The high price of drug patents: Australia, patent law, pharmaceutical drugs and the Trans-Pacific Partnership

This week, the secrecy surrounding an independent Australian report on patent law and pharmaceutical drugs has been lifted, and the work has been published to great acclaim...

The High Court of Australia and the Marlboro Man: The Battle Over the Plain Packaging of Tobacco Products

In 2012, the High Court of Australia handed down a landmark decision on the plain packaging of tobacco products. This chapter considers the historic ruling in the case of JT International SA v Commonwealth; British American Tobacco Australasia Ltd v Commonwealth. This chapter explores several themes in the decision. First, it highlights the historical work by the High Court of Australia on the role of health regulation, the use of health warnings, and tobacco control. Second, the chapter considers the High Court of Australia's view that intellectual property law promotes the public interest.Third, it explores the High Court of Australia’s analysis of the constitutional law on acquisition of property on just terms. Finally, this chapter contends that the High Court of Australia's ruling on plain packaging of tobacco products will spark an 'Olive Revolution' — and will encourage superior courts and policy-makers to follow suit.

Pull-through strength of high tensile steel cladding systems

The profiled steel roof and wall cladding systems in Australia are commonly made of very thin high tensile steels, and are crest-fixed with screw fasteners. A review of current literature and design standards indicated the need to improve the understanding of the behaviour of crest-fixed steel cladding systems under wind uplift/suction loading, in particular, the local failures. Therefore a detailed experimental study using a series of small scale tests and some two-span cladding tests was conducted to investigate the local pull-through and dimpling failures in the commonly used steel cladding systems. The applicability of the current design formulae for the pull-through strength of crest-fixed steel classing systems was investigated first. An improved design formula was then developed in terms of the thickness and ultimate tensile strenth of steel cladding material and diameter of screw head or washer. This paper presents the details of this investigation and its results. A review of current design and test methods is also included.

The Cougar Point tuff: Implications for thermochemical zonation and longevity of high-temperature, large-volume silicic magmas of the Miocene Yellowstone hotspot

The 12.7-10.5 Ma Cougar Point Tuff in southern Idaho, USA, consists of 10 large-volume (>10²-10³ km³ each), high-temperature (800-1000 °C), rhyolitic ash-flow tuffs erupted from the Bruneau-Jarbidge volcanic center of the Yellowstone hotspot. These tuffs provide evidence for compositional and thermal zonation in pre-eruptive rhyolite magma, and suggest the presence of a long-lived reservoir that was tapped by numerous large explosive eruptions. Pyroxene compositions exhibit discrete compositional modes with respect to Fe and Mg that define a linear spectrum punctuated by conspicuous gaps. Airfall glass compositions also cluster into modes, and the presence of multiple modes indicates tapping of different magma volumes during early phases of eruption. Equilibrium assemblages of pigeonite and augite are used to reconstruct compositional and thermal gradients in the pre-eruptive reservoir. The recurrence of identical compositional modes and of mineral pairs equilibrated at high temperatures in successive eruptive units is consistent with the persistence of their respective liquids in the magma reservoir. Recurrence intervals of identical modes range from 0.3 to 0.9 Myr and suggest possible magma residence times of similar duration. Eruption ages, magma temperatures, Nd isotopes, and pyroxene and glass compositions are consistent with a long-lived, dynamically evolving magma reservoir that was chemically and thermally zoned and composed of multiple discrete magma volumes.

High-temperature, low-H₂O silicic magmas of the Yellowstone Hotspot: an experimental study of Rhyolite from the Bruneau-Jarbidge eruptive center, Central Snake River Plain, USA

The phase relations have been investigated experimentally at 200 and 500 MPa as a function of water activity for one of the least evolved (Indian Batt Rhyolite) and of a more evolved rhyolite composition (Cougar Point Tuff XV) from the 12·8-8·1 Ma Bruneau-Jarbidge eruptive center of the Yellowstone hotspot. Particular priority was given to accurate determination of the water content of the quenched glasses using infrared spectroscopic techniques. Comparison of the composition of natural and experimentally synthesized phases confirms that high temperatures (>900°C) and extremely low melt water contents (<1·5 wt % H₂O) are required to reproduce the natural mineral assemblages. In melts containing 0·5-1·5 wt % H₂O, the liquidus phase is clinopyroxene (excluding Fe-Ti oxides, which are strongly dependent on fO₂), and the liquidus temperature of the more evolved Cougar Point Tuff sample (BJR; 940-1000°C) is at least 30°C lower than that of the Indian Batt Rhyolite lava sample (IBR2; 970-1030°C). For the composition BJR, the comparison of the compositions of the natural and experimental glasses indicates a pre-eruptive temperature of at least 900°C. The composition of clinopyroxene and pigeonite pairs can be reproduced only for water contents below 1·5 wt % H₂O at 900°C, or lower water contents if the temperature is higher. For the composition IBR2, a minimum temperature of 920°C is necessary to reproduce the main phases at 200 and 500 MPa. At 200 MPa, the pre-eruptive water content of the melt is constrained in the range 0·7-1·3 wt % at 950°C and 0·3-1·0 wt % at 1000°C. At 500 MPa, the pre-eruptive temperatures are slightly higher (by 30-50°C) for the same ranges of water concentration. The experimental results are used to explore possible proxies to constrain the depth of magma storage. The crystallization sequence of tectosilicates is strongly dependent on pressure between 200 and 500 MPa. In addition, the normative Qtz-Ab-Or contents of glasses quenched from melts coexisting with quartz, sanidine and plagioclase depend on pressure and melt water content, assuming that the normative Qtz and Ab/Or content of such melts is mainly dependent on pressure and water activity, respectively. The combination of results from the phase equilibria and from the composition of glasses indicates that the depth of magma storage for the IBR2 and BJR compositions may be in the range 300-400 MPa (13 km) and 200-300 MPa (10 km), respectively.

