The feral horse foot. Part B : radiographic, gross visual and histopathological parameters of foot health in 100 Australian feral horses

Background It has been proposed that the feral horse foot is a benchmark model for foot health in horses. However, the foot health of feral horses has not been formally investigated. Objectives To investigate the foot health of Australian feral horses and determine if foot health is affected by environmental factors, such as substrate properties and distance travelled. Methods Twenty adult feral horses from five populations (n = 100) were investigated. Populations were selected on the basis of substrate hardness and the amount of travel typical for the population. Feet were radiographed and photographed, and digital images were surveyed by two experienced assessors blinded to each other's assessment and to the population origin. Lamellar samples from 15 feet from three populations were investigated histologically for evidence of laminitis. Results There was a total of 377 gross foot abnormalities identified in 100 left forefeet. There were no abnormalities detected in three of the feet surveyed. Each population had a comparable prevalence of foot abnormalities, although the type and severity of abnormality varied among populations. Of the three populations surveyed by histopathology, the prevalence of chronic laminitis ranged between 40% and 93%. Conclusions Foot health appeared to be affected by the environment inhabited by the horses. The observed chronic laminitis may be attributable to either nutritional or traumatic causes. Given the overwhelming evidence of suboptimal foot health, it may not be appropriate for the feral horse foot to be the benchmark model for equine foot health.

The feral horse foot. Part A : observational study of the effect of environment on the morphometrics of the feet of 100 Australian feral horses

Aim To better understand the morphology of, and the effect of different travel patterns and varying substrate environments on, the feral horse foot to better manage the feet of domestic horses. Methods The left forefeet of 20 adult feral horses from each of five geographically separated populations in Australia (n = 100) were investigated. Populations were selected on the basis of substrate hardness under foot and the amount of travel typical for the population. Feet were radiographed and photographed and 40 morphometric measurements of each foot were obtained. Results Of the 40 parameters, 37 differed significantly (P < 0.05) among the populations, which suggested that substrate hardness and travel distance have an effect on foot morphology. Harder substrates and longer travel distances were associated with short hoof walls and minimal hoof wall flaring. Softer substrates and moderate travel distances were associated with long flared walls, similar to that of typical untrimmed feet of domestic horses. Conclusions The morphology of the feral horse foot appeared to be affected by the distance travelled and by the abrasive qualities and mechanical properties of the substrate under foot. There were marked differences in some conformation parameters between the feral horses in the current study and domestic horses in previous studies. Although the conformation of the feral horse foot may have some prescriptive value, concerns regarding abnormal foot anatomy warrant further investigation.

A comprehensive investigation of the risky driving behaviour of young novice drivers

