New insights into appetite, inflammation and the use of fish oil in hemodialysis patients

Protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD). The condition is characterised by chronic, systemic low-grade inflammation which affects nutritional status by a variety of mechanisms including reducing appetite and food intake and increasing muscle catabolism. PEW is linked with co-morbidities such as cardiovascular disease, and is associated with lower quality of life, increased hospitalisations and a 6-fold increase in risk of death1. Significant gender differences have been found in the severity and effects of several markers of PEW. There have been limited studies testing the ability of anti-inflammatory agents or nutritional interventions to reduce the effects of PEW in dialysis patients. This thesis makes a significant contribution to the understanding of PEW in dialysis patients. It advances understanding of measurement techniques for two of the key components, appetite and inflammation, and explores the effect of fish oil, an anti-inflammatory agent, on markers of PEW in dialysis patients. The first part of the thesis consists of two methodological studies conducted using baseline data. The first study aims to validate retrospective ratings of hunger, desire to eat and fullness on visual analog scales (VAS) (paper and pen and electronic) as a new method of measuring appetite in dialysis patients. The second methodological study aims to assess the ability of a variety of methods available in routine practice to detect the presence of inflammation. The second part of the thesis aims to explore the effect of 12 weeks supplementation with 2g per day of Eicosapentaenoic Acid (EPA), a longchain fatty acid found in fish oil, on markers of PEW. A combination of biomarkers and psychomarkers of appetite and inflammation are the main outcomes being explored, with nutritional status, dietary intake and quality of life included as secondary outcomes. A lead in phase of 3 months prior to baseline was used so that each person acts as their own historical control. The study also examines whether there are gender differences in response to the treatment. Being an exploratory study, an important part of the work is to test the feasibility of the intervention, thus the level of adherence and factors associated with adherence are also presented. The studies were conducted at the hemodialysis unit of the Wesley Hospital. Participants met the following criteria: adult, stage 5 CKD on hemodialysis for at least 3 months, not expected to receive a transplant or switch to another dialysis modality during the study, absence of intellectual impairment or mental illness impairing ability to follow instructions or complete the intervention. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and 12 weeks. Inflammation was measured using five biomarkers: c-reactive protein (CRP), interleukin-6 (IL6), intercellular adhesion molecule (sICAM-1), vascular cell adhesion molecule (sVCAM-1) and white cell count (WCC). Subjective appetite was measured using the first question from the Appetite and Dietary Assessment (ADAT) tool and VAS for measurements of hunger, desire to eat and fullness. A novel feature of the study was the assessment of the appetite peptides leptin, ghrelin and peptide YY as biomarkers of appetite. Nutritional status/inflammation was assessed using the Malnutrition-Inflammation Score (MIS) and the Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day records. Quality of life was measured using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™ v1.3 © RAND University), which combines the Short-Form 36 (SF36) with a kidney-disease specific module2. A smaller range of these variables was available for analysis during the control phase (CRP, ADAT, dietary intake and nutritional status). Statistical analysis was carried out using SPSS version 14 (SPSS Inc, Chicago IL, USA). Analysis of the first part of the thesis involved descriptive and bivariate statistics, as well as Bland-Altman plots to assess agreement between methods, and sensitivity analysis/ROC curves to test the ability of methods to predict the presence of inflammation. The unadjusted (paired ttests) and adjusted (linear mixed model) change over time is presented for the main outcome variables of inflammation and appetite. Results are shown for the whole group followed by analyses according to gender and adherence to treatment. Due to the exploratory nature of the study, trends and clinical significance were considered as important as statistical significance. Twenty-eight patients (mean age 61±17y, 50% male, dialysis vintage 19.5 (4- 101) months) underwent baseline assessment. Seven out of 28 patients (25%) reported sub-optimal appetite (self-reported as fair, poor or very poor) despite all being well nourished (100% SGA A). Using the VAS, ratings of hunger, but not desire to eat or fullness, were significantly (p<0.05) associated with a range of relevant clinical variables including age (r=-0.376), comorbidities (r=-0.380) nutritional status (PG-SGA score, r=-0.451), inflammatory markers (CRP r=-0.383; sICAM-1 r=-0.387) and seven domains of quality of life. Patients expressed a preference for the paper and pen method of administering VAS. None of the tools (appetite, MIS, PG-SGA, albumin or iron) showed an acceptable ability to detect patients who are inflamed. It is recommended that CRP should be tested more frequently as a matter of course rather than seeking alternative methods of measuring inflammation. 27 patients completed the 12 week intervention. 20 patients were considered adherent based on changes in % plasma EPA, which rose from 1.3 (0.94)% to 5.2 (1.1)%, p<0.001, in this group. The major barriers to adherence were forgetting to take the tablets as well as their size. At 12 weeks, inflammatory markers remained steady apart from the white cell count which decreased (7.6(2.5) vs 7.0(2.2) x109/L, p=0.058) and sVCAM-1 which increased (1685(654) vs 2249(925) ng/mL, p=0.001). Subjective appetite using VAS increased (51mm to 57mm, +12%) and there was a trend towards reduction in peptide YY (660(31) vs 600(30) pg/mL, p=0.078). There were some gender differences apparent, with the following adjusted change between baseline and week 12: CRP (males -3% vs females +17%, p=0.19), IL6 (males +17% vs females +48%, p=0.77), sICAM-1 (males -5% vs females +11%, p=0.07), sVCAM-1 (males +54% vs females +19%, p=0.08) and hunger ratings (males 20% vs females -5%, p=0.18). On balance, males experienced a maintainence or reduction in three inflammatory markers and an improvement in hunger ratings, and therefore appeared to have responded better to the intervention. Compared to those who didn’t adhere, adherent patients maintained weight (mean(SE) change: +0.5(1.6) vs - 0.8(1.2) kg, p=0.052) and fat-free mass (-0.1 (1.6) vs -1.8 (1.8) kg, p=0.045). There was no difference in change between the intervention and control phase for CRP, appetite, nutritional status or dietary intake. The thesis makes a significant contribution to the evidence base for understanding of PEW in dialysis patients. It has advanced knowledge of methods of assessing inflammation and appetite. Retrospective ratings of hunger on a VAS appear to be a valid method of assessing appetite although samples which include patients with very poor appetite are required to confirm this. Supplementation with fish oil appeared to improve subjective appetite and dampen the inflammatory response. The effectiveness of the intervention is influenced by gender and adherence. Males appear to be more responsive to the primary outcome variables than females, and the quality of response is improved with better adherence. These results provide evidence to support future interventions aimed at reducing the effects of PEW in dialysis patients.

