Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling.

The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex. To date, most in vitro BBB models utilize endothelial cells, pericytes and astrocytes. We report a 3D spheroid model of the BBB comprising all major cell types, including neurons, microglia and oligodendrocytes, to recapitulate more closely normal human brain tissue. Spheroids show expression of tight junctions, adherens junctions, adherens junction-associated proteins and cell specific markers. Functional assessment using MPTP, MPP+ and mercury chloride indicate charge selectivity through the barrier. Junctional protein distribution was altered under hypoxic conditions. Our spheroid model may have potential applications in drug discovery, disease modeling, neurotoxicity and cytotoxicity testing.

The Economic Impact of Space Weather: Where Do We Stand?

Space weather describes the way in which the Sun, and conditions in space more generally, impact human activity and technology both in space and on the ground. It is now well understood that space weather represents a significant threat to infrastructure resilience, and is a source of risk that is wide-ranging in its impact and the pathways by which this impact may occur. Although space weather is growing rapidly as a field, work rigorously assessing the overall economic cost of space weather appears to be in its infancy. Here, we provide an initial literature review to gather and assess the quality of any published assessments of space weather impacts and socioeconomic studies. Generally speaking, there is a good volume of scientific peer-reviewed literature detailing the likelihood and statistics of different types of space weather phenomena. These phenomena all typically exhibit "power-law" behavior in their severity. The literature on documented impacts is not as extensive, with many case studies, but few statistical studies. The literature on the economic impacts of space weather is rather sparse and not as well developed when compared to the other sections, most probably due to the somewhat limited data that are available from end-users. The major risk is attached to power distribution systems and there is disagreement as to the severity of the technological footprint. This strongly controls the economic impact. Consequently, urgent work is required to better quantify the risk of future space weather events.

Spatial and temporal evaluation of veterinarians and veterinary employers relative to human and domesticated animal populations in Australia 2002-2012.

OBJECTIVES: To examine the distribution of veterinarians, humans, domestic animals and non-private practice employers in Australia and assess whether a relationship exists between them. To identify trends in the number of veterinarians, humans and domestic animals between 2002 and 2012 that may influence future demands for veterinary services. METHODS: Australian data on registered veterinarians, veterinary practices, the human population and various domestic animal species were obtained for the years 2002, 2007 and 2012. The data were mapped to assess distribution and temporal trends in number and distribution were assessed. RESULTS: Nationally, registered veterinarians were distributed similarly to the general population, with a slight bias to regional areas. The number of veterinarians nationally increased both in absolute terms and relative to the human population between 2002 and 2012. Companion animals were distributed similarly to the human population and livestock occurred in highest density in the more productive agricultural areas. The areas with highest density of domestic animals were within 100 km of an existing veterinary practice. There was moderate correlation between the number of registered veterinarians and the number of people or companion animals, but poor correlation for livestock. The number of domestic animal species decreased between 2002 and 2012, with the exceptions of cattle and poultry. CONCLUSIONS: There is not a simple relationship between the number of veterinarians, people or domestic animals. Better data are needed to describe the drivers for demand for veterinary services and enable future workforce planning.

Kinetic scale turbulence and dissipation in the solar wind: key observational results and future outlook.

Turbulence is ubiquitous in the solar wind. Turbulence causes kinetic and magnetic energy to cascade to small scales where they are eventually dissipated, adding heat to the plasma. The details of how this occurs are not well understood. This article reviews the evidence for turbulent dissipation and examines various diagnostics for identifying solar wind regions where dissipation is occurring. We also discuss how future missions will further enhance our understanding of the importance of turbulence to solar wind dynamics.

Permutation entropy and statistical complexity analysis of turbulence in laboratory plasmas and the solar wind.

