Neuronal network dynamics during epileptogenesis in the medial temporal lobe

Epilepsy is one of the most common neurological disorders, a large fraction of which is resistant to pharmacotherapy. In this light, understanding the mechanisms of epilepsy and its intractable forms in particular could create new targets for pharmacotherapeutic intervention. The current project explores the dynamic changes in neuronal network function in the chronic temporal lobe epilepsy (TLE) in rat and human brain in vitro. I focused on the process of establishment of epilepsy (epileptogenesis) in the temporal lobe. Rhythmic behaviour of the hippocampal neuronal networks in healthy animals was explored using spontaneous oscillations in the gamma frequency band (SγO). The use of an improved brain slice preparation technique resulted in the natural occurence (in the absence of pharmacological stimulation) of rhythmic activity, which was then pharmacologically characterised and compared to other models of gamma oscillations (KA- and CCh-induced oscillations) using local field potential recording technique. The results showed that SγO differed from pharmacologically driven models, suggesting higher physiological relevance of SγO. Network activity was also explored in the medial entorhinal cortex (mEC), where spontaneous slow wave oscillations (SWO) were detected. To investigate the course of chronic TLE establishment, a refined Li-pilocarpine-based model of epilepsy (RISE) was developed. The model significantly reduced animal mortality and demonstrated reduced intensity, yet high morbidy with almost 70% mean success rate of developing spontaneous recurrent seizures. We used SγO to characterize changes in the hippocampal neuronal networks throughout the epileptogenesis. The results showed that the network remained largely intact, demonstrating the subtle nature of the RISE model. Despite this, a reduction in network activity was detected during the so-called latent (no seizure) period, which was hypothesized to occur due to network fragmentation and an abnormal function of kainate receptors (KAr). We therefore explored the function of KAr by challenging SγO with kainic acid (KA). The results demonstrated a remarkable decrease in KAr response during the latent period, suggesting KAr dysfunction or altered expression, which will be further investigated using a variety of electrophysiological and immunocytochemical methods. The entorhinal cortex, together with the hippocampus, is known to play an important role in the TLE. Considering this, we investigated neuronal network function of the mEC during epileptogenesis using SWO. The results demonstrated a striking difference in AMPAr function, with possible receptor upregulation or abnormal composition in the early development of epilepsy. Alterations in receptor function inevitably lead to changes in the network function, which may play an important role in the development of epilepsy. Preliminary investigations were made using slices of human brain tissue taken following surgery for intratctable epilepsy. Initial results showed that oscillogenesis could be induced in human brain slices and that such network activity was pharmacologically similar to that observed in rodent brain. Overall, our findings suggest that excitatory glutamatergic transmission is heavily involved in the process of epileptogenesis. Together with other types of receptors, KAr and AMPAr contribute to epilepsy establishment and may be the key to uncovering its mechanism.

(Table 2) Radiocarbon dating on cold-water corals collected in the Mediterranean Sea

This study presents newly obtained coral ages of the cold-water corals Lophelia pertusa and Madrepora oculata collected in the Alboran Sea and the Strait of Sicily (Urania Bank). These data were combined with all available Mediterranean Lophelia and Madrepora ages compiled from literature to conduct a basin-wide assessment of the spatial and temporal occurrence of these prominent framework-forming scleractinian species in the Mediterranean realm and to unravel the palaeo-environmental conditions that controlled their proliferation or decline. For the first time special focus was placed on a closer examination of potential differences occurring between the eastern and western Mediterranean sub-basins. Our results clearly demonstrate that cold-water corals occurred sparsely in the entire Mediterranean during the last glacial before becoming abundant during the Bølling-Allerød warm interval, pointing to a basin-wide, almost concurrent onset in (re-)colonisation after ~13.5 ka. This time coincides with a peak in meltwater discharge originating from the northern Mediterranean borderlands which caused a major reorganisation of the Mediterranean thermohaline circulation. During the Younger Dryas and Holocene, some striking differences in coral proliferation were identified between the sub-basins such as periods of highly prolific coral growth in the eastern Mediterranean Sea during the Younger Dryas and in the western basin during the Early Holocene, whereas a temporary pronounced coral decline during the Younger Dryas was exclusively affecting coral sites in the Alboran Sea. Comparison with environmental and oceanographic data revealed that the proliferation of the Mediterranean corals is linked with enhanced productivity conditions. Moreover, corals thrived in intermediate depths and showed a close relationship with intermediate water mass circulation in the Mediterranean sub-basins. For instance, reduced Levantine Intermediate Water formation hampered coral growth in the eastern Mediterranean Sea during sapropel S1 event as reduced Winter Intermediate Water formation did in the westernmost part of the Mediterranean (Alboran Sea) during the Mid-Holocene. Overall, this study clearly demonstrates the importance to consider region-specific environmental changes as well as species-specific environmental preferences in interpreting coral chronologies. Moreover, it highlights that the occurrence or decline of cold-water corals is not controlled by one key parameter but rather by a complex interplay of various environmental variables.

