The skin awareness study : promoting thorough skin self-examination for skin cancer among men 50 years or older

Background: Incidence and mortality from skin cancers including melanoma are highest among men 50 years or older. Thorough skin self-examination may be beneficial to improve skin cancers outcomes.--------- Objectives: To develop and conduct a randomized-controlled trial of a video-based intervention to improve skin self-examination behavior among men 50 years or older.--------- Methods: Pilot work ascertained appropriate targeting of the 12-minute intervention video towards men 50 years or older. Overall, 968 men were recruited and 929 completed baseline telephone assessment. Baseline analysis assessed randomization balance and demographic, skin cancer risk and attitudinal factors associated with conducting a whole-body skin self-examination or receiving a whole-body clinical skin examination by a doctor during the past 12 months.--------- Results: Randomization resulted in well-balanced intervention and control groups. Overall 13% of men reported conducting a thorough skin self-examination using a mirror or the help of another person to check difficult to see areas, while 39% reported having received a whole-body skin examination by a doctor within the past 12 months. Confidence in finding time for and receiving advice or instructions by a doctor to perform a skin self-examination were among the factors associated with thorough skin self-examination at baseline.---------- Conclusions: Men 50 years or older can successfully be recruited to a video-based intervention trial with the aim reduce their burden through skin cancer. Randomization by computer generated randomization list resulted in good balance between control and intervention group and baseline analysis determined factors associated with skin cancer early detection behavior at baseline.

Introduction to the development of the ISPCAN child abuse screening tools

The World Report on Children and Violence, (Pinheiro, 2006) was produced at the request of the UN Secretary General and the UN General Assembly. This report recommended improvement in research on child abuse. ISPCAN representatives took this charge and developed 3 new instruments. We describe this background and introduce three new measures designed to assess the incidence and prevalence of child abuse and neglect.

Quality issues for the National Bowel Cancer Screening Program (NBCSP)

