Head motion and Inattention/Hyperactivity share common genetic influences: Implications for fMRI studies of ADHD

Head motion (HM) is a well known confound in analyses of functional MRI (fMRI) data. Neuroimaging researchers therefore typically treat HM as a nuisance covariate in their analyses. Even so, it is possible that HM shares a common genetic influence with the trait of interest. Here we investigate the extent to which this relationship is due to shared genetic factors, using HM extracted from resting-state fMRI and maternal and self report measures of Inattention and Hyperactivity-Impulsivity from the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scales. Our sample consisted of healthy young adult twins (N = 627 (63% females) including 95 MZ and 144 DZ twin pairs, mean age 22, who had mother-reported SWAN; N = 725 (58% females) including 101 MZ and 156 DZ pairs, mean age 25, with self reported SWAN). This design enabled us to distinguish genetic from environmental factors in the association between head movement and ADHD scales. HM was moderately correlated with maternal reports of Inattention (r = 0.17, p-value = 7.4E-5) and Hyperactivity-Impulsivity (r = 0.16, p-value = 2.9E-4), and these associations were mainly due to pleiotropic genetic factors with genetic correlations [95% CIs] of rg = 0.24 [0.02, 0.43] and rg = 0.23 [0.07, 0.39]. Correlations between self-reports and HM were not significant, due largely to increased measurement error. These results indicate that treating HM as a nuisance covariate in neuroimaging studies of ADHD will likely reduce power to detect between-group effects, as the implicit assumption of independence between HM and Inattention or Hyperactivity-Impulsivity is not warranted. The implications of this finding are problematic for fMRI studies of ADHD, as failing to apply HM correction is known to increase the likelihood of false positives. We discuss two ways to circumvent this problem: censoring the motion contaminated frames of the RS-fMRI scan or explicitly modeling the relationship between HM and Inattention or Hyperactivity-Impulsivity

Feature - No pain, no gain: Pleasure and suffering in technologies of leidenschaft

Training for bodybuilding competition is clearly a serious business that inflicts serious demands on the competitor. Not only did Francis commit time and money to compete, but he also arguably put winning before his physical well-being—enduring pain and suffering from his injury. Bodybuilding may seem like an extreme example, but it is not the only activity in which people suffer in pursuit of their goals. Boxers fight each other in the ring; soccer players risk knee and ankle injuries, sometimes playing despite being hurt; and mountaineers risk their lives in dangerous climbs. In the arts there are many examples of people suffering to achieve their goals: Beethoven kept composing, conducting, and performing despite his hearing loss; van Gogh grappled with depression but kept painting, finding fame only posthumously; and Mozart lived the final years of his life impoverished but still composing. These examples show that many great achievements come at a price: severe suffering...

A comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information

The insulin receptor (IR), the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor-related receptor (IRR) are covalently-linked homodimers made up of several structural domains. The molecular mechanism of ligand binding to the ectodomain of these receptors and the resulting activation of their tyrosine kinase domain is still not well understood. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Importantly, we have also predicted the likely location of the insulin binding site 2 on the surface of the fibronectin type III domains of the IR. An evolutionary conserved surface on the second leucine-rich domain that may interact with the ligand could not be detected. We suggest a possible mechanical trigger of the activation of the IR that involves a slight ‘twist’ rotation of the last two fibronectin type III domains in order to face the likely location of insulin. Finally, a strong selective pressure was found amongst the IRR orthologous sequences, suggesting that this orphan receptor has a yet unknown physiological role which may be conserved from amphibians to mammals.

Unthinkable

'Unthinkable' is an installation comprising drawings and fabric works, which were placed onto a large-scale wall painting. This work engages with the gender politics of art criticism through strategies of redrawing, in particular the commentary that Helen Frankenthaler's painting practice was 'unthinkable' without Jackson Pollock. 'Unthinkable' was developed and presented as part of BEAF 2013: Brisbane Experimental Art Festival, curated by Rachael Parsons and Stephen Russell, held at the Judith Wright Centre of Contemporary Arts.

