of the Wealthy Clubs 1886 to 1890

This volume continues the story of football in Marvellous Melbourne during the 1880s. At this time the VFA continued to expand as Melbourne’s boom continued apace. In 1886 Port Melbourne, Prahran, St Kilda, Footscray and South Williamstown joined the competition, and the Ballarat clubs Ballarat, Ballarat Imperial and South Ballarat were also contending for the VFA premiership. In 1886 matches were divided into four quarters, goal umpires waved two flags to announce a goal, and time clocks and bells were employed to mark the end of quarters. Victoria also played inter-colonial matches against New South Wales, Tasmania and South Australia. VFA secretary T.S. Marshall was at the forefront of fighting the game’s turn towards professionalism, but although it was illegal to pay players, the practice continued. The period 1886 to 1890 also set the stage for the eventual formation of the Victorian Football League, for by the end of the 1880s the Victorian Football Association had become in effect a two-tier competition. The most popular clubs in the VFA, South Melbourne, Geelong, Carlton and Essendon collected the lion’s share of the gate money, which they used to build their wealth and entrench their position as the dominant Victorian teams. The lower tier clubs had to make do with paltry gate money and season fixtures that advantaged the strong clubs. In these fixtures the strong clubs elected to play each other first to increase their gate money, and only deemed to play the poorer clubs at the start of the season. This led to an increasing divide between the VFA’s rich and poor, and by 1890 South Williamstown and Prahran merged with Williamstown and St Kilda respectively, University dropped out of senior ranks, and the Ballarat clubs were excluded from competing for the VFA premiership, which left 12 senior clubs until Collingwood’s emergence in 1892. At this time, no team was as powerful as South Melbourne, which experienced the greatest success in the club’s VFA and VFL history when it collected triple premiership crowns in 1888, 1889, and 1890. South Melbourne was a most ambitious club and spearheaded the move towards professionalism, although this could not be made public. The fine teams it produced at this time contained some of the greatest players of the era, such as Peter Burns, “Sonny” Elms and “Dinny” McKay, and it looked after players with health insurance, jobs, inter-colonial trips, and other incentives. Geelong’s premiership in 1886 was perhaps its greatest triumph, but this success was followed by a premiership drought that would last for 39 years. Carlton remained one of Victorian football’s power clubs, and after securing the premiership in 1887 continued to compete for top honours. As always, the game became ever more popular and world record crowds of over 30,000 attended matches between South Melbourne, Carlton, Geelong and Essendon.

RNASeqBrowser: A genome browser for simultaneous visualization of raw strand specific RNAseq reads and UCSC genome browser custom tracks

Background Strand specific RNAseq data is now more common in RNAseq projects. Visualizing RNAseq data has become an important matter in Analysis of sequencing data. The most widely used visualization tool is the UCSC genome browser that introduced the custom track concept that enabled researchers to simultaneously visualize gene expression at a particular locus from multiple experiments. Our objective of the software tool is to provide friendly interface for visualization of RNAseq datasets. Results This paper introduces a visualization tool (RNASeqBrowser) that incorporates and extends the functionality of the UCSC genome browser. For example, RNASeqBrowser simultaneously displays read coverage, SNPs, InDels and raw read tracks with other BED and wiggle tracks -- all being dynamically built from the BAM file. Paired reads are also connected in the browser to enable easier identification of novel exon/intron borders and chimaeric transcripts. Strand specific RNAseq data is also supported by RNASeqBrowser that displays reads above (positive strand transcript) or below (negative strand transcripts) a central line. Finally, RNASeqBrowser was designed for ease of use for users with few bioinformatic skills, and incorporates the features of many genome browsers into one platform. Conclusions The features of RNASeqBrowser: (1) RNASeqBrowser integrates UCSC genome browser and NGS visualization tools such as IGV. It extends the functionality of the UCSC genome browser by adding several new types of tracks to show NGS data such as individual raw reads, SNPs and InDels. (2) RNASeqBrowser can dynamically generate RNA secondary structure. It is useful for identifying non-coding RNA such as miRNA. (3) Overlaying NGS wiggle data is helpful in displaying differential expression and is simple to implement in RNASeqBrowser. (4) NGS data accumulates a lot of raw reads. Thus, RNASeqBrowser collapses exact duplicate reads to reduce visualization space. Normal PC’s can show many windows of NGS individual raw reads without much delay. (5) Multiple popup windows of individual raw reads provide users with more viewing space. This avoids existing approaches (such as IGV) which squeeze all raw reads into one window. This will be helpful for visualizing multiple datasets simultaneously. RNASeqBrowser and its manual are freely available at http://www.australianprostatecentre.org/research/software/rnaseqbrowser webcite or http://sourceforge.net/projects/rnaseqbrowser/ webcite