Modeling corneal surfaces with rational functions for high-speed videokeratoscopy data compression

High-speed videokeratoscopy is an emerging technique that enables study of the corneal surface and tear-film dynamics. Unlike its static predecessor, this new technique results in a very large amount of digital data for which storage needs become significant. We aimed to design a compression technique that would use mathematical functions to parsimoniously fit corneal surface data with a minimum number of coefficients. Since the Zernike polynomial functions that have been traditionally used for modeling corneal surfaces may not necessarily correctly represent given corneal surface data in terms of its optical performance, we introduced the concept of Zernike polynomial-based rational functions. Modeling optimality criteria were employed in terms of both the rms surface error as well as the point spread function cross-correlation. The parameters of approximations were estimated using a nonlinear least-squares procedure based on the Levenberg-Marquardt algorithm. A large number of retrospective videokeratoscopic measurements were used to evaluate the performance of the proposed rational-function-based modeling approach. The results indicate that the rational functions almost always outperform the traditional Zernike polynomial approximations with the same number of coefficients.

Port decoupling for small arrays by means of an eigenmode feed network

An alternative approach to port decoupling and matching of arrays with tightly coupled elements is proposed. The method is based on the inherent decoupling effect obtained by feeding the orthogonal eigenmodes of the array. For this purpose, a modal feed network is connected to the array. The decoupled external ports of the feed network may then be matched independently by using conventional matching circuits. Such a system may be used in digital beam forming applications with good signal-to-noise performance. The theory is applicable to arrays with an arbitrary number of elements, but implementation is only practical for smaller arrays. The principle is illustrated by means of two examples.

Modeling videokeratoscopic height data with spherical harmonics

Purpose: All currently considered parametric models used for decomposing videokeratoscopy height data are viewercentered and hence describe what the operator sees rather than what the surface is. The purpose of this study was to ascertain the applicability of an object-centered representation to modeling of corneal surfaces. Methods: A three-dimensional surface decomposition into a series of spherical harmonics is considered and compared with the traditional Zernike polynomial expansion for a range of videokeratoscopic height data. Results: Spherical harmonic decomposition led to significantly better fits to corneal surfaces (in terms of the root mean square error values) than the corresponding Zernike polynomial expansions with the same number of coefficients, for all considered corneal surfaces, corneal diameters, and model orders. Conclusions: Spherical harmonic decomposition is a viable alternative to Zernike polynomial decomposition. It achieves better fits to videokeratoscopic height data and has the advantage of an object-centered representation that could be particularly suited to the analysis of multiple corneal measurements.