The Bandt-Pompe permutation entropy and the Jensen-Shannon statistical complexity are used to analyze fluctuating time series of three different turbulent plasmas: the magnetohydrodynamic (MHD) turbulence in the plasma wind tunnel of the Swarthmore Spheromak Experiment (SSX), drift-wave turbulence of ion saturation current fluctuations in the edge of the Large Plasma Device (LAPD), and fully developed turbulent magnetic fluctuations of the solar wind taken from the Wind spacecraft. The entropy and complexity values are presented as coordinates on the CH plane for comparison among the different plasma environments and other fluctuation models. The solar wind is found to have the highest permutation entropy and lowest statistical complexity of the three data sets analyzed. Both laboratory data sets have larger values of statistical complexity, suggesting that these systems have fewer degrees of freedom in their fluctuations, with SSX magnetic fluctuations having slightly less complexity than the LAPD edge I(sat). The CH plane coordinates are compared to the shape and distribution of a spectral decomposition of the wave forms. These results suggest that fully developed turbulence (solar wind) occupies the lower-right region of the CH plane, and that other plasma systems considered to be turbulent have less permutation entropy and more statistical complexity. This paper presents use of this statistical analysis tool on solar wind plasma, as well as on an MHD turbulent experimental plasma.

Options for managing animal welfare on intensive pig farms confined by movement restrictions during an outbreak of foot and mouth disease.

An outbreak of foot and mouth disease in Australia would trigger a major disease control and eradication program that would include restriction of movement of live animals within defined disease control zones. Experiences from outbreaks in other countries show that restrictions that limit the ability to turn off stock can lead to animal welfare compromise on intensively managed farms that are not infected with the disease. Intensive pig farms are considered to be at high risk of developing welfare problems during a control program due to the imposed movement restrictions and limited space available to house growing pigs. This study was designed to investigate strategies that could be used to mitigate animal welfare problems on intensive pig farms during a simulated outbreak of foot and mouth disease in a livestock dense region of Australia. Three strategies for managing farms affected by animal welfare problems were assessed, including on-farm culling of grower and finisher pigs, on-farm culling of finisher pigs only, and permit-based movement of finisher pigs to slaughter at abattoir. Under traditional approaches of giving infected premises (IP) priority over culling of farms with welfare problems (WP), delays of up to 25 days were experienced prior to culling of WPs. Deployment of vaccination did little to reduce the delay to culling of WPs. These delays were sensitive to resources available for control, with reduced resources increasing the time until welfare problems were addressed. Assigning equal priority to all farms requiring culling regardless of status as IP or WP and culling each as they arose reduced the delay to culling of WPs to no more than 4 days without large increases in either the duration or the size of the outbreaks observed.

How do resources influence control measures during a simulated outbreak of foot and mouth disease in Australia?

An outbreak of foot and mouth disease (FMD) could seriously impact Australia's livestock sector and economy. As an FMD-free country, an outbreak would trigger a major disease control and eradication program that would include the culling of infected and at risk animals ('stamping out'), movement restrictions and zoo-sanitary measures. Additional control measures may also include pre-emptive culling or vaccination. However, it is unclear what disease strategy would be most effective under Australian conditions and different resource levels. Using a stochastic simulation model that describes FMD transmission between farms in a livestock dense region of Australia, our results suggest that using current estimates of human resource capacity for surveillance, infected premises operations and vaccination, outbreaks were effectively controlled under a stamping out strategy. However, under more constrained resource allocations, ring vaccination was more likely to achieve eradication faster than stamping out or pre-emptive culling strategies.

Ensemble downscaling in coupled solar wind-magnetosphere modeling for space weather forecasting.

Advanced forecasting of space weather requires simulation of the whole Sun-to-Earth system, which necessitates driving magnetospheric models with the outputs from solar wind models. This presents a fundamental difficulty, as the magnetosphere is sensitive to both large-scale solar wind structures, which can be captured by solar wind models, and small-scale solar wind "noise," which is far below typical solar wind model resolution and results primarily from stochastic processes. Following similar approaches in terrestrial climate modeling, we propose statistical "downscaling" of solar wind model results prior to their use as input to a magnetospheric model. As magnetospheric response can be highly nonlinear, this is preferable to downscaling the results of magnetospheric modeling. To demonstrate the benefit of this approach, we first approximate solar wind model output by smoothing solar wind observations with an 8 h filter, then add small-scale structure back in through the addition of random noise with the observed spectral characteristics. Here we use a very simple parameterization of noise based upon the observed probability distribution functions of solar wind parameters, but more sophisticated methods will be developed in the future. An ensemble of results from the simple downscaling scheme are tested using a model-independent method and shown to add value to the magnetospheric forecast, both improving the best estimate and quantifying the uncertainty. We suggest a number of features desirable in an operational solar wind downscaling scheme. KEY POINTS: Solar wind models must be downscaled in order to drive magnetospheric models Ensemble downscaling is more effective than deterministic downscaling The magnetosphere responds nonlinearly to small-scale solar wind fluctuations.

