Resorbable composite scaffolds for bone tissue engineering

Bone loss associated with trauma osteo-degenerative diseases and tumors has tremendous socioeconomic impact related to personal and occupation disability and health care costs. Bone grafting is often critical to surgical therapies. Autogenous bone is presently the preferred grafting material; however, this holds several disadvantages such as donor site morbidity. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone-grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. Our group at Queensland University of Technology (QUT) have developed, characterised and tested polycaprolactone/ tricalcium phosphate (PCL/TCP) composite scaffolds for low load-bearing bone defects. These scaffolds are being further developed for application in higher load bearing sites. Our approach emphasizes the importance of the biomaterials’ structural design, the scaffold architecture and structural and nutritional requirements for cell culture. These first-generation scaffolds made from medical grade PCL (mPCL) have been studied for more than 5 years within a clinical setting 1. This paper describes the application of second-generation scaffolds in small and large animal bone defect models and the ensuing bone regeneration as shown by histology and µCT.

Exploring the relationship between grandparents and their grandchild who has a disability

This thesis reports on the findings of a study which sought to explore the relationship between grandparents and their grandchild who has a disability. In contrast to previous studies, it presents the grandparents’ perspective on the roles and relationships they maintain within their families and adopts a qualitative approach to identify the meanings, symbols and beliefs grandparents attribute to their experiences. Grandparents have played and continue to play an important role in the lives of many families, contributing both symbolic and instrumental support to their grandchildren. Changing life expectancy for older people has meant that many more grandparents and grandchildren now have the opportunity to participate in meaningful interactions and to develop strong relationships. In the future, this will be true for great grandparents and in some cases great great grandparents as well. This presents a number of challenges to all concerned as family members negotiate the often complex arena of family life in the 21st Century. Realizing that a grandchild has a disability adds another degree of complexity to the negotiation of roles and responsibilities of grandparents within families. By focussing on grandparents experiences when their grandchild has a disability, this research both explores a knowledge gap in the current literature and more practicably, will inform both grandparents and their families as they negotiate these challenges. This research makes a significant contribution to knowledge in this area by exploring grandparents’ views on the differences in the relationship they have with their typically developing grandchildren and their grandchild with a disability; the impact having a grandchild with a disability had had on their grandparent identity and whether it impacted on quality of life. As well as reporting on the aims of the study, the papers presented in this thesis report on the key topics and themes identified in the analysis of the transcribed interviews conducted with 22 grandparents whose grandchild has a disability. Article 1 presents an overview of the literature which informs current knowledge in relation to grandparents, presenting a historical and theoretical perspective. Additionally, it presents previous literature which discusses the roles and styles grandparents adopt thus providing a framework which is later used to examine the roles and styles adopted by the grandparents in the study. Article 2 addresses the emotional responses grandparents in the study experienced as they grandparented a child with a disability. Comparing these emotions to that of a roller coaster ride, ranging from absolute sadness and grief to pride and delight, these findings highlight their unique experiences and will be reassuring for other grandparents who experience similar emotional responses. Article 3 discusses from the grandparents’ perspective, how having a grandchild with a disability has impacted on their family. Whilst reporting on the day to day challenges of competing family commitments and conflict, a number of grandparents in this study also commented that the experience had made them closer as a family and that there had been significant changes in how some individual family members now viewed people with disability. Article 4 explores the impact having a grandchild with a disability may have on the grandparents’ sense of identity and enactment of the grandparent role, utilising Neugarten and Weinstein’s (1964) classic grandparenting styles and Kornhaber’s (1996) concepts of latent and functional grandparent identity as a basis for comparison. It provides important insight into grandparenting identity when a child has a disability, suggesting that the grandparenting experience and role enactment may be universal with only the context and delivery varying. In summary, this thesis confirms the valuable role grandparents play in the lives of grandchildren who have a disability and their families. It identifies a number of implications and makes recommendations for future research and practice.

In situ preparation and protein delivery of silicate/alginate composite microspheres with core-shell structure

It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

Endogenous mortality, human capital and economic growth

We consider growth and welfare effects of lifetime-uncertainty in an economy with human capital-led endogenous growth. We argue that lifetime uncertainty reduces private incentives to invest in both physical and human capital. Using an overlapping generations framework with finite-lived households we analyze the relevance of government expenditure on health and education to counter such growth-reducing forces. We focus on three different models that differ with respect to the mode of financing of education: (i) both private and public spending, (ii) only public spending, and (iii) only private spending. Results show that models (i) and (iii) outperform model (ii) with respect to long-term growth rates of per capita income, welfare levels and other important macroeconomic indicators. Theoretical predictions of model rankings for these macroeconomic indicators are also supported by observed stylized facts.

