943 resultados para Drugs - Structure-activity relationships


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Estimating and predicting degradation processes of engineering assets is crucial for reducing the cost and insuring the productivity of enterprises. Assisted by modern condition monitoring (CM) technologies, most asset degradation processes can be revealed by various degradation indicators extracted from CM data. Maintenance strategies developed using these degradation indicators (i.e. condition-based maintenance) are more cost-effective, because unnecessary maintenance activities are avoided when an asset is still in a decent health state. A practical difficulty in condition-based maintenance (CBM) is that degradation indicators extracted from CM data can only partially reveal asset health states in most situations. Underestimating this uncertainty in relationships between degradation indicators and health states can cause excessive false alarms or failures without pre-alarms. The state space model provides an efficient approach to describe a degradation process using these indicators that can only partially reveal health states. However, existing state space models that describe asset degradation processes largely depend on assumptions such as, discrete time, discrete state, linearity, and Gaussianity. The discrete time assumption requires that failures and inspections only happen at fixed intervals. The discrete state assumption entails discretising continuous degradation indicators, which requires expert knowledge and often introduces additional errors. The linear and Gaussian assumptions are not consistent with nonlinear and irreversible degradation processes in most engineering assets. This research proposes a Gamma-based state space model that does not have discrete time, discrete state, linear and Gaussian assumptions to model partially observable degradation processes. Monte Carlo-based algorithms are developed to estimate model parameters and asset remaining useful lives. In addition, this research also develops a continuous state partially observable semi-Markov decision process (POSMDP) to model a degradation process that follows the Gamma-based state space model and is under various maintenance strategies. Optimal maintenance strategies are obtained by solving the POSMDP. Simulation studies through the MATLAB are performed; case studies using the data from an accelerated life test of a gearbox and a liquefied natural gas industry are also conducted. The results show that the proposed Monte Carlo-based EM algorithm can estimate model parameters accurately. The results also show that the proposed Gamma-based state space model have better fitness result than linear and Gaussian state space models when used to process monotonically increasing degradation data in the accelerated life test of a gear box. Furthermore, both simulation studies and case studies show that the prediction algorithm based on the Gamma-based state space model can identify the mean value and confidence interval of asset remaining useful lives accurately. In addition, the simulation study shows that the proposed maintenance strategy optimisation method based on the POSMDP is more flexible than that assumes a predetermined strategy structure and uses the renewal theory. Moreover, the simulation study also shows that the proposed maintenance optimisation method can obtain more cost-effective strategies than a recently published maintenance strategy optimisation method by optimising the next maintenance activity and the waiting time till the next maintenance activity simultaneously.

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Aim To identify relationships between preventive activities, psychosocial factors and leg ulcer recurrence in patients with chronic venous leg ulcers. Background Chronic venous leg ulcers are slow to heal and frequently recur, resulting in years of suffering and intensive use of health care resources. Methods A prospective longitudinal study was undertaken with a sample of 80 patients with a venous leg ulcer recruited when their ulcer healed. Data were collected from 2006–2009 from medical records on demographics, medical history and ulcer history; and from self-report questionnaires on physical activity, nutrition, preventive activities and psychosocial measures. Follow-up data were collected via questionnaires every three months for 12 months after healing. Median time to recurrence was calculated using the Kaplan-Meier method. A Cox proportional-hazards regression model was used to adjust for potential confounders and determine effects of preventive strategies and psychosocial factors on recurrence. Results: There were 35 recurrences in a sample of 80 participants. Median time to recurrence was 27 weeks. After adjustment for potential confounders, a Cox proportional hazards regression model found that at least an hour/day of leg elevation, six or more days/week in Class 2 (20–25mmHg) or 3 (30–40mmHg) compression hosiery, higher social support scale scores and higher General Self-Efficacy scores remained significantly associated (p<0.05) with a lower risk of recurrence, while male gender and a history of DVT remained significant risk factors for recurrence. Conclusion Results indicate that leg elevation, compression hosiery, high levels of self-efficacy and strong social support will help prevent recurrence.