Use of a multi-criteria analysis framework to inform the design of risk based general surveillance systems for animal disease in Australia.

Australia is a major exporter of livestock and livestock products; a trade assisted by a favourable animal health status. However, increasing international travel and trade, land use changes and climatic change increase the risks of exotic and emerging diseases. At the same time, public sector resources for managing these risks are static or declining. Animal health authorities in Australia identified the need to develop a consistent national approach to surveillance that allocates resources according to risk. A study was undertaken to assess the relative likelihood of occurrence of eight significant diseases of concern to animal health authorities with the aim of producing risk maps to better manage animal disease surveillance. The likelihood of disease occurrence was considered in terms of the likelihood that a disease is introduced and the likelihood that the disease establishes and spreads. Pathways for introduction and exposure and for establishment and spread were identified and data layers representing the factors contributing to each pathway produced as raster maps. A multi-criteria analysis process was used to combine data layers into pathways and pathways into likelihood maps using weightings that reflect the relative importance of each layer and pathway. The likelihood maps for introduction and exposure and for establishment and spread were combined to generate national likelihood maps for each disease. To inform Australia's general surveillance system that exists to detect any disease of importance, the spatial profiles of the eight diseases were subsequently combined using weightings to reflect their relative consequences. The result was a map of relative likelihood of occurrence of any significant disease. Current surveillance activity was assessed by combining data layers for government disease investigations, proximity to vets and wildlife disease investigations. Comparison of the overall risk and current surveillance maps showed that the distribution of current effort was well matched to the distribution of risk.

Alignment and scaling of large-scale fluctuations in the solar wind.

We investigate the dependence of solar wind fluctuations measured by the Wind spacecraft on scale and on the degree of alignment between oppositely directed Elsasser fields. This alignment controls the strength of the nonlinear interactions and, therefore, the turbulence. We find that at scales larger than the outer scale of the turbulence the Elsasser fluctuations become on average more antialigned as the outer scale is approached from above. Conditioning structure functions using the alignment angle reveals turbulent scaling of unaligned fluctuations at scales previously believed to lie outside the turbulent cascade in the "1/f range." We argue that the 1/f range contains a mixture of a noninteracting antialigned population of Alfvén waves and magnetic force-free structures plus a subdominant population of unaligned cascading turbulent fluctuations.

Descriptive overview of the 2011 epidemic of arboviral disease in horses in Australia.

OBJECTIVE: To provide an overview and descriptive analysis of the 2011 arboviral disease epidemic in horses that involved three important Australian mosquito-borne viruses: Murray Valley encephalitis virus, West Nile virus (Kunjin strain) and Ross River virus. METHODS: Data from states affected between January and June 2011 were collated and comprised reports of horses showing signs of neuromuscular disease and the associated laboratory findings. A summary of the data is presented, together with a spatiotemporal analysis of cases and preliminary assessment of rainfall patterns and case distribution. RESULTS: A total of 982 cases of equine arboviral disease were reported across Australia between January and June 2011. The majority of cases were reported from south-east Australia and included horses that developed neurological signs consistent with encephalitis. It was the largest epidemic of equine arboviral disease in Australia's history. Two likely causes for this unprecedented epidemic were the unusual weather events that preceded the epidemic and the emergence of a new strain of Kunjin virus. CONCLUSIONS: The epidemic highlights to horse owners and policy makers the potential for future outbreaks of arboviral diseases and the need for vigilance. It also highlights the complex interactions among hosts, vectors and climatic conditions that are required for such an outbreak to occur.

