ORCID Profile
0000-0001-6011-3013
Current Organisation
University of Newcastle Australia
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Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.NEUROSCIENCE.2015.09.061
Abstract: Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite complex behaviors. In the current study, we were interested in examining whether we could identify any significant morphological disturbances in microglia associated with these sickness-like behaviors in adult male Sprague-Dawley rats. We chose lipopolysaccharide (LPS 100 μg/kg/i.p.), to induce sickness-like behaviors as it is the most well-validated approach to do so in rodents and humans. We were particularly interested in examining changes in microglia within the prefrontal cortex (PFC) as several recent neuroimaging studies have highlighted significant functional changes in this region following peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from animals 24h post LPS administration and labeled immunohistochemically with an antibody directed to bind to Iba-1, a protein known to be involved in the structural remodeling of microglia. To analyze changes, we have made use of two recently described image analysis procedures. The first is known as cumulative threshold spectra (CTS) analysis. The second involves the unsupervised digital reconstruction of microglia. We undertook these complementary analysis of microglial cells in the both the pre- and infralimbic isions of the PFC. Our results indicated that microglial soma size was significantly enlarged, while cell processes had contracted slightly following LPS administration. To our knowledge this study is to first to definitely demonstrate substantial microglial disturbances within the PFC following LPS delivered at a dose that was sufficient to induce significant sickness-like behavior.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2015
Publisher: Cold Spring Harbor Laboratory
Date: 02-04-2020
DOI: 10.1101/2020.03.30.20048223
Abstract: Reflected pressure waves are key to the understanding of vascular ageing, a prominent factor in major cardiovascular events. Several different metrics have been proposed to index the effect of wave reflection on the pressure waveform and thereby serve as an indicator of vascular ageing. The extent to which these indices are influenced by factors other than vascular health remains a matter of concern. In this paper, we use transmission-line theory to derive a mathematical model for the reflection time (T refl ), and the augmentation index (AI), assuming a general extended model of the arterial system. Then, we test the proposed model against values reported in the literature. Finally, we discuss insights from the model to common observations in the literature such as age-related “shift” in the reflection site, the variation of AI with heart rate, and the flattening of T refl in older participants.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: Elsevier BV
Date: 05-2020
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2019
Publisher: IEEE
Date: 2001
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2003
Publisher: IEEE
Date: 07-2011
Publisher: IEEE
Date: 08-2016
Publisher: IEEE
Date: 12-07-2021
Publisher: BMJ
Date: 05-2022
DOI: 10.1136/BMJOPEN-2021-058244
Abstract: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.
Publisher: Frontiers Media SA
Date: 24-03-2021
DOI: 10.3389/FNEUR.2021.585189
Abstract: Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognized to be notoriously difficult to treat. Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke. There is also emerging evidence that LOPC may improve cognitive function post-stroke. In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke. Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL/6 mice. At 72 h post-stroke animals were randomly assigned to either normal atmospheric air or to one of two low oxygen (11% O 2 ) exposure groups (either 8 or 24 h/day for 14 days). Cognition was assessed during the treatment phase using a touchscreen based paired-associate learning assessment. At the end of treatment (17 days post-stroke) mice were euthanized and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 h) enhanced learning and memory in the 2nd week post-stroke when compared with stroke animals exposed to atmospheric air. Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several vascular deficits, as well as a reduction in the severity of the amyloid-beta (Aβ) burden. These findings provide further insight into the pro-cognitive benefits of LOPC.
Publisher: IOP Publishing
Date: 02-2017
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2004
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 06-2017
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.BBI.2014.05.017
Abstract: A number of studies have identified that mutations in the P2X7 receptor occur with a significantly higher incidence in in iduals with major depression. Consistent with these findings, a number of preclinical studies have identified that mice in which the P2X7 receptor has been deleted exhibit a higher level of resilience-like behaviour to acutely aversive situations. At present, however, no studies have examined changes in P2X7 receptor expression in otherwise healthy animals exposed to persistently stressful situations. This is significant as several lines of evidence have demonstrated that it is exposure to persistently aversive, rather than acutely aversive, situations that is associated with the emergence of mood disturbance. Accordingly, the objective of the current study was to examine whether chronic exposure to restraint stress was associated with alterations in the expression of P2X7 within the hippoc al formation. The study involved three principal groups: acute stress (1 session), chronic stress (21 sessions, 1 per day) and a chronic stress with recovery group (21 sessions, 1 per day followed by 7days of no stress) and appropriate control groups. The results of the analysis indicate that all forms of stress, regardless of the duration, provoked a reduction in P2X7 receptor expression. Comparative analysis on normalised data indicated that the magnitude of the P2X7 reduction was significantly greater in the chronic stress relative to the acute stress group. We additionally found that there was a gradual rebound in P2X7 expression, in two of nine regions examined, in animals that were allowed to recover for 7days following the final stress session. Collectively, these findings provide the first evidence that exposure to chronic restraint stress produces a pronounced and relatively persistent suppression of the P2X7 receptor within the hippoc us.