Young novice drivers - that is, drivers aged 16-25 years who are relatively inexperienced in driving on the road and have a novice (Learner, Provisional) driver's licence - have been overrepresented in car crash, injury and fatality statistics around the world for decades. There are numerous persistent characteristics evident in young novice driver crashes, fatalities and offences, including variables relating to the young driver themselves, broader social influences which include their passengers, the car they drive, and when and how they drive, and their risky driving behaviour in particular. Moreover, there are a range of psychosocial factors influencing the behaviour of young novice drivers, including the social influences of parents and peers, and person-related factors such as age-related factors, attitudes, and sensation seeking. Historically, a range of approaches have been developed to manage the risky driving behaviour of young novice drivers. Traditional measures predominantly relying upon education have had limited success in regulating the risky driving behaviour of the young novice driver. In contrast, interventions such as graduated driver licensing (GDL) which acknowledges young novice drivers' limitations - principally pertaining to their chronological and developmental age, and their driving inexperience - have shown to be effective in ameliorating this pervasive public health problem. In practice, GDL is a risk management tool that is designed to reduce driving at risky times (e.g., at night) or in risky driving conditions (e.g., with passengers), while still enabling novice drivers to obtain experience. In this regard, the GDL program in Queensland, Australia, was considerably enhanced in July 2007, and major additions to the program include mandated Learner practice of 100 hours recorded in a logbook, and passenger limits during night driving in the Provisional phase. Road safety researchers have also continued to consider the influential role played by the young driver's psychosocial characteristics, including psychological traits and states. In addition, whilst the majority of road safety user research is epidemiological in nature, contemporary road safety research is increasingly applying psychological and criminological theories. Importantly, such theories not only can guide young novice driver research, they can also inform the development and evaluation of countermeasures targeting their risky driving behaviour. The research is thus designed to explore the self-reported behaviours - and the personal, psychosocial, and structural influences upon the behaviours - of young novice drivers This thesis incorporates three stages of predominantly quantitative research to undertake a comprehensive investigation of the risky driving behaviour of young novices. Risky driving behaviour increases the likelihood of the young novice driver being involved in a crash which may harm themselves or other road users, and deliberate risky driving such as driving in excess of the posted speed limits is the focus of the program of research. The extant literature examining the nature of the risky behaviour of the young novice driver - and the contributing factors for this behaviour - while comprehensive, has not led to the development of a reliable instrument designed specifically to measure the risky behaviour of the young novice driver. Therefore the development and application of such a tool (the Behaviour of Young Novice Drivers Scale, or BYNDS) was foremost in the program of research. In addition to describing the driving behaviours of the young novice, a central theme of this program of research was identifying, describing, and quantifying personal, behavioural, and environmental influences upon young novice driver risky behaviour. Accordingly the 11 papers developed from the three stages of research which comprise this thesis are framed within Bandura's reciprocal determinism model which explicitly considers the reciprocal relationship between the environment, the person, and their behaviour. Stage One comprised the foundation research and operationalised quantitative and qualitative methodologies to finalise the instrument used in Stages Two and Three. The first part of Stage One involved an online survey which was completed by 761 young novice drivers who attended tertiary education institutions across Queensland. A reliable instrument for measuring the risky driving behaviour of young novices was developed (the BYNDS) and is currently being operationalised in young novice driver research in progress at the Centre for Injury Research and Prevention in Philadelphia, USA. In addition, regression analyses revealed that psychological distress influenced risky driving behaviour, and the differential influence of depression, anxiety, sensitivity to punishments and rewards, and sensation seeking propensity were explored. Path model analyses revealed that punishment sensitivity was mediated by anxiety and depression; and the influence of depression, anxiety, reward sensitivity and sensation seeking propensity were moderated by the gender of the driver. Specifically, for males, sensation seeking propensity, depression, and reward sensitivity were predictive of self-reported risky driving, whilst for females anxiety was also influential. In the second part of Stage One, 21 young novice drivers participated in individual and small group interviews. The normative influences of parents, peers, and the Police were explicated. Content analysis supported four themes of influence through punishments, rewards, and the behaviours and attitudes of parents and friends. The Police were also influential upon the risky driving behaviour of young novices. The findings of both parts of Stage One informed the research of Stage Two. Stage Two was a comprehensive investigation of the pre-Licence and Learner experiences, attitudes, and behaviours, of young novice drivers. In this stage, 1170 young novice drivers from across Queensland completed an online or paper survey exploring their experiences, behaviours and attitudes as a pre- and Learner driver. The majority of novices did not drive before they were licensed (pre-Licence driving) or as an unsupervised Learner, submitted accurate logbooks, intended to follow the road rules as a Provisional driver, and reported practicing predominantly at the end of the Learner period. The experience of Learners in the enhanced-GDL program were also examined and compared to those of Learner drivers who progressed through the former-GDL program (data collected previously by Bates, Watson, & King, 2009a). Importantly, current-GDL Learners reported significantly more driving practice and a longer Learner period, less difficulty obtaining practice, and less offence detection and crash involvement than Learners in the former-GDL program. The findings of Stage Two informed the research of Stage Three. Stage Three was a comprehensive exploration of the driving experiences, attitudes and behaviours of young novice drivers during their first six months of Provisional 1 licensure. In this stage, 390 of the 1170 young novice drivers from Stage Two completed another survey, and data collected during Stages Two and Three allowed a longitudinal investigation of self-reported risky driving behaviours, such as GDL-specific and general road rule compliance; risky behaviour such as pre-Licence driving, crash involvement and offence detection; and vehicle ownership, paying attention to Police presence, and punishment avoidance. Whilst the majority of Learner and Provisional drivers reported compliance with GDL-specific and general road rules, 33% of Learners and 50% of Provisional drivers reported speeding by 10-20 km/hr at least occasionally. Twelve percent of Learner drivers reported pre-Licence driving, and these drivers were significantly more risky as Learner and Provisional drivers. Ten percent of males and females reported being involved in a crash, and 10% of females and 18% of males had been detected for an offence, within the first six months of independent driving. Additionally, 75% of young novice drivers