Genomic consequences of mating system evolution in the Pacific coastal dune endemic, Abronia umbellata (Nyctaginaceae)

The advent of next-generation sequencing has significantly reduced the cost of obtaining large-scale genetic resources, opening the door for genomic studies of non-model but ecologically interesting species. The shift in mating system, from outcrossing to selfing, has occurred thousands of times in angiosperms and is accompanied by profound changes in the population genetics and ecology of a species. A large body of work has been devoted to understanding why the shift occurs and the impact of the shift on the genetics of the resulting selfing populations, however, the causes and consequences of the transition to selfing involve a complicated interaction of genetic and demographic factors which are difficult to untangle. Abronia umbellata is a Pacific coastal dune endemic which displays a striking shift in mating system across its geographic range, with large-flowered outcrossing populations south of San Francisco and small-flowered selfing populations to the north. Abronia umbellata is an attractive model system for the study of mating system transitions because the shift appears to be recent and therefore less obscured by post-shift processes, it has a near one-dimensional geographic range which simplifies analysis and interpretation, and demographic data has been collected for many of the populations. In this study, we generated transcriptome-level data for 12 plants including individuals from both subspecies, along with a resequencing study of 48 individuals from populations across the range. The genetic analysis revealed a recent transition to selfing involving a drastic reduction in genetic diversity in the selfing lineage, potentially indicative of a recent population bottleneck and a transition to selfing due to reproductive assurance. Interestingly, the genetic structure of the populations was not coincident with the current subspecies demarcation, and two large-flowered populations were classified with the selfing subspecies, suggesting a potential need for re-evaluation of the current subspecies classification. Our finding of low diversity in selfing populations may also have implications for the conservation value of the threatened selfing subspecies.

