Defining the InstaBooth: Facilitating debate and content creation from situated users

Through ubiquitous computing and location-based social media, information is spreading outside the traditional domains of home and work into the urban environment. Digital technologies have changed the way people relate to the urban form supporting discussion on multiple levels, allowing more citizens to be heard in new ways (Fredericks et al. 2013; Houghton et al. 2014; Caldwell et al. 2013). Face-to-face and digitally mediated discussions, facilitated by tangible and hybrid interaction, such as multi-touch screens and media façades, are initiated through a telephone booth inspired portable structure: The InstaBooth. The InstaBooth prototype employs a multidisciplinary approach to engage local communities in a situated debate on the future of their urban environment. With it, we capture citizens’ past stories and opinions on the use and design of public places. The way public consultations are currently done often engages only a section of the population involved in a proposed development; the more vocal citizens are not necessarily the more representative of the communities (Jenkins 2006). Alternative ways to engage urban dwellers in the debate about the built environment are explored at the moment, including the use of social media or online tools (Foth 2009). This project fosters innovation by providing pathways for communities to participate in the decision making process that informs the urban form. The InstaBooth promotes dialogue and mediation between a bottom-up and a top-down approach to urban design, with the aim of promoting community connectedness with the urban environment. The InstaBooth provides an engagement and discussion platform that leverages a number of locally developed display and interaction technologies in order to facilitate a dialogue of ideas and commentary. The InstaBooth combines multiple interaction techniques into a hybrid (digital and analogue) media space. Through the InstaBooth, urban design and architectural proposals are displayed encouraging commentary from visitors. Inside the InstaBooth, visitors can activate a multi-touch screen in order to browse media, write a note, or draw a picture to provide feedback. The purpose of the InstaBooth is to engage with a broader section of society, including those who are often marginalised. The specific design of the internal and external interfaces, the mutual relationship between these interfaces with regards to information display and interaction, and the question how visitors can engage with the system, are part of the research agenda of the project.

Information technology investment governance: What is it and does it matter?

While the growth in the number of IT investments remains strong, research in the IT investment field is limited, resulting in suboptimal practical guidance on effectively governing IT investments. Based on resource-based theory, this paper reports the initial work involved in developing a construct names IT investment governance (ITIG), because it can be used to measure organizations' capability to govern their IT investments. This paper then empirically examines the association of ITIG and corporate performance. The preliminary result is a four-factor, 16-item instrument for assessing the ITIG construct. This method's factors are IT investment value governance, IT investment value monitoring, IT investment appraisals and IT investment project management. The impact of ITIG on corporate performance was demonstrated with a significant and positive relationship found to exist between the ITIG construct and corporate performance, thus supporting the effectiveness of the ITIG construct. Corporations with higher levels of ITIG capability are more likely to maximize the contribution of their IT investments to firm value.

The influence of technology-mediated environments on international business experience for internationalisation: Does international experience matter?

This paper examines the role and importance of international business experience for firms operating in technologically-mediated environments. Although the key success factors of international expansion have been subject to extensive research in the international business literature, the analysis of technology-mediated environments on international business experience remains limited. This finding is unexpected given that the Internet and the technologies that have enabled it have profoundly transformed the ways in which international business is conducted. This is especially so for firms in the Australian region where the Internet has allowed business to access the scale of markets they need to grow and operate globally (Google and PWC, 2015). Given that businesses of the future will need to innovate quicker and more effectively in online settings to remain competitive, it seems appropriate that we re-visit the more traditional facets of internationalisation; such as the necessity of international business experience for firm performance. In doing so, the empirical section of this paper focuses on twelve Australian international entrepreneurial firms, who in varying degrees utilise technology to leverage their internationalisation activities. The findings suggest that international entrepreneurs with lower levels of international business experience still achieve international performance outcomes. The findings indicate that firms are recognising that the ability to adapt and evolve quickly in technologically-advanced settings is imperative. The findings also suggest that international entrepreneurs are relying less on traditional facets of international business experience, and are learning in self-taught or autodidactic ways. This is because businesses in the current global climate are now operating in complex and highly dynamic environments, characterised by rapid change; thus, the findings suggest that international business experience is becoming less important due to the evolving nature of international business environments.

