Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model

This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion. By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.

Nutrient provision increases signalling and protein synthesis in human skeletal muscle after repeated sprints

The effect of nutrient availability on the acute molecular responses following repeated sprint exercise is unknown. The aim of this study was to determine skeletal muscle cellular and protein synthetic responses following repeated sprint exercise with nutrient provision. Eight healthy young male subjects undertook two sprint cycling sessions (10 × 6 s, 0.75 N m torque kg -1, 54 s recovery) with either pre-exercise nutrient (24 g whey, 4.8 g leucine, 50 g maltodextrin) or non-caloric placebo ingestion. Muscle biopsies were taken from vastus lateralis at rest, and after 15 and 240 min post-exercise recovery to determine muscle cell signalling responses and protein synthesis by primed constant infusion of L-[ring- 13C 6] phenylalanine. Peak and mean power outputs were similar between nutrient and placebo trials. Post-exercise myofibrillar protein synthetic rate was greater with nutrient ingestion compared with placebo ( ? 48%, P<0.05) but the rate of mitochondrial protein synthesis was similar between treatments. The increased myofibrillar protein synthesis following sprints with nutrient ingestion was associated with coordinated increases in Akt-mTOR-S6KrpS6 phosphorylation 15 min post-exercise (?200-600%, P<0.05), while there was no effect on these signalling molecules when exercise was undertaken in the fasted state. For the first time we report a beneficial effect of nutrient provision on anabolic signalling and muscle myofibrillar protein synthesis following repeated sprint exercise. Ingestion of protein/carbohydrate in close proximity to high-intensity sprint exercise provides an environment that increases cell signalling and protein synthesis.

Effect of consecutive repeated sprint and resistance exercise bouts on acute adaptive responses in human skeletal muscle

We examined acute molecular responses in skeletal muscle to repeated sprint and resistance exercise bouts. Six men [age, 24.7 ± 6.3 yr; body mass, 81.6 ± 7.3 kg; peak oxygen uptake, 47 ± 9.9 ml·kg -1 ·min -1; one repetition maximum (1-RM) leg extension 92.2 ± 12.5 kg; means ± SD] were randomly assigned to trials consisting of either resistance exercise (8 × 5 leg extension, 80% 1-RM) followed by repeated sprints (10 × 6 s, 0.75 N·m torque·kg -1) or vice-versa. Muscle biopsies from vastus lateralis were obtained at rest, 15 min after each exercise bout, and following 3-h recovery to determine early signaling and mRNA responses. There was divergent exercise order-dependent phosphorylation of p70 S6K (S6K). Specifically, initial resistance exercise increased S6K phosphorylation (?75% P < 0.05), but there was no effect when resistance exercise was undertaken after sprints. Exercise decreased IGF-I mRNA following 3-h recovery (?50%, P = 0.06) independent of order, while muscle RING finger mRNA was elevated with a moderate exercise order effect (P < 0.01). When resistance exercise was followed by repeated sprints PGC-1? mRNA was increased (REX1-SPR2; P = 0.02) with a modest distinction between exercise orders. Repeated sprints may promote acute interference on resistance exercise responses by attenuating translation initiation signaling and exacerbating ubiquitin ligase expression. Indeed, repeated sprints appear to generate the overriding acute exercise-induced response when undertaking concurrent repeated sprint and resistance exercise. Accordingly, we suggest that sprint-activities are isolated from resistance training and that adequate recovery time is considered within periodized training plans that incorporate these divergent exercise modes.

Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle

We examined acute molecular responses in skeletal muscle to divergent exercise stimuli by combining consecutive bouts of resistance and endurance exercise. Eight men [22.9 ± 6.3 yr, body mass of 73.2 ± 4.5 kg, peak O2 uptake (V?O2peak) of 54.0 ± 5.7 ml·kg-1·min-1] were randomly assigned to complete trials consisting of either resistance exercise (8 x 5 leg extension, 80% 1 repetition maximum) followed by a bout of endurance exercise (30 min cycling, 70% V?O2peak) or vice versa. Muscle biopsies were obtained from the vastus lateralis at rest, 15 min after each exercise bout, and after 3 h of passive recovery to determine early signaling and mRNA responses. Phosphorylation of Akt and Akt1Ser473 were elevated 15 min after resistance exercise compared with cycling, with the greatest increase observed when resistance exercise followed cycling (?55%; P < 0.01). TSC2-mTOR-S6 kinase phosphorylation 15 min after each bout of exercise was similar regardless of the exercise mode. The cumulative effect of combined exercise resulted in disparate mRNA responses. IGF-I mRNA content was reduced when cycling preceded resistance exercise (-42%), whereas muscle ring finger mRNA was elevated when cycling was undertaken after resistance exercise (?52%; P < 0.05). The hexokinase II mRNA level was higher after resistance cycling (?45%; P < 0.05) than after cycling-resistance exercise, whereas modest increases in peroxisome proliferator-activated receptor gamma coactivator-1? mRNA did not reveal an order effect. We conclude that acute responses to diverse bouts of contractile activity are modified by the exercise order. Moreover, undertaking divergent exercise in close proximity influences the acute molecular profile and likely exacerbates acute "interference".

Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle

Skeletal muscle contraction stimulates multiple signaling cascades that govern a variety of metabolic and transcriptional events. Akt/protein kinase B regulates metabolism and growth/muscle hypertrophy, but contraction effects on this target and its substrates are varied and may depend on the mode of the contractile stimulus. Accordingly, we determined the effects of endurance or resistance exercise on phosphorylation of Akt and downstream substrates in six trained cyclists who performed a single bout of endurance or resistance exercise separated by ?7 days. Muscle biopsies were taken from the vastus lateralis at rest and immediately after exercise. Akt Ser 473 phosphorylation was increased (1.8-fold; P = 0.011) after endurance but was unchanged after resistance exercise. Conversely, Akt Thr 308 phosphorylation was unaltered after either bout of exercise. Several exercise-responsive phosphoproteins were detected by immunoblot analysis with a phospho-Akt substrate antibody. pp160 and pp300 were identified as AS160 and filamin A, respectively, with increased phosphorylation (2.0- and 4.9-fold, respectively; P < 0.05) after endurance but not resistance exercise. In conclusion, AS160 and filamin A may provide an important link to mediate endurance exercise-induced bioeffects in skeletal muscle.

The health effects of temperature : current estimates, future projections, and adaptation strategies

Climate change is expected to be one of the biggest global health threats in the 21st century. In response to changes in climate and associated extreme events, public health adaptation has become imperative. This thesis examined several key issues in this emerging research field. The thesis aimed to identify the climate-health (particularly temperature-health) relationships, then develop quantitative models that can be used to project future health impacts of climate change, and therefore help formulate adaptation strategies for dealing with climate-related health risks and reducing vulnerability. The research questions addressed by this thesis were: (1) What are the barriers to public health adaptation to climate change? What are the research priorities in this emerging field? (2) What models and frameworks can be used to project future temperature-related mortality under different climate change scenarios? (3) What is the actual burden of temperature-related mortality? What are the impacts of climate change on future burden of disease? and (4) Can we develop public health adaptation strategies to manage the health effects of temperature in response to climate change? Using a literature review, I discussed how public health organisations should implement and manage the process of planned adaptation. This review showed that public health adaptation can operate at two levels: building adaptive capacity and implementing adaptation actions. However, there are constraints and barriers to adaptation arising from uncertainty, cost, technologic limits, institutional arrangements, deficits of social capital, and individual perception of risks. The opportunities for planning and implementing public health adaptation are reliant on effective strategies to overcome likely barriers. I proposed that high priorities should be given to multidisciplinary research on the assessment of potential health effects of climate change, projections of future health impacts under different climate and socio-economic scenarios, identification of health cobenefits of climate change policies, and evaluation of cost-effective public health adaptation options. Heat-related mortality is the most direct and highly-significant potential climate change impact on human health. I thus conducted a systematic review of research and methods for projecting future heat-related mortality under different climate change scenarios. The review showed that climate change is likely to result in a substantial increase in heatrelated mortality. Projecting heat-related mortality requires understanding of historical temperature-mortality relationships, and consideration of future changes in climate, population and acclimatisation. Further research is needed to provide a stronger theoretical framework for mortality projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution and mortality displacement. Most previous studies were designed to examine temperature-related excess deaths or mortality risks. However, if most temperature-related deaths occur in the very elderly who had only a short life expectancy, then the burden of temperature on mortality would have less public health importance. To guide policy decisions and resource allocation, it is desirable to know the actual burden of temperature-related mortality. To achieve this, I used years of life lost to provide a new measure of health effects of temperature. I conducted a time-series analysis to estimate years of life lost associated with changes in season and temperature in Brisbane, Australia. I also projected the future temperaturerelated years of life lost attributable to climate change. This study showed that the association between temperature and years of life lost was U-shaped, with increased years of life lost on cold and hot days. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 °C increase and without any adaptation to higher temperatures. The excess mortality during prolonged extreme temperatures is often greater than the predicted using smoothed temperature-mortality association. This is because sustained period of extreme temperatures produce an extra effect beyond that predicted by daily temperatures. To better estimate the burden of extreme temperatures, I estimated their effects on years of life lost due to cardiovascular disease using data from Brisbane, Australia. The results showed that the association between daily mean temperature and years of life lost due to cardiovascular disease was U-shaped, with the lowest years of life lost at 24 °C (the 75th percentile of daily mean temperature in Brisbane), rising progressively as temperatures become hotter or colder. There were significant added effects of heat waves, but no added effects of cold spells. Finally, public health adaptation to hot weather is necessary and pressing. I discussed how to manage the health effects of temperature, especially with the context of climate change. Strategies to minimise the health effects of high temperatures and climate change can fall into two categories: reducing the heat exposure and managing the health effects of high temperatures. However, policy decisions need information on specific adaptations, together with their expected costs and benefits. Therefore, more research is needed to evaluate cost-effective adaptation options. In summary, this thesis adds to the large body of literature on the impacts of temperature and climate change on human health. It improves our understanding of the temperaturehealth relationship, and how this relationship will change as temperatures increase. Although the research is limited to one city, which restricts the generalisability of the findings, the methods and approaches developed in this thesis will be useful to other researchers studying temperature-health relationships and climate change impacts. The results may be helpful for decision-makers who develop public health adaptation strategies to minimise the health effects of extreme temperatures and climate change.

