Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study

Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds. Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating.

Examination of relationships and mediating effects of self-efficacy, locus of control, coping and the practice environment on caring efficacy and job satisfaction in Australian registered nurses

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.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Bayesian hierarchical models in statistical quality control methods to improve healthcare in hospitals

Quality oriented management systems and methods have become the dominant business and governance paradigm. From this perspective, satisfying customers’ expectations by supplying reliable, good quality products and services is the key factor for an organization and even government. During recent decades, Statistical Quality Control (SQC) methods have been developed as the technical core of quality management and continuous improvement philosophy and now are being applied widely to improve the quality of products and services in industrial and business sectors. Recently SQC tools, in particular quality control charts, have been used in healthcare surveillance. In some cases, these tools have been modified and developed to better suit the health sector characteristics and needs. It seems that some of the work in the healthcare area has evolved independently of the development of industrial statistical process control methods. Therefore analysing and comparing paradigms and the characteristics of quality control charts and techniques across the different sectors presents some opportunities for transferring knowledge and future development in each sectors. Meanwhile considering capabilities of Bayesian approach particularly Bayesian hierarchical models and computational techniques in which all uncertainty are expressed as a structure of probability, facilitates decision making and cost-effectiveness analyses. Therefore, this research investigates the use of quality improvement cycle in a health vii setting using clinical data from a hospital. The need of clinical data for monitoring purposes is investigated in two aspects. A framework and appropriate tools from the industrial context are proposed and applied to evaluate and improve data quality in available datasets and data flow; then a data capturing algorithm using Bayesian decision making methods is developed to determine economical sample size for statistical analyses within the quality improvement cycle. Following ensuring clinical data quality, some characteristics of control charts in the health context including the necessity of monitoring attribute data and correlated quality characteristics are considered. To this end, multivariate control charts from an industrial context are adapted to monitor radiation delivered to patients undergoing diagnostic coronary angiogram and various risk-adjusted control charts are constructed and investigated in monitoring binary outcomes of clinical interventions as well as postintervention survival time. Meanwhile, adoption of a Bayesian approach is proposed as a new framework in estimation of change point following control chart’s signal. This estimate aims to facilitate root causes efforts in quality improvement cycle since it cuts the search for the potential causes of detected changes to a tighter time-frame prior to the signal. This approach enables us to obtain highly informative estimates for change point parameters since probability distribution based results are obtained. Using Bayesian hierarchical models and Markov chain Monte Carlo computational methods, Bayesian estimators of the time and the magnitude of various change scenarios including step change, linear trend and multiple change in a Poisson process are developed and investigated. The benefits of change point investigation is revisited and promoted in monitoring hospital outcomes where the developed Bayesian estimator reports the true time of the shifts, compared to priori known causes, detected by control charts in monitoring rate of excess usage of blood products and major adverse events during and after cardiac surgery in a local hospital. The development of the Bayesian change point estimators are then followed in a healthcare surveillances for processes in which pre-intervention characteristics of patients are viii affecting the outcomes. In this setting, at first, the Bayesian estimator is extended to capture the patient mix, covariates, through risk models underlying risk-adjusted control charts. Variations of the estimator are developed to estimate the true time of step changes and linear trends in odds ratio of intensive care unit outcomes in a local hospital. Secondly, the Bayesian estimator is extended to identify the time of a shift in mean survival time after a clinical intervention which is being monitored by riskadjusted survival time control charts. In this context, the survival time after a clinical intervention is also affected by patient mix and the survival function is constructed using survival prediction model. The simulation study undertaken in each research component and obtained results highly recommend the developed Bayesian estimators as a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances as well as industrial and business contexts. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The empirical results and simulations indicate that the Bayesian estimators are a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The advantages of the Bayesian approach seen in general context of quality control may also be extended in the industrial and business domains where quality monitoring was initially developed.

Nonlinear H_infinity control of UAVs for collision avoidance in gusty environments

This paper proposes a nonlinear H_infinity controller for stabilization of velocities, attitudes and angular rates of a fixed-wing unmanned aerial vehicle (UAV) in a windy environment. The suggested controller aims to achieve a steady-state flight condition in the presence of wind gusts such that the host UAV can be maneuvered to avoid collision with other UAVs during cruise flight with safety guarantees. This paper begins with building a proper model capturing flight aerodynamics of UAVs. Then a nonlinear controller is developed with gust attenuation and rapid response properties. Simulations are conducted for the Shadow UAV to verify performance of the proposed con- troller. Comparative studies with the proportional-integral-derivative (PID) controllers demonstrate that the proposed controller exhibits great performance improvement in a gusty environment, making it suitable for integration into the design of flight control systems for cruise flight of UAVs.