Publisher: IEEE
Date: 12-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2018
DOI: 10.1161/STROKEAHA.117.020557
Abstract: Cognitive impairment is a common outcome for stroke survivors. Growth hormone (GH) could represent a potential therapeutic option as this peptide hormone has been shown to improve cognition in various clinical conditions. In this study, we evaluated the effects of peripheral administration of GH at 48 hours poststroke for 28 days on cognitive function and the underlying mechanisms. Experimental stroke was induced by photothrombotic occlusion in young adult mice. We assessed the associative memory cognitive domain using mouse touchscreen platform for paired-associate learning task. We also evaluated neural tissue loss, neurotrophic factors, and markers of neuroplasticity and cerebrovascular remodeling using biochemical and histology analyses. Our results show that GH-treated stroked mice made a significant improvement on the paired-associate learning task relative to non–GH-treated mice at the end of the study. Furthermore, we observed reduction of neural tissue loss in GH-treated stroked mice. We identified that GH treatment resulted in significantly higher levels of neurotrophic factors (IGF-1 [insulin-like growth factor-1] and VEGF [vascular endothelial growth factor]) in both the circulatory and peri-infarct regions. GH treatment in stroked mice not only promoted protein levels and density of presynaptic marker (SYN-1 [synapsin-1]) and marker of myelination (MBP [myelin basic protein]) but also increased the density and area coverage of 2 major vasculature markers (CD31 and collagen-IV), within the peri-infarct region. These findings provide compelling preclinical evidence for the usage of GH as a potential therapeutic tool in the recovery phase of patients after stroke.
Publisher: Wiley
Date: 13-08-2014
DOI: 10.1002/ETT.2561
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2022
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2021
Publisher: IEEE
Date: 2016
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.BBI.2017.09.012
Abstract: Over the last decade, evidence supporting a link between microglia enhanced neuro-inflammatory signalling and mood disturbance has continued to build. One issue that has not been well addressed yet are the factors that drive microglia to enter into a higher pro-inflammatory state. The current study addressed the potential role of the extracellular matrix protein Laminin. C57BL6 adult mice were either exposed to chronic stress or handled for 6 consecutive weeks. Changes in Laminin, microglial morphology and pro-inflammatory cytokine expression were examined in tissue obtained from mice exposed to a chronic restraint stress procedure. These in vivo investigations were complemented by an extensive set of in vitro experiments utilising both a primary microglia and BV2 cell line to examine how Laminin influenced microglial pro-inflammatory tone. Chronic stress enhanced the expression of Laminin, microglial de-ramification and pro-inflammatory cytokine signalling. We further identified that microglia when cultured in the presence of Laminin produced and released significantly greater levels of pro-inflammatory cytokines took longer to return to baseline following stimulation and exhibited enhanced phagocytic activity. These results suggest that chronic restraint stress is capable of modulating Laminin within the CNS, an effect that has implications for understanding environmental mediated disturbances of microglial function.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2013
Publisher: MDPI AG
Date: 22-06-2021
DOI: 10.3390/IJMS22136693
Abstract: White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus callosum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.
Publisher: American Medical Association (AMA)
Date: 07-1994
Publisher: Cold Spring Harbor Laboratory
Date: 23-04-2020
DOI: 10.1101/2020.04.20.20073197
Abstract: Transcranial Doppler (TCD) blood flow velocity has been extensively used in biomedical research as it provides a cost-effective and relatively simple approach to assess changes in cerebral blood flow dynamics and track cerebrovascular health status. In this paper, we introduce a new TCD based timing index, TI tcd , as an indicator of vascular stiffening and vascular health. We investigate the correlations of the new index and the existing indices, namely the pulsatility index (PI t cd ) and the augmentation index (AI TCD ), with age, cardiorespiratory fitness (CRF) and magnetic resonance imaging (MRI) blood flow pulsatility index (PI mri ). Notably, the new TI tcd index showed stronger correlations with CRF ( r = −0.79) and PI mri ( r = 0.53) compared to AI tcd ( r = −0.65 with CRF and no significant correlation with PI mri ) and PI TCD (no significant correlations with CRF or PI mri ) and similar correlations with age as AI tcd . The clearer relationship of the proposed timing index with vascular aging factors represented by cerebrovascular resistance (CVR) suggests its utility as an early indicator of vascular stiffening.