Brain fiber architecture, genetics, and intelligence: a high angular resolution diffusion imaging (HARDI) study

We developed an analysis pipeline enabling population studies of HARDI data, and applied it to map genetic influences on fiber architecture in 90 twin subjects. We applied tensor-driven 3D fluid registration to HARDI, resampling the spherical fiber orientation distribution functions (ODFs) in appropriate Riemannian manifolds, after ODF regularization and sharpening. Fitting structural equation models (SEM) from quantitative genetics, we evaluated genetic influences on the Jensen-Shannon divergence (JSD), a novel measure of fiber spatial coherence, and on the generalized fiber anisotropy (GFA) a measure of fiber integrity. With random-effects regression, we mapped regions where diffusion profiles were highly correlated with subjects' intelligence quotient (IQ). Fiber complexity was predominantly under genetic control, and higher in more highly anisotropic regions; the proportion of genetic versus environmental control varied spatially. Our methods show promise for discovering genes affecting fiber connectivity in the brain.

Mapping genetic influences on brain fiber architecture with high angular resolution diffusion imaging (HARDI)

We report the first 3D maps of genetic effects on brain fiber complexity. We analyzed HARDI brain imaging data from 90 young adult twins using an information-theoretic measure, the Jensen-Shannon divergence (JSD), to gauge the regional complexity of the white matter fiber orientation distribution functions (ODF). HARDI data were fluidly registered using Karcher means and ODF square-roots for interpol ation; each subject's JSD map was computed from the spatial coherence of the ODFs in each voxel's neighborhood. We evaluated the genetic influences on generalized fiber anisotropy (GFA) and complexity (JSD) using structural equation models (SEM). At each voxel, genetic and environmental components of data variation were estimated, and their goodness of fit tested by permutation. Color-coded maps revealed that the optimal models varied for different brain regions. Fiber complexity was predominantly under genetic control, and was higher in more highly anisotropic regions. These methods show promise for discovering factors affecting fiber connectivity in the brain.

Development of insula connectivity between ages 12 and 30 revealed by high angular resolution diffusion imaging

The insula, hidden deep within the Sylvian fissures, has proven difficult to study from a connectivity perspective. Most of our current information on the anatomical connectivity of the insula comes from studies of nonhuman primates and post mortem human dissections. To date, only two neuroimaging studies have successfully examined the connectivity of the insula. Here we examine how the connectivity of the insula develops between ages 12 and 30, in 307 young adolescent and adult subjects scanned with 4-Tesla high angular resolution diffusion imaging (HARDI). The density of fiber connections between the insula and the frontal and parietal cortex decreased with age, but the connection density between the insula and the temporal cortex generally increased with age. This trajectory is in line with well-known patterns of cortical development in these regions. In addition, males and females showed different developmental trajectories for the connection between the left insula and the left precentral gyrus. The insula plays many different roles, some of them affected in neuropsychiatric disorders; this information on the insula's connectivity may help efforts to elucidate mechanisms of brain disorders in which it is implicated.

Sex differences in the human connectome: 4-Tesla high angular resolution diffusion imaging (HARDI) tractography in 234 young adult twins

Cortical connectivity is associated with cognitive and behavioral traits that are thought to vary between sexes. Using high-angular resolution diffusion imaging at 4 Tesla, we scanned 234 young adult twins and siblings (mean age: 23.4 2.0 SD years) with 94 diffusion-encoding directions. We applied a novel Hough transform method to extract fiber tracts throughout the entire brain, based on fields of constant solid angle orientation distribution functions (ODFs). Cortical surfaces were generated from each subject's 3D T1-weighted structural MRI scan, and tracts were aligned to the anatomy. Network analysis revealed the proportions of fibers interconnecting 5 key subregions of the frontal cortex, including connections between hemispheres. We found significant sex differences (147 women/87 men) in the proportions of fibers connecting contralateral superior frontal cortices. Interhemispheric connectivity was greater in women, in line with long-standing theories of hemispheric specialization. These findings may be relevant for ongoing studies of the human connectome.