That's what governments do : exploring fundamental barriers to public–philanthropic interaction : the example of indigenous well-being

Decades of intervention have made variable impact on the inequality between indigenous and non-indigenous well-being across the world. Unacceptable differences in life expectancy alone mark indigenous need as an area where greater understanding of public and private funding approaches and their interaction may deliver real benefits. Both the public and the third sector have been active in trying to address the disadvantage experienced by Australia’s indigenous people. The interaction between the indigenous cause philanthropy system and the wider geopolitical landscape in Australia is revealing barriers and insights that may apply in other challenging policy terrain. The research reported here draws upon two empirical studies aimed at understanding the issues facing philanthropy in Australia,including the impact of government agency both independently and as it contrasts with philanthropy. The two different cultures are evident and two levers (greater system flexibility and closer engagement) are suggested as important in moving forward the philanthropy/government relationship in this area.

Attitudes of employees and employers towards older workers in a climate of anti-discrimination

Attitudes and practices towards older workers were surveyed in Brisbane with 525 employees randomly sampled from the electoral roll and executives of 104 companies obtained by stratified random sampling from the Register of Workplaces (response rates, 60% and 80% respectively). The results indicated that “older workers” are young in terms of contemporary life expectancy, and younger for employers than employees; they have some desirable personal qualities (eg. loyalty), but are not perceived as adaptable; workers aged 25–39 were preferred on qualities held to be important in the workplace and there was minimal interest in recruiting anyone over 45 years.

The future for public health

What is the future for public health in the twenty first century? Can we glean an idea about the future of public health from its past? As Winston Churchill once said ‘the further backward you look, the further forward you can see’. What then can we see in the history of public health that gives us an idea of where public health might be headed in the future? In the twentieth century there was substantial progress in public health in Australia. These improvements were brought about through a number of factors. In part, improvements were due to improved knowledge about the natural history of disease and its treatment. Added to this knowledge was a shifting focus from legislative measures to protect health, to the emergence of improved promotion and prevention strategies and a general improvement in social and economic conditions for people living in countries like Australia. The same could not, however, be said for poorer countries, many of whom have the most fundamental of sanitary and health protection issues still to deal with. For example, in sub-Saharan Africa and Russia, the decline in life expectancy may be an aberration or it may be related to a range of interconnected factors. In Russia, factors such as alcoholism, violence, suicide, accidents and cardiovascular disease could be contributing to the falling life expectancy (McMichael & Butler 2007). In sub-Saharan Africa, a range of issues such as HIV/AIDS, poverty, malaria, tuberculosis, undernutrition, totally inadequate infrastructure, gender inequality, conflict and violence, political taboos and a complete lack of political will, have all contributed to a dramatic drop in life expectancy (McMichael & Butler 2007).

The 'obesity paradox' in chronic obstructive pulmonary disease

Poor nutritional status in chronic obstructive pulmonary disease (COPD) is associated with increased mortality independently of disease-severity (Collins et al).1 Epidemiological studies have suggested a protective role of obesity against mortality in COPD (Vestbo et al)2 which is contrary to data from the general population where obesity is associated with decreased life expectancy. This relationship has been referred to as the ‘obesity paradox’ and has been demonstrated in a number of chronic wasting conditions (Kalantar-Zadeh et al).3 This study investigated the existence of the obesity paradox in outpatients with COPD by examining the effect of body mass index (BMI) on 1-year healthcare use and clinical outcome in terms of hospital admission rates, length of hospital stay, outpatient appointments and mortality. BMI was assessed in 424 outpatients with COPD, with measurements performed by specialist respiratory nurses during outpatient clinics. 1-year healthcare use was retrospectively collected from the date of BMI measurement. Abstract S163 Table 1 Patients classified as overweight (25.0–29.9 kg/m2) or obese (>30 kg/m2) experienced significantly fewer emergency hospital admissions, as well as a reduced length of hospital stay, in comparison to normal weight (20.0–24.9 kg/m2) or underweight (<20 kg/m2) outpatients. There was a significant negative trend between BMI classification and mortality. This study supports the existence of the ‘obesity paradox’ in COPD, not only in relation to reduced 1 year mortality rates but also in terms of reduced emergency hospital admissions and reduced length of hospital stay.

Ageing of people with an intellectual disability: Effective training for frontline workers

While the attainment of late life represents a significant achievement for people with an intellectual disability, increased life expectancy has resulted in growing concerns about the extent to which disability service providers are ready to meet the changing needs of increasing numbers of older people and facilitate their ongoing social inclusion. Training of frontline disability staff is widely accepted as an effective strategy for increasing organisational capacity to contribute to improved quality of life for people with an intellectual disability. The study identifies training needs analyses and 'ready-to-deliver' training programs for frontline disability services staff working with adults with an intellectual disability who are ageing, assesses whether the training programs contribute to improved quality of life outcomes for service users, and makes recommendations for future research and development of training for disability services staff who work with older people with intellectual disability.

A qualitative exploration of drivers of eating habits in young Australian men

Australian men’s health status is poor, with a lower life expectancy than women and higher chronic disease risk due in part to poorer dietary habits. Previous studies and sociological theories have: - linked gender norms around food and masculine ideals to men’s eating patterns; and - aligned these forms of masculinity with certain occupations. This study sought to explore the drivers of young, Australian men’s diets, the link to ideas of masculinity and occupation groups to assist in the development of strategies to support healthier eating habits in this population.