Publisher: IEEE
Date: 2009
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2018
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
DOI: 10.1038/S41598-017-06864-Y
Abstract: Intrinsic Optical Signal (IOS) imaging has been used extensively to examine activity-related changes within the cerebral cortex. A significant technical challenge with IOS imaging is the presence of large noise, artefact components and periodic interference. Signal processing is therefore important in obtaining quality IOS imaging results. Several signal processing techniques have been deployed, however, the performance of these approaches for IOS imaging has never been directly compared. The current study aims to compare signal processing techniques that can be used when quantifying stimuli-response IOS imaging data. Data were gathered from the somatosensory cortex of mice following piezoelectric stimulation of the hindlimb. The effectiveness of each technique to remove noise and extract the IOS signal was compared for both spatial and temporal responses. Careful analysis of the advantages and disadvantages of each method were carried out to inform the choice of signal processing for IOS imaging. We conclude that spatial Gaussian filtering is the most effective choices for improving the spatial IOS response, whilst temporal low pass and bandpass filtering produce the best results for producing temporal responses when periodic stimuli are an option. Global signal regression and truncated difference also work well and do not require periodic stimuli.
Publisher: IEEE
Date: 06-2010
Publisher: IEEE
Date: 11-2014
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 04-2010
Publisher: Elsevier BV
Date: 06-2021
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2012
Publisher: MDPI AG
Date: 15-08-2019
DOI: 10.3390/A12080170
Abstract: This work addresses the physical layer channel code design for an uncoordinated, frame- and slot-asynchronous random access protocol. Starting from the observation that collisions between two users yield very specific interference patterns, we define a surrogate channel model and propose different protograph low-density parity-check code designs. The proposed codes are both tested in a setup where the physical layer is abstracted, as well as on a more realistic channel model, where finite-length physical layer simulations of the entire asynchronous random access scheme, including decoding, are carried out. We find that the abstracted physical layer model overestimates the performance when short blocks are considered. Additionally, the optimized codes show gains in supported channel traffic, a measure of the number of terminals that can be concurrently accommodated on the channel, of around 17% at a packet loss rate of 10 − 2 w.r.t. off-the-shelf codes.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 05-2009
Publisher: IEEE
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 03-11-2021
DOI: 10.1007/S00199-021-01395-0
Abstract: This paper provides four theorems on the existence of a free-disposal equilibrium in a Walrasian economy: the first with an arbitrary set of agents with compact consumption sets, the next highlighting the trade-offs involved in the relaxation of the compactness assumption, and the last two with a countable set of agents endowed with a weighting structure. The results generalize theorems in the antecedent literature pioneered by Shafer–Sonnenschein in 1975, and currently in the form taken in He–Yannelis 2016. The paper also provides counterex les to the existence of non-free-disposal equilibrium in cases of both a countable set of agents and an atomless measure space of agents. One of the ex les is related to one Chiaki Hara presented in 2005. The ex les are of interest because they satisfy all the hypotheses of Shafer’s 1976 result on the existence of a non-free-disposal equilibrium, except for the assumption of a finite set of agents. The work builds on recent work of the authors on abstract economies, and contributes to the ongoing discussion on the modelling of “large” societies.
Publisher: IEEE
Date: 06-2015
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2017
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2003
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 05-2017
Publisher: JMIR Publications Inc.