Rethinking emergency management and climate adaptation policies

Emergency management and climate change adaptation will increasingly challenge all levels of government because of three main factors. First, Australia is extremely vulnerable to the impacts of climate change, particularly through the increasing frequency and/or intensity of disasters such as floods and bushfires. Second, the system of government that divides powers by function and level can often act as a barrier to a well-integrated response. Third, policymaking processes struggle to cope with such complex inter-jurisdictional issues. This paper discusses these factors and explores the nature of the challenge for Australian governments. Investigations into the 2009 Victorian bushfires, the 2011 Perth Hills bushfires, and the 2011 Brisbane floods offer an indication of the challenges ahead and it is argued that there is a need to: improve community engagement and communication; refocus attention on resilience; improve interagency communication and collaboration; and, develop institutional arrangements that support continual improvement and policy learning. These findings offer an opportunity for improving responses as well as a starting point for integrating disaster risk management and climate change adaptation policies. The paper is based on the preliminary findings of an NCCARF funded research project: The Right Tool for the Job – Achieving climate change adaptation outcomes through improved disaster management policies, planning and risk management strategies involving Griffith University and RMIT.

Simulating land cover changes and their impacts on land surface temperature in Dhaka, Bangladesh

Despite research that has been conducted elsewhere, little is known, to-date, about land cover dynamics and their impacts on land surface temperature (LST) in fast growing mega cities of developing countries. Landsat satellite images of 1989, 1999, and 2009 of Dhaka Metropolitan (DMP) area were used for analysis. This study first identified patterns of land cover changes between the periods and investigated their impacts on LST; second, applied artificial neural network to simulate land cover changes for 2019 and 2029; and finally, estimated their impacts on LST in respective periods. Simulation results show that if the current trend continues, 56% and 87% of the DMP area will likely to experience temperatures in the range of greater than or equal to 30°C in 2019 and 2029, respectively. The findings possess a major challenge for urban planners working in similar contexts. However, the technique presented in this paper would help them to quantify the impacts of different scenarios (e.g., vegetation loss to accommodate urban growth) on LST and consequently to devise appropriate policy measures.

Formalising human recognition : a fundamental building block for security proofs

A fundamental part of many authentication protocols which authenticate a party to a human involves the human recognizing or otherwise processing a message received from the party. Examples include typical implementations of Verified by Visa in which a message, previously stored by the human at a bank, is sent by the bank to the human to authenticate the bank to the human; or the expectation that humans will recognize or verify an extended validation certificate in a HTTPS context. This paper presents general definitions and building blocks for the modelling and analysis of human recognition in authentication protocols, allowing the creation of proofs for protocols which include humans. We cover both generalized trawling and human-specific targeted attacks. As examples of the range of uses of our construction, we use the model presented in this paper to prove the security of a mutual authentication login protocol and a human-assisted device pairing protocol.

The ECOS Project. An interactive simulation to promote an ECO-friendly universe.