The empire of cancer: Gene patents and cancer voices

In his book, The Emperor of All Maladies, Siddhartha Mukherjee writes a history of cancer — "It is a chronicle of an ancient disease — once a clandestine, 'whispered-about' illness — that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation." Increasingly, an important theme in the history of cancer is the role of law, particularly in the field of intellectual property law. It is striking that a number of contemporary policy debates over intellectual property and public health have concerned cancer research, diagnosis, and treatment. In the area of access to essential medicines, there has been much debate over Novartis’ patent application in respect of Glivec, a treatment for leukaemia. India’s Supreme Court held that the Swiss company’s patent application violated a safeguard provision in India’s patent law designed to stop evergreening. In the field of tobacco control, the Australian Government introduced plain packaging for tobacco products in order to address the health burdens associated with the tobacco epidemic. This regime was successfully defended in the High Court of Australia. In the area of intellectual property and biotechnology, there have been significant disputes over the Utah biotechnology company Myriad Genetics and its patents in respect of genetic testing for BRCA1 and BRCA2, which are related to breast cancer and ovarian cancer. The Federal Court of Australia handed down a decision on the validity of Myriad Genetics’ patent in respect of genetic testing for BRCA1 in February 2013. The Supreme Court of the United States heard a challenge to the validity of Myriad Genetics’ patents in this area in April 2013, and handed down a judgment in July 2013. Such disputes have involved tensions between intellectual property rights, and public health. This article focuses upon one of these important test cases involving intellectual property, public health, and cancer research. In June 2010, Cancer Voices Australia and Yvonne D’Arcy brought an action in the Federal Court of Australia against the validity of a BRCA1 patent — held by Myriad Genetics Inc, the Centre de Recherche du Chul, the Cancer Institute of Japan and Genetic Technologies Limited. Yvonne D’Arcy — a Brisbane woman who has had treatment for breast cancer — maintained: "I believe that what they are doing is morally and ethically corrupt and that big companies should not control any parts of the human body." She observed: "For my daughter, I've had her have [sic] mammograms, etc, because of me but I would still like her to be able to have the test to see if the mutation gene is in there from me." The applicants made the following arguments: "Genes and the information represented by human gene sequences are products of nature universally present in each individual, and the information content of a human gene sequence is fixed. Genetic variations or mutations are products of nature. The isolation of the BRCA1 gene mutation from the human body constitutes no more than a medical or scientific discovery of a naturally occurring phenomenon and does not give rise to a patentable invention." The applicants also argued that "the alleged invention is not a patentable invention in that, so far as claimed in claims 1–3, it is not a manner of manufacture within the meaning of s 6 of the Statute of Monopolies". The applicants suggested that "the alleged invention is a mere discovery". Moreover, the applicants contended that "the alleged invention of each of claims 1-3 is not a patentable invention because they are claims for biological processes for the generation of human beings". The applicants, though, later dropped the argument that the patent claims related to biological processes for the generation of human beings. In February 2013, Nicholas J of the Federal Court of Australia considered the case brought by Cancer Voices Australia and Yvonne D’Arcy against Myriad Genetics. The judge presented the issues in the case, as follows: "The issue that arises in this case is of considerable importance. It relates to the patentability of genes, or gene sequences, and the practice of 'gene patenting'. Briefly stated, the issue to be decided is whether under the Patents Act 1990 (Cth) a valid patent may be granted for a claim that covers naturally occurring nucleic acid — either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) — that has been 'isolated'". In this context, the word "isolated" implies that naturally occurring nucleic acid found in the cells of the human body, whether it be DNA or RNA, has been removed from the cellular environment in which it naturally exists and separated from other cellular components also found there. The genes found in the human body are made of nucleic acid. The particular gene with which the patent in suit is concerned (BRCA1) is a human breast and ovarian cancer disposing gene. Various mutations that may be present in this gene have been linked to various forms of cancer including breast cancer and ovarian cancer.' The judge held in this particular case that Myriad Genetics’ patent claims were a "manner of manufacture" under s 6 of the Statute of Monopolies and s 18(1)(a) of the Patents Act 1990 (Cth). The matter is currently under appeal in the Full Court of the Federal Court of Australia. This article interprets the dispute over Myriad Genetics in light of the scholarly work of Nobel Laureate Professor Joseph Stiglitz on inequality. Such work has significant explanatory power in the context of intellectual property and biotechnology. First, Stiglitz has contended that "societal inequality was a result not just of the laws of economics, but also of how we shape the economy — through politics, including through almost every aspect of our legal system". Stiglitz is concerned that "our intellectual property regime … contributes needlessly to the gravest form of inequality." He maintains: "The right to life should not be contingent on the ability to pay." Second, Stiglitz worries that "some of the most iniquitous aspects of inequality creation within our economic system are a result of 'rent-seeking': profits, and inequality, generated by manipulating social or political conditions to get a larger share of the economic pie, rather than increasing the size of that pie". He observes that "the most iniquitous aspect of this wealth appropriation arises when the wealth that goes to the top comes at the expense of the bottom." Third, Stiglitz comments: "When the legal regime governing intellectual property rights is designed poorly, it facilitates rent-seeking" and "the result is that there is actually less innovation and more inequality." He is concerned that intellectual property regimes "create monopoly rents that impede access to health both create inequality and hamper growth more generally." Finally, Stiglitz has recommended: "Government-financed research, foundations, and the prize system … are alternatives, with major advantages, and without the inequality-increasing disadvantages of the current intellectual property rights system.’" This article provides a critical analysis of the Australian litigation and debate surrounding Myriad Genetics’ patents in respect of genetic testing for BRCA1. First, it considers the ruling of Nicholas J in the Federal Court of Australia that Myriad Genetics’ patent was a manner of manufacture as it related to an artificially created state of affairs, and not mere products of nature. Second, it examines the policy debate over gene patents in Australia, and its relevance to the litigation involving Myriad Genetics. Third, it examines comparative law, and contrasts the ruling by Nicholas J in the Federal Court of Australia with developments in the United States, Canada, and the European Union. Fourth, this piece considers the reaction to the decision of Nicholas at first instance in Australia. Fifth, the article assesses the prospects of an appeal to the Full Federal Court of Australia over the Myriad Genetics’ patents. Finally, this article observes that, whatever happens in respect of litigation against Myriad Genetics, there remains controversy over Genetic Technologies Limited. The Melbourne firm has been aggressively licensing and enforcing its related patents on non-coding DNA and genomic mapping.

Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults

The NTRK1 gene (also known as TRKA) encodes a high-affinity receptor for NGF, a neurotrophin involved in nervous system development and myelination. NTRK1 has been implicated in neurological function via links between the T allele at rs6336 (NTRK1-T) and schizophrenia risk. A variant in the neurotrophin gene, BDNF, was previously associated with white matter integrity in young adults, highlighting the importantce of neurotrophins to white matter development. We hypothesized that NTRK1-T would relate to lower fractional anisotropy in healthy adults. We scanned 391 healthy adult human twins and their siblings (mean age: 23.6 ± 2.2 years; 31 NTRK1-T carriers, 360 non-carriers) using 105-gradient diffusion tensor imaging at 4 tesla. We evaluated in brain white matter how NTRK1-T and NTRK1 rs4661063 allele A (rs4661063-A, which is in moderate linkage disequilibrium with rs6336) related to voxelwise fractional anisotropy-acommondiffusion tensor imaging measure of white matter microstructure. We used mixed-model regression to control for family relatedness, age, and sex. The sample was split in half to test reproducibility of results. The false discovery rate method corrected for voxelwise multiple comparisons. NTRK1-T and rs4661063-A correlated with lower white matter fractional anisotropy, independent of age and sex (multiple-comparisons corrected: false discovery rate critical p=0.038 forNTRK1-Tand0.013 for rs4661063-A). In each half-sample, theNTRK1-T effectwasreplicated in the cingulum, corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, superior corona radiata, and uncinate fasciculus. Our results suggest that NTRK1-T is important for developing white matter microstructure.

Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ~88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLUvariant was associated with lower fractional anisotropy-a widely accepted measure of white matter integrity-in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

Information-theoretic analysis of brain white matter fiber orientation distribution functions

We propose a new information-theoretic metric, the symmetric Kullback-Leibler divergence (sKL-divergence), to measure the difference between two water diffusivity profiles in high angular resolution diffusion imaging (HARDI). Water diffusivity profiles are modeled as probability density functions on the unit sphere, and the sKL-divergence is computed from a spherical harmonic series, which greatly reduces computational complexity. Adjustment of the orientation of diffusivity functions is essential when the image is being warped, so we propose a fast algorithm to determine the principal direction of diffusivity functions using principal component analysis (PCA). We compare sKL-divergence with other inner-product based cost functions using synthetic samples and real HARDI data, and show that the sKL-divergence is highly sensitive in detecting small differences between two diffusivity profiles and therefore shows promise for applications in the nonlinear registration and multisubject statistical analysis of HARDI data.

Genetics of white matter development: A DTI study of 705 twins and their siblings aged 12 to 29

White matter microstructure is under strong genetic control, yet it is largely unknown how genetic influences change from childhood into adulthood. In one of the largest brain mapping studies ever performed, we determined whether the genetic control over white matter architecture depends on age, sex, socioeconomic status (SES), and intelligence quotient (IQ). We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4-Tesla), in 705 twins and their siblings (age range 12-29; 290. M/415. F). White matter integrity was quantified using a widely accepted measure, fractional anisotropy (FA). We fitted gene-environment interaction models pointwise, to visualize brain regions where age, sex, SES and IQ modulate heritability of fiber integrity. We hypothesized that environmental factors would start to outweigh genetic factors during late childhood and adolescence. Genetic influences were greater in adolescence versus adulthood, and greater in males than in females. Socioeconomic status significantly interacted with genes that affect fiber integrity: heritability was higher in those with higher SES. In people with above-average IQ, genetic factors explained over 80% of the observed FA variability in the thalamus, genu, posterior internal capsule, and superior corona radiata. In those with below-average IQ, however, only around 40% FA variability in the same regions was attributable to genetic factors. Genes affect fiber integrity, but their effects vary with age, sex, SES and IQ. Gene-environment interactions are vital to consider in the search for specific genetic polymorphisms that affect brain integrity and connectivity.