Date: 07-05-2023
Abstract: ollowing total knee arthroplasty (TKA), 10% to 20% of patients report dissatisfaction with procedural outcomes. There is growing recognition that postsurgical satisfaction is shaped not only by the quality of surgery but also by psychological and social factors. Surprisingly, information on the psychological and social determinants of surgical outcomes is rarely collected before surgery. A comprehensive collection of biopsychosocial information could assist clinicians in making recommendations in relation to rehabilitation, particularly if there is robust evidence to support the ability of presurgical constructs to predict postsurgical outcomes. Clinical decision support tools can help identify factors influencing patient outcomes and support the provision of interventions or services that can be tailored to meet in iduals’ needs. However, despite their potential clinical benefit, the application of such tools remains limited. his study aims to develop a clinical decision tool that will assist with patient stratification and more precisely targeted clinical decision-making regarding prehabilitation and rehabilitation for TKA, based on the identified in idual biopsychosocial needs. n this prospective observational study, all participants provided written or electronic consent before study commencement. Patient-completed questionnaires captured information related to a broad range of biopsychosocial parameters during the month preceding TKA. These included demographic factors (sex, age, and rurality), psychological factors (mood status, pain catastrophizing, resilience, and committed action), quality of life, social support, lifestyle factors, and knee symptoms. Physical measures assessing mobility, balance, and functional lower body strength were performed via video calls with patients in their home. Information related to preexisting health issues and concomitant medications was derived from hospital medical records. Patient recovery outcomes were assessed 3 months after the surgical procedure and included quality of life, patient-reported knee symptoms, satisfaction with the surgical procedure, and mood status. Machine learning data analysis techniques will be applied to determine which presurgery parameters have the strongest power for predicting patient recovery following total knee replacement. On the basis of these analyses, a predictive model will be developed. Predictive models will undergo internal validation, and Bayesian analysis will be applied to provide additional metrics regarding prediction accuracy. atient recruitment and data collection commenced in November 2019 and was completed in June 2022. A total of 1050 patients who underwent TKA were enrolled in this study. ur findings will facilitate the development of the first comprehensive biopsychosocial prediction tool, which has the potential to objectively predict a patient’s in idual recovery outcomes following TKA once selected by an orthopedic surgeon to undergo TKA. If successful, the tool could also inform the evolution rehabilitation services, such that factors in addition to physical performance can be addressed and have the potential to further enhance patient recovery and satisfaction. ERR1-10.2196/48801
Publisher: IEEE
Date: 07-2016
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.NEUROSCIENCE.2017.03.005
Abstract: Exposure to chronic stress following stroke has been shown, both clinically and pre-clinically, to impact negatively on the recovery process. While this phenomenon is well established, the specific mechanisms involved have remained largely unexplored. One obvious signaling pathway through which chronic stress may impact on the recovery process is via corticosterone, and its effects on microglial activity and vascular remodeling. In the current study, we were interested in examining how orally delivered corticosterone at a stress-like concentration impacted on microglial activity and vascular remodeling after stroke. We identified that corticosterone administration for two weeks following stroke significantly increased tissue loss and decreased the weight of the spleen and thymus. We also identified that corticosterone administration significantly altered the expression of the key microglial complement receptor, CD11b after stroke. Corticosterone administration did not alter the expression of the vessel basement membrane protein, Collagen IV after stroke. Together, these results suggest that corticosterone is likely to represent only one of the major stress signals responsible for driving the negative impacts of chronic stress on recovery.
Publisher: SAGE Publications
Date: 11-09-2019
Abstract: It has recently been identified that after motor cortex stroke, the ability of microglia processes to respond to local damage cues is lost from the thalamus, a major site of secondary neurodegeneration (SND). In this study, we combine a photothrombotic stroke model in mice, acute slice and fluorescent imaging to analyse the loss of microglia process responsiveness. The peri-infarct territories and thalamic areas of SND were investigated at time-points 3, 7, 14, 28 and 56 days after stroke. We confirmed the highly specific nature of non-responsive microglia processes to sites of SND. Non-responsiveness was at no time observed at the peri-infarct but started in the thalamus seven days post-stroke and persisted for 56 days. Loss of directed process extension is not a reflection of general functional paralysis as phagocytic function continued to increase over time. Additionally, we identified that somal P 2 Y 12 was present on non-responsive microglia in the first two weeks after stroke but not at later time points. Finally, both classical microglia activation and loss of process extension are highly correlated with neuronal damage. Our findings highlight the importance of microglia, specifically microglia dynamic functions, to the progression of SND post-stroke, and their potential relevance as modulators or therapeutic targets during stroke recovery.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2009
Publisher: Wiley
Date: 24-08-2017
DOI: 10.1002/GLIA.23201
Abstract: Stroke induces tissue death both at the site of infarction and at secondary sites connected to the primary infarction. This latter process has been referred to as secondary neurodegeneration (SND). Using predominantly fixed tissue analyses, microglia have been implicated in regulating the initial response at both damage sites post-stroke. In this study, we used acute slice based multiphoton imaging, to investigate microglia dynamic process movement in mice 14 days after a photothrombotic stroke. We evaluated the baseline motility and process responses to locally induced laser damage in both the peri-infarct (PI) territory and the ipsilateral thalamus, a major site of post-stroke SND. Our findings show that microglia process extension toward laser damage within the thalamus is lost, yet remains robustly intact within the PI territory. However, microglia at both sites displayed an activated morphology and elevated levels of commonly used activation markers (CD68, CD11b), indicating that the standardly used fixed tissue metrics of microglial "activity" are not necessarily predictive of microglia function. Analysis of the purinergic P
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2008
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: MDPI AG
Date: 23-03-2017
DOI: 10.3390/E19040138
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 25-10-2014
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 04-2014
Publisher: IEEE
Date: 10-2015
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 28-08-2019
DOI: 10.1007/S12975-018-0656-5
Abstract: Low oxygen post conditioning (LOPC) has shown promising results in terms of neuroprotection after stroke, but the effects on motor function have not been considered. Cortical stroke targeting the motor and sensory cortex was induced by photothrombotic occlusion and after 48 h allocated to LOPC (11% O
Publisher: Springer Science and Business Media LLC
Date: 06-04-2022
DOI: 10.1057/S41599-022-01136-1
Abstract: The number of women employed in STEM in Australia is increasing, however, they continue to remain underrepresented in most industries. A significant corpus of literature on female underrepresentation has emerged in the past 20 years, however, many of those studies focus on educational access and retention and not many look at the lived experiences of women after they have left higher education. In this article, we take a different stance and explore the heterogeneous experiences of female STEM professionals in regional Australia. Through the qualitative analysis of 25 interviews, we learn what women have endured, accepted, and valued on their in idual STEM journeys. While these journeys are often quite different, our interviewees independently reported having experienced similar societal prejudices and possessing similar personality traits. Our data reveals that resilience and determination proved vital for these women, as did a strong early interest in STEM. Our interviews also unearth issues in which women’s opinions are fiercely ided, such as whether positive discrimination has been a barrier or an enabler for their careers. Based on what we have learnt from their accounts, we argue that these women have ‘survived’ their work environments despite structural barriers, only due to their determination, resilience and fervent interest.