reported owning their own car within six months of gaining their Provisional driver's licence. Vehicle owners reported significantly shorter Learner periods and more risky driving exposure as a Provisional driver. Paying attention to Police presence on the roads appeared normative for young novice drivers: 91% of Learners and 72% of Provisional drivers reported paying attention. Provisional drivers also reported they actively avoided the Police: 25% of males and 13% of females; 23% of rural drivers and 15% of urban drivers. Stage Three also allowed the refinement of the risky behaviour measurement tool (BYNDS) created in Stage One; the original reliable 44-item instrument was refined to a similarly reliable 36-item instrument. A longitudinal exploration of the influence of anxiety, depression, sensation seeking propensity and reward sensitivity upon the risky behaviour of the Provisional driver was also undertaken using data collected in Stages Two and Three. Consistent with the research of Stage One, structural equation modeling revealed anxiety, reward sensitivity and sensation seeking propensity predicted self-reported risky driving behaviour. Again, gender was a moderator, with only reward sensitivity predicting risky driving for males. A measurement model of Akers' social learning theory (SLT) was developed containing six subscales operationalising the four constructs of differential association, imitation, personal attitudes, and differential reinforcement, and the influence of parents and peers was captured within the items in a number of these constructs. Analyses exploring the nature and extent of the psychosocial influences of personal characteristics (step 1), Akers' SLT (step 2), and elements of the prototype/willingness model (PWM) (step 3) upon self-reported speeding by the Provisional driver in a hierarchical multiple regression model found the following significant predictors: gender (male), car ownership (own car), reward sensitivity (greater sensitivity), depression (greater depression), personal attitudes (more risky attitudes), and speeding (more speeding) as a Learner. The research findings have considerable implications for road safety researchers, policy-makers, mental health professionals and medical practitioners alike. A broad range of issues need to be considered when developing, implementing and evaluating interventions for both the intentional and unintentional risky driving behaviours of interest. While a variety of interventions have been historically utilised, including education, enforcement, rehabilitation and incentives, caution is warranted. A multi-faceted approach to improving novice road safety is more likely to be effective, and new and existing countermeasures should capitalise on the potential of parents, peers and Police to be a positive influence upon the risky behaviour of young novice drivers. However, the efficacy of some interventions remains undetermined at this time. Notwithstanding this caveat, countermeasures such as augmenting and strengthening Queensland's GDL program and targeting parents and adolescents particularly warrant further attention. The findings of the research program suggest that Queensland's current-GDL can be strengthened by increasing compliance of young novice drivers with existing conditions and restrictions. The rates of speeding reported by the young Learner driver are particularly alarming for a number of reasons. The Learner is inexperienced in driving, and travelling in excess of speed limits places them at greater risk as they are also inexperienced in detecting and responding appropriately to driving hazards. In addition, the Learner period should provide the foundation for a safe lifetime driving career, enabling the development and reinforcement of non-risky driving habits. Learners who sped reported speeding by greater margins, and at greater frequencies, when they were able to drive independently. Other strategies could also be considered to enhance Queensland's GDL program, addressing both the pre-Licence adolescent and their parents. Options that warrant further investigation to determine their likely effectiveness include screening and treatment of novice drivers by mental health professionals and/or medical practitioners; and general social skills training. Considering the self-reported pre-licence driving of the young novice driver, targeted education of parents may need to occur before their child obtains a Learner licence. It is noteworthy that those participants who reported risky driving during the Learner phase also were more likely to report risky driving behaviour during the Provisional phase; therefore it appears vital that the development of safe driving habits is encouraged from the beginning of the novice period. General education of parents and young novice drivers should inform them of the considerably-increased likelihood of risky driving behaviour, crashes and offences associated with having unlimited access to a vehicle in the early stages of intermediate licensure. Importantly, parents frequently purchase the car that is used by the Provisional driver, who typically lives at home with their parents, and therefore parents are ideally positioned to monitor the journeys of their young novice driver during this early stage of independent driving. Parents are pivotal in the development of their driving child: they are models who are imitated and are sources of attitudes, expectancies, rewards and punishments; and they provide the most driving instruction for the Learner. High rates of self-reported speeding by Learners suggests that GDL programs specifically consider the nature of supervision during the Learner period, encouraging supervisors to be vigilant to compliance with general and GDL-specific road rules, and especially driving in excess of speed limit. Attitudes towards driving are formed before the adolescent reaches the age when they can be legally licensed. Young novice drivers with risky personal attitudes towards driving reported more risky driving behaviour, suggesting that countermeasures should target such attitudes and that such interventions might be implemented before the adolescent is licensed. The risky behaviours and attitudes of friends were also found to be influential, and given that young novice drivers tend to carry their friends as their passengers, a group intervention such as provided in a school class context may prove more effective. Social skills interventions that encourage the novice to resist the negative influences of their friends and their peer passengers, and to not imitate the risky driving behaviour of their friends, may also be effective. The punishments and rewards anticipated from and administered by friends were also found to influence the self-reported risky behaviour of the young novice driver; therefore young persons could be encouraged to sanction the risky, and to reward the non-risky, driving of their novice friends. Adolescent health programs and related initiatives need to more specifically consider the risks associated with driving. Young novice drivers are also adolescents, a developmental period associated with depression and anxiety. Depression, anxiety, and sensation seeking propensity were found to be predictive of risky driving; therefore interventions targeting psychological distress, whilst discouraging the expression of sensation seeking propensity whilst driving, warrant development and trialing. In addition, given that reward sensitivity was also predictive, a scheme which rewards novice drivers for safe driving behaviour - rather than rewarding the novice through emotional and instrumental rewards for risky driving behaviour - requires further investigation. The Police were also influential in the risky driving behaviour of young novices. Young novice drivers who had been detected for an offence, and then avoided punishment, reacted differentially, with some drivers appearing to become less risky after the encounter, whilst for others their risky behaviour appeared to be reinforced and therefore was more likely to be performed again. Such drivers saw t