Material matters [curators]

The exhibition material matters brings together new works by Amy Commins, Jamie Behrendorff, Grace Kevill-Davies, Zoe Knight, Ruth McConchie and Courtney Pedersen – Brisbane-based artists whose experimental practices engage with materiality in specific ways. These works explore incidental viewpoints, suspended moments, constructed environments, cultural memory and repetitive processes. The artists in the exhibition investigate the temporal in terms of making and experiencing art in various modes – installation, sculpture, video, sound and works on paper. Through these material engagements, the artists question and re-imagine ways of connecting in the contemporary world, drawing together considerations of humour, history, politics, nature and everyday life. This exhibition was part of the 2014 Brisbane Experimental Art Festival, held at the Judith Wright Centre of Contemporary Arts.

How cancer doctors use personalized medicine to target variations unique to each tumour

The Children’s Cancer Institute in Sydney recently launched an ambitious program. From early next year, scientists will analyse the unique cancer cells of 12 children diagnosed with the most aggressive forms of the disease to find the best treatment for each child. By 2020, they aim to have these individualised treatment options available to all children diagnosed with cancers that have a less than 30% survival rate. This way of tailoring treatment to each person is known as personalised medicine, and advances in DNA sequencing have paved the way for a new era in cancer management.

Heritability of the network architecture of intrinsic brain functional connectivity

The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23±2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h2 (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤15%), and when global signal regression was implemented, heritability estimates decreased substantially h2 (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.

Heritability analysis of surface-based cortical thickness estimation on a large twin cohort

The aim of this paper is to assess the heritability of cerebral cortex, based on measurements of grey matter (GM) thickness derived from structural MR images (sMRI). With data acquired from a large twin cohort (328 subjects), an automated method was used to estimate the cortical thickness, and EM-ICP surface registration algorithm was used to establish the correspondence of cortex across the population. An ACE model was then employed to compute the heritability of cortical thickness. Heritable cortical thickness measures various cortical regions, especially in frontal and parietal lobes, such as bilateral postcentral gyri, superior occipital gyri, superior parietal gyri, precuneus, the orbital part of the right frontal gyrus, right medial superior frontal gyrus, right middle occipital gyrus, right paracentral lobule, left precentral gyrus, and left dorsolateral superior frontal gyrus.

Heritability of brain network topology in 853 twins and siblings

Anatomical brain networks change throughout life and with diseases. Genetic analysis of these networks may help identify processes giving rise to heritable brain disorders, but we do not yet know which network measures are promising for genetic analyses. Many factors affect the downstream results, such as the tractography algorithm used to define structural connectivity. We tested nine different tractography algorithms and four normalization methods to compute brain networks for 853 young healthy adults (twins and their siblings). We fitted genetic structural equation models to all nine network measures, after a normalization step to increase network consistency across tractography algorithms. Probabilistic tractography algorithms with global optimization (such as Probtrackx and Hough) yielded higher heritability statistics than 'greedy' algorithms (such as FACT) which process small neighborhoods at each step. Some global network measures (probtrackx-derived GLOB and ST) showed significant genetic effects, making them attractive targets for genome-wide association studies.

Genetic analysis of structural brain connectivity using DICCCOL models of diffusion MRI in 522 twins

Genetic and environmental factors affect white matter connectivity in the normal brain, and they also influence diseases in which brain connectivity is altered. Little is known about genetic influences on brain connectivity, despite wide variations in the brain's neural pathways. Here we applied the 'DICCCOL' framework to analyze structural connectivity, in 261 twin pairs (522 participants, mean age: 21.8 y ± 2.7SD). We encoded connectivity patterns by projecting the white matter (WM) bundles of all 'DICCCOLs' as a tracemap (TM). Next we fitted an A/C/E structural equation model to estimate additive genetic (A), common environmental (C), and unique environmental/error (E) components of the observed variations in brain connectivity. We found 44 'heritable DICCCOLs' whose connectivity was genetically influenced (α2>1%); half of them showed significant heritability (α2>20%). Our analysis of genetic influences on WM structural connectivity suggests high heritability for some WM projection patterns, yielding new targets for genome-wide association studies.