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Hyperthermia and local drug delivery have been proposed the potential therapeutic approaches for bone defects resulting from malignant bone tumors. Development of bioactive materials with magnetic and drug-delivery properties may potentially meet this target. The aim of this study is to develop a multifunctional mesoporous bioactive glass (MBG) scaffold system for both hyperthermia and local-drug delivery application potentially. For this aim, Iron (Fe) containing MBG (Fe-MBG) scaffolds with hierarchically large pores (300-500 µm) and fingerprint-like mesopores (4.5 nm) have been successfully prepared. The effect of Fe on the mesopore structure, physiochemical, magnetism, drug delivery and biological properties of MBG scaffolds has been systematically investigated. The results showed that the morphology of the mesopore varied from straight channels to curved fingerprint-like channels after incorporated parts of Fe into MBG scaffolds. The magnetism magnitude of MBG scaffolds can be tailored by controlling Fe contents. Furthermore, the incorporating of Fe into mesoporous MBG glass scaffolds enhanced the mitochondrial activity and bone-relative gene (ALP and OCN) expression of human bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. The obtained Fe-MBG scaffolds also possessed high specific surface areas and sustained drug delivery. Therefore, Fe-MBG scaffolds are magnetic, degradable and bioactive. The multifunction of Fe-MBG scaffolds indicates that there is a great potential for Fe-MBG scaffolds to be used for the therapy and regeneration of large-bone defects caused by malignant bone tumors through the combination of hyperthermia, local drug delivery and their osteoconductivity.

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Background It is well known that lifestyle factors including overweight/obesity, physical inactivity, smoking and alcohol use are largely related with morbidity and mortality of chronic diseases including diabetes and cardiovascular diseases. The effect of lifestyle factors on people’s mental health who have a chronic disease is less defined in the research. The World Health Organisation has defined health as “a state of complete physical, mental and social well-being”. It is important, therefore to develop an understanding of the relationships between lifestyle and mental health as this may have implications for maximising the efficacy of health promotion in people with chronic diseases. Objectives The overall aim of the research was to examine the relationships between lifestyle factors and mental health among Australian midlife and older women. Methodology The current research measured four lifestyle factors including weight status, physical activity, smoking and alcohol use. Three interconnecting studies were undertaken to develop a comprehensive understanding of the relationships between lifestyle factors and mental health. Study 1 investigated the longitudinal effect of lifestyle factors on mental health by using midlife and older women randomly selected from the community. Study 2 adopted a cross-sectional design, and compared the effect of lifestyle factors on mental health between midlife and older women with and without diabetes. Study 3 examined the mediating effect of self-efficacy in the relationships between lifestyle factors and mental health among midlife and older women with diabetes. A questionnaire survey was chosen as the means to gather information, and multiple linear regression analysis was conducted as the primary statistical approach. Results The research showed that the four lifestyle factors including weight status, physical activity, smoking and alcohol use did impact on mental health among Australian midlife and older women. First, women with a higher BMI had lower levels of mental health than women with normal weight, but as women age, the mental health of women who were overweight and obese becomes better than that of women with normal weight. Second, women who were physically active had higher levels of mental health than those who were not. Third, smoking adversely impacted on women’s mental health. Finally, those who were past-drinkers had less anxiety symptoms than women who were non-drinkers as they age. Women with diabetes appeared to have lower levels of mental health compared to women without. However, the disparities of mental health between two groups were confounded by low levels of physical activity and co-morbidities. This finding underlines the effect of physical activity on women’s mental health, and highlights the potential of reducing the gap of mental health by promoting physical activity. In addition, self-efficacy was shown to be the mediator of the relationships between BMI, physical activity and depression, suggesting that enhancing people’s self-efficacy may be useful for mental health improvement. Conclusions In conclusion, Australian midlife and older women who live with a healthier lifestyle have higher levels of mental health. It is suggested that strategies aiming to improve people’s mental health may be more effective if they focus on enhancing people’s self-efficacy levels. This study has implications to both health education and policy development. It indicates that health professionals may need to consider clients’ mental health as an integrated part of lifestyle changing process. Furthermore, given that lifestyle factors impact on both physical and mental health, lifestyle modification should continue to be the focus of policy development.

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Porous SiO2 scaffolds with mesopore structure (named as MS scaffolds) have been proposed as suitable for bone tissue engineering due to their excellent drug-delivery ability; however, the mineralization and cytocompatibility of MS scaffolds are far from optimal for bone tissue engineering, and it is also unclear how the delivery of drugs from MS scaffolds affects osteoblastic cells. The aims of the present study were to improve the mineralization and cytocompatibility of MS scaffolds by coating mussel-inspired polydopamine on the pore walls of scaffolds. The effects of polydopamine modification on MS scaffolds was investigated with respect to apatite mineralization and the attachment, proliferation and differentiation of bone marrow stromal cells (BMSCs), as was the release profile of the drug dexamethasone (DEX). Our results show that polydopamine can readily coat the pore walls of MS scaffolds and that polydopamine-modified MS scaffolds have a significantly improved apatite-mineralization ability as well as better attachment and proliferation of BMSCs in the scaffolds, compared to controls. Polydopamine modification did not alter the release profile of DEX from MS scaffolds but the sustained delivery of DEX significantly improved alkaline phosphatase (ALP) activity of BMSCs in the scaffolds. These results suggest that polydopamine modification is a viable option to enhance the bioactivity of bone tissue engineering scaffolds and, further, that DEX-loaded polydopamine MS scaffolds have potential uses as a release system to enhance the osteogenic properties of bone tissue engineering applications.

