1,236 research outputs found

    Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate

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    Deformation of brain tissue in response to mechanical loading of the head is the root-cause of traumatic brain injury (TBI). Even below ultimate failure limits, deformation activates pathophysiological cascades resulting in delayed cell death. Injury response of soft tissues, such as the chest and spinal cord, is dependent on the product of deformation and velocity, a parameter termed the viscous criterion. We set out to test if hippocampal cell death could be predicted by a similar combination of strain and strain rate and if the viscous criterion was valid for hippocampus. Quantitative prediction of the brain's biological response to mechanical stimuli is difficult to achieve in animal models of TBI, so we utilized an in vitro model of TBI based on hippocampal slice cultures. We quantified the temporal development of cell death after precisely controlled deformations for 30 combinations of strain (0.05-0.50) and strain rate (0.1-50 s(-1)) relevant to TBI. Loading conditions for a subset of cultures were verified by analysis of highspeed video. Cell death was found to be significantly dependent on time-post injury, on strain magnitude, and to a lesser extent, on anatomical region by a repeated-measures, three-way ANOVA. The responses of the CA1 and CA3 regions of the hippocampus were not statistically different in contrast to some in vivo TBI studies. Surprisingly, cell death was not dependent on strain rate leading us to conclude that the viscous criterion is not a valid predictor for hippocampal tissue injury. Given the large data set and extensive combinations of biomechanical parameters, predictive mathematical functions relating independent variables (strain, region, and time post-injury) to the resultant cell death were defined. These functions can be used as tolerance criteria to equip finite element models of TBI with the added capability to predict biological consequences

    Creating a Digital Commons

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    The phrase information commons refers to our shared knowledge base. Heather Morrison presents examples of the commons in action, ranging from open access and open source scholarly resources to the blogosphere. The concept of sampling in music is discussed, and applied to librarianship. Key policy for the commons are identified and discussed, including open access, telecommunications issues (net neutrality, access issues), and copyright laws that facilitate sharing. Olivier Charbonneau presents "tools for the shepherd", or when digital projects are fit for collaboration, in the context of Lessig's regulatory framework, Benkler's "commons based peer production" framework, and Alter's "Work Centered Analysis Framework for Systems Analysis". The Canadian Legal Information Institute (CANLII), created to enable free access to authoritative versions of Canadian case law and statutes on the Internet through a uniform search interface, is presented as an example of a collaboratively produced digital commons

    Lactate and glucose as energy substrates during, and after, oxygen deprivation in rat hippocampal acute and cultured slices

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    The effects of raised brain lactate levels on neuronal survival following hypoxia or ischemia is still a source of controversy among basic and clinical scientists. We have sought to address this controversy by studying the effects of glucose and lactate on neuronal survival in acute and cultured hippocampal slices. Following a 1-h hypoxic episode, neuronal survival in cultured hippocampal slices was significantly higher if glucose was present in the medium compared with lactate. However, when the energy substrate during the hypoxic period was glucose and then switched to lactate during the normoxic recovery period, the level of cell damage in the CA1 region of organotypic cultures was significantly improved from 64.3 +/- 2.1 to 74.6 +/- 2.1% compared with cultures receiving glucose during and after hypoxia. Extracellular field potentials recorded from the CA1 region of acute slices were abolished during oxygen deprivation for 20 min, but recovered almost fully to baseline levels with either glucose (82.6 +/- 10.0%) or lactate present in the reperfusion medium (108.1 +/- 8.3%). These results suggest that lactate alone cannot support neuronal survival during oxygen deprivation, but a combination of glucose followed by lactate provides for better neuroprotection than either substrate alone

    An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures

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    Traumatic brain injury (TBI) is caused by rapid deformation of the brain, resulting in a cascade of pathological events and ultimately neurodegeneration. Understanding how the biomechanics of brain deformation leads to tissue damage remains a considerable challenge. We have developed an in vitro model of TBI utilising organotypic hippocampal slice cultures on deformable silicone membranes, and an injury device, which generates tissue deformation through stretching the silicone substrate. Our injury device controls the biomechanical parameters of the stretch via feedback control, resulting in a reproducible and equi-biaxial deformation stimulus. Organotypic cultures remain well adhered to the membrane during deformation, so that tissue strain is 93 and 86% of the membrane strain in the x- and y-axis, respectively. Cell damage following injury is positively correlated with strain. In conclusion, we have developed a unique in vitro model to study the effects of mechanical stimuli within a complex cellular environment that mimics the in vivo environment. We believe this model could be a powerful tool to study the acute phases of TBI and the induced cell degeneration could provide a good platform for the development of potential therapeutic approaches and may be a useful in vitro alternative to animal models of TBI

    Stretch-induced injury in organotypic hippocampal slice cultures reproduces in vivo post-traumatic neurodegeneration: role of glutamate receptors and voltage-dependent calcium channels

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    The relationship between an initial mechanical event causing brain tissue deformation and delayed neurodegeneration in vivo is complex because of the multiplicity of factors involved. We have used a simplified brain surrogate based on rat hippocampal slices grown on deformable silicone membranes to study stretch-induced traumatic brain injury. Traumatic injury was induced by stretching the culture substrate, and the biological response characterized after 4 days. Morphological abnormalities consistent with traumatic injury in humans were widely observed in injured cultures. Synaptic function was significantly reduced after a severe injury. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 attenuated neuronal damage, prevented loss of microtubule-associated protein 2 immunoreactivity and attenuated reduction of synaptic function. In contrast, the NMDA receptor antagonists 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and GYKI53655, were neuroprotective in a moderate but not a severe injury paradigm. Nifedipine, an L-type voltage-dependent calcium channel antagonist was protective only after a moderate injury, whereas omega-conotoxin attenuated damage following severe injury. These results indicate that the mechanism of damage following stretch injury is complex and varies depending on the severity of the insult. In conclusion, the pharmacological, morphological and electrophysiological responses of organotypic hippocampal slice cultures to stretch injury were similar to those observed in vivo. Our model provides an alternative to animal testing for understanding the mechanisms of post-traumatic delayed cell death and could be used as a high-content screen to discover neuroprotective compounds before advancing to in vivo models