The evolution of imperfect mimicry in hoverflies

Ideas about the evolution of imperfect mimicry are reviewed. Their relevance to the colours patterns of hoverflies (Diptera, Syrphidae) are discussed in detail. Most if not all of the hoverflies labelled as mimetic actually are mimics. The apparently poor nature of their resemblance does not prevent them from obtaining at least some protection from suitably experienced birds. Mimicry is a dominant theme of this very large family of Diptera, with at least a quarter of all species in Europe being mimetic. Hoverfly mimics fall into three major groups according to their models, involving bumblebees, honeybees and social wasps. There are striking differences in the general levels of mimetic fidelity and relative abundances of the three groups, with accurate mimicry, low abundance and polymorphism characterizing the bumblebee mimics: more than half of all the species of bumblebee mimics are polymorphic. Mimics of social wasps tend to be poor mimics, have high relative abundance, and polymorphism is completely absent. Bumblebee models fall into a small number of Muellerian mimicry rings which are very different between the Palaearctic and Nearctic regions. Social wasps and associated models form one large Muellerian complex. Together with honeybees, these complexes probably form real clusters of forms as perceived by many birds. All three groups of syrphid mimics contain both good and poor mimics; some mimics are remarkably accurate, and have close morphological and behavioural resemblance. At least some apparently 'poor' mimetic resemblances may be much closer in birds' perception than we imagine, and more work needs to be done on this. Bumblebees are the least noxious and wasps the most noxious of the three main model groups. The basis of noxiousness is different, with bumblebees being classified as non-food, whereas honeybees and wasps are nasty-tasting and (rarely) stinging. The distribution of mimicry is exactly what would be expected from this ordering, with polymorphic and accurate forms being a key feature of mimics of the least noxious models, while highly noxious models have poor-quality mimicry. Even if the high abundance of many syrphid mimics relative to their models is a recent artefact of man-made environmental change, this does not preclude these species from being mimics. It seems unlikely that bird predation actually controls the populations of adult syrphids. Being rare relative to a model may have promoted or accelerated the evolution of perfect mimicry: theoretically this might account for the pattern of rare good mimics and abundant poor ones, but the idea is intrinsically unlikely. Many mimics seem to have hour-to-hour abundances related to those of their models, presumably as a result of behavioural convergence. We need to know much more about the psychology of birds as predators. There are at least four processes that need elucidating: (a) learning about the noxiousness of models; (b) the erasing of that learning through contact with mimics (extinction, or learned forgetting); (c) forgetting; (d) deliberate risk-taking and the physiological states that promote it. Johnston's (2002) model of the stabilization of imperfect mimicry by kin selection is unlikely to account for the colour patterns of hoverflies. Sherratt's (2002) model of the influence of multiple models potentially accounts for all the patterns of hoverfly mimicry, and is the most promising avenue for testing.

Seeing it my way: a case of a selective deficit in inhibiting self-perspective

Little is known about the functional and neural architecture of social reasoning, one major obstacle being that we crucially lack the relevant tools to test potentially different social reasoning components. In the case of belief reasoning, previous studies tried to separate the processes involved in belief reasoning per se from those involved in the processing of the high incidental demands such as the working memory demands of typical belief tasks (e.g., Stone et al., 1998; Samson et al., 2004). In this study, we developed new belief tasks in order to disentangle, for the first time, two perspective taking components involved in belief reasoning: (1) the ability to inhibit one’s own perspective (self-perspective inhibition) and (2) the ability to infer someone else’s perspective as such (other-perspective taking). The two tasks had similar demands in other-perspective taking as they both required the participant to infer that a character has a false belief about an object’s location. However, the tasks varied in the self-perspective inhibition demands. In the task with the lowest self-perspective inhibition demands, at the time the participant had to infer the character’s false belief, he or she had no idea what the new object’s location was. In contrast, in the task with the highest self-perspective inhibition demands, at the time the participant had to infer the character’s false belief, he or she knew where the object was actually located (and this knowledge had thus to be inhibited). The two tasks were presented to a stroke patient, WBA, with right prefrontal and temporal damage. WBA performed well in the low-inhibition false belief task but showed striking difficulty in the task placing high self-perspective inhibition demands, showing a selective deficit in inhibiting self-perspective. WBA also made egocentric errors in other social and visual perspective taking tasks, indicating a difficulty with belief attribution extending to the attribution of emotions, desires and visual experiences to other people. The case of WBA, together with the recent report of three patients impaired in belief reasoning even when self-perspective inhibition demands were reduced (Samson et al., 2004), provide the first neuropsychological evidence that (a) the inhibition of one’s own point of view and (b) the ability to infer someone else’ s point of view, rely on distinct neural and functional processes.

