Evaluation of fibroin-based scaffolds for ocular tissue reconstruction

The epithelium of the corneolimbus contains stem cells for regenerating the corneal epithelium. Diseases and injuries affecting the limbus can lead to a condition known as limbal stem cell deficiency (LSCD), which results in loss of the corneal epithelium, and subsequent chronic inflammation and scarring of the ocular surface. Advances in the treatment of LSCD have been achieved through use of cultured human limbal epithelial (HLE) grafts to restore epithelial stem cells of the ocular surface. These epithelial grafts are usually produced by the ex vivo expansion of HLE cells on human donor amniotic membrane (AM), but this is not without limitations. Although AM is the most widely accepted substratum for HLE transplantation, donor variation, risk of disease transfer, and rising costs have led to the search for alternative biomaterials to improve the surgical outcome of LSCD. Recent studies have demonstrated that Bombyx mori silk fibroin (hereafter referred to as fibroin) membranes support the growth of primary HLE cells, and thus this thesis aims to explore the possibility of using fibroin as a biomaterial for ocular surface reconstruction. Optimistically, the grafted sheets of cultured epithelium would provide a replenishing source of epithelial progenitor cells for maintaining the corneal epithelium, however, the HLE cells lose their progenitor cell characteristics once removed from their niche. More severe ocular surface injuries, which result in stromal scarring, damage the epithelial stem cell niche, which subsequently leads to poor corneal re-epithelialisation post-grafting. An ideal solution to repairing the corneal limbus would therefore be to grow and transplant HLE cells on a biomaterial that also provides a means for replacing underlying stromal cells required to better simulate the normal stem cell niche. The recent discovery of limbal mesenchymal stromal cells (L-MSC) provides a possibility for stromal repair and regeneration, and therefore, this thesis presents the use of fibroin as a possible biomaterial to support a three dimensional tissue engineered corneolimbus with both an HLE and underlying L-MSC layer. Investigation into optimal scaffold design is necessary, including adequate separation of epithelial and stromal layers, as well as direct cell-cell contact. Firstly, the attachment, morphology and phenotype of HLE cells grown on fibroin were directly compared to that observed on donor AM, the current clinical standard substrate for HLE transplantation. The production, transparency, and permeability of fibroin membranes were also evaluated in this part of the study. Results revealed that fibroin membranes could be routinely produced using a custom-made film casting table and were found to be transparent and permeable. Attachment of HLE cells to fibroin after 4 hours in serum-free medium was similar to that supported by tissue culture plastic but approximately 6-fold less than that observed on AM. While HLE cultured on AM displayed superior stratification, epithelia constructed from HLE on fibroin maintained evidence of corneal phenotype (cytokeratin pair 3/12 expression; CK3/12) and displayed a comparable number and distribution of ÄNp63+ progenitor cells to that seen in cultures grown on AM. These results confirm the suitability of membranes constructed from silk fibroin as a possible substrate for HLE cultivation. One of the most important aspects in corneolimbal tissue engineering is to consider the reconstruction of the limbal stem cell niche to help form the natural limbus in situ. MSC with similar properties to bone marrow derived-MSC (BM-MSC) have recently been grown from the limbus of the human cornea. This thesis evaluated methods for culturing L-MSC and limbal keratocytes using various serum-free media. The phenotype of resulting cultures was examined using photography, flow cytometry for CD34 (keratocyte marker), CD45 (bone marrow-derived cell marker), CD73, CD90, CD105 (collectively MSC markers), CD141 (epithelial/vascular endothelial marker), and CD271 (neuronal marker), immunocytochemistry (alpha-smooth muscle actin; á-sma), differentiation assays (osteogenesis, adipogenesis