The AusD Study: A population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Towards a capabilities database to inform inclusive design : Experimental investigation of effective survey-based predictors of human-product interaction

A key issue in the field of inclusive design is the ability to provide designers with an understanding of people's range of capabilities. Since it is not feasible to assess product interactions with a large sample, this paper assesses a range of proxy measures of design-relevant capabilities. It describes a study that was conducted to identify which measures provide the best prediction of people's abilities to use a range of products. A detailed investigation with 100 respondents aged 50-80 years was undertaken to examine how they manage typical household products. Predictor variables included self-report and performance measures across a variety of capabilities (vision, hearing, dexterity and cognitive function), component activities used in product interactions (e.g. using a remote control, touch screen) and psychological characteristics (e.g. self-efficacy, confidence with using electronic devices). Results showed, as expected, a higher prevalence of visual, hearing, dexterity, cognitive and product interaction difficulties in the 65-80 age group. Regression analyses showed that, in addition to age, performance measures of vision (acuity, contrast sensitivity) and hearing (hearing threshold) and self-report and performance measures of component activities are strong predictors of successful product interactions. These findings will guide the choice of measures to be used in a subsequent national survey of design-relevant capabilities, which will lead to the creation of a capability database. This will be converted into a tool for designers to understand the implications of their design decisions, so that they can design products in a more inclusive way.

The confidence of speech-language pathology students regarding communicating with people with aphasia