Approaches to designing for older adults' intuitive interaction with complex devices

Many older people have difficulties using modern consumer products due to increased product complexity both in terms of functionality and interface design. Previous research has shown that older people have more difficulty in using complex devices intuitively when compared to the younger. Furthermore, increased life expectancy and a falling birth rate have been catalysts for changes in world demographics over the past two decades. This trend also suggests a proportional increase of older people in the work-force. This realisation has led to research on the effective use of technology by older populations in an effort to engage them more productively and to assist them in leading independent lives. Ironically, not enough attention has been paid to the development of interaction design strategies that would actually enable older users to better exploit new technologies. Previous research suggests that if products are designed to reflect people's prior knowledge, they will appear intuitive to use. Since intuitive interfaces utilise domain-specific prior knowledge of users, they require minimal learning for effective interaction. However, older people are very diverse in their capabilities and domain-specific prior knowledge. In addition, ageing also slows down the process of acquiring new knowledge. Keeping these suggestions and limitations in view, the aim of this study was set to investigate possible approaches to developing interfaces that facilitate their intuitive use by older people. In this quest to develop intuitive interfaces for older people, two experiments were conducted that systematically investigated redundancy (the use of both text and icons) in interface design, complexity of interface structure (nested versus flat), and personal user factors such as cognitive abilities, perceived self-efficacy and technology anxiety. All of these factors could interfere with intuitive use. The results from the first experiment suggest that, contrary to what was hypothesised, older people (65+ years) completed the tasks on the text only based interface design faster than on the redundant interface design. The outcome of the second experiment showed that, as expected, older people took more time on a nested interface. However, they did not make significantly more errors compared with younger age groups. Contrary to what was expected, older age groups also did better under anxious conditions. The findings of this study also suggest that older age groups are more heterogeneous in their capabilities and their intuitive use of contemporary technological devices is mediated more by domain-specific technology prior knowledge and by their cognitive abilities, than chronological age. This makes it extremely difficult to develop product interfaces that are entirely intuitive to use. However, by keeping in view the cognitive limitations of older people when interfaces are developed, and using simple text-based interfaces with flat interface structure, would help them intuitively learn and use complex technological products successfully during early encounter with a product. These findings indicate that it might be more pragmatic if interfaces are designed for intuitive learning rather than for intuitive use. Based on this research and the existing literature, a model for adaptable interface design as a strategy for developing intuitively learnable product interfaces was proposed. An adaptable interface can initially use a simple text only interface to help older users to learn and successfully use the new system. Over time, this can be progressively changed to a symbols-based nested interface for more efficient and intuitive use.

'Sarcobesity' : a metabolic conundrum

Two independent but inter-related conditions that have a growing impact on healthy life expectancy and health care costs in developed nations are an age-related loss of muscle mass (i.e., sarcopenia) and obesity. Sarcopenia is commonly exacerbated in overweight and obese individuals. Progression towards obesity promotes an increase in fat mass and a concomitant decrease in muscle mass, producing an unfavourable ratio of fat to muscle. The coexistence of diminished muscle mass and increased fat mass (so-called 'sarcobesity') is ultimately manifested by impaired mobility and/or development of life-style-related diseases. Accordingly, the critical health issue for a large proportion of adults in developed nations is how to lose fat mass while preserving muscle mass. Lifestyle interventions to prevent or treat sarcobesity include energy-restricted diets and exercise. The optimal energy deficit to reduce body mass is controversial. While energy restriction in isolation is an effective short-term strategy for rapid and substantial weight loss, it results in a reduction of both fat and muscle mass and therefore ultimately predisposes one to an unfavourable body composition. Aerobic exercise promotes beneficial changes in whole-body metabolism and reduces fat mass, while resistance exercise preserves lean (muscle) mass. Current evidence strongly supports the inclusion of resistance and aerobic exercise to complement mild energy-restricted high-protein diets for healthy weight loss as a primary intervention for sarcobesity.

Long-term survival after intensive care unit discharge in Thailand : a retrospective study

Introduction Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country. Methods In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy. Results This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population. Conclusions Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.

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.

Commentary on Nutrition and older Indigenous Australians : service delivery implications in remote communities. A narrative review

Indigenous Australians are the most socially and economically disadvantaged population group in Australia and have the poorest health status. The statistics describe and highlight the degree of sicknesses and disadvantage along with lower life expectancy, elevated mortality rate and increased risk of cardiovascular disease, cancer, diabetes, respiratory disease and kidney disease. While these statistics reflect poor health status and a high level of illness within Indigenous communities, it is known that individual, family and community behaviours play a key role in Indigenous health and wellbeing outcomes. These behavioural issues include use of tobacco, alcohol and other substances along with lack of physical activity and poor nutrition. The paper Nutrition and older Indigenous Australians: Service delivery implications in remote communities. A narrative view explores some of the issues specific to nutrition. Bronwyn Fredericks was invited to provide this commentary by the Editor of the Australasian Journal on Aging.