and chrondrogenesis), and co-culture experiments with HLE cells. While all techniques supported to varying degrees establishment of keratocyte and L-MSC cultures, sustained growth and serial propagation was only achieved in serum-supplemented medium or the MesenCult-XF„¥ culture system (Stem Cell Technologies). Cultures established in MesenCult-XF„¥ grew faster than those grown in serum-supplemented medium and retained a more optimal MSC phenotype. L-MSC cultivated in MesenCult-XFR were also positive for CD141, rarely expressed £\-sma, and displayed multi-potency. L-MSC supported growth of HLE cells, with the largest epithelial islands being observed in the presence of L-MSC established in MesenCult-XF„¥ medium. All HLE cultures supported by L-MSC widely expressed the progenitor cell marker £GNp63, along with the corneal differentiation marker CK3/12. Our findings conclude that MesenCult-XFR is a superior culture system for L-MSC, but further studies are required to explore the significance of CD141 expression in these cells. Following on from the findings of the previous two parts, silk fibroin was tested as a novel dual-layer construct containing both an epithelium and underlying stroma for corneolimbal reconstruction. In this section, the growth and phenotype of HLE cells on non-porous versus porous fibroin membranes was compared. Furthermore, the growth of L-MSC in either serum-supplemented medium or the MesenCult-XFR culture system within fibroin fibrous mats was investigated. Lastly, the co-culture of HLE and L-MSC in serum-supplemented medium on and within fibroin dual-layer constructs was also examined. HLE on porous membranes displayed a flattened and squamous monolayer; in contrast, HLE on non-porous fibroin appeared cuboidal and stratified closer in appearance to a normal corneal epithelium. Both constructs maintained CK3/12 expression and distribution of £GNp63+ progenitor cells. Dual-layer fibroin scaffolds consisting of HLE cells and L-MSC maintained a similar phenotype as on the single layers alone. Overall, the present study proposed to create a three dimensional limbal tissue substitute of HLE cells and L-MSC together, ultimately for safe and beneficial transplantation back into the human eye. The results show that HLE and L-MSC can be cultivated separately and together whilst maintaining a clinically feasible phenotype containing a majority of progenitor cells. In addition, L-MSC were able to be cultivated routinely in the MesenCult-XF® culture system while maintaining a high purity for the MSC characteristic phenotype. However, as a serum-free culture medium was not found to sustain growth of both HLE and L-MSC, the combination scaffold was created in serum-supplemented medium, indicating that further refinement of this cultured limbal scaffold is required. This thesis has also demonstrated a potential novel marker for L-MSC, and has generated knowledge which may impact on the understanding of stromal-epithelial interactions. These results support the feasibility of a dual-layer tissue engineered corneolimbus constructed from silk fibroin, and warrant further studies into the potential benefits it offers to corneolimbal tissue regeneration. Further refinement of this technology should explore the potential benefits of using epithelial-stromal co-cultures with MesenCult-XF® derived L-MSC. Subsequent investigations into the effects of long-term culture on the phenotype and behaviour of the cells in the dual-layer scaffolds are also required. While this project demonstrated the feasibility in vitro for the production of a dual-layer tissue engineered corneolimbus, further studies are required to test the efficacy of the limbal scaffold in vivo. Future in vivo studies are essential to fully understand the integration and degradation of silk fibroin biomaterials in the cornea over time. Subsequent experiments should also investigate the use of both AM and silk fibroin with epithelial and stromal cell co-cultures in an animal model of LSCD. The outcomes of this project have provided a foundation for research into corneolimbal reconstruction using biomaterials and offer a stepping stone for future studies into corneolimbal tissue engineering.