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Background: It is predicted that China will have the largest number of cases of dementia in the world by 2025 (Ferri et al., 2005). Research has demonstrated that caring for family members with dementia can be a long-term, burdensome activity resulting in physical and emotional distress and impairment (Pinquart & Sorensen, 2003b). The establishment of family caregiver supportive services in China can be considered urgent; and the knowledge of the caregiving experience and related influencing factors is necessary to inform such services. Nevertheless, in the context of rapid demographic and socioeconomic change, the impact of caregiving for rural and urban Chinese adult-child caregivers may be different, and different needs in supportive services may therefore be expected. Objectives: The aims of this research were 1) to examine the potential differences existing in the caregiving experience between rural and urban adult-child caregivers caring for parents with dementia in China; and 2) to examine the potential differences existing in the influencing factors of the caregiving experience for rural as compared with urban adult-child caregivers caring for parents with dementia in China. Based on the literature review and Kramer.s (1997) caregiver adaptation model, six concepts and their relationships of caregiving experience were studied: severity of the care receivers. dementia, caregivers. appraisal of role strain and role gain, negative and positive well-being outcomes, and health related quality of life. Furthermore, four influencing factors (i.e., filial piety, social support, resilience, and personal mastery) were studied respectively. Methods: A cross-sectional, comparative design was used to achieve the aims of the study. A questionnaire, which was designed based on the literature review and on Kramer.s (1997) caregiver adaptation model, was completed by 401 adult-child caregivers caring for their parents with dementia from the mental health outpatient departments in five hospitals in the Yunnan province, P.R. China. Structural equation modelling (SEM) was employed as the main statistical technique for data analyses. Other statistical techniques (e.g., t-tests and Chi-Square tests) were also conducted to compare the demographic characteristics and the measured variables between rural and urban groups. Results: For the first research aim, the results indicated that urban adult-child caregivers in China experienced significantly greater strain and negative well-being outcomes than their rural peers; whereas, the difference on the appraisal of role gain and positive outcomes was nonsignificant between the two groups. The results also indicated that the amounts of severity of care receivers. dementia and caregivers. health related quality of life do not have the same meanings between the two groups. Thus, the levels of these two concepts were not comparable between the rural and urban groups in this study. Moreover, the results also demonstrated that the negative direct effect of gain on negative outcomes in urban caregivers was stronger than that in rural caregivers, suggesting that the urban caregivers tended to use appraisal of role gain to protect themselves from negative well-being outcomes to a greater extent. In addition, the unexplained variance in strain in the urban group was significantly more than that in the rural group, suggesting that there were other unmeasured variables besides the severity of care receivers. dementia which would predict strain in urban caregivers compared with their rural peers. For the second research aim, the results demonstrated that rural adult-child caregivers reported a significantly higher level of filial piety and more social support than their urban counterparts, although the two groups did not significantly differ on the levels of their resilience and personal mastery. Furthermore, although the mediation effects of these four influencing factors on both positive and negative aspects remained constant across rural and urban adult-child caregivers, urban caregivers tended to be more effective in using personal mastery to protect themselves from role strain than rural caregivers, which in turn protects them more from the negative well-being outcomes than was the case with their rural peers. Conclusions: The study extends the application of Kramer.s caregiving adaptation process model (Kramer, 1997) to a sample of adult-child caregivers in China by demonstrating that both positive and negative aspects of caregiving may impact on the caregiver.s health related quality of life, suggesting that both aspects should be targeted in supportive interventions for Chinese family caregivers. Moreover, by demonstrating partial mediation effects, the study provides four influencing factors (i.e., filial piety, social support, resilience, and personal mastery) as specific targets for clinical interventions. Furthermore, the study found evidence that urban adult-child caregivers had more negative but similar positive experience compared to their rural peers, suggesting that the establishment of supportive services for urban caregivers may be more urgent at present stage in China. Additionally, since urban caregivers tended to use appraisal of role gain and personal mastery to protect themselves from negative well-being outcomes than rural caregivers to a greater extend, interventions targeting utility of gain or/and personal mastery to decrease negative outcomes might be more effective in urban caregivers than in rural caregivers. On the other hand, as cultural expectations and expression of filial piety tend to be more traditional in rural areas, interventions targeting filial piety could be more effective among rural caregivers. Last but not least, as rural adult-child caregivers have more existing natural social support than their urban counterparts, mobilising existing natural social support resources may be more beneficial for rural caregivers, whereas, formal supports (e.g., counselling services, support groups and adult day care centres) should be enhanced for urban caregivers.