Assessment of body composition of Sri Lankan Australian children using ethnic specific equations

Since ethnic differences exist in body composition, assessment methods need to be validated prior to use in different populations. This study attempts to validate the use of Sri Lankan based body composition assessment tools on a group of 5 - 15 year old Australian children of Sri Lankan origin. The study was conducted at the Body Composition Laboratory of the Children’s Nutrition Research Centre at the Royal Children’s Hospital, Brisbane, Australia. Height (Ht), weight (Wt), segmental length (Lsegment name) and skinfold thickness (SFT) were measured. The whole body and segmental bio impedance analysis (BIA) were also measured. The body composition determined by the deuterium dilution technique (criterion method) was compared with the assessments done using prediction equations developed on Sri Lankan children. 27 boys and 15 girls were studied. All predictions of body composition parameters, except percentage fat mass (FM) assessed by the SFT-FM equation in girls gave statistically significant correlations with the criterion method. They had a low mean bias and most were not influenced by the measured parameter. Although living in a different socioeconomic state, the equations developed on children of the same ethnic background gives a better predictive value of body composition. This highlights the ethnic influence on body composition.

Assessing specific deterrence effects of increased speeding penalties using four measures of recidivism

Traffic law enforcement sanctions can impact on road user behaviour through general and specific deterrence mechanisms. The manner in which specific deterrence can influence recidivist behaviour can be conceptualised in different ways. While any reduction in speeding will have road safety benefits, the ways in which a ‘reduction’ is determined deserves greater methodological attention and has implications for countermeasure evaluation more generally. The primary aim of this research was to assess the specific deterrent impact of penalty increases for speeding offences in Queensland, Australia, in 2003 on two cohorts of drivers detected for speeding prior to and after the penalty changes were investigated. Since the literature is relatively silent on how to assess recidivism in the speeding context, the secondary research aim was to contribute to the literature regarding ways to conceptualise and measure specific deterrence in the speeding context. We propose a novel way of operationalising four measures which reflect different ways in which a specific deterrence effect could be conceptualised: (1) the proportion of offenders who re-offended in the follow up period; (2) the overall frequency of re-offending in the follow up period; (3) the length of delay to re-offence among those who re-offended; and (4) the average number of re-offences during the follow up period among those who re-offended. Consistent with expectations, results suggested an absolute deterrent effect of penalty changes, as evidenced by significant reductions in the proportion of drivers who re-offended and the overall frequency of re-offending, although effect sizes were small. Contrary to expectations, however, there was no evidence of a marginal specific deterrent effect among those who re-offended, with a significant reduction in the length of time to re-offence and no significant change in the average number of offences committed. Additional exploratory analyses investigating potential influences of the severity of the index offence, offence history, and method of detection revealed mixed results. Access to additional data from various sources suggested that the main findings were not influenced by changes in speed enforcement activity, public awareness of penalty changes, or driving exposure during the study period. Study limitations and recommendations for future research are discussed with a view to promoting more extensive evaluations of penalty changes and better understanding of how such changes may impact on motorists’ perceptions of enforcement and sanctions, as well as on recidivist behaviour.

Prototyping the self-authored video interview : Challenges and opportunities

Self-authored video- where participants are in control of the creation of their own footage- is a means of creating innovative design material and including all members of a family in design activities. This paper describes our adaptation to this process called Self Authored Video Interviews (SAVIs) that we created and prototyped to better understand how families engage with situated technology in the home. We find the methodology produces unique insights into family dynamics in the home, uncovering assumptions and tensions unlikely to be discovered using more conventional methods. The paper outlines a number of challenges and opportunities associated with the methodology, specifically, maximising the value of the insights gathered by appealing to children to champion the cause, and how to counter perceptions of the lingering presence of researchers.

Predicting surgical outcomes for paediatric spinal deformity patients using subject specific finite element models

INTRODUCTION Adolescent idiopathic scoliosis (AIS) is a spinal deformity, which may require surgical correction by attaching rods to the patient’s spine using screws inserted into the vertebrae. Complication rates for deformity correction surgery are unacceptably high. Determining an achievable correction without overloading the adjacent spinal tissues or implants requires an understanding of the mechanical interaction between these components. Our novel patient specific modelling software creates individualized finite element models (FEM) representing the thoracolumbar spine and ribcage of scoliosis patients. We have recently applied the model to investigate the influence of increasing magnitudes of surgically applied corrective force on predicted deformity correction...