Exploratory factor analysis and psychometric evaluation of the Teachers Reporting Attitude Scale for Child Sexual Abuse

This paper presents an evaluation of an instrument to measure teachers’ attitudes towards reporting child sexual abuse and discusses the instrument’s merit for research into reporting practice. Based on responses from 444 Australian teachers, the Teachers’ Reporting Attitude Scale for Child Sexual Abuse (TRAS - CSA) was evaluated using exploratory factor analysis. The scale isolated three dimensions: commitment to the reporting role; confidence in the system’s response to reports; and concerns about reporting. These three factors accounted for 37.5% of the variance in the 14-item measure. Alpha coefficients for the subscales were 0.769 (commitment), 0.617 (confidence), and 0.661 (concerns). The findings provide insights into the complexity of studying teachers’ attitudes towards reporting of child sexual abuse, and have implications for future research.

The effect of Tenofovir on vitamin D metabolism in HIV-infected adults is dependent on sex and ethnicity

Background: Tenofovir has been associated with renal phosphate wasting, reduced bone mineral density, and higher parathyroid hormone levels. The aim of this study was to carry out a detailed comparison of the effects of tenofovir versus non-tenofovir use on calcium, phosphate and, vitamin D, parathyroid hormone (PTH), and bone mineral density. Methods: A cohort study of 56 HIV-1 infected adults at a single centre in the UK on stable antiretroviral regimes comparing biochemical and bone mineral density parameters between patients receiving either tenofovir or another nucleoside reverse transcriptase inhibitor. Principal Findings: In the unadjusted analysis, there was no significant difference between the two groups in PTH levels (tenofovir mean 5.9 pmol/L, 95% confidence intervals 5.0 to 6.8, versus non-tenofovir; 5.9, 4.9 to 6.9; p = 0.98). Patients on tenofovir had significantly reduced urinary calcium excretion (median 3.01 mmol/24 hours) compared to non-tenofovir users (4.56; p,0.0001). Stratification of the analysis by age and ethnicity revealed that non-white men but not women, on tenofovir had higher PTH levels than non-white men not on tenofovir (mean difference 3.1 pmol/L, 95% CI 5.3 to 0.9; p = 0.007). Those patients with optimal 25-hydroxyvitamin D (.75 nmol/L) on tenofovir had higher 1,25-dihydroxyvitamin D [1,25(OH)2D] (median 48 pg/mL versus 31; p = 0.012), fractional excretion of phosphate (median 26.1%, versus 14.6;p = 0.025) and lower serum phosphate (median 0.79 mmol/L versus 1.02; p = 0.040) than those not taking tenofovir. Conclusions: The effects of tenofovir on PTH levels were modified by sex and ethnicity in this cohort. Vitamin D status also modified the effects of tenofovir on serum concentrations of 1,25(OH)2D and phosphate.

Spot the differences in traditional and social entrepreneurial intention : highlighting the role of human and social capital

There is general agreement in the scientific community that entrepreneurship plays a central role in the growth and development of an economy in rapidly changing environments (Acs & Virgill 2010). In particular, when business activities are regarded as a vehicle for sustainable growth at large, that goes beyond mere economic returns of singular entities, encompassing also social problems and heavily relying on collaborative actions, then we more precisely fall into the domain of ‘social entrepreneurship’(Robinson et al. 2009). In the entrepreneurship literature, prior studies demonstrated the role of intentionality as the best predictor of planned behavior (Ajzen 1991), and assumed that the intention to start a business derives from the perception of desirability and feasibility and from a propensity to act upon an opportunity (Fishbein & Ajzen 1975). Recognizing that starting a business is an intentional act (Krueger et al. 2000) and entrepreneurship is a planned behaviour (Katz & Gartner 1988), models of entrepreneurial intentions have substantial implications for intentionality research in entrepreneurship. The purpose of this paper is to explore the emerging practice of social entrepreneurship by comparing the determinants of entrepreneurial intention in general versus those leading to startups with a social mission. Social entrepreneurial intentions clearly merit to be investigated given that the opportunity identification process is an intentional process not only typical of for profit start-ups, and yet there is a lack of research examining opportunity recognition in social entrepreneurship (Haugh 2005). The key argument is that intentionality in both traditional and social entrepreneurs during the decision-making process of new venture creation is influenced by an individual's perceptions toward opportunities (Fishbein & Ajzen 1975). Besides opportunity recognition, at least two other aspects can substantially influence intentionality: human and social capital (Davidsson, 2003). This paper is set to establish if and to what extent the social intentions of potential entrepreneurs, at the cognitive level, are influenced by opportunities recognition, human capital, and social capital. By applying established theoretical constructs, the paper draws comparisons between ‘for-profit’ and ‘social’ intentionality using two samples of students enrolled in Economy and Business Administration at the University G. d’Annunzio in Pescara, Italy. A questionnaire was submitted to 310 potential entrepreneurs to test the robustness of the model. The collected data were used to measure the theoretical constructs of the paper. Reliability of the multi-item scale for each dimension was measured using Cronbach alpha, and for all the dimensions measures of reliability are above 0.70. We empirically tested the model using structural equation modeling with AMOS. The results allow us to empirically contribute to the argument regarding the influence of human and social cognitive capital on social and non-social entrepreneurial intentions. Moreover, we highlight the importance for further researchers to look deeper into the determinants of traditional and social entrepreneurial intention so that governments can one day define better polices and regulations that promote sustainable businesses with a social imprint, rather than inhibit their formation and growth.