Voter behaviour and constitutional change in Australia since 1967

Australian Constitutional referendums have been part of the Australian political system since federation. Up to the year 1999 (the time of the last referendum in Australia), constitutional change in Australia does not have a good history of acceptance. Since 1901, there have been 44 proposed constitutional changes with eight gaining the required acceptance according to section 128 of the Australian Constitution. In the modern era since 1967, there have been 20 proposals over seven referendum votes for a total of four changes. Over this same period, there have been 13 federal general elections which have realised change in government just five times. This research examines the electoral behaviour of Australian voters from 1967 to 1999 for each referendum. Party identification has long been a key indicator in general election voting. This research considers whether the dominant theory of voter behaviour in general elections (the Michigan Model) provides a plausible explanation for voting in Australian referendums. In order to explain electoral behaviour in each referendum, this research has utilised available data from the Australian Electoral Commission, the 1996 Australian Bureau of Statistics Census data, and the 1999 Australian Constitutional Referendum Study. This data has provided the necessary variables required to measure the impact of the Michigan Model of voter behaviour. Measurements have been conducted using bivariate and multivariate analyses. Each referendum provides an overview of the events at the time of the referendum as well as the =yes‘ and =no‘ cases at the time each referendum was initiated. Results from this research provide support for the Michigan Model of voter behaviour in Australian referendum voting. This research concludes that party identification, as a key variable of the Michigan Model, shows that voters continue to take their cues for voting from the political party they identify with in Australian referendums. However, the outcome of Australian referendums clearly shows that partisanship is only one of a number of contributory factors in constitutional referendums.

Factors associated with recurrence of venous leg ulcers : a survey and retrospective chart review

Background: Chronic venous leg ulcers have a significant impact on older individuals’ well-being and health care resources. Unfortunately after healing, up to 70% recur. ----- Objective: To examine the relationships between leg ulcer recurrence and physical activity, compression, nutrition, health, psychosocial indicators and self-care activities in order to provide information for preventive strategies. ----- Design: Survey and retrospective chart review Settings: Two metropolitan hospital and three community-based leg ulcer clinics. ----- Subjects: A sample of 122 community living patients with leg ulcer of venous aetiology which had healed between 12 and 36 months prior to the survey. ---- Methods: Data were collected from medical records on demographics, medical history and previous ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer recurrences and history, compression and other self-care activities. All variables significantly associated with recurrence at the bivariate level were entered into a logistic regression model to determine their independent influences on recurrence. ----- Results: Median follow-up time was 24 months (range 12–40 months). Sixty-eight percent of participants had recurred. Bivariate analysis found recurrence was positively associated with ulcer duration, cardiac disease, a Body Mass Index ≤20, scoring as at-risk of malnutrition and depression; and negatively associated with increased physical activity, leg elevation, wearing Class 2 (20–25mmHg) or Class 3 (30–40mmHg) compression hosiery, and higher self-efficacy scores. After adjusting for all variables, an hour/day of leg elevation (OR=0.04, 95% CI=0.01–0.17), days/week in Class 2 or 3 compression hosiery (OR=0.53, 95% CI=0.34–0.81), Yale Physical Activity Survey score (OR=0.95, 95% CI=0.92–0.98), cardiac disease (OR=5.03, 95% CI=1.01–24.93) and General Self-Efficacy scores (OR=0.83, 95% CI=0.72–0.94) remained significantly associated (p<0.05) with recurrence. ----- Conclusions: Results indicate a history of cardiac disease is a risk factor for recurrence; while leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence.