‘Failure to maintain’: care rationing and the clinical and financial burden of nurse sensitive hospital-acquired complications in complex older patients

Background: The ageing population, with concomitant increase in chronic conditions, is increasing the presence of older people with complex needs in hospital. People with dementia are one of these complex populations and are particularly vulnerable to complications in hospital. Registered nurses can offer simultaneous assessment and intervention to prevent or mitigate hospital-acquired complications through their skilled brokerage between patient needs and hospital functions. A range of patient outcome measures that are sensitive to nursing care has been tested in nursing work environments across the world. However, none of these measures have focused on hospitalised older patients. Method: This thesis explores nursing-sensitive complications for older patients with and without dementia using an internationally recognised, risk-adjusted patient outcome approach. Specifically explored are: the differences between rates of complications; the costs of complications; and cost comparisons of patient complexity. A retrospective cohort study of an Australian state’s 2006–07 public hospital discharge data was utilised to identify patient episodes for people over age 50 (N=222,440) where dementia was identified as a primary or secondary diagnosis (N=44,422). Extra costs for patient episodes were estimated based on length of stay (LOS) above the average for each patient’s Diagnosis Related Group (DRG) (N=157,178) and were modelled using linear regression analysis to establish the strongest patient complexity predictors of cost. Results: Hospitalised patients with a primary or secondary diagnosis of dementia had higher rates of complications than did their same-age peers. The highest rates and relative risk for people with dementia were found in four key complications: urinary tract infections; pressure injuries; pneumonia, and delirium. While 21.9% of dementia patients (9,751/44,488, p<0.0001) suffered a complication, only 8.8% of non-dementia patients did so (33,501/381,788, p<0.0001), giving dementia patients a 2.5 relative risk of acquiring a complication (p<0.0001). These four key complications in patients over 50 both with and without dementia were associated with an eightfold increase in length of stay (813%, or 3.6 days/0.4 days) and double the increased estimated mean episode cost (199%, or A$16,403/ A$8,240). These four complications were associated with 24.7% of the estimated cost of additional days spent in hospital in 2006–07 in NSW (A$226million/A$914million). Dementia patients accounted for 22.0% of these costs (A$49million/A$226million) even though they were only 10.4% of the population (44,488/426,276 episodes). Hospital-acquired complications, particularly for people with a comorbidity of dementia, cost more than other kinds of inpatient complexity but admission severity was a better predictor of excess cost. Discussion: Four key complications occur more often in older patients with dementia and the high rate of these complications makes them expensive. These complications are potentially preventable. However, the care that can prevent them (such as mobility, hydration, nutrition and communication) is known to be rationed or left unfinished by nurses. Older hospitalised people who have complex needs, such as those with dementia, are more likely to experience care rationing as their care tends to take longer, be less predictable and less curative in nature. This thesis offers the theoretical proposition that evidence-based nursing practices are rationed for complex older patients and that this rationed care contributes to functional and cognitive decline during hospitalisation. This, in turn, contributes to the high rates of complications observed. Thus four key complications can be seen as a ‘Failure to Maintain’ complex older people in hospital. ‘Failure to Maintain’ is the inadequate delivery of essential functional and cognitive care for a complex older person in hospital resulting in a complication, and is recommended as a useful indicator for hospital quality. Conclusions: When examining extra length of stay in hospital, complications and comorbid dementia are costly. Complications are potentially preventable, and dementia care in hospitals can be improved. Hospitals and governments looking to decrease costs can engage in risk-reduction strategies for common nurse sensitive complications such as healthy nursing work environments that minimise nurses’ rationing of functional and cognitive care. The conceptualisation of complex older patients as ‘business as usual’ rather than a ‘burden’ is likely necessary for sustainable health care services of the future. The use of the ‘Failure to Maintain’ indicators at institution and state levels may aid in embedding this approach for complex older patients into health organisations. Ongoing investigation is warranted into the relationships between the largest health services expense (hospitals), the largest hospital population (complex older patients), and the largest hospital expense (nurses). The ‘Failure to Maintain’ quality indicator makes a useful and substantive contribution to further clinical, administrative and research developments.

BRITE report 2004

This document reports on an innovation survey of the Australian construction industry undertaken by the BRITE Project of the CRC for Construction Innovation in 2004. The survey sample was drawn from 3,500 businesses in the road/bridge and commercial building sectors in NSW, Vic and Qld, covering main contractors, trade contractors, consultants, suppliers and clients. One-third of this population was sampled and a response rate of 30% was achieved. The survey investigates innovation determinants in the industry, comprising various aspects of business strategy and business environment.