Characterisation of the impact of open biomass burning on urban air quality in Brisbane, Australia

Open biomass burning from wildfires and the prescribed burning of forests and farmland is a frequent occurrence in South-East Queensland (SEQ), Australia. This work reports on data collected from 10-30 September 2011, which covers the days before (10-14 September), during (15-20 September) and after (21-30 September) a period of biomass burning in SEQ. The aim of this project was to comprehensively quantify the impact of the biomass burning on air quality in Brisbane, the capital city of Queensland. A multi-parameter field measurement campaign was conducted and ambient air quality data from 13 monitoring stations across SEQ were analysed. During the burning period, the average concentrations of all measured pollutants increased (from 20% to 430%) compared to the non-burning period (both before and after burning), except for total xylenes. The average concentration of O3, NO2, SO2, benzene, formaldehyde, PM10, PM2.5 and visibility-reducing particles reached their highest levels for the year, which were up to 10 times higher than annual average levels, while PM10, PM2.5 and SO2 concentrations exceeded the WHO 24-hour guidelines and O3 concentration exceeded the WHO maximum 8-hour average threshold during the burning period. Overall spatial variations showed that all measured pollutants, with the exception of O3, were closer to spatial homogeneity during the burning compared to the non-burning period. In addition to the above, elevated concentrations of three biomass burning organic tracers (levoglucosan, mannosan and galactosan), together with the amount of non-refractory organic particles (PM1) and the average value of f60 (attributed to levoglucosan), reinforce that elevated pollutant concentration levels were due to emissions from open biomass burning events, 70% of which were prescribed burning events. This study, which is the first and most comprehensive of its kind in Australia, provides quantitative evidence of the significant impact of open biomass burning events, especially prescribed burning, on urban air quality. The current results provide a solid platform for more detailed health and modelling investigations in the future.

Participation in Urban Interaction Design for Civic Engagement

The future of civic engagement is characterised by both technological innovation as well as new technological user practices that are fuelled by trends towards mobile, personal devices; broadband connectivity; open data; urban interfaces; and cloud computing. These technology trends are progressing at a rapid pace, and have led global technology vendors to package and sell the “Smart City” as a centralised service delivery platform predicted to optimise and enhance cities’ key performance indicators – and generate a profitable market. The top-down deployment of these large and proprietary technology platforms have helped sectors such as energy, transport, and healthcare to increase efficiencies. However, an increasing number of scholars and commentators warn of another “IT bubble” emerging. Along with some city leaders, they argue that the top-down approach does not fit the governance dynamics and values of a liberal democracy when applied across sectors. A thorough understanding is required, of the socio-cultural nuances of how people work, live, play across different environments, and how they employ social media and mobile devices to interact with, engage in, and constitute public realms. Although the term “slacktivism” is sometimes used to denote a watered down version of civic engagement and activism that is reduced to clicking a “Like” button and signing online petitions, we believe that we are far from witnessing another Biedermeier period that saw people focus on the domestic and the non-political. There is plenty of evidence to the contrary, such as post-election violence in Kenya in 2008, the Occupy movements in New York, Hong Kong and elsewhere, the Arab Spring, Stuttgart 21, Fukushima, the Taksim Gezi Park in Istanbul, and the Vinegar Movement in Brazil in 2013. These examples of civic action shape the dynamics of governments, and in turn, call for new processes to be incorporated into governance structures. Participatory research into these new processes across the triad of people, place and technology is a significant and timely investment to foster productive, sustainable, and liveable human habitats. With this article, we want to reframe the current debates in academia and priorities in industry and government to allow citizens and civic actors to take their rightful centrepiece place in civic movements. This calls for new participatory approaches for co-inquiry and co-design. It is an evolving process with an explicit agenda to facilitate change, and we propose participatory action research (PAR) as an indispensable component in the journey to develop new governance infrastructures and practices for civic engagement. We do not limit our definition of civic technologies to tools specifically designed to simply enhance government and governance, such as renewing your car registration online or casting your vote electronically on election day. Rather, we are interested in civic media and technologies that foster citizen engagement in the widest sense, and particularly the participatory design of such civic technologies that strive to involve citizens in political debate and action as well as question conventional approaches to political issues. The rationale for this approach is an alternative to smart cities in a “perpetual tomorrow,” based on many weak and strong signals of civic actions revolving around technology seen today. It seeks to emphasise and direct attention to active citizenry over passive consumerism, human actors over human factors, culture over infrastructure, and prosperity over efficiency. First, we will have a look at some fundamental issues arising from applying simplistic smart city visions to the kind of a problem a city poses. We focus on the touch points between “the city” and its civic body, the citizens. In order to provide for meaningful civic engagement, the city must provide appropriate interfaces.