Purpose: This two-part research project was undertaken as part of the planning process by Queensland Health (QH), Cancer Screening Services Unit (CSSU), Queensland Bowel Cancer Screening Program (QBCSP), in partnership with the National Bowel Cancer Screening Program (NBCSP), to prepare for the implementation of the NBCSP in public sector colonoscopy services in QLD in late 2006. There was no prior information available on the quality of colonoscopy services in Queensland (QLD) and no prior studies that assessed the quality of colonoscopy training in Australia. Furthermore, the NBCSP was introduced without extra funding for colonoscopy service improvement or provision for increases in colonoscopic capacity resulting from the introduction of the NBCSP. The main purpose of the research was to record baseline data on colonoscopy referral and practice in QLD and current training in colonoscopy Australia-wide. It was undertaken from a quality improvement perspective. Implementation of the NBCSP requires that all aspects of the screening pathway, in particular colonoscopy services for the assessment of positive Faecal Occult Blood Tests (FOBTs), will be effective, efficient, equitable and evidence-based. This study examined two important aspects of the continuous quality improvement framework for the NBCSP as they relate to colonoscopy services: (1) evidence-based practice, and (2) quality of colonoscopy training. The Principal Investigator was employed as Senior Project Officer (Training) in the QBCSP during the conduct of this research project. Recommendations from this research have been used to inform the development and implementation of quality improvement initiatives for provision of colonoscopy in the NBCSP, its QLD counterpart the QBCSP and colonoscopy services in QLD, in general. Methods – Part 1 Chart audit of evidence-based practice: The research was undertaken in two parts from 2005-2007. The first part of this research comprised a retrospective chart audit of 1484 colonoscopy records (some 13% of all colonoscopies conducted in public sector facilities in the year 2005) in three QLD colonoscopy services. Whilst some 70% of colonoscopies are currently conducted in the private sector, only public sector colonoscopy facilities provided colonoscopies under the NBCSP. The aim of this study was to compare colonoscopy referral and practice with explicit criteria derived from the National Health & Medical Research Council (NHMRC) (1999) Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer, and describe the nature of variance with the guidelines. Symptomatic presentations were the most common indication for colonoscopy (60.9%). These comprised per rectal bleeding (31.0%), change of bowel habit (22.1%), abdominal pain (19.6%), iron deficiency anaemia (16.2%), inflammatory bowel disease (8.9%) and other symptoms (11.4%). Surveillance and follow-up colonoscopies accounted for approximately one-third of the remaining colonoscopy workload across sites. Gastroenterologists (GEs) performed relatively more colonoscopies per annum (59.9%) compared to general surgeons (GS) (24.1%), colorectal surgeons (CRS) (9.4%) and general physicians (GPs) (6.5%). Guideline compliance varied with the designation of the colonoscopist. Compliance was lower for CRS (62.9%) compared to GPs (76.0%), GEs (75.0%), GSs (70.9%, p<0.05). Compliance with guideline recommendations for colonoscopic surveillance for family history of colorectal cancer (23.9%), polyps (37.0%) and a past history of bowel cancer (42.7%), was by comparison significantly lower than for symptomatic presentations (94.4%), (p<0.001). Variation with guideline recommendations occurred more frequently for polyp surveillance (earlier than guidelines recommend, 47.9%) and follow-up for past history of bowel cancer (later than recommended, 61.7%, p<0.001). Bowel cancer cases detected at colonoscopy comprised 3.6% of all audited colonoscopies. Incomplete colonoscopies occurred in 4.3% of audited colonoscopies and were more common among women (76.6%). For all colonoscopies audited, the rate of incomplete colonoscopies for GEs was 1.6% (CI 0.9-2.6), GPs 2.0% (CI 0.6-7.2), GS 7.0% (CI 4.8-10.1) and CRS 16.4% (CI 11.2-23.5). 18.6% (n=55) of patients with a documented family history of bowel cancer had colonoscopy performed against guidelines recommendations (for general (category 1) population risk, for reasons of patient request or family history of polyps, rather than for high risk status for colorectal cancer). In general, family history was inadequately documented and subsequently applied to colonoscopy referral and practice. Methods - Part 2 Surveys of quality of colonoscopy training: The second part of the research consisted of Australia-wide anonymous, self-completed surveys of colonoscopy trainers and their trainees to ascertain their opinions on the current apprenticeship model of colonoscopy in Australia and to identify any training needs. Overall, 127 surveys were received from colonoscopy trainers (estimated response rate 30.2%). Approximately 50% of trainers agreed and 27% disagreed that current numbers of training places were adequate to maintain a skilled colonoscopy workforce in preparation for the NBCSP. Approximately 70% of trainers also supported UK-style colonoscopy training within dedicated accredited training centres using a variety of training approaches including simulation. A collaborative approach with the private sector was seen as beneficial by 65% of trainers. Non-gastroenterologists (non-GEs) were more likely than GEs to be of the opinion that simulators are beneficial for colonoscopy training (χ2-test = 5.55, P = 0.026). Approximately 60% of trainers considered that the current requirements for recognition of training in colonoscopy could be insufficient for trainees to gain competence and 80% of those indicated that ≥ 200 colonoscopies were needed. GEs (73.4%) were more likely than non-GEs (36.2%) to be of the opinion that the Conjoint Committee standard is insufficient to gain competence in colonoscopy (χ2-test = 16.97, P = 0.0001). The majority of trainers did not support training either nurses (73%) or GPs in colonoscopy (71%). Only 81 (estimated response rate 17.9%) surveys were received from GS trainees (72.1%), GE trainees (26.3%) and GP trainees (1.2%). The majority were males (75.9%), with a median age 32 years and who had trained in New South Wales (41.0%) or Victoria (30%). Overall, two-thirds (60.8%) of trainees indicated that they deemed the Conjoint Committee standard sufficient to gain competency in colonoscopy. Between specialties, 75.4% of GS trainees indicated that the Conjoint Committee standard for recognition of colonoscopy was sufficient to gain competence in colonoscopy compared to only 38.5% of GE trainees. Measures of competency assessed and recorded by trainees in logbooks centred mainly on caecal intubation (94.7-100%), complications (78.9-100%) and withdrawal time (51-76.2%). Trainees described limited access to colonoscopy training lists due to the time inefficiency of the apprenticeship model and perceived monopolisation of these by GEs and their trainees. Improvements to the current training model suggested by trainees included: more use of simulation, training tools, a United Kingdom (UK)-style training course, concentration on quality indicators, increased access to training lists, accreditation of trainers and interdisciplinary colonoscopy training. Implications for the NBCSP/QBCSP: The introduction of the NBCSP/QBCSP necessitates higher quality colonoscopy services if it is to achieve its ultimate goal of decreasing the incidence of morbidity and mortality associated with bowel cancer in Australia. This will be achieved under a new paradigm for colonoscopy training and implementation of evidence-based practice across the screening pathway and specifically targeting areas highlighted in this thesis. Recommendations for improvement of NBCSP/QBCSP effectiveness and efficiency include the following: 1. Implementation of NBCSP and QBCSP health promotion activities that target men, in particular, to increase FOBT screening uptake. 2. Improved colonoscopy training for trainees and refresher courses or retraining for existing proceduralists to improve completion rates (especially for female NBCSP/QBCSP participants), and polyp and adenoma detection and removal, including newer techniques to detect flat and depressed lesions. 3. Introduction of colonoscopy training initiatives for trainees that are aligned with NBCSP/QBCSP colonoscopy quality indicators, including measurement of training outcomes using objective quality indicators such as caecal intubation, withdrawal time, and adenoma detection rate. 4. Introduction of standardised, interdisciplinary colonoscopy training to reduce apparent differences between specialties with regard to compliance with guideline recommendations, completion rates, and quality of polypectomy. 5. Improved quality of colonoscopy training by adoption of a UK-style training program with centres of excellence, incorporating newer, more objective assessment methods, use of a variety of training tools such as simulation and rotations of trainees between metropolitan, rural, and public and private sector training facilities. 6. Incorporation of NHMRC guidelines into colonoscopy information systems to improve documentation, provide guideline recommendations at the point of care, use of gastroenterology nurse coordinators to facilitate compliance with guidelines and provision of guideline-based colonoscopy referral letters for GPs. 7. Provision of information and education about the NBCSP/QBCSP, bowel cancer risk factors, including family history and polyp surveillance guidelines, for participants, GPs and proceduralists. 8. Improved referral of NBCSP/QBCSP participants found to have a high-risk family history of bowel cancer to appropriate genetics services.