Background Aphasia is an acquired language disorder that can present a significant barrier to patient involvement in healthcare decisions. Speech-language pathologists (SLPs) are viewed as experts in the field of communication. However, many SLP students do not receive practical training in techniques to communicate with people with aphasia (PWA) until they encounter PWA during clinical education placements. Methods This study investigated the confidence and knowledge of SLP students in communicating with PWA prior to clinical placements using a customised questionnaire. Confidence in communicating with people with aphasia was assessed using a 100-point visual analogue scale. Linear, and logistic, regressions were used to examine the association between confidence and age, as well as confidence and course type (graduate-entry masters or undergraduate), respectively. Knowledge of strategies to assist communication with PWA was examined by asking respondents to list specific strategies that could assist communication with PWA. Results SLP students were not confident with the prospect of communicating with PWA; reporting a median 29-points (inter-quartile range 17–47) on the visual analogue confidence scale. Only, four (8.2%) of respondents rated their confidence greater than 55 (out of 100). Regression analyses indicated no relationship existed between confidence and students‘ age (p = 0.31, r-squared = 0.02), or confidence and course type (p = 0.22, pseudo r-squared = 0.03). Students displayed limited knowledge about communication strategies. Thematic analysis of strategies revealed four overarching themes; Physical, Verbal Communication, Visual Information and Environmental Changes. While most students identified potential use of resources (such as images and written information), fewer students identified strategies to alter their verbal communication (such as reduced speech rate). Conclusions SLP students who had received aphasia related theoretical coursework, but not commenced clinical placements with PWA, were not confident in their ability to communicate with PWA. Students may benefit from an educational intervention or curriculum modification to incorporate practical training in effective strategies to communicate with PWA, before they encounter PWA in clinical settings. Ensuring students have confidence and knowledge of potential communication strategies to assist communication with PWA may allow them to focus their learning experiences in more specific clinical domains, such as clinical reasoning, rather than building foundation interpersonal communication skills.

A retrospective cohort investigation of active range of motion within one week of open reduction and internal fixation of distal radius fractures

Distal radius fractures stabilized by open reduction internal fixation (ORIF) have become increasingly common. There is currently no consensus on the optimal time to commence range of motion (ROM) exercises post-ORIF. A retrospective cohort review was conducted over a five-year period to compare wrist and forearm range of motion outcomes and number of therapy sessions between patients who commenced active ROM exercises within the first seven days and from day eight onward following ORIF of distal radius fractures. One hundred and twenty-one patient cases were identified. Clinical data, active ROM at initial and discharge therapy assessments, fracture type, surgical approaches, and number of therapy sessions attended were recorded. One hundred and seven (88.4%) cases had complete datasets. The early active ROM group (n = 37) commenced ROM a mean (SD) of 4.27 (1.8) days post-ORIF. The comparator group (n = 70) commenced ROM exercises 24.3 (13.6) days post-ORIF. No significant differences were identified between groups in ROM at initial or discharge assessments, or therapy sessions attended. The results from this study indicate that patients who commenced active ROM exercises an average of 24 days after surgery achieved comparable ROM outcomes with similar number of therapy sessions to those who commenced ROM exercises within the first week.

Children's understanding of graphic representations of quantitative data

Children are encountering more and more graphic representations of data in their learning and everyday life. Much of this data occurs in quantitative forms as different forms of measurement are incorporated into the graphics during their construction. In their formal education, children are required to learn to use a range of these quantitative representations in subjects across the school curriculum. Previous research that focuses on the use of information processing and traditional approaches to cognitive psychology concludes that the development of an understanding of such representations of data is a complex process. An alternative approach is to investigate the experiences of children as they interact with graphic representations of quantitative data in their own life-worlds. This paper demonstrates how a phenomenographic approach may be used to reveal the qualitatively different ways in which children in Australian primary and secondary education understand the phenomenon of graphic representations of quantitative data. Seven variations of the children’s understanding were revealed. These have been described interpretively in the article and confirmed through the words of the children. A detailed outcome space demonstrates how these seven variations are structurally related.

Very sensitive fiber Bragg grating accelerometer using transverse forces with an easy over-range protection and low cross axial sensitivity

The first fiber Bragg grating (FBG) accelerometer using direct transverse forces is demonstrated by fixing the FBG by its two ends and placing a transversely moving inertial object at its middle. It is very sensitive because a lightly stretched FBG is more sensitive to transverse forces than axial forces. Its resonant frequency and static sensitivity are analyzed by the classic spring-mass theory, assuming the axial force changes little. The experiments show that the theory can be modified for cases where the assumption does not hold. The resonant frequency can be modified by a linear relationship experimentally achieved, and the static sensitivity by an alternative method proposed. The principles of the over-range protection and low cross axial sensitivity are achieved by limiting the movement of the FBG and were validated experimentally. The sensitivities 1.333 and 0.634 nm/g were experimentally achieved by 5.29 and 2.83 gram inertial objects at 10 Hz from 0.1 to 0.4 g (g = 9.8 m/s 2), respectively, and their resonant frequencies were around 25 Hz. Their theoretical static sensitivities and resonant frequencies found by the modifications are 1.188 nm/g and 26.81 Hz for the 5.29 gram one and 0.784 nm/g and 29.04 Hz for the 2.83 gram one, respectively.

