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.

Determining a set of surrogate parameters to evaluate urban stormwater quality

This thesis details methodology to estimate urban stormwater quality based on a set of easy to measure physico-chemical parameters. These parameters can be used as surrogate parameters to estimate other key water quality parameters. The key pollutants considered in this study are nitrogen compounds, phosphorus compounds and solids. The use of surrogate parameter relationships to evaluate urban stormwater quality will reduce the cost of monitoring and so that scientists will have added capability to generate a large amount of data for more rigorous analysis of key urban stormwater quality processes, namely, pollutant build-up and wash-off. This in turn will assist in the development of more stringent stormwater quality mitigation strategies. The research methodology was based on a series of field investigations, laboratory testing and data analysis. Field investigations were conducted to collect pollutant build-up and wash-off samples from residential roads and roof surfaces. Past research has identified that these impervious surfaces are the primary pollutant sources to urban stormwater runoff. A specially designed vacuum system and rainfall simulator were used in the collection of pollutant build-up and wash-off samples. The collected samples were tested for a range of physico-chemical parameters. Data analysis was conducted using both univariate and multivariate data analysis techniques. Analysis of build-up samples showed that pollutant loads accumulated on road surfaces are higher compared to the pollutant loads on roof surfaces. Furthermore, it was found that the fraction of solids smaller than 150 ìm is the most polluted particle size fraction in solids build-up on both roads and roof surfaces. The analysis of wash-off data confirmed that the simulated wash-off process adopted for this research agrees well with the general understanding of the wash-off process on urban impervious surfaces. The observed pollutant concentrations in wash-off from road surfaces were different to pollutant concentrations in wash-off from roof surfaces. Therefore, firstly, the identification of surrogate parameters was undertaken separately for roads and roof surfaces. Secondly, a common set of surrogate parameter relationships were identified for both surfaces together to evaluate urban stormwater quality. Surrogate parameters were identified for nitrogen, phosphorus and solids separately. Electrical conductivity (EC), total organic carbon (TOC), dissolved organic carbon (DOC), total suspended solids (TSS), total dissolved solids (TDS), total solids (TS) and turbidity (TTU) were selected as the relatively easy to measure parameters. Consequently, surrogate parameters for nitrogen and phosphorus were identified from the set of easy to measure parameters for both road surfaces and roof surfaces. Additionally, surrogate parameters for TSS, TDS and TS which are key indicators of solids were obtained from EC and TTU which can be direct field measurements. The regression relationships which were developed for surrogate parameters and key parameter of interest were of a similar format for road and roof surfaces, namely it was in the form of simple linear regression equations. The identified relationships for road surfaces were DTN-TDS:DOC, TP-TS:TOC, TSS-TTU, TDS-EC and TSTTU: EC. The identified relationships for roof surfaces were DTN-TDS and TSTTU: EC. Some of the relationships developed had a higher confidence interval whilst others had a relatively low confidence interval. The relationships obtained for DTN-TDS, DTN-DOC, TP-TS and TS-EC for road surfaces demonstrated good near site portability potential. Currently, best management practices are focussed on providing treatment measures for stormwater runoff at catchment outlets where separation of road and roof runoff is not found. In this context, it is important to find a common set of surrogate parameter relationships for road surfaces and roof surfaces to evaluate urban stormwater quality. Consequently DTN-TDS, TS-EC and TS-TTU relationships were identified as the common relationships which are capable of providing measurements of DTN and TS irrespective of the surface type.

Robustness in health research : do differences in health measures, techniques, and time frame matter?