Analysing Seasonal Health Data

Seasonal patterns have been found in a remarkable range of health conditions, including birth defects, respiratory infections and cardiovascular disease. Accurately estimating the size and timing of seasonal peaks in disease incidence is an aid to understanding the causes and possibly to developing interventions. With global warming increasing the intensity of seasonal weather patterns around the world, a review of the methods for estimating seasonal effects on health is timely. This is the first book on statistical methods for seasonal data written for a health audience. It describes methods for a range of outcomes (including continuous, count and binomial data) and demonstrates appropriate techniques for summarising and modelling these data. It has a practical focus and uses interesting examples to motivate and illustrate the methods. The statistical procedures and example data sets are available in an R package called ‘season’. Adrian Barnett is a senior research fellow at Queensland University of Technology, Australia. Annette Dobson is a Professor of Biostatistics at The University of Queensland, Australia. Both are experienced medical statisticians with a commitment to statistical education and have previously collaborated in research in the methodological developments and applications of biostatistics, especially to time series data. Among other projects, they worked together on revising the well-known textbook "An Introduction to Generalized Linear Models," third edition, Chapman Hall/CRC, 2008. In their new book they share their knowledge of statistical methods for examining seasonal patterns in health.

Delirium in early-stage Alzheimer's disease : enhancing cognitive reserve as a possible preventive measure

Delirium is a disorder of acute onset with fluctuating symptoms and is characterized by inattention, disorganized thinking, and altered levels of consciousness. The risk for delirium is greatest in individuals with dementia, and the incidence of both is increasing worldwide because of the aging of our population. Although several clinical trials have tested interventions for delirium prevention in individuals without dementia, little is known about the mechanisms for the prevention of delirium in early-stage Alzheimer’s disease (AD). The purpose of this article is to explore ways of preventing delirium and slowing the rate of cognitive decline in early-stage AD by enhancing cognitive reserve. An agenda for future research on interventions to prevent delirium in individuals with early-stage AD is also presented.