Novice riders and the predictors of riding without motorcycle protective clothing

Background While helmet usage is often mandated, few motorcycle and scooter riders make full use of protection for the rest of the body. Little is known about the factors associated with riders’ usage or non-usage of protective clothing. Methods Novice riders were surveyed prior to their provisional licence test in NSW, Australia. Questions related to usage and beliefs about protective clothing, riding experience and exposure, risk taking and demographic details. Multivariable Poisson regression models were used to identify factors associated with two measures of usage, comparing those who sometimes vs rarely/never rode unprotected and who usually wore non-motorcycle pants vs motorcycle pants. Results Ninety-four percent of eligible riders participated and usable data was obtained from 66% (n = 776). Factors significantly associated with riding unprotected were: youth (17–25 years) (RR = 2.00, 95% CI: 1.50–2.65), not seeking protective clothing information (RR = 1.29, 95% CI = 1.07–1.56), non-usage in hot weather (RR = 3.01, 95% CI: 2.38–3.82), awareness of social pressure to wear more protection (RR = 1.48, 95% CI: 1.12–1.95), scepticism about protective benefits (RR = 2.00, 95% CI: 1.22–3.28) and riding a scooter vs any type of motorcycle. A similar cluster of factors including youth (RR = 1.17, 95% CI: 1.04–1.32), social pressure (RR = 1.32, 95% CI: 1.16–1.50), hot weather (RR = 1.30, 95% CI: 1.19–1.41) and scooter vs motorcycles were also associated with wearing non-motorcycle pants. There was no evidence of an association between use of protective clothing and other indicators of risk taking behaviour. Conclusions Factors strongly associated with non-use of protective clothing include not having sought information about protective clothing and not believing in its injury reduction value. Interventions to increase use may therefore need to focus on development of credible information sources about crash risk and the benefits of protective clothing. Further work is required to develop motorcycle protective clothing suitable for hot climates.

Not just another ball game : young adult and adult football fictions are different

Current media attention on the crossover novel highlights the increasing permeability of the boundaries between young adult and adult fiction. This paper will focus upon some of the difficulties around definitions of young adult fiction before considering the fiction of football, or soccer as it is more commonly known in Australia. The football genre exhibits a number of discrete and identifiable differences between young adult and adult readerships including, for example, the role of the protagonist, and the narrative’s distance from the game. This paper will use Franco Moretti’s Mapping as Distant Reading model of abstraction to highlight and unpack these and other characteristic differences in the narratological and stylistic techniques employed across adult and young adult texts. Close reading analysis of the adult football fiction Striker (1992) by Hunter Davies and young adult football fiction Lucy Zeezou’s Goal (2008) by Liz Deep-Jones’ will further illustrate the range of tensions and divergences as they are reflected across those readerships. The texts have been selected because they speak to themes of fear and safety; Joe Swift (Striker) is driven by a need to move away from childhood poverty and insecurity, while Lucy Zeezou shelters a homeless friend. With both protagonists being kidnapped for ransom for example, the texts have also been selected for their striking similarities in form and content.

Success or failure : the NRAS

Many Australian families are unable to access homeownership. This is because house prices are very high to the severely or seriously unaffordable level. Therefore, many low income families will need to rely on affordable rental housing supply. The Australian governments introduced National Rental Affordability Scheme (NRAS) in July 2008. The scheme aims to increase the supply of affordable rental housing by 50,000 dwellings across Australia by June 2014. It provides financial incentive for investors to purchase new affordable housing that must be rented at a minimum of 20% below the market rent. The scheme has been in place for four years to June 2012. There are debates on the success or failure of the scheme. One argues that the scheme is more successful in Queensland but it failed to meet its aims in NSW. This paper examines NRAS incentive designed to encourage affordable housing supply in Australia and demonstrates reasons for developing properties that are crowded in areas where the land prices are relatively lower in the NSW using a discounted cash flow analysis in a hypothetical case study. The findings suggest that the high land values and the increasing cost of development were the main constraints of implementing the scheme in the NSW and government should not provide a flat rate subsidy which is inadequate to ensure that affordable housing projects in high cost areas.