Anisotropy of imbalanced Alfvénic turbulence in fast solar wind.

We present the first measurement of the scale-dependent power anisotropy of Elsasser variables in imbalanced fast solar wind turbulence. The dominant Elsasser mode is isotropic at lower spacecraft frequencies but becomes increasingly anisotropic at higher frequencies. The subdominant mode is anisotropic throughout. There are two distinct subranges exhibiting different scalings within what is normally considered the inertial range. The low Alfvén ratio and the different scaling of the Elsasser modes suggests an interpretation of the observed discrepancy between the velocity and magnetic field scalings, the total energy is dominated by the latter. These results do not appear to be fully explained by any of the current theories of incompressible imbalanced MHD turbulence.

Scale-free texture of the fast solar wind.

The higher-order statistics of magnetic field magnitude fluctuations in the fast quiet solar wind are quantified systematically, scale by scale. We find a single global non-Gaussian scale-free behavior from minutes to over 5 h. This spans the signature of an inertial range of magnetohydrodynamic turbulence and a ~1/f range in magnetic field components. This global scaling in field magnitude fluctuations is an intrinsic component of the underlying texture of the solar wind and puts a strong constraint on any theory of solar corona and the heliosphere. Intriguingly, the magnetic field and velocity components show scale-dependent dynamic alignment outside of the inertial range.

Anisotropy of solar wind turbulence between ion and electron scales.

The anisotropy of turbulence in the fast solar wind, between the ion and electron gyroscales, is directly observed using a multispacecraft analysis technique. Second order structure functions are calculated at different angles to the local magnetic field, for magnetic fluctuations both perpendicular and parallel to the mean field. In both components, the structure function value at large angles to the field S{⊥} is greater than at small angles S{∥}: in the perpendicular component S{⊥}/S{∥}=5±1 and in the parallel component S{⊥}/S{∥}>3, implying spatially anisotropic fluctuations, k{⊥}>k{∥}. The spectral index of the perpendicular component is -2.6 at large angles and -3 at small angles, in broad agreement with critically balanced whistler and kinetic Alfvén wave predictions. For the parallel component, however, it is shallower than -1.9, which is considerably less steep than predicted for a kinetic Alfvén wave cascade.

Characterizing the detection system nonlinearity, internal inelastic background, and transmission function of an electron spectrometer for use in x-ray photoelectron spectroscopy.

We present a method for removing spectrometer specific contributions to x-ray photoelectron spectroscopy data. We consider the degree of linearity of the detection system, the strength of the internal analyzer inelastic background, and finally determine the spectrometer's transmission function. The procedures presented here are performed on a SPECS Phoibos 150 hemispherical analyzer with a two-dimensional detection system, but are applicable to a wide variety of different electron spectrometers. The spectrometer's detection system is found to deviate from linear behavior by a few percent over the whole intensity range studied. The size of the analyzer internal inelastic scattering has been measured, and we find that it can normally be neglected at large pass energies or high kinetic energies for most types of analysis (contributing less than 1% at 100 eV pass energy). Finally, we measure the transmission function of the analyzer and lens system for a variety of different settings with the preceding corrections applied, and find that the form of the transmission function is dependent on small changes in the system's settings.

Computer-assisted learning and simulation lab with 40 DentSim units.

There are an increasing number of studies about the computer-assisted dental patient simulator DentSim (DenX, Israel), by which dental students can acquire cognitive motor skills in a multimedia environment. However, only a very few studies have been published dealing with efficient ways to use and to manage a computer-assisted dental simulation lab with 40 DentSim units. The current approach and optimization steps of the College of Dentistry at the University of Tennessee Health Science Center were evaluated based on theoretical and practical tests and by questionnaires (partial 5-point Likert scale). Half of the D1 (first-year) students (2004/05) already had experience with computer-assisted learning at their undergraduate college and most of the students even expected to be taught via computer-assisted learning systems (83.5%) at the dental school. 87.3% of the students working with DentSim found the experience to be very interesting or interesting. Before the students carried out the preparation exercises, they were trained in the skills they needed to work with the sophisticated technology, eg, system-specific operation skills (66.6% attained maximal reachable points) and information searching skills (79.5% attained maximal reachable points). The indirect knowledge retention rate / incidental learning rate of the preparation exercises in the sense of computer-assisted problem-oriented learning regarding anatomy, preparation procedures, and cavity design was promising. The wide- ranging number of prepared teeth needed to acquire the necessary skills shows the varied individual learning curves of the students. The acceptance of, and response to, additional elective training time in the computer-assisted simulation lab were very high. Integrating the DentSim technology into the existing curriculum is a way to improve dental education, but it is also a challenge for both teachers and the students. It requires a shift in both curriculum and instructional goals that have to be reevaluated and optimized continuously.