Investigation of MEMS inertial sensors and aircraft dynamic models in global positioning system integrity monitoring for approaches with vertical guidance

An Approach with Vertical Guidance (APV) is an instrument approach procedure which provides horizontal and vertical guidance to a pilot on approach to landing in reduced visibility conditions. APV approaches can greatly reduce the safety risk to general aviation by improving the pilot’s situational awareness. In particular the incidence of Controlled Flight Into Terrain (CFIT) which has occurred in a number of fatal air crashes in general aviation over the past decade in Australia, can be reduced. APV approaches can also improve general aviation operations. If implemented at Australian airports, APV approach procedures are expected to bring a cost saving of millions of dollars to the economy due to fewer missed approaches, diversions and an increased safety benefit. The provision of accurate horizontal and vertical guidance is achievable using the Global Positioning System (GPS). Because aviation is a safety of life application, an aviation-certified GPS receiver must have integrity monitoring or augmentation to ensure that its navigation solution can be trusted. However, the difficulty with the current GPS satellite constellation alone meeting APV integrity requirements, the susceptibility of GPS to jamming or interference and the potential shortcomings of proposed augmentation solutions for Australia such as the Ground-based Regional Augmentation System (GRAS) justifies the investigation of Aircraft Based Augmentation Systems (ABAS) as an alternative integrity solution for general aviation. ABAS augments GPS with other sensors at the aircraft to help it meet the integrity requirements. Typical ABAS designs assume high quality inertial sensors to provide an accurate reference trajectory for Kalman filters. Unfortunately high-quality inertial sensors are too expensive for general aviation. In contrast to these approaches the purpose of this research is to investigate fusing GPS with lower-cost Micro-Electro-Mechanical System (MEMS) Inertial Measurement Units (IMU) and a mathematical model of aircraft dynamics, referred to as an Aircraft Dynamic Model (ADM) in this thesis. Using a model of aircraft dynamics in navigation systems has been studied before in the available literature and shown to be useful particularly for aiding inertial coasting or attitude determination. In contrast to these applications, this thesis investigates its use in ABAS. This thesis presents an ABAS architecture concept which makes use of a MEMS IMU and ADM, named the General Aviation GPS Integrity System (GAGIS) for convenience. GAGIS includes a GPS, MEMS IMU, ADM, a bank of Extended Kalman Filters (EKF) and uses the Normalized Solution Separation (NSS) method for fault detection. The GPS, IMU and ADM information is fused together in a tightly-coupled configuration, with frequent GPS updates applied to correct the IMU and ADM. The use of both IMU and ADM allows for a number of different possible configurations. Three are investigated in this thesis; a GPS-IMU EKF, a GPS-ADM EKF and a GPS-IMU-ADM EKF. The integrity monitoring performance of the GPS-IMU EKF, GPS-ADM EKF and GPS-IMU-ADM EKF architectures are compared against each other and against a stand-alone GPS architecture in a series of computer simulation tests of an APV approach. Typical GPS, IMU, ADM and environmental errors are simulated. The simulation results show the GPS integrity monitoring performance achievable by augmenting GPS with an ADM and low-cost IMU for a general aviation aircraft on an APV approach. A contribution to research is made in determining whether a low-cost IMU or ADM can provide improved integrity monitoring performance over stand-alone GPS. It is found that a reduction of approximately 50% in protection levels is possible using the GPS-IMU EKF or GPS-ADM EKF as well as faster detection of a slowly growing ramp fault on a GPS pseudorange measurement. A second contribution is made in determining how augmenting GPS with an ADM compares to using a low-cost IMU. By comparing the results for the GPS-ADM EKF against the GPS-IMU EKF it is found that protection levels for the GPS-ADM EKF were only approximately 2% higher. This indicates that the GPS-ADM EKF may potentially replace the GPS-IMU EKF for integrity monitoring should the IMU ever fail. In this way the ADM may contribute to the navigation system robustness and redundancy. To investigate this further, a third contribution is made in determining whether or not the ADM can function as an IMU replacement to improve navigation system redundancy by investigating the case of three IMU accelerometers failing. It is found that the failed IMU measurements may be supplemented by the ADM and adequate integrity monitoring performance achieved. Besides treating the IMU and ADM separately as in the GPS-IMU EKF and GPS-ADM EKF, a fourth contribution is made in investigating the possibility of fusing the IMU and ADM information together to achieve greater performance than either alone. This is investigated using the GPS-IMU-ADM EKF. It is found that the GPS-IMU-ADM EKF can achieve protection levels approximately 3% lower in the horizontal and 6% lower in the vertical than a GPS-IMU EKF. However this small improvement may not justify the complexity of fusing the IMU with an ADM in practical systems. Affordable ABAS in general aviation may enhance existing GPS-only fault detection solutions or help overcome any outages in augmentation systems such as the Ground-based Regional Augmentation System (GRAS). Countries such as Australia which currently do not have an augmentation solution for general aviation could especially benefit from the economic savings and safety benefits of satellite navigation-based APV approaches.