Publisher: IEEE
Date: 06-2015
Publisher: IEEE
Date: 11-2014
Publisher: SAGE Publications
Date: 17-03-2017
Abstract: How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.
Publisher: IEEE
Date: 09-2018
Publisher: IEEE
Date: 2005
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2023
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2013
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 19-03-2019
DOI: 10.1038/S41598-019-39493-8
Abstract: In the current study, we were interested in investigating whether Low oxygen post-conditioning (LOPC) was capable of limiting the severity of stroke-induced secondary neurodegeneration (SND). To investigate the effect of LOPC we exposed adult male C57/BL6 mice to photothrombotic occlusion (PTO) of the motor and somatosensory cortex. This is known to induce progressive neurodegeneration in the thalamus within two weeks of infarction. Two days after PTO induction mice were randomly assigned to one of four groups: (i) LOPC-15 day exposure group (ii) a LOPC 15 day exposure followed by a 15 day exposure to normal atmosphere (iii) normal atmosphere for 15 days and (iv) normal atmosphere for 30 days (n = 20/group). We observed that LOPC reduced the extent of neuronal loss, as indicated by assessment of both area of loss and NeuN + cell counts, within the thalamus. Additionally, we identified that LOPC reduced microglial activity and decreased activity within the excitotoxic signalling pathway of the NMDAR axis. Together, these findings suggest that LOPC limits neuronal death caused by excitotoxicity in sites of secondary damage and promotes neuronal survival. In conclusion, this work supports the potential of utilising LOPC to intervene in the sub-acute phase post-stroke to restrict the severity of SND.
Publisher: Wiley
Date: 2003
DOI: 10.1002/ETT.939
Publisher: Springer Science and Business Media LLC
Date: 11-12-2015
DOI: 10.1007/S11064-014-1487-8
Abstract: While astrocytes are recognised to play a central role in repair processes following stroke, at this stage we do not have a clear understanding of how these cells are engaged during the chronic recovery phase. Accordingly, the principal aim of this study was to undertake a quantitative multi-regional investigation of astrocytes throughout the recovery process. Specifically, we have induced experimental vascular occlusion using cold-light photothrombotic occlusion of the somatosensory/motor cortex in adult male C57B6 mice. Four weeks following occlusion we collected, processed, and immunolabelled tissue using an antibody directed at the glial fibrillary acidic protein (GFAP), an astrocyte specific cytoskeletal protein marker. We investigated GFAP changes in 13 regions in both the contra- and ipsi-lateral hemispheres from control and occluded animals. Specifically, we examined the infra-limbic (A24a), pre-limbic (A25), anterior cingulate (A32), motor (M1 and M2) cortices, the forceps minor fibre tract, as well the shell of the accumbens, thalamus, cingulate cortex (A29c), hippoc us (CA1-3) and lateral hypothalamus. Tissue from occluded animals was compared against sham treated controls. We have identified that the focal occlusion produced significant astrogliosis (p < 0.05), as defined by a marked elevation in GFAP expression, within all 13 sites assessed within the ipsilateral (lesioned) hemisphere. We further observed significant increases in GFAP expression (p < 0.05) in 9 of the 13 contralesional sites examined. This work underscores that both the ipsilateral and contralesional hemispheres, at sites distal to the infarct, are very active many weeks after the initial occlusion, a finding that potentially has significant implications for understanding and improving the regeneration of the damaged brain.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2017
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2018
Publisher: IEEE
Date: 06-2009
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2022
Publisher: Springer Science and Business Media LLC
Date: 12-06-2019
DOI: 10.1038/S41598-019-44917-6
Abstract: Microglia play a central role in modulating synaptic structure and physiology, learning and memory processes. They exhibit morphological changes to perform these roles, therefore the morphological study of microglia can help to understand their functionality. Many promising methods are proposed to automatically segment the blood vessels or reconstruct the neuronal morphology. However, they often fail to accurately capture microglia organizations due to the striking structural differences. This requires a more sophisticated approach of reconstruction taking into account the varying nature of branch structures and soma sizes. To this end, we propose an automated method to reconstruct microglia, and quantify their features from 2D/3D image datasets. We first employ multilevel thresholding to segment soma volumes(3D)/areas(2D) and recognize foreground voxels ixels. Seed points s led from the foreground, are connected to form the skeleton of the branches via the tracing process. The reconstructed data is quantified and written in SWC standard file format. We have applied our method to 3D image datasets of microglia, then evaluated the results using ground truth data, and compared them to those achieved via the state-of-the-art methods. Our method outperforms the others both in accuracy and computational time.