Custom designed for display on the Cube Installation situated in the new Science and Engineering Centre (SEC) at QUT, the ECOS project is a playful interface that uses real-time weather data to simulate how a five-star energy building operates in climates all over the world. In collaboration with the SEC building managers, the ECOS Project incorporates energy consumption and generation data of the building into an interactive simulation, which is both engaging to users and highly informative, and which invites play and reflection on the roles of green buildings. ECOS focuses on the principle that humans can have both a positive and negative impact on ecosystems with both local and global consequence. The ECOS project draws on the practice of Eco-Visualisation, a term used to encapsulate the important merging of environmental data visualization with the philosophy of sustainability. Holmes (2007) uses the term Eco-Visualisation (EV) to refer to data visualisations that ‘display the real time consumption statistics of key environmental resources for the goal of promoting ecological literacy’. EVs are commonly artifacts of interaction design, information design, interface design and industrial design, but are informed by various intellectual disciplines that have shared interests in sustainability. As a result of surveying a number of projects, Pierce, Odom and Blevis (2008) outline strategies for designing and evaluating effective EVs, including ‘connecting behavior to material impacts of consumption, encouraging playful engagement and exploration with energy, raising public awareness and facilitating discussion, and stimulating critical reflection.’ Consequently, Froehlich (2010) and his colleagues also use the term ‘Eco-feedback technology’ to describe the same field. ‘Green IT’ is another variation which Tomlinson (2010) describes as a ‘field at the juncture of two trends… the growing concern over environmental issues’ and ‘the use of digital tools and techniques for manipulating information.’ The ECOS Project team is guided by these principles, but more importantly, propose an example for how these principles may be achieved. The ECOS Project presents a simplified interface to the very complex domain of thermodynamic and climate modeling. From a mathematical perspective, the simulation can be divided into two models, which interact and compete for balance – the comfort of ECOS’ virtual denizens and the ecological and environmental health of the virtual world. The comfort model is based on the study of psychometrics, and specifically those relating to human comfort. This provides baseline micro-climatic values for what constitutes a comfortable working environment within the QUT SEC buildings. The difference between the ambient outside temperature (as determined by polling the Google Weather API for live weather data) and the internal thermostat of the building (as set by the user) allows us to estimate the energy required to either heat or cool the building. Once the energy requirements can be ascertained, this is then balanced with the ability of the building to produce enough power from green energy sources (solar, wind and gas) to cover its energy requirements. Calculating the relative amount of energy produced by wind and solar can be done by, in the case of solar for example, considering the size of panel and the amount of solar radiation it is receiving at any given time, which in turn can be estimated based on the temperature and conditions returned by the live weather API. Some of these variables can be altered by the user, allowing them to attempt to optimize the health of the building. The variables that can be changed are the budget allocated to green energy sources such as the Solar Panels, Wind Generator and the Air conditioning to control the internal building temperature. These variables influence the energy input and output variables, modeled on the real energy usage statistics drawn from the SEC data provided by the building managers.

A sustainable tourism development in Alacati, Turkey: (Re) invention of public space with clean energy

Although there is an increasing recognition of the impacts of climate change on communities, residents often resist changing their lifestyle to reduce the effects of the problem. By using a landscape architectural design medium, this paper argues that public space, when designed as an ecological system, has the capacity to create social and environmental change and to increase the quality of the human environment. At the same time, this ecological system can engage residents, enrich the local economy, and increase the social network. Through methods of design, research and case study analysis, an alternative master plan is proposed for a sustainable tourism development in Alacati, Turkey. Our master plan uses local geographical, economic and social information within a sustainable landscape architectural design scheme that addresses the key issues of ecology, employment, public space and community cohesion. A preliminary community empowerment model (CEM) is proposed to manage the designs. The designs address: the coexistence of local agricultural and sustainable energy generation; state of the art water management; and the functional and sustainable social and economic interrelationship of inhabitants, NGOs, and local government.

Time course-dependent changes in the transcriptome of human skeletal muscle during recovery from endurance exercise: From inflammation to adaptive remodeling

Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time-course dependent changes in the muscular transcriptome following an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h post-exercise from eight healthy, endurance-trained, male individuals. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three h post-exercise, 102 gene sets were up-regulated [family wise error rate (FWER), P < 0.05]; including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1-signaling. Forty-eight h post-exercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were up-regulated. Ninety-six h post-exercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were up-regulated; including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h post-exercise transcriptome indicates substantial transcriptional activity, potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.