Rodent Models of Conditioned Fear: Behavioral Measures of Fear and Memory

Pavlovian fear conditioning is a robust technique for examining behavioral and cellular components of fear learning and memory. In fear conditioning, the subject learns to associate a previously neutral stimulus with an inherently noxious co-stimulus. The learned association is reflected in the subjects' behavior upon subsequent re-exposure to the previously neutral stimulus or the training environment. Using fear conditioning, investigators can obtain a large amount of data that describe multiple aspects of learning and memory. In a single test, researchers can evaluate functional integrity in fear circuitry, which is both well characterized and highly conserved across species. Additionally, the availability of sensitive and reliable automated scoring software makes fear conditioning amenable to high-throughput experimentation in the rodent model; thus, this model of learning and memory is particularly useful for pharmacological and toxicological screening. Due to the conserved nature of fear circuitry across species, data from Pavlovian fear conditioning are highly translatable to human models. We describe equipment and techniques needed to perform and analyze conditioned fear data. We provide two examples of fear conditioning experiments, one in rats and one in mice, and the types of data that can be collected in a single experiment. © 2012 Springer Science+Business Media, LLC.

Pavlovian fear memory circuits and phenotype models of PTSD

Pavlovian fear conditioning, also known as classical fear conditioning is an important model in the study of the neurobiology of normal and pathological fear. Progress in the neurobiology of Pavlovian fear also enhances our understanding of disorders such as posttraumatic stress disorder (PTSD) and with developing effective treatment strategies. Here we describe how Pavlovian fear conditioning is a key tool for understanding both the neurobiology of fear and the mechanisms underlying variations in fear memory strength observed across different phenotypes. First we discuss how Pavlovian fear models aspects of PTSD. Second, we describe the neural circuits of Pavlovian fear and the molecular mechanisms within these circuits that regulate fear memory. Finally, we show how fear memory strength is heritable; and describe genes which are specifically linked to both changes in Pavlovian fear behavior and to its underlying neural circuitry. These emerging data begin to define the essential genes, cells and circuits that contribute to normal and pathological fear.

Communication models of institutional online communities : the role of the ABC cultural intermediary

The co-creation of cultural artefacts has been democratised given the recent technological affordances of information and communication technologies. Web 2.0 technologies have enabled greater possibilities of citizen inclusion within the media conversations of their nations. For example, the Australian audience has more opportunities to collaboratively produce and tell their story to a broader audience via the public service media (PSM) facilitated platforms of the Australian Broadcasting Corporation (ABC). However, providing open collaborative production for the audience gives rise to the problem, how might the PSM manage the interests of all the stakeholders and align those interests with its legislated Charter? This paper considers this problem through the ABC’s user-created content participatory platform, ABC Pool and highlights the cultural intermediary as the role responsible for managing these tensions. This paper also suggests cultural intermediation is a useful framework for other media organisations engaging in co-creative activities with their audiences.

Communication models of institutional online communities : the role of the ABC cultural intermediary

The co-creation of cultural artefacts has been democratised given the recent technological affordances of information and communication technologies. Web 2.0 technologies have enabled greater possibilities of citizen inclusion within the media conversations of their nations. For example, the Australian audience has more opportunities to collaboratively produce and tell their story to a broader audience via the public service media (PSM) facilitated platforms of the Australian Broadcasting Corporation (ABC). However, providing open collaborative production for the audience gives rise to the problem, how might the PSM manage the interests of all the stakeholders and align those interests with its legislated Charter? This paper considers this problem through the ABC’s user-created content participatory platform, ABC Pool and highlights the cultural intermediary as the role responsible for managing these tensions. This paper also suggests cultural intermediation is a useful framework for other media organisations engaging in co-creative activities with their audiences.

An IEEE 802.11p empirical performance model for cooperative systems applications

IEEE 802.11p is the new standard for Inter-Vehicular Communications (IVC) using the 5.9 GHz frequency band, as part of the DSRC framework; it will enable applications based on Cooperative Systems. Simulation is widely used to estimate or verify the potential benefits of such cooperative applications, notably in terms of safety for the drivers. We have developed a performance model for 802.11p that can be used by simulations of cooperative applications (e.g. collision avoidance) without requiring intricate models of the whole IVC stack. Instead, it provide a a straightforward yet realistic modelisation of IVC performance. Our model uses data from extensive field trials to infer the correlation between speed, distance and performance metrics such as maximum range, latency and frame loss. Then, we improve this model to limit the number of profiles that have to be generated when there are more than a few couples of emitter-receptor in a given location. Our model generates realistic performance for rural or suburban environments among small groups of IVC-equipped vehicles and road side units.

Complex Modelling in the Primary and Middle School Years : An Interdisciplinary Approach

The world’s increasing complexity, competitiveness, interconnectivity, and dependence on technology generate new challenges for nations and individuals that cannot be met by continuing education as usual. With the proliferation of complex systems have come new technologies for communication, collaboration, and conceptualisation. These technologies have led to signifi cant changes in the forms of mathematical and scientifi c thinking required beyond the classroom. Modelling, in its various forms, can develop and broaden students’ mathematical and scientific thinking beyond the standard curriculum. This chapter first considers future competencies in the mathematical sciences within an increasingly complex world. Consideration is then given to interdisciplinary problem solving and models and modelling, as one means of addressing these competencies. Illustrative case studies involving complex, interdisciplinary modelling activities in Years 1 and 7 are presented.

Do pioneer cells exist?