Integrating Poverty and Gender into Health Programmes : a Source Book for Health Professionals : Module on Curricular Integration

Over the past two to three decades, our understanding of poverty has broadened from a narrow focus on income and consumption to a multidimensional notion of education, health, social and political 1 participation, personal security and freedom and environmental quality. Thus, it encompasses not just low income, but lack of access to services, resources and skills; vulnerability; insecurity; and voicelessness and powerlessness. Multidimensional poverty is a determinant of health risks, health seeking behaviour, health care access and health outcomes. As analysis of health outcomes becomes more refined, it is increasingly apparent that the impressive gains in health experienced over recent decades are unevenly distributed. Aggregate indicators, whether at the global, regional or national level, often tend to mask striking variations in health outcomes between men and women, rich and poor, both across and within countries...

The Chidiac case : another miscarriage of justice?

On 25 March 1997 the Witness program on Channel 7 screened a story about the conviction of Neil Chidiac in February 1989 for conspiracy to import a trafficable quantity of heroin in NSW. The program questioned the justice of Chidiac's conviction and filmed his recent release from prison on parole after serving over eight years in prison, still protesting his innocence. Witness featured an interview with the chief Crown witness against Chidiac, Alfred Oti, in which Oti completely repudiated the testimony he gave at the trial and admitted to lying at the behest of the police in order to secure advantages for himself...

Not just another ball game : young adult and adult football fictions are different

Current media attention on the crossover novel highlights the increasing permeability of the boundaries between young adult and adult fiction. This paper will focus upon some of the difficulties around definitions of young adult fiction before considering the fiction of football, or soccer as it is more commonly known in Australia. The football genre exhibits a number of discrete and identifiable differences between young adult and adult readerships including, for example, the role of the protagonist, and the narrative’s distance from the game. This paper will use Franco Moretti’s Mapping as Distant Reading model of abstraction to highlight and unpack these and other characteristic differences in the narratological and stylistic techniques employed across adult and young adult texts. Close reading analysis of the adult football fiction Striker (1992) by Hunter Davies and young adult football fiction Lucy Zeezou’s Goal (2008) by Liz Deep-Jones’ will further illustrate the range of tensions and divergences as they are reflected across those readerships. The texts have been selected because they speak to themes of fear and safety; Joe Swift (Striker) is driven by a need to move away from childhood poverty and insecurity, while Lucy Zeezou shelters a homeless friend. With both protagonists being kidnapped for ransom for example, the texts have also been selected for their striking similarities in form and content.

Tandem mass spectrometry of deprotonated iodothyronines

In order to assist with the development of more selective and sensitive methods for thyroid hormone analysis the \[M-H](-) anions of the iodothyronines T4, T3, rT3, (3,5)-T2 and the non-iodinated thyronine (TO) have been generated by negative ion electrospray mass spectrometry. Tandem mass spectra of these ions were recorded on a triple-quadrupole mass spectrometer and show a strong analogy with the fragmentation pathways of the parent compound, tyrosine. All iodothyronines also show significant abundances of the iodide anion in their tandem mass spectra, which represents an attractive target for multiple reaction monitoring (MRM) analysis, given that iodothyronines are the only iodine bearing endogenous molecules. Characteristic fragments are observed at m/z 359.7 and 604.5 for rT3 but are absent in the spectrum of T3, thus differentiating the two positional isomers. The striking difference in the fragmentation patterns of these regioisomeric species is attributed to the increased acidity of the phenol moiety in rT3 compared with T3. Copyright (C) 2005 John Wiley & Sons, Ltd.

Fun with Fibonacci

We introduce a function which measures the number of distinct ways in which a number can be expressed as the sum of Fibonacci numbers. Using a binary table and other devices, we explore the values that can take and reveal some interesting patterns. The article shows how standard spreadsheet functionalities make it possible to reveal quite striking patterns in data, and is intended to be used in the classroom.