Publisher: IEEE
Date: 06-2010
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.BBI.2016.10.001
Abstract: Exposure to psychological stress is known to seriously disrupt the operation of the substantia nigra (SN) and may in fact initiate the loss of dopaminergic neurons within the SN. In this study, we aimed to investigate how chronic stress modified the SN in adult male mice. Using a paradigm of repeated restraint stress (an average of 20h per week for 6weeks), we examined changes within the SN using western blotting and immunohistochemistry. We demonstrated that chronic stress was associated with a clear loss of dopaminergic neurons within the SN. The loss of dopaminergic neurons was accompanied by higher levels of oxidative stress damage, indexed by levels of protein carbonylation and strong suppression of both microglial and astrocytic responses. In addition, we demonstrated for the first time, that chronic stress alone enhanced the aggregation of α-synuclein into the insoluble protein fraction. These results indicate that chronic stress triggered loss of dopaminergic neurons by increasing oxidative stress, suppressing glial neuroprotective functions and enhancing the aggregation of the neurotoxic protein, α-synuclein. Collectively, these results reinforce the negative effects of chronic stress on the viability of dopaminergic cells within the SN.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2020
Publisher: IEEE
Date: 12-2016
Publisher: Elsevier BV
Date: 04-2021
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2012
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2012
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2009
Publisher: Springer Science and Business Media LLC
Date: 14-03-2019
DOI: 10.1038/S41598-019-38813-2
Abstract: Automated cell nucleus segmentation is the key to gain further insight into cell features and functionality which support computer-aided pathology in early diagnosis of diseases such as breast cancer and brain tumour. Despite considerable advances in automated segmentation, it still remains a challenging task to split heavily clustered nuclei due to intensity variations caused by noise and uneven absorption of stains. To address this problem, we propose a novel method applicable to variety of histopathological images stained for different proteins, with high speed, accuracy and level of automation. Our algorithm is initiated by applying a new locally adaptive thresholding method on watershed regions. Followed by a new splitting technique based on multilevel thresholding and the watershed algorithm to separate clustered nuclei. Finalized by a model-based merging step to eliminate oversegmentation and a model-based correction step to improve segmentation results and eliminate small objects. We have applied our method to three image datasets: breast cancer stained for hematoxylin and eosin (H& E), Drosophila Kc167 cells stained for DNA to label nuclei, and mature neurons stained for NeuN. Evaluated results show our method outperforms the state-of-the-art methods in terms of accuracy, precision, F1-measure, and computational time.
Publisher: Springer Science and Business Media LLC
Date: 11-06-2015
DOI: 10.1038/SREP10607
Abstract: Binary image thresholding is the most commonly used technique to quantitatively examine changes in immunolabelled material. In this article we demonstrate that if implicit assumptions predicating this technique are not met then the resulting analysis and data interpretation can be incorrect. We then propose a transparent approach to image quantification that is straightforward to execute using currently available software and therefore can be readily and cost-effectively implemented.