Pharmacokinetics of cimifugin in rat plasma after oral administration of the extract of Saposhnikovia divaricatae root : Determination of cimifugin by high performance liquid chromatography coupled with solid phase extraction

High performance liquid chromatography (HPLC) coupled with the solid phase extraction method was developed for determining cimifugin (a coumarin derivative; one of Saposhnikovia divaricatae's constituents) in rat plasma after oral administration of Saposhnikovia divaricatae extract (SDE), and the pharmacokinetics of cimifugin either in SDE or as a single compound was investigated. The HPLC analysis was performed on a commercially available column (4.6 mm x 200 mm, 5 pm) with the isocratic elution of solvent A (Methanol) and solvent B (Water) (A:B=60:40) and the detection wavelength was set at 250 nm. The calibration curve was linear over the range of 0.100-10.040 microg/mL. The limit of detection was 30 ng/mL. At the rat plasma concentrations of 0.402, 4.016, 10.040 microg/mL, the intra-day precision was 6.21%, 3.98%, and 2.23%; the inter-day precision was 7.59%, 4.26%, and 2.09%, respectively. The absolute recovery was 76.58%, 76.61%, and 77.67%, respectively. When the dosage of SDE was equal to the pure compound calculated by the amount of cimifugin, it was found to have two maximum peaks while the pure compound only showed one peak in the plasma concentration-time curve. The pharmacokinetic characteristics of SDE showed the superiority of the extract and the properties of traditional Chinese medicine.

Selenium status of the Australian population : effect of age, gender and cardiovascular disease

Selenium (Se) is an essential trace element and the clinical consequences of Se deficiency have been well-documented. Se is primarily obtained through the diet and recent studies have suggested that the level of Se in Australian foods is declining. Currently there is limited data on the Se status of the Australian population so the aim of this study was to determine the plasma concentration of Se and glutathione peroxidase (GSH-Px), a well-established biomarker of Se status. Furthermore, the effect of gender, age and presence of cardiovascular disease (CVD) was also examined. Blood plasma samples from healthy subjects (140 samples, mean age = 54 years; range, 20-86 years) and CVD patients (112 samples, mean age = 67 years; range, 40-87 years) were analysed for Se concentration and GSH-Px activity. The results revealed that the healthy Australian cohort had a mean plasma Se level of 100.2 +/- 1.3 microg Se/L and a mean GSH-Px activity of 108.8 +/- 1.7 U/L. Although the mean value for plasma Se reached the level required for optimal GSH-Px activity (i.e. 100 microg Se/L), 47% of the healthy individuals tested fell below this level. Further evaluation revealed that certain age groups were more at risk of a lowered Se status, in particular, the oldest age group of over 81 years (females = 97.6 +/- 6.1 microg Se/L; males = 89.4 +/- 3.8 microg Se/L). The difference in Se status between males and females was not found to be significant. The presence of CVD did not appear to influence Se status, with the exception of the over 81 age group, which showed a trend for a further decline in Se status with disease (plasma Se, 93.5 +/- 3.6 microg Se/L for healthy versus 88.2 +/- 5.3 microg Se/L for CVD; plasma GSH-Px, 98.3 +/- 3.9 U/L for healthy versus 87.0 +/- 6.5 U/L for CVD). These findings emphasise the importance of an adequate dietary intake of Se for the maintenance of a healthy ageing population, especially in terms of cardiovascular health.

Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

Background Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. Methods To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential. Results Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. Conclusion We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.

Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area : a cohort study

Objectives Early childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services. Design Cost-effectiveness analysis using a Markov model. Setting Public dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia. Participants Children aged 6 months to 6 years received either a telephone prevention programme or usual care. Primary and secondary outcome measures A mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates. Results By age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios. Conclusions A telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.