Survey-based health research is in a boom phase following an increased amount of health spending in OECD countries and the interest in ageing. A general characteristic of survey-based health research is its diversity. Different studies are based on different health questions in different datasets; they use different statistical techniques; they differ in whether they approach health from an ordinal or cardinal perspective; and they differ in whether they measure short-term or long-term effects. The question in this paper is simple: do these differences matter for the findings? We investigate the effects of life-style choices (drinking, smoking, exercise) and income on six measures of health in the US Health and Retirement Study (HRS) between 1992 and 2002: (1) self-assessed general health status, (2) problems with undertaking daily tasks and chores, (3) mental health indicators, (4) BMI, (5) the presence of serious long-term health conditions, and (6) mortality. We compare ordinal models with cardinal models; we compare models with fixed effects to models without fixed-effects; and we compare short-term effects to long-term effects. We find considerable variation in the impact of different determinants on our chosen health outcome measures; we find that it matters whether ordinality or cardinality is assumed; we find substantial differences between estimates that account for fixed effects versus those that do not; and we find that short-run and long-run effects differ greatly. All this implies that health is an even more complicated notion than hitherto thought, defying generalizations from one measure to the others or one methodology to another.

The efficacy of the Sortino ratio and other benchmarked performance measures under skewed return distributions

This paper will investigate the suitability of existing performance measures under the assumption of a clearly defined benchmark. A range of measures are examined including the Sortino Ratio, the Sharpe Selection ratio (SSR), the Student’s t-test and a decay rate measure. A simulation study is used to assess the power and bias of these measures based on variations in sample size and mean performance of two simulated funds. The Sortino Ratio is found to be the superior performance measure exhibiting more power and less bias than the SSR when the distribution of excess returns are skewed.

Dynamic Performance Measures for Object Tracking Systems

Performance evaluation of object tracking systems is typically performed after the data has been processed, by comparing tracking results to ground truth. Whilst this approach is fine when performing offline testing, it does not allow for real-time analysis of the systems performance, which may be of use for live systems to either automatically tune the system or report reliability. In this paper, we propose three metrics that can be used to dynamically asses the performance of an object tracking system. Outputs and results from various stages in the tracking system are used to obtain measures that indicate the performance of motion segmentation, object detection and object matching. The proposed dynamic metrics are shown to accurately indicate tracking errors when visually comparing metric results to tracking output, and are shown to display similar trends to the ETISEO metrics when comparing different tracking configurations.

Visual impairment, postural stability and falls among older adults with glaucoma

Purpose: To investigate the impact of glaucomatous visual impairment on postural sway and falls among older adults.Methods: The sample comprised 72 community-dwelling older adults with open-angle glaucoma, aged 74.0 5.8 years (range 62 to 90 years). Measures of visual function included binocular visual acuity (high-contrast), binocular contrast sensitivity (Pelli- Robson) and binocular visual fields (merged monocular HFA 24-2 SITA-Std). Postural stability was assessed under four conditions: eyes open and closed, on a firm and on a foam surface. Falls were monitored for six months with prospective falls diaries. Regression models, adjusting for age and gender, examined the association between vision measures and postural stability (linear regression) and the number of falls (negative binomial regression). Results: Greater visual field loss was significantly associated with poorer postural stability with eyes open, both on firm (r = 0.34, p < 0.01) and foam (r = 0.45, p < 0.001) surfaces. Eighteen (25 per cent) participants experienced at least one fall: 12 (17 per cent) participants fell only once and six (eight per cent) participants fell two or more times (up to five falls). Visual field loss was significantly associated with falling; the rate of falls doubled for every 10 dB reduction in field sensitivity (rate ratio = 1.08, 95% CI = 1.02–1.13). Importantly, in a model comprising upper and lower field sensitivity, only lower field loss was significantly associated with the number of falls (rate ratio = 1.17, 95% CI = 1.04–1.33). Conclusions: Binocular visual field loss was significantly associated with postural instability and falls among older adults with glaucoma. These findings provide valuable directions for developing falls risk assessment and falls prevention strategies for this population.