Performance evaluation of onsite sewage treatment : summary report

The following summary report provides a concise overview of the research undertaken and the outcomes derived from the performance evaluation study of onsite sewage treatment systems. Additionally, a number of recommendations have been provided to enhance the treatment performance of these systems. This report also identifies a number of areas, which merit further investigations. The focus of the study was on subsurface effluent disposal systems. The reader is referred to the three project reports that were produced for more detailed information.

Finding your research voice : the application of bibliometrics as an analytic literature tool on the pedagogic field of higher education

This paper documents the use of bibliometrics as a methodology to bring forth a structured, systematic and rigorous way to analyse and evaluate a range of literature. When starting out and reading broadly for my doctoral studies, one article by Trigwell and Prosser (1996b) led me to reflect about my level of comprehension as the content, concepts and methodology did not resonate with my epistemology. A disconnection between our paradigms emerged. Further reading unveiled the work by Doyle (1987) who categorised research in teaching and teacher education by three main areas: teacher characteristics, methods research and teacher behaviour. My growing concerns that there were gaps in the knowledge also exposed the difficulties in documenting said gaps. As an early researcher who required support to locate myself in the field and to find my research voice, I identified bibliometrics (Budd, 1988; Yeoh & Kaur, 2007) as an appropriate methodology to add value and rigour in three ways. Firstly, the application of bibliometrics to analyse articles is systematic, builds a picture from the characteristics of the literature, and offers a way to elicit themes within the categories. Secondly, by systematic analysis there is occasion to identify gaps within the body of work, limitations in methodology or areas in need of further research. Finally, extension and adaptation of the bibliometrics methodology, beyond citation or content analysis, to investigate the merit of methodology, participants and instruments as a determinant for research worth allowed the researcher to build confidence and contribute new knowledge to the field. Therefore, this paper frames research in the pedagogic field of Higher Education through teacher characteristics, methods research and teacher behaviour, visually represents the literature analysis and locates my research self within methods research. Through my research voice I will present the bibliometrics methodology, the outcomes and document the landscape of pedagogy in the field of Higher Education.

Increasing physical activity among women with young children: Results from the Proactive Mums Project