Publisher: Springer Science and Business Media LLC
Date: 20-07-2021
DOI: 10.1038/S41598-021-94348-5
Abstract: Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, $$\\text {TI}_{\\rm NiRS}$$ TI NiRS , of cerebrovascular health. $$\\text {TI}_{\\rm NiRS}$$ TI NiRS is a novel use of the NiRS technology. $$\\text {TI}_{\\rm NiRS}$$ TI NiRS is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both $$\\text {TI}_{\\rm NiRS}$$ TI NiRS and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, $$\\text {AI}_{\\rm TCD}$$ AI TCD , and magnetic resonance imaging (MRI) blood flow pulsatility index, $$\\text {PI}_{\\rm MRI}$$ PI MRI . The $$\\text {TI}_{\\rm NiRS}$$ TI NiRS correlations with Age, CRF, $$\\text {PI}_{\\rm MRI}$$ PI MRI and $$\\text {AI}_{\\rm TCD}$$ AI TCD all are significant, i.e., $$r=0.53$$ r = 0.53 ( $$p=0.002$$ p = 0.002 ), $$r=-0.44$$ r = - 0.44 ( $$p=0.011$$ p = 0.011 ), $$r=0.45$$ r = 0.45 ( $$p=0.012$$ p = 0.012 ) and $$r=0.46$$ r = 0.46 ( $$p=0.010$$ p = 0.010 ), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.
Publisher: IEEE
Date: 12-2007
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: IEEE
Date: 08-2010
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2012
Publisher: No publisher found
Date: 2009
Publisher: IEEE
Date: 06-2014
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.BBI.2015.02.014
Abstract: Post-stroke patients describe suffering from persistent and unremitting levels of distress. Using an experimental model of focal cortical ischemia in adult male C57BL/6 mice, we examined whether exposure to chronic stress could modify the development of secondary thalamic neurodegeneration (STND), which is commonly reported to be associated with impaired functional recovery. We were particularly focused on the modulatory role of microglia-like cells, as several clinical studies have linked microglial activation to the development of STND. One month following the induction of cortical ischemia we identified that numbers of microglial-like cells, as well as putative markers of microglial structural reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and antigen presentation (MHC-II) were all significantly elevated in response to occlusion. We further identified that these changes co-occurred with a decrease in the numbers of mature neurons within the thalamus. Occluded animals that were also exposed to chronic stress exhibited significantly lower levels of Iba-1 positive cells and a reduced expression of Iba-1 and CD11b compared to the 'occlusion-alone' group. Interestingly, the d ened expression of microglial/monocyte markers observed in stressed animals was associated with significant additional loss of neurons. These findings indicate that the process of STND can be negatively modified, potentially in a microglial dependent manner, by exposure to chronic stress.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2019
Publisher: IEEE
Date: 2005
Publisher: IEEE
Date: 07-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 05-2011
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2013
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.BBI.2017.11.014
Abstract: Secondary neurodegeneration (SND) is an insidious and progressive condition involving the death of neurons in regions of the brain that were connected to but undamaged by the initial stroke. Our group have published compelling evidence that exposure to psychological stress can significantly exacerbate the severity SND, a finding that has considerable clinical implications given that stroke-survivors often report experiencing high and unremitting levels of psychological stress. It may be possible to use one or more targeted pharmacological approaches to limit the negative effects of stress on the recovery process but in order to move forward with this approach the most critical stress signals have to be identified. Accordingly, in the current study we have directed our attention to examining the potential effects of corticosterone, delivered orally at stress-like levels. Our interest is to determine how similar the effects of corticosterone are to stress on repair and remodelling that is known to occur after stroke. The study involved 4 groups, sham and stroke, either administered corticosterone or normal drinking water. The functional impact was assessed using the cylinder task for paw asymmetry, grid walk for sensorimotor function, inverted grid for muscle strength and coordination and open field for anxiety-like behaviour. Biochemically and histologically, we considered disturbances in main cellular elements of the neurovascular unit, including microglia, astrocytes, neurons and blood vessels using both immunohistochemistry and western blotting. In short, we identified that corticosterone delivery after stroke results in significant suppression of key microglial and astroglial markers. No changes were observed on the vasculature and in neuronal specific markers. No changes were identified for sensorimotor function or anxiety-like behaviour. We did, however, observe a significant change in motor function as assessed using the inverted grid walk test. Collectively, these results suggest that pharmacologically targeting corticosterone levels in the future may be warranted but that such an approach is unlikely to limit all the negative effects associated with exposure to chronic stress.
Publisher: IEEE
Date: 08-2015
Publisher: IEEE
Date: 05-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: IEEE
Date: 11-2010
Publisher: IEEE
Date: 11-2010
Publisher: IEEE
Date: 07-2011
Publisher: Institution of Engineering and Technology (IET)
Date: 11-2014
Publisher: Wiley
Date: 11-08-2011
DOI: 10.1002/ETT.1492
Publisher: IEEE
Date: 07-2012
Publisher: IEEE
Date: 07-2012
Publisher: Frontiers Media SA
Date: 29-05-2020
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2017
Publisher: IEEE
Date: 06-2014
Publisher: IEEE
Date: 2005
Publisher: JMIR Publications Inc.