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With the growing number of XML documents on theWeb it becomes essential to effectively organise these XML documents in order to retrieve useful information from them. A possible solution is to apply clustering on the XML documents to discover knowledge that promotes effective data management, information retrieval and query processing. However, many issues arise in discovering knowledge from these types of semi-structured documents due to their heterogeneity and structural irregularity. Most of the existing research on clustering techniques focuses only on one feature of the XML documents, this being either their structure or their content due to scalability and complexity problems. The knowledge gained in the form of clusters based on the structure or the content is not suitable for reallife datasets. It therefore becomes essential to include both the structure and content of XML documents in order to improve the accuracy and meaning of the clustering solution. However, the inclusion of both these kinds of information in the clustering process results in a huge overhead for the underlying clustering algorithm because of the high dimensionality of the data. The overall objective of this thesis is to address these issues by: (1) proposing methods to utilise frequent pattern mining techniques to reduce the dimension; (2) developing models to effectively combine the structure and content of XML documents; and (3) utilising the proposed models in clustering. This research first determines the structural similarity in the form of frequent subtrees and then uses these frequent subtrees to represent the constrained content of the XML documents in order to determine the content similarity. A clustering framework with two types of models, implicit and explicit, is developed. The implicit model uses a Vector Space Model (VSM) to combine the structure and the content information. The explicit model uses a higher order model, namely a 3- order Tensor Space Model (TSM), to explicitly combine the structure and the content information. This thesis also proposes a novel incremental technique to decompose largesized tensor models to utilise the decomposed solution for clustering the XML documents. The proposed framework and its components were extensively evaluated on several real-life datasets exhibiting extreme characteristics to understand the usefulness of the proposed framework in real-life situations. Additionally, this research evaluates the outcome of the clustering process on the collection selection problem in the information retrieval on the Wikipedia dataset. The experimental results demonstrate that the proposed frequent pattern mining and clustering methods outperform the related state-of-the-art approaches. In particular, the proposed framework of utilising frequent structures for constraining the content shows an improvement in accuracy over content-only and structure-only clustering results. The scalability evaluation experiments conducted on large scaled datasets clearly show the strengths of the proposed methods over state-of-the-art methods. In particular, this thesis work contributes to effectively combining the structure and the content of XML documents for clustering, in order to improve the accuracy of the clustering solution. In addition, it also contributes by addressing the research gaps in frequent pattern mining to generate efficient and concise frequent subtrees with various node relationships that could be used in clustering.

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A multi-billion dollar industry, electronic games have been experiencing strong and rapid growth in recent times. The world of games is not only exciting due to the magnificent growth of the industry however, but due to a host of other factors. This chapter explores electronic games, providing an analysis of the industry, key motivators for game play, the game medium and academic research concerning the effects of play. It also reviews the emerging relationship games share with sport, recognizing that they can replicate sports, facilitate sports participation and be played as a sport. These are complex relationships that have not yet been comprehensively studied. The current chapter serves to draw academic attention to the area and presents ideas for future research.

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Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.

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The proteasome (multicatalytic proteinase complex) is a large multimeric complex which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of protein degradation. Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the c~ and /3 subunits of the simpler proteasome isolated from Thermoplasma acidophilum. Proteasomes have a cylindrical structure composed of four rings of seven subunits. The 26S form of the proteasome, which is responsible for ubiquitin-dependent proteolysis, contains additional regulatory complexes. Eukaryotic proteasomes have multiple catalytic activities which are catalysed at distinct sites. Since proteasomes are unrelated to other known proteases, there are no clues as to which are the catalytic components from sequence alignments. It has been assumed from studies with yeast mutants that /3-type subunits play a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat liver proteasomes we have directly identified RC7 as a catalytic component. Interestingly, mutants in Prel, the yeast homologue of RC7, have already been reported to have defective chymotrypsin-like activity. These results taken together confirm a direct catalytic role for these/3-type subunits. Proteasome activities are sensitive to conformational changes and there are several ways in which proteasome function may be modulated in vivo. Our recent studies have shown that in animal cells at least two proteasome subunits can undergo phosphorylation, the level of which is likely to be important for determining proteasome localization, activity or ability to form larger complexes. In addition, we have isolated two isoforms of the 26S proteinase.