Modeling corneal surfaces with three-dimensional basis functions

Purpose: To ascertain the effectiveness of object-centered three-dimensional representations for the modeling of corneal surfaces. Methods: Three-dimensional (3D) surface decomposition into series of basis functions including: (i) spherical harmonics, (ii) hemispherical harmonics, and (iii) 3D Zernike polynomials were considered and compared to the traditional viewer-centered representation of two-dimensional (2D) Zernike polynomial expansion for a range of retrospective videokeratoscopic height data from three clinical groups. The data were collected using the Medmont E300 videokeratoscope. The groups included 10 normal corneas with corneal astigmatism less than −0.75 D, 10 astigmatic corneas with corneal astigmatism between −1.07 D and 3.34 D (Mean = −1.83 D, SD = ±0.75 D), and 10 keratoconic corneas. Only data from the right eyes of the subjects were considered. Results: All object-centered decompositions led to significantly better fits to corneal surfaces (in terms of the RMS error values) than the corresponding 2D Zernike polynomial expansions with the same number of coefficients, for all considered corneal surfaces, corneal diameters (2, 4, 6, and 8 mm), and model orders (4th to 10th radial orders) The best results (smallest RMS fit error) were obtained with spherical harmonics decomposition which lead to about 22% reduction in the RMS fit error, as compared to the traditional 2D Zernike polynomials. Hemispherical harmonics and the 3D Zernike polynomials reduced the RMS fit error by about 15% and 12%, respectively. Larger reduction in RMS fit error was achieved for smaller corneral diameters and lower order fits. Conclusions: Object-centered 3D decompositions provide viable alternatives to traditional viewer-centered 2D Zernike polynomial expansion of a corneal surface. They achieve better fits to videokeratoscopic height data and could be particularly suited to the analysis of multiple corneal measurements, where there can be slight variations in the position of the cornea from one map acquisition to the next.

Evolutionary algorithms for sustainable building design

This approach to sustainable design explores the possibility of creating an architectural design process which can iteratively produce optimised and sustainable design solutions. Driven by an evolution process based on genetic algorithms, the system allows the designer to “design the building design generator” rather than to “designs the building”. The design concept is abstracted into a digital design schema, which allows transfer of the human creative vision into the rational language of a computer. The schema is then elaborated into the use of genetic algorithms to evolve innovative, performative and sustainable design solutions. The prioritisation of the project’s constraints and the subsequent design solutions synthesised during design generation are expected to resolve most of the major conflicts in the evaluation and optimisation phases. Mosques are used as the example building typology to ground the research activity. The spatial organisations of various mosque typologies are graphically represented by adjacency constraints between spaces. Each configuration is represented by a planar graph which is then translated into a non-orthogonal dual graph and fed into the genetic algorithm system with fixed constraints and expected performance criteria set to govern evolution. The resultant Hierarchical Evolutionary Algorithmic Design System is developed by linking the evaluation process with environmental assessment tools to rank the candidate designs. The proposed system generates the concept, the seed, and the schema, and has environmental performance as one of the main criteria in driving optimisation.

Identifying aggregate demand and supply shocks in a small open economy

The standard Blanchard-Quah (BQ) decomposition forces aggregate demand and supply shocks to be orthogonal. However, this assumption is problematic for a nation with an inflation target. The very notion of inflation targeting means that monetary policy reacts to changes in aggregate supply. This paper employs a modification of the BQ procedure that allows for correlated shifts in aggregate supply and demand. It is found that shocks to Australian aggregate demand and supply are highly correlated. The estimated shifts in the aggregate demand and supply curves are then used to measure the effects of inflation targeting on the Australian inflation rate and level of GDP.

Peak-to-average power ratio of IEEE 802.11a PHY layer signals

In this chapter we propose clipping with amplitude and phase corrections to reduce the peak-to-average power ratio (PAR) of orthogonal frequency division multiplexed (OFDM) signals in high-speed wireless local area networks defined in IEEE 802.11a physical layer. The proposed techniques can be implemented with a small modification at the transmitter and the receiver remains standard compliant. PAR reduction as much as 4dB can be achieved by selecting a suitable clipping ratio and a correction factor depending on the constellation used. Out of band noise (OBN) is also reduced.

Interleaved PC-OFDM to reduce peak-to-average power ratio

Parallel combinatory orthogonal frequency division multiplexing (PC-OFDM yields lower maximum peak-to-average power ratio (PAR), high bandwidth efficiency and lower bit error rate (BER) on Gaussian channels compared to OFDM systems. However, PC-OFDM does not improve the statistics of PAR significantly. In this chapter, the use of a set of fixed permutations to improve the statistics of the PAR of a PC-OFDM signal is presented. For this technique, interleavers are used to produce K-1 permuted sequences from the same information sequence. The sequence with the lowest PAR, among K sequences is chosen for the transmission. The PAR of a PC-OFDM signal can be further reduced by 3-4 dB by this technique. Mathematical expressions for the complementary cumulative density function (CCDF)of PAR of PC-OFDM signal and interleaved PC-OFDM signal are also presented.