Adaptive dual control of topic-based information retrieval

Information Retrieval is an important albeit imperfect component of information technologies. A problem of insufficient diversity of retrieved documents is one of the primary issues studied in this research. This study shows that this problem leads to a decrease of precision and recall, traditional measures of information retrieval effectiveness. This thesis presents an adaptive IR system based on the theory of adaptive dual control. The aim of the approach is the optimization of retrieval precision after all feedback has been issued. This is done by increasing the diversity of retrieved documents. This study shows that the value of recall reflects this diversity. The Probability Ranking Principle is viewed in the literature as the “bedrock” of current probabilistic Information Retrieval theory. Neither the proposed approach nor other methods of diversification of retrieved documents from the literature conform to this principle. This study shows by counterexample that the Probability Ranking Principle does not in general lead to optimal precision in a search session with feedback (for which it may not have been designed but is actively used). Retrieval precision of the search session should be optimized with a multistage stochastic programming model to accomplish the aim. However, such models are computationally intractable. Therefore, approximate linear multistage stochastic programming models are derived in this study, where the multistage improvement of the probability distribution is modelled using the proposed feedback correctness method. The proposed optimization models are based on several assumptions, starting with the assumption that Information Retrieval is conducted in units of topics. The use of clusters is the primary reasons why a new method of probability estimation is proposed. The adaptive dual control of topic-based IR system was evaluated in a series of experiments conducted on the Reuters, Wikipedia and TREC collections of documents. The Wikipedia experiment revealed that the dual control feedback mechanism improves precision and S-recall when all the underlying assumptions are satisfied. In the TREC experiment, this feedback mechanism was compared to a state-of-the-art adaptive IR system based on BM-25 term weighting and the Rocchio relevance feedback algorithm. The baseline system exhibited better effectiveness than the cluster-based optimization model of ADTIR. The main reason for this was insufficient quality of the generated clusters in the TREC collection that violated the underlying assumption.

Comparison of multiple and novel measures of dietary glycemic carbohydrate with insulin resistant status in older women

BACKGROUND:Previous epidemiological investigations of associations between dietary glycemic intake and insulin resistance have used average daily measures of glycemic index (GI) and glycemic load (GL). We explored multiple and novel measures of dietary glycemic intake to determine which was most predictive of an association with insulin resistance.METHODS:Usual dietary intakes were assessed by diet history interview in women aged 42-81 years participating in the Longitudinal Assessment of Ageing in Women. Daily measures of dietary glycemic intake (n = 329) were carbohydrate, GI, GL, and GL per megacalorie (GL/Mcal), while meal based measures (n = 200) were breakfast, lunch and dinner GL; and a new measure, GL peak score, to represent meal peaks. Insulin resistant status was defined as a homeostasis model assessment (HOMA) value of >3.99; HOMA as a continuous variable was also investigated.RESULTS:GL, GL/Mcal, carbohydrate (all P < 0.01), GL peak score (P = 0.04) and lunch GL (P = 0.04) were positively and independently associated with insulin resistant status. Daily measures were more predictive than meal-based measures, with minimal difference between GL/Mcal, GL and carbohydrate. No significant associations were observed with HOMA as a continuous variable.CONCLUSION:A dietary pattern with high peaks of GL above the individual's average intake was a significant independent predictor of insulin resistance in this population, however the contribution was less than daily GL and carbohydrate variables. Accounting for energy intake slightly increased the predictive ability of GL, which is potentially important when examining disease risk in more diverse populations with wider variations in energy requirements.

Infrared spectroscopic investigation of the effects of titania photocatalyst on the degradation of linear low density polyethylene film for commercial applications