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Human activity-induced vibrations in slender structural sys tems become apparent in many different excitation modes and consequent action effects that cause discomfort to occupants, crowd panic and damage to public infrastructure. Resulting loss of public confidence in safety of structures, economic losses, cost of retrofit and repairs can be significant. Advanced computational and visualisation techniques enable engineers and architects to evolve bold and innovative structural forms, very often without precedence. New composite and hybrid materials that are making their presence in structural systems lack historical evidence of satisfactory performance over anticipated design life. These structural systems are susceptible to multi-modal and coupled excitation that are very complex and have inadequate design guidance in the present codes and good practice guides. Many incidents of amplified resonant response have been reported in buildings, footbridges, stadia a nd other crowded structures with adverse consequences. As a result, attenuation of human-induced vibration of innovative and slender structural systems very ofte n requires special studies during the design process. Dynamic activities possess variable characteristics and thereby induce complex responses in structures that are sensitive to parametric variations. Rigorous analytical techniques are available for investigation of such complex actions and responses to produce acceptable performance in structural systems. This paper presents an overview and a critique of existing code provisions for human-induced vibration followed by studies on the performance of three contrasting structural systems that exhibit complex vibration. The dynamic responses of these systems under human-induced vibrations have been carried out using experimentally validated computer simulation techniques. The outcomes of these studies will have engineering applications for safe and sustainable structures and a basis for developing design guidance.

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Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

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The structure of the travel, meant as cultural activity, is proposed as a key to read and design the urban or rural landscape.

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Background to the Problem: Improving nurses' self-efficacy and job satisfaction may improve the quality of nursing care to patients. Moreover, to work effectively and consistently with professional nursing standards, nurses have to believe they are able to make decisions about their practice. In order to identify what strategies and professional development programmes should be developed and implemented for registered nurses in the Australian context, a comprehensive profile of registered nurses and factors that affect nursing care in Australia needs to be available. However, at present, there is limited information available on a) the perceived caring efficacy and job satisfaction of registered nurses in Australia, and b) the relationships between the demographic variables general self-efficacy, work locus of control, coping styles, the professional nursing practice environment and caring efficacy and job satisfaction of registered nurses in Australia. This is the first study to 1) investigate relationships between caring efficacy and job satisfaction with factors such as general self-efficacy, locus of control and coping, 2) the nursing practice environment in the Australian context and 3) conceptualise a model of caring efficacy and job satisfaction in the Australian context. Research Design and Methods: This study used a two-phase cross-sectional survey design. A pilot study was conducted in order to determine the validity and reliability of the survey instruments and to assess the effectiveness of the participant recruitment process. The second study of the research involved investigating the relationships between the socio-demographic, dependent and independent variables. Socio-demographic variables included age, gender, level of education, years of experience, years in current job, employment status, geographical location, specialty area, health sector, state and marital status. Other independent variables in this study included general self-efficacy, work locus of control, coping styles and the professional nursing practice environment. The dependent variables were job satisfaction and caring efficacy. Results: A confirmatory factor analysis of the Brisbane Practice Environment Measure (B-PEM) was conducted. A five-factor structure of the B-PEM was confirmed. Relationships between socio-demographic variables, caring efficacy and job satisfaction, were identified at the bivariate and multivariable levels. Further, examination using structural equation modelling revealed general self-efficacy, work locus of control, coping style and the professional nursing practice environment contributed to caring efficacy and job satisfaction of registered nurses in Australia. Conclusion: This research contributes to the literature on how socio-demographic, personal and environmental variables (work locus of control, general self-efficacy and the nursing practice environment) influence caring efficacy and job satisfaction in registered nurses in Australia. Caring efficacy and job satisfaction may be improved if general self-efficacy is high in those that have an internal work locus of control. The study has also shown that practice environments that provide the necessary resources improve job satisfaction in nurses. The results have identified that the development and implementation of strategies for professional development and orientation programmes that enhance self-efficacy and work locus of control may contribute to better quality nursing practice and job satisfaction. This may further assist registered nurses towards focusing on improving their practice abilities. These strategies along with practice environments that provide the necessary resources for nurses to practice effectively may lead to better job satisfaction. This information is important for nursing leaders, healthcare organisations and policymakers, as the development and implementation of these strategies may lead to better recruitment and retention of nurses. The study results will contribute to the national and international literature on self-efficacy, job satisfaction and nursing practice.