Texting while driving : psychosocial influences on young people’s texting intentions and behaviour

Despite the dangers and illegality, there is a continued prevalence of texting while driving amongst young Australian drivers. The present study tested an extended theory of planned behaviour (TPB) to predict young drivers’ (17 to 24 years) intentions to [1] send and [2] read text messages while driving. Participants (N = 169 university students) completed measures of attitudes, subjective norm, perceived behavioural control, intentions, and the additional social influence measures of group norm and moral norm. One week later, participants reported on the number of texts sent and read while driving in the previous week. Attitude predicted intentions to both send and read texts while driving, and subjective norm and perceived behavioural control determined sending, but not reading, intentions. Further, intention, but not perceptions of control, predicted both texting behaviours 1 week later. In addition, both group norm and moral norm added predictive ability to the model. These findings provide support for the TPB in understanding students’ decisions to text while driving as well as the inclusion of additional normative influences within this context, suggesting that a multi-strategy approach is likely to be useful in attempts to reduce the incidence of these risky driving behaviours.

Fraud detection in ERP systems using scenario matching

ERP systems generally implement controls to prevent certain common kinds of fraud. In addition however, there is an imperative need for detection of more sophisticated patterns of fraudulent activity as evidenced by the legal requirement for company audits and the common incidence of fraud. This paper describes the design and implementation of a framework for detecting patterns of fraudulent activity in ERP systems. We include the description of six fraud scenarios and the process of specifying and detecting the occurrence of those scenarios in ERP user log data using the prototype software which we have developed. The test results for detecting these scenarios in log data have been verified and confirm the success of our approach which can be generalized to ERP systems in general.

The impact of globalisation on health

After reading this chapter, you should be able to: • understand the concept of globalisation and appreciate its complexity • identify the significant impacts of globalisation on population health, particularly the incidence of communicable and non-communicable diseases • understand the distribution of the global burden of disease in high-, middle- and low-income countries • critically evaluate the factors contributing to the major causes of death in low-income countries • understand some of the achievements of the global public health community and appreciate the challenges it faces.

Outrage management in cases of sexual harassment as revealed in judicial decisions

Sexual harassment can be conceptualized as a series of interactions between harassers and targets that either inhibit or increase outrage by third parties. The outrage management model predicts the kinds of actions likely to be used by perpetrators to minimize outrage, predicts the consequences of failing to use these tactics—namely backfire, and recommends countertactics to increase outrage. Using this framework, our archival study examined outrage-management tactics reported as evidence in 23 judicial decisions of sexual harassment cases in Australia. The decisions contained precise, detailed information about the circumstances leading to the claim; the events which transpired in the courtroom, including direct quotations; and the judges' interpretations and findings. We found evidence that harassers minimize outrage by covering up the actions, devaluing the target, reinterpreting the events, using official channels to give an appearance of justice, and intimidating or bribing people involved. Targets can respond using countertactics of exposure, validation, reframing, mobilization of support, and resistance. Although there are limitations to using judicial decisions as a source of information, our study points to the value of studying tactics and the importance to harassers of minimizing outrage from their actions. The findings also highlight that, given the limitations of statutory and organizational protections in reducing the incidence and severity of sexual harassment in the community, individual responses may be effective as part of a multilevel response in reducing the incidence and impact of workplace sexual harassment as a gendered harm.

Turning Around Talipes: Nursing Considerations

The management of congenital talipes equinovarus (TEV) has received much clinical and research attention within the disciplines of medicine and physiotherapy. However, few articles have been published about the role of the registered nurse in contributing to the optimum health and wellbeing of the child and family presenting for assessment and treatment of the condition. Much of the most intense treatment for TEV occurs in the first few weeks of the child’s life; a time of critical growth and development when the infant is both sensitive and vulnerable to the environment within which it is nurtured. This is also a crucial time for developing a secure attachment to the caregiver and nurses can assist parents in optimising their infant’s opportunities for a secure attachment relationship. This paper thus provides an overview of the medical and physiotherapy management of TEV and highlights the role nurses have in providing nursing care and psycho-social support to parents of infants with TEV, in areas such as the maintenance of skin integrity and circulation, providing effective pain relief, and optimising growth, development, and a secure attachment relationship. Congenital TEV or 'club foot' is one of the most common congenital orthopaedic anomalies of infants. In Queensland in 2000, in approximately 50,000 births, 244 infants were born with talipes; almost five infants per 1000 births. National statistics are not as specific, with coding providing only 'other lower limb' as the category that would encompass talipes; the 1997 national incidence of such lower limb congenital malformations is reported as 1.7 per 10,000 births 1.