Date: 09-08-2023
DOI: 10.2196/48801
Abstract: Following total knee arthroplasty (TKA), 10% to 20% of patients report dissatisfaction with procedural outcomes. There is growing recognition that postsurgical satisfaction is shaped not only by the quality of surgery but also by psychological and social factors. Surprisingly, information on the psychological and social determinants of surgical outcomes is rarely collected before surgery. A comprehensive collection of biopsychosocial information could assist clinicians in making recommendations in relation to rehabilitation, particularly if there is robust evidence to support the ability of presurgical constructs to predict postsurgical outcomes. Clinical decision support tools can help identify factors influencing patient outcomes and support the provision of interventions or services that can be tailored to meet in iduals’ needs. However, despite their potential clinical benefit, the application of such tools remains limited. This study aims to develop a clinical decision tool that will assist with patient stratification and more precisely targeted clinical decision-making regarding prehabilitation and rehabilitation for TKA, based on the identified in idual biopsychosocial needs. In this prospective observational study, all participants provided written or electronic consent before study commencement. Patient-completed questionnaires captured information related to a broad range of biopsychosocial parameters during the month preceding TKA. These included demographic factors (sex, age, and rurality), psychological factors (mood status, pain catastrophizing, resilience, and committed action), quality of life, social support, lifestyle factors, and knee symptoms. Physical measures assessing mobility, balance, and functional lower body strength were performed via video calls with patients in their home. Information related to preexisting health issues and concomitant medications was derived from hospital medical records. Patient recovery outcomes were assessed 3 months after the surgical procedure and included quality of life, patient-reported knee symptoms, satisfaction with the surgical procedure, and mood status. Machine learning data analysis techniques will be applied to determine which presurgery parameters have the strongest power for predicting patient recovery following total knee replacement. On the basis of these analyses, a predictive model will be developed. Predictive models will undergo internal validation, and Bayesian analysis will be applied to provide additional metrics regarding prediction accuracy. Patient recruitment and data collection commenced in November 2019 and was completed in June 2022. A total of 1050 patients who underwent TKA were enrolled in this study. Our findings will facilitate the development of the first comprehensive biopsychosocial prediction tool, which has the potential to objectively predict a patient’s in idual recovery outcomes following TKA once selected by an orthopedic surgeon to undergo TKA. If successful, the tool could also inform the evolution rehabilitation services, such that factors in addition to physical performance can be addressed and have the potential to further enhance patient recovery and satisfaction. DERR1-10.2196/48801
Publisher: MDPI AG
Date: 21-06-2019
DOI: 10.3390/E21060615
Abstract: This paper studies index coding with two senders. In this setup, source messages are distributed among the senders possibly with common messages. In addition, there are multiple receivers, with each receiver having some messages a priori, known as side-information, and requesting one unique message such that each message is requested by only one receiver. Index coding in this setup is called two-sender unicast index coding (TSUIC). The main goal is to find the shortest aggregate normalized codelength, which is expressed as the optimal broadcast rate. In this work, firstly, for a given TSUIC problem, we form three independent sub-problems each consisting of the only subset of the messages, based on whether the messages are available only in one of the senders or in both senders. Then, we express the optimal broadcast rate of the TSUIC problem as a function of the optimal broadcast rates of those independent sub-problems. In this way, we discover the structural characteristics of TSUIC. For the proofs of our results, we utilize confusion graphs and coding techniques used in single-sender index coding. To adapt the confusion graph technique in TSUIC, we introduce a new graph-coloring approach that is different from the normal graph coloring, which we call two-sender graph coloring, and propose a way of grouping the vertices to analyze the number of colors used. We further determine a class of TSUIC instances where a certain type of side-information can be removed without affecting their optimal broadcast rates. Finally, we generalize the results of a class of TSUIC problems to multiple senders.
Start Date: 2019
End Date: 2022
Funder: Australian Research Council
View Funded ActivityStart Date: 2022
End Date: 2025
Funder: Australian Research Council
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End Date: 2010
Funder: Australian Research Council
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End Date: 2012
Funder: Australian Research Council
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End Date: 2006
Funder: Australian Research Council
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End Date: 2015
Funder: Australian Research Council
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End Date: 2014
Funder: Australian Research Council
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End Date: 2008
Funder: Australian Research Council
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End Date: 2016
Funder: Australian Research Council
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End Date: 2017
Funder: Australian Research Council
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: Australian Research Council
View Funded ActivityStart Date: 2004
End Date: 2009
Funder: Australian Research Council
View Funded ActivityStart Date: 2003
End Date: 2003
Funder: Australian Research Council
View Funded ActivityStart Date: 2021
End Date: 2024
Funder: Australian Research Council
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