Zeta-potential and morphology of electrospun nano- and microfibers from biopolymers and their blends used as scaffolds in tissue engineering

Electrostatic spinning or electrospinning is a fiber spinning technique driven by a high-voltage electric field that produces fibers with diameters in a submicrometer to nanometer range.1 Nanofibers are typical one-dimensional colloidal objects with an increased tensile strength, whose length can achieve a few kilometers and the specific surface area can be 100 m2 g–1 or higher.2 Nano- and microfibers from biocompatible polymers and biopolymers have received much attention in medical applications3 including biomedical structural elements (scaffolding used in tissue engineering,2,4–6 wound dressing,7 artificial organs and vascular grafts8), drug and vaccine delivery,9–11 protective shields in speciality fabrics, multifunctional membranes, etc. Other applications concern superhydrophobic coatings,12 encapsulation of solid materials,13 filter media for submicron particles in separation industry, composite reinforcement and structures for nano-electronic machines.

The function and mechanisms of action of ghrelin and obestatin in ovarian cancer

In this study, we have demonstrated that the preproghrelin derived hormones, ghrelin and obestatin, may play a role in ovarian cancer. Ghrelin and obestatin stimulated an increase in cell migration in ovarian cancer cell lines and may play a role in cancer progression. Ovarian cancer is the leading cause of death among gynaecological cancers and is the sixth most common cause of cancer-related deaths in women in developed countries. As ovarian cancer is difficult to diagnose at a low tumour grade, two thirds of ovarian cancers are not diagnosed until the late stages of cancer development resulting in a poor prognosis for the patient. As a result, current treatment methods are limited and not ideal. There is an urgent need for improved diagnostic markers, as well better therapeutic approaches and adjunctive therapies for this disease. Ghrelin has a number of important physiological effects, including roles in appetite regulation and the stimulation of growth hormone release. It is also involved in regulating the immune, cardiovascular and reproductive systems and regulates sleep, memory and anxiety, and energy metabolism. Over the last decade, the ghrelin axis, (which includes the hormones ghrelin and obestatin and their receptors), has been implicated in the pathogenesis of many human diseases and it may t may also play an important role in the development of cancer. Ghrelin is a 28 amino acid peptide hormone that exists in two forms. Acyl ghrelin (usually referred to as ghrelin), has a unique n-octanoic acid post-translational modification (which is catalysed by ghrelin O-acyltransferase, GOAT), and desacyl ghrelin, which is a non-octanoylated form. Octanoylated ghrelin acts through the growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1b, an alternatively spliced isoform of GHSR, is C-terminally truncated and does not bind ghrelin. Ghrelin has been implicated in the pathophysiology of a number of diseases Obestatin is a 23 amino acid, C-terminally amidated peptide which is derived from preproghrelin. Although GPR39 was originally thought to be the obestatin receptor this has been disproven, and its receptor remains unknown. Obestatin may have as diverse range of roles as ghrelin. Obestatin improves memory, inhibits thirst and anxiety, increases pancreatic juice secretion and has cardioprotective effects. Obestatin also has been shown to regulate cell proliferation, differentiation and apoptosis in some cell types. Prior to this study, little was known regarding the functions and mechanisms of action ghrelin and obestatin in ovarian cancer. In this study it was demonstrated that the full length ghrelin, GHSR1b and GOAT mRNA transcripts were expressed in all of the ovarian-derived cell lines examined (SKOV3, OV-MZ-6 and hOSE 17.1), however, these cell lines did not express GHSR1a. Ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for ghrelin, obestatin, and GOAT, but not GHSR1a, or GHSR1b. No correlations between cancer grade and the level of expression of these transcripts were observed. This study demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines. Treatment with ghrelin (for 72 hours) significantly increased cell migration in the SKOV3 and OV-MZ-6 ovarian cancer cell lines. Ghrelin (100 nM) stimulated cell migration in the SKOV3 (2.64 +/- 1.08 fold, p <0.05) and OV-MZ-6 (1.65 +/- 0.31 fold, p <0.05) ovarian cancer cell lines, but not in the representative normal cell line hOSE 17.1. This increase in migration was not accompanied by an increase in cell invasion through Matrigel. In contrast to other