There is a need in industry for a commodity polyethylene film with controllable degradation properties that will degrade in an environmentally neutral way, for applications such as shopping bags and packaging film. Additives such as starch have been shown to accelerate the degradation of plastic films, however control of degradation is required so that the film will retain its mechanical properties during storage and use, and then degrade when no longer required. By the addition of a photocatalyst it is hoped that polymer film will breakdown with exposure to sunlight. Furthermore, it is desired that the polymer film will degrade in the dark, after a short initial exposure to sunlight. Research has been undertaken into the photo- and thermo-oxidative degradation processes of 25 ìm thick LLDPE (linear low density polyethylene) film containing titania from different manufacturers. Films were aged in a suntest or in an oven at 50 °C, and the oxidation product formation was followed using IR spectroscopy. Degussa P25, Kronos 1002, and various organic-modified and doped titanias of the types Satchleben Hombitan and Hunstsman Tioxide incorporated into LLDPE films were assessed for photoactivity. Degussa P25 was found to be the most photoactive with UVA and UVC exposure. Surface modification of titania was found to reduce photoactivity. Crystal phase is thought to be among the most important factors when assessing the photoactivity of titania as a photocatalyst for degradation. Pre-irradiation with UVA or UVC for 24 hours of the film containing 3% Degussa P25 titania prior to aging in an oven resulted in embrittlement in ca. 200 days. The multivariate data analysis technique PCA (principal component analysis) was used as an exploratory tool to investigate the IR spectral data. Oxidation products formed in similar relative concentrations across all samples, confirming that titania was catalysing the oxidation of the LLDPE film without changing the oxidation pathway. PCA was also employed to compare rates of degradation in different films. PCA enabled the discovery of water vapour trapped inside cavities formed by oxidation by titania particles. Imaging ATR/FTIR spectroscopy with high lateral resolution was used in a novel experiment to examine the heterogeneous nature of oxidation of a model polymer compound caused by the presence of titania particles. A model polymer containing Degussa P25 titania was solvent cast onto the internal reflection element of the imaging ATR/FTIR and the oxidation under UVC was examined over time. Sensitisation of 5 ìm domains by titania resulted in areas of relatively high oxidation product concentration. The suitability of transmission IR with a synchrotron light source to the study of polymer film oxidation was assessed as the Australian Synchrotron in Melbourne, Australia. Challenges such as interference fringes and poor signal-to-noise ratio need to be addressed before this can become a routine technique.

What measure of temperature is the best predictor of mortality?

Hot and cold temperatures significantly increase mortality rates around the world, but which measure of temperature is the best predictor of mortality is not known. We used mortality data from 107 US cities for the years 1987–2000 and examined the association between temperature and mortality using Poisson regression and modelled a non-linear temperature effect and a non-linear lag structure. We examined mean, minimum and maximum temperature with and without humidity, and apparent temperature and the Humidex. The best measure was defined as that with the minimum cross-validated residual. We found large differences in the best temperature measure between age groups, seasons and cities, and there was no one temperature measure that was superior to the others. The strong correlation between different measures of temperature means that, on average, they have the same predictive ability. The best temperature measure for new studies can be chosen based on practical concerns, such as choosing the measure with the least amount of missing data.

Incorporating sustainability measures in life-cycle financial decision making for highway construction

Public awareness and the nature of highway construction works demand that sustainability measures are first on the development agenda. However, in the current economic climate, individual volition and enthusiasm for such high capital investments do not present as strong cases for decision making as the financial pictures of pursuing sustainability. Some stakeholders consider sustainability to be extra work that costs additional money. Though, stakeholders realised its importance in infrastructure development. They are keen to identify the available alternatives and financial implications on a lifecycle basis. Highway infrastructure development is a complex rocess which requires expertise and tools to evaluate investment options, such as environmentally sustainable features for road and highway development. Life-cycle cost analysis (LCCA) is a valuable approach for investment decision making for construction works. However, LCCA applications in highway development are still limited. Current models, for example focus on economic issues alone and do not deal with sustainability factors, which are more difficult to quantify and encapsulate in estimation modules. This paper reports the research which identifies sustainability related factors in highway construction projects, in quantitative and qualitative forms of a multi-criteria analysis. These factors are then incorporated into past and proven LCCA models to produce a new long term decision support model. The research via questionnaire, model building, analytical hierarchy processes (AHP) and case studies have identified, evaluated and then processed highway sustainability related cost elements. These cost elements need to be verified by industry before being integrated for further development of the model. Then the Australian construction industry will have a practical tool to evaluate investment decisions which provide an optimum balance between financial viability and sustainability deliverables.