Context Evidence from the Australian Longitudinal Study of Women's Health suggests that mothers of young children have lower levels of physical activity (PA) than women of similar age without children. Objectives The aim of the ProActive Mums project was to determine the relative efficacy of two strategies designed to increase the proportion of mothers of young children who are meeting current PA guidelines, utilising child care centres (CCCs) as the setting for recruitment. Study Design The project used a randomised (after stratification to ensure even representation of CCCs from differing socio-economic areas) design incorporating repeated data collection from women in three groups, each consisting of 7 childcare centres (CCCs). Baseline surveys were completed by 554 mothers, with follow-up data collection immediately post-Intervention (8 weeks after baseline) and again 5 months later. Women from CCCs in Group 1 (control) received only the surveys throughout the duration of the project. Women from CCCs in Group 2 (information only) were given a print intervention, and women from CCCs in Group 3 were (in addition to being given the same print intervention as women from CCCs in Group 2) invited to to contribute to the development of, and participate in, strategies for the promotion of PA among mothers of young children. The two intervention strategies were extensively evaluated through a series of surveys and interviews. The Intervention The print intervention prescribed for women from CCCs in Group 2 and Group 3 consisted of an 8-page booklet containing motivational messages and information about physical activity. Women from CCCs in Group 3 were also invited to attend meetings at their CCC to identify strategies for increasing their PA. Contacts were made with key stakeholders in the community, including managers of sporting and recreation facilities, childcare service providers, and local councils. A wide range of strategies was developed during the intervention phase of the project, which specifically focused on the need to increase partner support and self-efficacy (or the confidence to be physically active). Results The mean age of participants was 33 (+ 4.8) years, and the mean number of children per family unit was 2.2 (± 0.9). At baseline, fewer than half the women were meeting current guidelines for adequate PA for health benefit, and there were no significant differences between groups in the proportion of women who were adequately active for health benefit. Women in Group 3 were significantly more likely to meet the guidelines at post-intervention follow-up than controls [OR = 1.71 (1.05-2.77)] after controlling for age and PA at baseline. There was no significant effect of the print intervention alone on meeting guidelines at post-intervention follow-up compared with controls, after controlling for age and PA at baseline [OR = 1.15 (0.70-1.89)]. Changes in Partner Support (PS) and Self Efficacy (SE) significantly predicted meeting current PA guidelines at post-intervention follow-up after controlling for baseline PA [∆ PS: OR = 2.29 (1.46-3.58); ∆ SE: OR = 1.86 (1.17- 2.94)]. The intervention effect in Group 3 was not maintained at long-term follow-up. Conclusions The findings indicate that a community participation approach that facilitates increased partner support and self-efficacy can be effective in increasing PA among mothers of young children. Changes in physical activity were found to be mediated by changes in partner support and self-efficacy for physical activity, suggesting that the intervention successfully targeted the individual characteristics it intended to, and that these variables do play an important role in increasing physical activity among women with young children. It is clear that further work needs to be done to explore methods of translating the short-term intervention effect shown in this study into long-term changes in PA behaviour. This study also provided insight into measurement issues in PA research and raised questions about self-report measures of PA and perceived constraints to being physically active. The results from post-study qualitative interviews suggest that many women at this life-stage experience time constraints which, when accompanied by a lack of partner support and financial constraints, make leisure-time PA virtually impossible for many women. Future strategies might focus on targeting this population immediately prior to this life-stage in an attempt to encourage habitual physical activity before women have children. Increasing PA in this population should also address the entire family unit, and consider the way leisure-time is negotiated among the adults within a household. Social change and increased awareness of the range of benefits of PA for women with children are additional strategies to be considered.

Employee perceptions regarding the effectiveness of occupational road safety initiatives

A range of risk management initiatives have been introduced in organisations in attempt to reduce occupational road incidents. However a discrepancy exists between the initiatives that are frequently implemented in organisations and the initiatives that have demonstrated scientific merit in improving occupational road safety. Given that employees’ beliefs may facilitate or act as a barrier to implementing initiatives, it is important to understand whether initiatives with scientific merit are perceived to be effective by employees. To explore employee perceptions pertaining to occupational road safety initiatives, a questionnaire was administered to 679 employees sourced from four Australian organisations. Participants ranged in age from 18 years to 65 years (M = 42, SD = 11). Participants rated 35 initiatives based on how effective they thought they would be in improving road safety in their organisation. The initiatives perceived by employees to be most effective in managing occupational road risks comprised: making vehicle safety features standard e.g. passenger airbags; practical driver skills training; and investigation of serious vehicle incidents. The initiatives perceived to be least effective in managing occupational road risks comprised: signing a promise card commitment to drive safely; advertising the organisation’s phone number on vehicles for complaints and compliments; and consideration of driving competency in staff selection process. Employee perceptions were analysed at a factor level and at an initiative level. The mean scores for the three extracted factors revealed that employees believed occupational road risks could best be managed by the employer implementing engineering and human resource methods to enhance road safety. Initiatives relating to employer management of identified risk factors were perceived to be more effective than feedback or motivational methods that required employees to accept responsibility for their driving safety. Practitioners can use the findings from this study to make informed decisions about how they select, manage and market occupational safety initiatives.

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10−8). More than 70 prostate cancer susceptibility loci, explaining ~30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.