Most mathematical models of collective cell spreading make the standard assumption that the cell diffusivity and cell proliferation rate are constants that do not vary across the cell population. Here we present a combined experimental and mathematical modeling study which aims to investigate how differences in the cell diffusivity and cell proliferation rate amongst a population of cells can impact the collective behavior of the population. We present data from a three–dimensional transwell migration assay which suggests that the cell diffusivity of some groups of cells within the population can be as much as three times higher than the cell diffusivity of other groups of cells within the population. Using this information, we explore the consequences of explicitly representing this variability in a mathematical model of a scratch assay where we treat the total population of cells as two, possibly distinct, subpopulations. Our results show that when we make the standard assumption that all cells within the population behave identically we observe the formation of moving fronts of cells where both subpopulations are well–mixed and indistinguishable. In contrast, when we consider the same system where the two subpopulations are distinct, we observe a very different outcome where the spreading population becomes spatially organized with the more motile subpopulation dominating at the leading edge while the less motile subpopulation is practically absent from the leading edge. These modeling predictions are consistent with previous experimental observations and suggest that standard mathematical approaches, where we treat the cell diffusivity and cell proliferation rate as constants, might not be appropriate.

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women

Lean body mass (LBM) and muscle mass remains difficult to quantify in large epidemiological studies due to non-availability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n= 2220; 36% females; age 18-79 y) representing a wide range of body mass index (14-44 kg/m2) participated in this study. Their LBM including ALST was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height and weight explained > 90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of SFTs) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all the above anthropometric variables could predict the DXA measured LBM and ALST accurately as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively) as well as good agreement by Bland Altman analyses. These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

Communication Interception Technology (CIT) and its use in the fight against Transnational Organised Crime (TOC) in Australia : a review of the literature

In recent times, technology has advanced in such a manner that the world can now communicate in means previously never thought possible. Transnational organised crime groups, who have exploited these new technologies as basis for their criminal success, however, have not overlooked this development, growth and globalisation. Law enforcement agencies have been confronted with an unremitting challenge as they endeavour to intercept, monitor and analyse these communications as a means of disrupting the activities of criminal enterprises. The challenge lies in the ability to recognise and change tactics to match an increasingly sophisticated adversary. The use of communication interception technology, such as phone taps or email interception, is a tactic that when used appropriately has the potential to cause serious disruption to criminal enterprises. Despite the research that exists on CIT and TOC, these two bodies of knowledge rarely intersect. This paper builds on current literature, drawing them together to provide a clearer picture of the use of CIT in an enforcement and intelligence capacity. It provides a review of the literature pertaining to TOC, the structure of criminal enterprises and the vulnerability of communication used by these crime groups. Identifying the current contemporary models of policing it reviews intelligence-led policing as the emerging framework for modern policing. Finally, it assesses the literature concerning CIT, its uses within Australia and the limitations and arguments that exist. In doing so, this paper provides practitioners with a clearer picture of the use, barriers and benefits of using CIT in the fight against TOC. It helps to bridge the current gaps in modern policing theory and offers a perspective that can help drive future research.

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

Purpose: This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 μg/ml for five days (5d) or 1 μg/ml for 15 days (15d), in previously untreated SCLC patients with extensive disease. Patients and methods: EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in patients receiving 5d EP and on days 2, 5, 8 and 11 in patients receiving 15d EP, with infusion modification to ensure target concentrations were achieved. Treatment was repeated every 21 days for up to six cycles, with a 25% reduction in target concentration in patients with toxicity. Results: The study has closed early after entry of 29 patients (14 with 5d EP, 15 with 15d EP). Objective responses were seen in seven of 12 (58%, confidence interval (CI): 27%-85%) evaluable patients after 5d EP, and two of 14 (14%, CI: 4%42%) evaluable patients after 15d EP (P = 0.038). Grade 3 or 4 neutropenia or leucopenia during the first cycle of treatment was observed in six of 12 patients after 5d EP and 0/14 patients after 15d EP (P = 0.004), with median nadir WBC count of 2.6 x 109/1 after 5d and 5.0 x 109/1 after 15d EP (P = 0.017). Only one of 49 cycles of 15d EP was associated with grade 3 or worse haematological toxicity, compared to 14 of 61 cycles of 5d EP. Conclusions: Although the number of patients entered into this trial was small, the low activity seen at 1 μg/ml in the 15d arm suggests that this concentration is below the therapeutic window in this setting. Further concentration- controlled studies with prolonged EP infusions are required.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

Lessons from the 4-hour standard in England for Australia

Australia is in the process of making the most important change to its health care system since the implementation of Medicare.1 We agree with Cameron and Cooke that there are important lessons for Australia from the implementation of the 4-hour rule in the United Kingdom. As in Robert Zemeckis’s 1985 movie classic, Back to the future, the old question of “If I had the opportunity to do something again, what would I have done differently?” applies. We challenge the assumption that Australia is embarking on something that the UK has recently abandoned. The UK has not actually abandoned the 4-hour rule but expanded it into a suite of eight indicators that include three time-based measures, including total time in the emergency department (ED).

Block models for improved earthwork allocation planning in linear infrastructure construction

Earthwork planning has been considered in this article and a generic block partitioning and modelling approach has been devised to provide strategic plans of various levels of detail. Conceptually this approach is more accurate and comprehensive than others, for instance those that are section based. In response to environmental concerns the metric for decision making was fuel consumption and emissions. Haulage distance and gradient are also included as they are important components of these metrics. Advantageously the fuel consumption metric is generic and captures the physical difficulties of travelling over inclines of different gradients, that is consistent across all hauling vehicles. For validation, the proposed models and techniques have been applied to a real world road project. The numerical investigations have demonstrated that the models can be solved with relatively little CPU time. The proposed block models also result in solutions of superior quality, i.e. they have reduced fuel consumption and cost. Furthermore the plans differ considerably from those based solely upon a distance based metric thus demonstrating a need for industry to reflect upon their current practices.