Modeling factors that influence exercise and dietary change among midlife Australian women: results from the Healthy Aging of Women Study

The objective of this study was to investigate the factors that influence midlife women to make positive exercise and dietary changes. In late 2005 questionnaires were mailed to 866 women aged 51–66 years from rural and urban locations in Queensland, Australia and participating in Stage 2 of the Healthy Aging of Women Study. The questionnaires sought data on socio-demographics, body mass index (BMI), chronic health conditions, self-efficacy, exercise and dietary behavior change since age 40, and health-related quality of life. Five hundred and sixty four (69%) were completed and returned by early 2006. Data analysis comprised descriptive and bivariate statistics and structural equation modeling. The results showed that midlife is a significant time for women to make positive health behavior changes. Approximately one-third of the sample (34.6%) indicated that they had increased their exercise and around 60% had made an effort to eat more healthily since age 40. Modeling showed self-efficacy to be important in making both exercise and dietary changes. Although education appeared to influence self-efficacy in relation to exercise change, this was not the case for dietary change. The study has application for programs promoting healthy aging among women, and implies that those with low education, high BMI and poor mental health may need considerable support to improve their lifestyles.

Identifying the presence of psychopathy in the community

Aim: Researchers have suggested that approximately 1% of individuals with psychopathic tendencies can successfully function within the community, although there has been a lack of research to support this claim. The current study aimed to identify individuals with psychopathic tendencies within a community sample and furthermore the socio-demographic correlates of this community integrated psychopath (e.g. relationship stability, substance use, and employment status). Procedure: 300 participants completed the Self-Reported Psychopathy scale – version 3 which contains four core psychopathy subfactors: (a) Interpersonal Manipulation, (b) Callous Affect, (c) Erratic Lifestyle and (d) Criminal Tendencies as well as the Paulhus Deception Scales to explore the effect of impression management and self-deception on the identification of psychopathy. Findings: Results indicated that at least 1% of the current community displayed characteristics consistent with psychopathic tendencies. A series of bivariate and multivariate statistical analyses were conducted which indicated that gender, age and alcohol misuse were predictive of psychopathy scores for this sample. More specifically, younger males who tend to misuse alcohol were found to be most likely to have psychopathic tendencies. Interestingly, impression management and self-deception was not associated with such tendencies. Discussion: The results provide some support for the assertion that individuals with psychopathic tendencies can be identified within the community (regardless of impression management techniques) and that such tendencies are associated with specific socio-demographic characteristics.

Vulnerability factors for disaster-induced child post-traumatic stress disorder : the case for low family resilience and previous mental illness

Objective: The aim of the present study was to investigate whether parent report of family resilience predicted children’s disaster-induced post-traumatic stress disorder (PTSD) and general emotional symptoms, independent of a broad range of variables including event-related factors, previous child mental illness and social connectedness. ---------- Methods: A total of 568 children (mean age = 10.2 years, SD = 1.3) who attended public primary schools, were screened 3 months after Cyclone Larry devastated the Innisfail region of North Queensland. Measures included parent report on the Family Resilience Measure and Strengths and Difficulties Questionnaire (SDQ)–emotional subscale and child report on the PTSD Reaction Index, measures of event exposure and social connectedness. ---------- Results: Sixty-four students (11.3%) were in the severe–very severe PTSD category and 53 families (28.6%) scored in the poor family resilience range. A lower family resilience score was associated with child emotional problems on the SDQ and longer duration of previous child mental health difficulties, but not disaster-induced child PTSD or child threat perception on either bivariate analysis, or as a main or moderator variable on multivariate analysis (main effect: adjusted odds ratio (ORadj) = 0.57, 95% confidence interval (CI) = 0.13–2.44). Similarly, previous mental illness was not a significant predictor of child PTSD in the multivariate model (ORadj = 0.75, 95%CI = 0.16–3.61). ---------- Conclusion: In this post-disaster sample children with existing mental health problems and those of low-resilience families were not at elevated risk of PTSD. The possibility that the aetiological model of disaster-induced child PTSD may differ from usual child and adolescent conceptualizations is discussed.