cancer types, ghrelin had no effect on proliferation. Ghrelin treatment (10nM) significantly decreased attachment of the SKOV3 ovarian cancer cell line to collagen IV (24.7 +/- 10.0 %, p <0.05), however, there were no changes in attachment to the other extracellular matrix molecules (ECM) tested (fibronectin, vitronectin and collagen I), and there were no changes in attachment to any of the ECM molecules in the OV-MZ-6 or hOSE 17.1 cell lines. It is, therefore, unclear if ghrelin plays a role in cell attachment in ovarian cancer. As ghrelin has previously been demonstrated to signal through the ERK1/2 pathway in cancer, we investigated ERK1/2 signalling in ovarian cancer cell lines. In the SKOV3 ovarian cancer cell line, a reduction in ERK1/2 phosphorylation (0.58 fold +/- 0.23, p <0.05) in response to 100 nM ghrelin treatment was observed, while no significant change in ERK1/2 signalling was seen in the OV-MZ-6 cell line with treatment. This suggests that this pathway is unlikely to be involved in mediating the increased migration seen in the ovarian cancer cell lines with ghrelin treatment. In this study ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for obestatin, however, no correlation between cancer grade and level of obestatin transcript expression was observed. In the ovarian-derived cell lines studied (SKOV3, OV-MZ-6 and hOSE 17.1) it was demonstrated that the full length preproghrelin mRNA transcripts were expressed in all cell lines, suggesting they have the ability to produce mature obestatin. This is the first study to demonstrate that obestatin stimulates cell migration and cell invasion. Obestatin induced a significant increase in migration in the SKOV3 ovarian cancer cell line with 10 nM (2.80 +/- 0.52 fold, p <0.05) and 100 nM treatments (3.12 +/- 0.68 fold, p <0.05) and in the OV-MZ-6 cancer cell line with 10 nM (2.04 +/- 0.10 fold, p <0.01) and 100 nM treatments (2.00 +/- 0.37 fold, p <0.05). Obestatin treatment did no affect cell migration in the hOSE 17.1normal ovarian epithelial cell line. Obestatin treatment (100 nM) also stimulated a significant increase in cell invasion in the OV-MZ-6 ovarian cancer cell line (1.45 fold +/- 0.13, p <0.05) and in the hOSE17.1 normal ovarian cell line cells (1.40 fold +/- 0.04 and 1.55 fold +/- 0.05 respectively, p <0.01) with 10 nM and 100 nM treatments. Obestatin treatment did not stimulate cell invasion in the SKOV3 ovarian cancer cell line. This lack of obestatin-stimulated invasion in the SKOV3 cell line may be a cell line specific result. In this study, obestatin did not stimulate cell proliferation in the ovarian cell lines and it has previously been shown to have no effect on cell proliferation in the BON-1 pancreatic neuroendocrine and GC rat somatotroph tumour cell lines. In contrast, obestatin has been shown to affect cell proliferation in gastric and thyroid cancer cell lines, and in some normal cell lines. Obestatin also had no effect on attachment of any of the cell lines to any of the ECM components tested (fibronectin, vitronectin, collagen I and collagen IV). The mechanism of action of obestatin was investigated further using a two dimensional-difference in gel electrophoresis (2D-DIGE) proteomic approach. After treatment with obestating (0, 10 and 100 nM), SKOV3 ovarian cancer and hOSE 17.1 normal ovarian cell lines were collected and 2D-DIGE analysis and mass spectrometry were performed to identify proteins that were differentially expressed in response to treatment. Twenty-six differentially expressed proteins were identified and analysed using Ingenuity Pathway Analysis (IPA). This linked 16 of these proteins in a network. The analysis suggested that the ERK1/2 MAPK pathway was a major mediator of obestatin action. ERK1/2 has previously been shown to be associated with obestatin-stimulated cell proliferation and with the anti-apoptotic effects of obestatin. Activation of the ERK1/2 signalling pathway by obestatin was, therefore, investigated in the SKOV3 and OV-MZ-6 ovarian cancer cell lines using anti-active antibodies and Western immunoblots. Obestatin treatment significantly decreased ERK1/2 phosphorylation at higher obestatin concentrations in both the SKOV3 (100 nM and 1000 nM) and OV-MZ-6 (1000 nM) cell lines compared to the untreated controls. Currently, very little is known about obestatin signalling in cancer. This thesis has demonstrated for the first time that the ghrelin axis may play a role in ovarian cancer migration. Ghrelin and obestatin increased cell migration in ovarian cancer cell lines, indicating that they may be a useful target for therapies that reduce ovarian cancer progression. Further studies investigating the role of the ghrelin axis using in vivo ovarian cancer metastasis models are warranted.