Visualization tools for high angular resolution diffusion imaging

There is a major effort in medical imaging to develop algorithms to extract information from DTI and HARDI, which provide detailed information on brain integrity and connectivity. As the images have recently advanced to provide extraordinarily high angular resolution and spatial detail, including an entire manifold of information at each point in the 3D images, there has been no readily available means to view the results. This impedes developments in HARDI research, which need some method to check the plausibility and validity of image processing operations on HARDI data or to appreciate data features or invariants that might serve as a basis for new directions in image segmentation, registration, and statistics. We present a set of tools to provide interactive display of HARDI data, including both a local rendering application and an off-screen renderer that works with a web-based viewer. Visualizations are presented after registration and averaging of HARDI data from 90 human subjects, revealing important details for which there would be no direct way to appreciate using conventional display of scalar images.

Analyzing multi-fiber reconstruction in high angular resolution diffusion imaging using the tensor distribution function

High-angular resolution diffusion imaging (HARDI) can reconstruct fiber pathways in the brain with extraordinary detail, identifying anatomical features and connections not seen with conventional MRI. HARDI overcomes several limitations of standard diffusion tensor imaging, which fails to model diffusion correctly in regions where fibers cross or mix. As HARDI can accurately resolve sharp signal peaks in angular space where fibers cross, we studied how many gradients are required in practice to compute accurate orientation density functions, to better understand the tradeoff between longer scanning times and more angular precision. We computed orientation density functions analytically from tensor distribution functions (TDFs) which model the HARDI signal at each point as a unit-mass probability density on the 6D manifold of symmetric positive definite tensors. In simulated two-fiber systems with varying Rician noise, we assessed how many diffusionsensitized gradients were sufficient to (1) accurately resolve the diffusion profile, and (2) measure the exponential isotropy (EI), a TDF-derived measure of fiber integrity that exploits the full multidirectional HARDI signal. At lower SNR, the reconstruction accuracy, measured using the Kullback-Leibler divergence, rapidly increased with additional gradients, and EI estimation accuracy plateaued at around 70 gradients.

The microwell-mesh: A novel device and protocol for the high throughput manufacturing of cartilage microtissues

Microwell platforms are frequently described for the efficient and uniform manufacture of 3-dimensional (3D) multicellular microtissues. Multiple partial or complete medium exchanges can displace microtissues from discrete microwells, and this can result in either the loss of microtissues from culture, or microtissue amalgamation when displaced microtissues fall into common microwells. Herein we describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells; the microwell-mesh. We show that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells. To demonstrate the utility of this platform, we used the microwell-mesh to manufacture hundreds of cartilage microtissues, each formed from 5 × 10(3) bone marrow-derived mesenchymal stem/stromal cells (MSC). The microwell-mesh enabled reliable microtissue retention over 21-day cultures that included multiple full medium exchanges. Cartilage-like matrix formation was more rapid and homogeneous in microtissues than in conventional large diameter control cartilage pellets formed from 2 × 10(5) MSC each. The microwell-mesh platform offers an elegant mechanism to retain microtissues in microwells, and we believe that this improvement will make this platform useful in 3D culture protocols that require multiple medium exchanges, such as those that mimic specific developmental processes or complex sequential drug exposures.

High-throughput approach for the identification of anilinium-based ionic liquids that are suitable for electropolymerisation

We report the synthesis of new protic ionic liquids (PILs) based on aniline derivatives and the use of high-throughput (HT) techniques to screen possible candidates. In this work, a simple HT method was applied to rapidly screen different aniline derivatives against different acids in order to identify possible combinations that produce PILs. This was followed by repeating the HT process with Chemspeed robotic synthesis platform for more accurate results. One of the successful combinations were then chosen to be synthesised on full scale for further analysis. The new PILs are of interest to the fields of ionic liquids, energy storage and especially, conducting polymers as they serve as solvents, electrolytes and monomers in the same time for possible electropolymerisation (i.e. a self-contained polymer precursor).

One-step synthesis of high quality kesterite Cu2ZnSnS4nanocrystals: A hydrothermal approach

The present work demonstrates a systematic approach for the synthesis of pure kesterite-phase Cu2ZnSnS4 (CZTS) nanocrystals with a uniform size distribution by a one-step, thioglycolic acid (TGA)-assisted hydrothermal route. The formation mechanism and the role of TGA in the formation of CZTS compound were thoroughly studied. It has been found that TGA interacted with Cu2+ to form Cu+ at the initial reaction stage and controlled the crystal-growth of CZTS nanocrystals during the hydrothermal reaction. The consequence of the reduction of Cu2+ to Cu+ led to the formation Cu2−xS nuclei, which acted as the crystal framework for the formation of CZTS compound. CZTS was formed by the diffusion of Zn2+ and Sn4+ cations to the lattice of Cu2−xS during the hydrothermal reaction. The as-synthesized CZTS nanocrystals exhibited strong light absorption over the range of wavelength beyond 1000 nm. The band gap of the material was determined to be 1.51 eV, which is optimal for application in photoelectric energy conversion device.