    Open Access for researchers and the public

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    Open Access has emerged in recent years as a major development in the world of scholarly communication. It may have the potential to greatly alter the university publishing environment and change the ways in which everyone accesses research material, particularly scholarly journals. This article will take a look at the basics of Open Access (or OA) as well as some direct and indirect benefits of OA inside and outside of academe

    Institutional Racism and the Dynamics of Privilege in Public Health

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    Institutional racism, a pattern of differential access to material resources and power determined by race, advantages one sector of the population while disadvantaging another. Such racism is not only about conspicuous acts of violence but can be carried in the hold of mono-cultural perspectives. Overt state violation of principles contributes to the backdrop against which much less overt yet insidious violations occur. New Zealand health policy is one such mono-cultural domain. It is dominated by western bio-medical discourses that preclude and under-value Māori, the indigenous peoples of this land, in the conceptualisation, structure, content, and processes of health policies, despite Te Tiriti o Waitangi guarantees to protect Māori interests. Since the 1980s, the Department of Health has committed to honouring the Treaty of Waitangi as the founding document of Māori-settler relationships and governance arrangements. Subsequent Waitangi Tribunal reports, produced by an independent Commission of Inquiry have documented the often-illegal actions of successive governments advancing the interests of Pākehā at the expense of Māori. Institutional controls have not prevented inequities between Māori and non-Māori across a plethora of social and economic indicators. Activist scholars work to expose and transform perceived inequities. My research interest lies in how Crown Ministers and officials within the public health sector practice institutional racism and privilege and how it can be transformed. Through dialogue with Māori working within the health sector, fuelled by critical analysis and strategic advice from a research whānau (family) of Māori health leaders and a Pākehā Tiriti worker, and embracing the traditions of feminist and critical race theory I provide evidence of racism that can invoke strong emotional reactions. More disturbing is its normalisation to nigh imperceptibility within ones personal and professional life. The exposure of racism as a socially created phenomenon is a strength of the research presented here. My action orientation is my ethical response. Honouring Te Tiriti o Waitangi is a pathway to transforming racism. Such change is likely to be resisted by the Pākehā majority. This anticipated resistance is not a credible reason to weaken responsibility for such necessary change. Transforming institutional racism needs to be driven by senior managers, professional bodies, unions, and by communities. Policies, practices and leadership that enable institutional racism need to be systematically eliminated from the health sector. Crown officials must be supported to strengthen their professional accountabilities and to embrace ethical bicultural practice. Greater transparency could enable more effective monitoring of Crown behaviour and support transformed practice

    Using imagery to solve spatial problems

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    This report focuses on the use of imagery to solve a range of spatial problems. The research projects reviewed in this report offer some insight into the range of strategies used by solvers of spatial problems and point to relationships between spatial and verbal skills

    Evaluating Research Impact through Open Access to Scholarly Communication

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    Scientific research is a competitive business – in order to secure funding, promotion and tenure researchers must demonstrate their work has impact in their field. To maximise impact researchers undertake high priority research, aim to get results first, and publish in the highest impact journals. The Internet now presents a new opportunity to the scholarly author seeking higher impact: s/he can now make their work instantly accessible on the Web through author self-archiving. This growing body of open access literature (coupled with new publishing models that make journals available for-free to the reader) maximises research impact by maximising the number of people who can read it, and making it available sooner. Open access also provides a new opportunity for bibliometric research. This thesis describes the relatively recent phenomenon of open access to research literature, tools that were built to collect and analyse that literature, and the results of analyses of the effect of open access and its effect on author behaviour. It shows that articles self-archived by authors receive between 50-250% more citations, that rapid pre-printing on the Web has dramatically reduced the peak citation rate from over a year to virtually instant and how citation-impact – now widely used for evaluation – can be expanded to include a new web metric of download impact

    Age Structure of Golden-cheeked Warblers in Areas of Low Abundance

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    Understanding how habitat use and reproductive performance vary among age classes is important to understanding population structure and viability. Habitat conditions can affect occupancy and productivity of many songbirds, including golden-cheeked warblers (Setophaga chrysoparia). Thus, it is important to know which members of the population are using habitat of varying conditions. Existing demographic literature on golden-cheeked warblers focuses on populations where warblers occur in high abundance. I examined the age structure of golden-cheeked warblers in areas of low abundance to determine if there are patterns of differential habitat use based on age in this species. Over two breeding seasons, I monitored 13 low-density and 10 high-density study sites in central Texas for arrival dates and productivity. Males arrived to low density sites on average 6 days later (11 March) and those that established territories on those sites tended to be younger (62% Second-year, n = 8) than those males that established territories on high density sites (5 March, 32% SY, n = 22) although there were no differences in age structure by territory density. I aged 30 males on my study sites, 26 of which were territorial. Productivity did not vary between low and high-density sites; however, SY males had lower pairing and territory success than After Second-year (ASY) males. Understanding which portions of the warbler population are using patches of varying condition could lead to the detection of potential demographic drivers in habitat selection and could inform future management
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