What can grassroots leadership teach us about school leadership

This paper explores grassroots leadership, an under-researched and often side-lined approach to leadership that operates outside of formal bureaucratic structures. The paper’s central purpose is the claim that an understanding of grassroots leadership and tactics used by grassroots leaders provides valuable insights for the study of school leadership. In this paper, we present and discuss an original model of grassroots leadership based on the argument that this under-researched area can further our understanding of school leadership. Drawing upon the limited literature in the field, we present a model consisting of two approaches to change (i.e. conflict and consensus) and two categories of change (i.e. reform and refinement) and then provide illustrations of how the model works in practice. We make the argument that the model has much merit for conceptualizing school leadership, and this is illustrated by applying the model to formal bureaucratic leadership within school contexts. Given the current climate in education where business and management language is pervasive within leadership-preparation programs, we argue that it is timely for university academics, who are responsible for preparing school leaders to consider broadening their approach by exposing school leaders to a variety of change-based strategies and tactics used by grassroots leaders.

Asset health prediction using the explicit hazard model

The ability to estimate the asset reliability and the probability of failure is critical to reducing maintenance costs, operation downtime, and safety hazards. Predicting the survival time and the probability of failure in future time is an indispensable requirement in prognostics and asset health management. In traditional reliability models, the lifetime of an asset is estimated using failure event data, alone; however, statistically sufficient failure event data are often difficult to attain in real-life situations due to poor data management, effective preventive maintenance, and the small population of identical assets in use. Condition indicators and operating environment indicators are two types of covariate data that are normally obtained in addition to failure event and suspended data. These data contain significant information about the state and health of an asset. Condition indicators reflect the level of degradation of assets while operating environment indicators accelerate or decelerate the lifetime of assets. When these data are available, an alternative approach to the traditional reliability analysis is the modelling of condition indicators and operating environment indicators and their failure-generating mechanisms using a covariate-based hazard model. The literature review indicates that a number of covariate-based hazard models have been developed. All of these existing covariate-based hazard models were developed based on the principle theory of the Proportional Hazard Model (PHM). However, most of these models have not attracted much attention in the field of machinery prognostics. Moreover, due to the prominence of PHM, attempts at developing alternative models, to some extent, have been stifled, although a number of alternative models to PHM have been suggested. The existing covariate-based hazard models neglect to fully utilise three types of asset health information (including failure event data (i.e. observed and/or suspended), condition data, and operating environment data) into a model to have more effective hazard and reliability predictions. In addition, current research shows that condition indicators and operating environment indicators have different characteristics and they are non-homogeneous covariate data. Condition indicators act as response variables (or dependent variables) whereas operating environment indicators act as explanatory variables (or independent variables). However, these non-homogenous covariate data were modelled in the same way for hazard prediction in the existing covariate-based hazard models. The related and yet more imperative question is how both of these indicators should be effectively modelled and integrated into the covariate-based hazard model. This work presents a new approach for addressing the aforementioned challenges. The new covariate-based hazard model, which termed as Explicit Hazard Model (EHM), explicitly and effectively incorporates all three available asset health information into the modelling of hazard and reliability predictions and also drives the relationship between actual asset health and condition measurements as well as operating environment measurements. The theoretical development of the model and its parameter estimation method are demonstrated in this work. EHM assumes that the baseline hazard is a function of the both time and condition indicators. Condition indicators provide information about the health condition of an asset; therefore they update and reform the baseline hazard of EHM according to the health state of asset at given time t. Some examples of condition indicators are the vibration of rotating machinery, the level of metal particles in engine oil analysis, and wear in a component, to name but a few. Operating environment indicators in this model are failure accelerators and/or decelerators that are included in the covariate function of EHM and may increase or decrease the value of the hazard from the baseline hazard. These indicators caused by the environment in which an asset operates, and that have not been explicitly identified by the condition indicators (e.g. Loads, environmental stresses, and other dynamically changing environment factors). While the effects of operating environment indicators could be nought in EHM; condition indicators could emerge because these indicators are observed and measured as long as an asset is operational and survived. EHM has several advantages over the existing covariate-based hazard models. One is this model utilises three different sources of asset health data (i.e. population characteristics, condition indicators, and operating environment indicators) to effectively predict hazard and reliability. Another is that EHM explicitly investigates the relationship between condition and operating environment indicators associated with the hazard of an asset. Furthermore, the proportionality assumption, which most of the covariate-based hazard models suffer from it, does not exist in EHM. According to the sample size of failure/suspension times, EHM is extended into two forms: semi-parametric and non-parametric. The semi-parametric EHM assumes a specified lifetime distribution (i.e. Weibull distribution) in the form of the baseline hazard. However, for more industry applications, due to sparse failure event data of assets, the analysis of such data often involves complex distributional shapes about which little is known. Therefore, to avoid the restrictive assumption of the semi-parametric EHM about assuming a specified lifetime distribution for failure event histories, the non-parametric EHM, which is a distribution free model, has been developed. The development of EHM into two forms is another merit of the model. A case study was conducted using laboratory experiment data to validate the practicality of the both semi-parametric and non-parametric EHMs. The performance of the newly-developed models is appraised using the comparison amongst the estimated results of these models and the other existing covariate-based hazard models. The comparison results demonstrated that both the semi-parametric and non-parametric EHMs outperform the existing covariate-based hazard models. Future research directions regarding to the new parameter estimation method in the case of time-dependent effects of covariates and missing data, application of EHM in both repairable and non-repairable systems using field data, and a decision support model in which linked to the estimated reliability results, are also identified.