The effect of a single intravenous fluid bolus on packed cell volume and plasma total solids concentration in Red-collared Lorikeets (Trichoglossus haematodus rubritorquis).

OBJECTIVE: To determine the effect of a single intravenous (IV) fluid bolus on the hydration of an avian patient, using packed cell volume (PCV) and plasma total solids (TS) to estimate hydration. PROCEDURE: Ten birds were allocated randomly to one of three groups, and administered 30 mL/kg or 50 mL/kg intravenous fluid, or were part of a control group and did not receive IV fluid. Blood was collected before the IV fluid bolus was administered, and at 1 minute, 3 hours and 6 hours after administration of the fluid. Samples were used to determine PCV and TS and results were compared between groups and between the different time points. RESULTS: Administration of 30 mL/kg or 50 mL/kg compound sodium lactate solution caused a statistically significant decrease in PCV. Within 3 hours, the PCV was not significantly different to the initial value or to the PCV of control birds. Administration of 30 mL/kg compound sodium lactate solution did not result in a significant decrease in TS. However, administration of 50 mL/kg produced a significant decrease in TS, which was still significantly less than controls 6 hours after the fluid was administered. CONCLUSION: These findings suggest that an intravenous bolus of fluid may be safely administered to an anaemic bird, since PCV is significantly decreased for less than 3 hours. Up to 50 mL/kg of fluid may be administered as an intravenous bolus to a bird, to produce significant haemodilution that persists for up to 6 hours.

Mutual information as a tool for identifying phase transitions in dynamical complex systems with limited data.

We use a well-known model [T. Vicsek, Phys. Rev. Lett. 15, 1226 (1995)] for flocking, to test mutual information as a tool for detecting order-disorder transitions, in particular when observations of the system are limited. We show that mutual information is a sensitive indicator of the phase transition location in terms of the natural dimensionless parameters of the system which we have identified. When only a few particles are tracked and when only a subset of the positional and velocity components is available, mutual information provides a better measure of the phase transition location than the susceptibility of the data.

Morphological and molecular characteristics of a species of Hepatozoon Miller, 1908 (Apicomplexa: Adeleorina) from the blood of Isoodon obesulus (Marsupialia: Peramelidae) in Western Australia.

Examination of blood films as part of a study to assess the health status of the southern brown bandicoot Isoodon obesulus (Shaw) in Western Australia revealed the gamonts of a haemogregarine parasite in some samples, the first to be recognised in a bandicoot in this state. Light microscope morphological characteristics and partial sequence of the 18S rRNA gene were used to describe these organisms. Morphological characters did not differentiate the organism in the current study from previously reported Hepatozoon peramelis (Welsh & Dalyell, 1909). Phylogenetic analysis has not previously been reported for any species of Hepatozoon from Australian marsupials and consequently could not be used to confirm the identity of the organism in the current study as that described in the 1900s. If this organism is H. peramelis, then it has a wide distribution, being found in three species of bandicoot, in western and eastern Australia and the in island state of Tasmania.

Direct tissue stops for distal extension removable partial dentures.

Supplemental impression++ strategies may be used to capture optimal registration of residual ridge tissues in distal extension-base RPDs. A procedure is described to adapt tissue stops in vivo and positively position the framework to the master cast when clinically using corrected impressions. This method is simple and cost-effective, and it promotes accurate prosthetic-tissue relationships during clinical and laboratory phase of RPD fabrication.