Optimising weed control by considering disturbance

Mounting scientific evidence suggests newly imposed disturbance and/or alterations to existing disturbances facilitate invasion. Several empirical studies have explored the role of disturbance in invasion, but little work has been done to fit current understanding into a format useful for practical control efforts. We are working towards addressing this shortcoming by developing a metapopulation model couched in a decision theory framework. This approach has allowed us to investigate how incorporating the negative effects of disturbance on native vegetation into decision-making can change optimal control measures. In this paper, we present some preliminary results.

Physical access control administration using building information models

Physical access control systems play a central role in the protection of critical infrastructures, where both the provision of timely access and preserving the security of sensitive areas are paramount. In this paper we discuss the shortcomings of existing approaches to the administration of physical access control in complex environments. At the heart of the problem is the current dependency on human administrators to reason about the implications of the provision or the revocation of staff access to an area within these facilities. We demonstrate how utilising Building Information Models (BIMs) and the capabilities they provide, including 3D representation of a facility and path-finding can reduce possible intentional or accidental errors made by security administrators.

Reducing actuator switchings for motion control of autonomous underwater vehicles

A priority when designing control strategies for autonomous underwater vehicles is to emphasize their cost of implementation on a real vehicle and at the same time to minimize a prescribed criterion such as time, energy, payload or combination of those. Indeed, the major issue is that due to the vehicles' design and the actuation modes usually under consideration for underwater platforms the number of actuator switchings must be kept to a small value to ensure feasibility and precision. This constraint is typically not verified by optimal trajectories which might not even be piecewise constants. Our goal is to provide a feasible trajectory that minimizes the number of switchings while maintaining some qualities of the desired trajectory, such as optimality with respect to a given criterion. The one-sided Lipschitz constant is used to derive theoretical estimates. The theory is illustrated on two examples, one is a fully actuated underwater vehicle capable of motion in six degrees-of-freedom and one is minimally actuated with control motions constrained to the vertical plane.

Rough fuzzy control of SVC for power system stability enhancement

This paper presents a new approach to the design of a rough fuzzy controller for the control loop of the SVC (static VAR system) in a two area power system for stability enhancement with particular emphasis on providing effective damping for oscillatory instabilities. The performances of the rough fuzzy and the conventional fuzzy controller are compared with that of the conventional PI controller for a variety of transient disturbances, highlighting the effectiveness of the rough fuzzy controller in damping the inter-area oscillations. The effect of the rough fuzzy controller in improving the CCT (critical clearing time) of the two area system is elaborated in this paper as well.

Factors affecting antihypertensive treatment adherence : a Saudi Arabian perspective

Hypertension is a global health issue among the adult population. Adherence to antihypertensive medications is an effective step for better control of blood pressure and preventing the risk of complications. Several factors support or hinder hypertensive patients’ adherence. Objectives: This article reviews the factors affecting adherence to antihypertensive treatments, and reflects on these factors from a Saudi Arabian perspective. Methods: Papers and studies about antihypertensive medication adherence were reviewed from different databases including MEDLINE, PubMed, ScienceDirect and Google scholar. Results: Factors affecting antihypertensive treatments adherence are classified into three domains: Patient (e.g. sociodemographic, individual knowledge and skills), Health System, and Provider related factors.

Videogame control device impact on the play experience

New types of control devices for videogames have emerged and expanded the demographics of the game playing public, yet little is known about which populations of gamers prefer which style of interaction and why. This paper presents data from a study that seeks to clarify the influence the control interface has on the play experience. Three commercial control devices were categorised using an existing typology, according to how the interface maps physical control inputs with the virtual gameplay actions. The devices were then used in a within-groups experimental design aimed at measuring differences in play experience across 64 participants. Descriptive analysis is undertaken on the performance, play experience and preference results for each device. Potential explanations for these results are discussed, as well as the direction of future work.

A review of the effectiveness of speed control measures in roadwork zones

Noncompliance with speed limits is one of the major safety concerns in roadwork zones. Although numerous studies have attempted to evaluate the effectiveness of safety measures on speed limit compliance, many report inconsistent findings. This paper aims to review the effectiveness of four categories of roadwork zone speed control measures: Informational, Physical, Enforcement, and Educational measures. While informational measures (static signage, variable message signage) evidently have small to moderate effects on speed reduction, physical measures (rumble strips, optical speed bars) are found ineffective for transient and moving work zones. Enforcement measures (speed camera, police presence) have the greatest effects, while educational measures also have significant potential to improve public awareness of roadworker safety and to encourage slower speeds in work zones. Inadequate public understanding of roadwork risks and hazards, failure to notice signs, and poor appreciation of safety measures are the major causes of noncompliance with speed limits.