Improving fluid registration through white matter segmentation in a twin study design

Robust and automatic non-rigid registration depends on many parameters that have not yet been systematically explored. Here we determined how tissue classification influences non-linear fluid registration of brain MRI. Twin data is ideal for studying this question, as volumetric correlations between corresponding brain regions that are under genetic control should be higher in monozygotic twins (MZ) who share 100% of their genes when compared to dizygotic twins (DZ) who share half their genes on average. When these substructure volumes are quantified using tensor-based morphometry, improved registration can be defined based on which method gives higher MZ twin correlations when compared to DZs, as registration errors tend to deplete these correlations. In a study of 92 subjects, higher effect sizes were found in cumulative distribution functions derived from statistical maps when performing tissue classification before fluid registration, versus fluidly registering the raw images. This gives empirical evidence in favor of pre-segmenting images for tensor-based morphometry.

Memory strength effects in fMRI studies: A matter of confidence

To investigate potentially dissociable recognition memory responses in the hippocampus and perirhinal cortex, fMRI studies have often used confidence ratings as an index of memory strength. Confidence ratings, although correlated with memory strength, also reflect sources of variability, including task-irrelevant item effects and differences both within and across individuals in terms of applying decision criteria to separate weak from strong memories. We presented words one, two, or four times at study in each of two different conditions, focused and divided attention, and then conducted separate fMRI analyses of correct old responses on the basis of subjective confidence ratings or estimates from single- versus dual-process recognition memory models. Overall, the effect of focussing attention on spaced repetitions at study manifested as enhanced recognition memory performance. Confidence- versus model-based analyses revealed disparate patterns of hippocampal and perirhinal cortex activity at both study and test and both within and across hemispheres. The failure to observe equivalent patterns of activity indicates that fMRI signals associated with subjective confidence ratings reflect additional sources of variability. The results are consistent with predictions of single-process models of recognition memory.

Obesity gene NEGR1 associated with white matter integrity in healthy young adults

Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes - NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF- AS, ATXN2L, ATP2A1, KCTD15, and TNN13K - are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30. years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.

Reducing structural variation to determine the genetics of white matter integrity across hemispheres - a dti study of 100 twins

Studies of cerebral asymmetry can open doors to understanding the functional specialization of each brain hemisphere, and how this is altered in disease. Here we examined hemispheric asymmetries in fiber architecture using diffusion tensor imaging (DTI) in 100 subjects, using high-dimensional fluid warping to disentangle shape differences from measures sensitive to myelination. Confounding effects of purely structural asymmetries were reduced by using co-registered structural images to fluidly warp 3D maps of fiber characteristics (fractional and geodesic anisotropy) to a structurally symmetric minimal deformation template (MDT). We performed a quantitative genetic analysis on 100 subjects to determine whether the sources of the remaining signal asymmetries were primarily genetic or environmental. A twin design was used to identify the heritable features of fiber asymmetry in various regions of interest, to further assist in the discovery of genes influencing brain micro-architecture and brain lateralization. Genetic influences and left/right asymmetries were detected in the fiber architecture of the frontal lobes, with minor differences depending on the choice of registration template.

Heritability of white matter fiber tract shapes: A HARDI study of 198 twins

Genetic analysis of diffusion tensor images (DTI) shows great promise in revealing specific genetic variants that affect brain integrity and connectivity. Most genetic studies of DTI analyze voxel-based diffusivity indices in the image space (such as 3D maps of fractional anisotropy) and overlook tract geometry. Here we propose an automated workflow to cluster fibers using a white matter probabilistic atlas and perform genetic analysis on the shape characteristics of fiber tracts. We apply our approach to large study of 4-Tesla high angular resolution diffusion imaging (HARDI) data from 198 healthy, young adult twins (age: 20-30). Illustrative results show heritability for the shapes of several major tracts, as color-coded maps.

Labeling white matter tracts in hardi by fusing multiple tract atlases with applications to genetics

Accurate identification of white matter structures and segmentation of fibers into tracts is important in neuroimaging and has many potential applications. Even so, it is not trivial because whole brain tractography generates hundreds of thousands of streamlines that include many false positive fibers. We developed and tested an automatic tract labeling algorithm to segment anatomically meaningful tracts from diffusion weighted images. Our multi-atlas method incorporates information from multiple hand-labeled fiber tract atlases. In validations, we showed that the method outperformed the standard ROI-based labeling using a deformable, parcellated atlas. Finally, we show a high-throughput application of the method to genetic population studies. We use the sub-voxel diffusion information from fibers in the clustered tracts based on 105-gradient HARDI scans of 86 young normal twins. The whole workflow shows promise for larger population studies in the future.