Validity of the Waterlow screening tool and risks for pressure injury in acute care

Objectives: To assess the validity of the Waterlow screening tool in a cohort of internal medicine patients and to identify factors contributing to pressure injury. Design: Longitudinal cohort study Setting: A tertiary hospital in Brisbane, Australia Participants: 274 patients admitted through the Emergency Department or outpatient clinics and expected to remain in hospital for at least three days were included in the study. The mean age was 65.3 years. Interventions: Patients were screened on admission using the Waterlow screening tool. Every second day, their pressure ulcer status was monitored and recorded. Main outcome measures: Pressure ulcer incidence Results: Fifteen participants (5.5%) had an existing pressure ulcer and a further 12 (4.4%) developed a pressure ulcer during their hospital stay. Sensitivity of the Waterlow scale was 0.67, (95% CI: 0.35 to 0.88); specificity 0.79, (95% CI: 0.73 to 0.85); PPV 0.13, (95% CI: 0.07 to 0.24); NPV 0.98, (95% CI: 0.94 to 0.99). Conclusion: This study provides further evidence of the poor predictive validity of the Waterlow scale. A suitably powered randomised controlled trial is urgently needed to provide definitive evidence about the usefulness of the Waterlow scale compared with other screening tools and with clinical judgement.

Wellness in older adults

Understanding perception of wellness in older adults is a question to be understood against the backdrop of concerns about whether global ageing and the ‘bulge’ of ageing baby boomers will increase health care cost beyond what modern economies can deal with. Older adults who age in a healthy way and who take responsibility for their own health offer a positive alternative and change the perception that older adults are a burden on their society’s health system. The concept of successful ageing introduced by Rowe and Kahn (1987; 1997) suggested that older adults age successfully if they avoid disease and disability, maintain high cognitive and physical functioning and remain actively engaged with life. This concept, however, did not reflect older adults’ own perceptions of what constitutes successful ageing or how perceptions of wellness or health-related quality of life influenced the older adult’s understanding of his or her own health and ageing. A research project was designed to examine older adults’ perceptions of wellness in order to gain an understanding of the factors that influence perception of their own wellness. Specifically, the research wanted to explore two aspects: whether belonging to a unique organisation, in this instance a Returned Services Club, influenced perceptions of wellness; and whether there are significant gender differences for the perception of wellness. A mixed method project with two consecutive studies was designed to answer these questions: a quantitative survey of members of a Returned Services Club and of the surrounding community in Queensland, Australia, and a qualitative study conducting focus groups to explore findings of the survey. The results of the survey were used to determine the composition of the focus groups. The participants for the first study, (N=257), community living adults 65 years and older, were chosen from the membership role of a Returned Services Club or recruited by personal approach from the community surrounding the Services Club. Participants completed a survey that consisted of a perception of wellness instrument, a health-related quality of life instrument, and questions on morbidities, modifiable life style factors and demographics. Data analysis found that a number of individual factors influenced perception of wellness and health-related quality of life. Positive influences were independent mobility, exercise and gambling at non-hazardous levels, and negative influences were hearing loss, memory problems, chronic disease and being single. Membership of the Services Club did not contribute to perception of wellness beyond being a member of a social group. While there may have been an expectation that members of an organisation that is traditionally associated with high alcohol use and problematic gambling may have lower perceptions of wellness, this study suggested that the negative influences may have been counteracted by the positive effects of social interaction, thus having neither negative nor positive influences on perception of wellness. There were significant differences in perception of wellness and in health-related quality of life for women and men. The most significant difference was for women aged 85-90 who had significantly lower scores for perception of wellness than men or than any other age group. This result was the impetus for conducting focus groups with adults aged 85-90 years of age. Focus groups were conducted with 24 women and four men aged 85-90 to explore the survey findings for this age group. Results from the focus groups indicated that for older adults perception of wellness was a multidimensional construct of more complexity than indicated by the survey instrument. Elite older women (women over 85 years of age) related their perception of wellness to their ability to do what they wanted to do, and what they wanted to do significantly more than anything else, was to stay connected to family, friends and the community to which they belonged. From the focus group results it appeared that elite older women identified with the three elements of successful ageing – low incidence of disability and disease, high physical and cognitive functioning, and active engagement with life – but not in a flat structure. It appears that for elite older women good physical and mental health function to enable social connectedness. It is the elements of health that impact on the ability to do what they wanted to do that were identified as key factors: independent mobility, hearing and memory - factors that impact on the ability to interact socially. These elements were only identified when they impacted on the person’s ability to do what they wanted to do, for example mobility problems that were managed were not considered a problem. The study also revealed that older women use selection, optimisation and compensation to meet their goal of staying socially connected. The shopping centre was a key factor in this goal and older women used shopping centres to stay connected to the community and for exercise as well as shopping. Personal and public safety and other environmental concerns were viewed in the same context of enabling or disabling social connectedness. This suggested that for elite older women the model of successful ageing was hierarchical rather than flat, with social connectedness at the top, supported by cognitive functioning and good physical and mental health. In conclusion, this research revealed that perception of wellness in older adults is a complex, multidimensional construct. For older adults good health is related to social connectedness and is not a goal in itself. Health professionals and the community at large have a responsibility to take into account the ability of the older adult to stay socially connected to their community and to enable this, if the goal is to keep older adults healthy for as long as possible. Maintaining or improving perception of wellness in older adults will require a broad biopsychosocial approach that utilises findings such as older adults’ use of shopping centres for non-shopping purposes, concerns about personal and environmental safety and supporting older adults to maintain or improve their social connectedness to their communities.