Comparison of self-reported driving behaviours and experiences of immediate-uptake and delayed-uptake licence holders

The objective of this paper was to explore experiences of ‘immediate-uptake’ (intermediate licensure at age 17-18 years, n = 928) and ‘delayed-uptake’ (intermediate licensure at age 19-20 years, n = 158) driver’s licence holders in the Australian state of Queensland. In Queensland, the graduated driver licence program applies to all novices irrespective of age. Drivers who obtained a Provisional 1 (intermediate) (P1) licence completed a survey exploring pre-Licence and Learner experiences, including the Behaviour of Young Novice Drivers Scale (BYNDS). Six months later, 351 drivers from this sample (n = 300 immediate-uptake) completed a survey exploring P1 driving. Delayed-uptake Learners reported significantly more difficulty gaining driving practice, which appeared to be associated with significantly greater engagement in unsupervised driving during the Learner period. Whilst a larger proportion of delayed-uptake novices, particularly males, reported the use of more active punishment avoidance strategies (avoiding Police, talking themselves out of a ticket) in the P1 phase, there was no significant difference in the BYNDS scores in the Learner and P1 phases according to licence-uptake category. Delayed-uptake novices report more difficulty meeting GDL requirements and place themselves at increased risk by driving unsupervised during the Learner licence phase. Additional efforts such as mentoring programs which can support the delayed-uptake Learner in meeting their GDL obligations merit further consideration to allow this novice group to gain the full benefits of the GDL program and to reduce their risk of harm in the short-term.

The effects of deep cracks on the rain-induced instability of slopes : A case study

Rainfall can disrupt the balance of natural soil slope. This imbalance will be accelerated by existence of cracks in soil slope, which lead to decreasing shear strength and increasing hydraulic conductivity of the soil slope. Some research works have been conducted on the effects of surface-cracks on slope stability. However, the influence of deep-cracks is yet to be investigated. Limited availability of deep crack data due to the lack of effective sub-soil investigation methods could be one of the obstacles. To emphasize the effects of deep cracks in soil slope on its rain-induced instability, a natural soil slope in Indonesia that failed in 31st October 2010 due to heavy rainfall was analyzed for stability with and without deep cracks in the slope. The slope stability analysis was conducted using SLOPE/W coupling with the results of transient seepage analysis (SEEP/W) that simulate the pore-water pressure development in the slope during the rainfall. The results of Electrical Resistivity Tomography (ERT) survey, bore-hole tests and geometrical survey conducted on the slope before its failure were used to identify the soil layers’ stratification including deep cracks, the properties of different soil layers, and geometrical parameters of the slope for the analysis. The results showed that it is vital to consider the existence of deep crack in soil slopes in analysing their instability induced by rainfalls.

Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs

Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid-form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.