Molecular markers of obesity and diabetes

Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined. It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes. Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription. To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present. Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.

Molecular epidemiology of respiratory viruses in a paediatric cohort from Indonesia

Acute lower respiratory tract infections (ALRTIs) are a common cause of morbidity and mortality among children under 5 years of age and are found worldwide, with pneumonia as the most severe manifestation. Although the incidence of severe disease varies both between individuals and countries, there is still no clear understanding of what causes this variation. Studies of community-acquired pneumonia (CAP) have traditionally not focused on viral causes of disease due to a paucity of diagnostic tools. However, with the emergence of molecular techniques, it is now known that viruses outnumber bacteria as the etiological agents of childhood CAP, especially in children under 2 years of age. The main objective of this study was to investigate viruses contributing to disease severity in cases of childhood ALRTI, using a two year cohort study following 2014 infants and children enrolled in Bandung, Indonesia. A total of 352 nasopharyngeal washes collected from 256 paediatric ALRTI patients were used for analysis. A subset of samples was screened using a novel microarray pathogen detection method that identified respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and human rhinovirus (HRV) in the samples. Real-time RT-PCR was used both for confirming and quantifying viruses found in the nasopharyngeal samples. Viral copy numbers were determined and normalised to the numbers of human cells collected with the use of 18S rRNA. Molecular epidemiology was performed for RSV A and hMPV using sequences to the glycoprotein gene and nucleoprotein gene respectively, to determine genotypes circulating in this Indonesian paediatric cohort. This study found that HRV (119/352; 33.8%) was the most common virus detected as the cause of respiratory tract infections in this cohort, followed by the viral pathogens RSV A (73/352; 20.7%), hMPV (30/352; 8.5%) and RSV B (12/352; 3.4%). Co-infections of more than two viruses were detected in 31 episodes (defined as an infection which occurred more than two weeks apart), accounting for 8.8% of the 352 samples tested or 15.4% of the 201 episodes with at least one virus detected. RSV A genotypes circulating in this population were predominantly GA2, GA5 and GA7, while hMPV genotypes circulating were mainly A2a (27/30; 90.0%), B2 (2/30; 6.7%) and A1 (1/30; 3.3%). This study found no evidence of disease severity associated either with a specific virus or viral strain, or with viral load. However, this study did find a significant association with co-infection of RSV A and HRV with severe disease (P = 0.006), suggesting that this may be a novel cause of severe disease.