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.

Digital kids, analogue students : a mixed methods study of students' engagement with a school-based Web 2.0 learning innovation

The inquiry documented in this thesis is located at the nexus of technological innovation and traditional schooling. As we enter the second decade of a new century, few would argue against the increasingly urgent need to integrate digital literacies with traditional academic knowledge. Yet, despite substantial investments from governments and businesses, the adoption and diffusion of contemporary digital tools in formal schooling remain sluggish. To date, research on technology adoption in schools tends to take a deficit perspective of schools and teachers, with the lack of resources and teacher ‘technophobia’ most commonly cited as barriers to digital uptake. Corresponding interventions that focus on increasing funding and upskilling teachers, however, have made little difference to adoption trends in the last decade. Empirical evidence that explicates the cultural and pedagogical complexities of innovation diffusion within long-established conventions of mainstream schooling, particularly from the standpoint of students, is wanting. To address this knowledge gap, this thesis inquires into how students evaluate and account for the constraints and affordances of contemporary digital tools when they engage with them as part of their conventional schooling. It documents the attempted integration of a student-led Web 2.0 learning initiative, known as the Student Media Centre (SMC), into the schooling practices of a long-established, high-performing independent senior boys’ school in urban Australia. The study employed an ‘explanatory’ two-phase research design (Creswell, 2003) that combined complementary quantitative and qualitative methods to achieve both breadth of measurement and richness of characterisation. In the initial quantitative phase, a self-reported questionnaire was administered to the senior school student population to determine adoption trends and predictors of SMC usage (N=481). Measurement constructs included individual learning dispositions (learning and performance goals, cognitive playfulness and personal innovativeness), as well as social and technological variables (peer support, perceived usefulness and ease of use). Incremental predictive models of SMC usage were conducted using Classification and Regression Tree (CART) modelling: (i) individual-level predictors, (ii) individual and social predictors, and (iii) individual, social and technological predictors. Peer support emerged as the best predictor of SMC usage. Other salient predictors include perceived ease of use and usefulness, cognitive playfulness and learning goals. On the whole, an overwhelming proportion of students reported low usage levels, low perceived usefulness and a lack of peer support for engaging with the digital learning initiative. The small minority of frequent users reported having high levels of peer support and robust learning goal orientations, rather than being predominantly driven by performance goals. These findings indicate that tensions around social validation, digital learning and academic performance pressures influence students’ engagement with the Web 2.0 learning initiative. The qualitative phase that followed provided insights into these tensions by shifting the analytics from individual attitudes and behaviours to shared social and cultural reasoning practices that explain students’ engagement with the innovation. Six indepth focus groups, comprising 60 students with different levels of SMC usage, were conducted, audio-recorded and transcribed. Textual data were analysed using Membership Categorisation Analysis. Students’ accounts converged around a key proposition. The Web 2.0 learning initiative was useful-in-principle but useless-in-practice. While students endorsed the usefulness of the SMC for enhancing multimodal engagement, extending peer-topeer networks and acquiring real-world skills, they also called attention to a number of constraints that obfuscated the realisation of these design affordances in practice. These constraints were cast in terms of three binary formulations of social and cultural imperatives at play within the school: (i) ‘cool/uncool’, (ii) ‘dominant staff/compliant student’, and (iii) ‘digital learning/academic performance’. The first formulation foregrounds the social stigma of the SMC among peers and its resultant lack of positive network benefits. The second relates to students’ perception of the school culture as authoritarian and punitive with adverse effects on the very student agency required to drive the innovation. The third points to academic performance pressures in a crowded curriculum with tight timelines. Taken together, findings from both phases of the study provide the following key insights. First, students endorsed the learning affordances of contemporary digital tools such as the SMC for enhancing their current schooling practices. For the majority of students, however, these learning affordances were overshadowed by the performative demands of schooling, both social and academic. The student participants saw engagement with the SMC in-school as distinct from, even oppositional to, the conventional social and academic performance indicators of schooling, namely (i) being ‘cool’ (or at least ‘not uncool’), (ii) sufficiently ‘compliant’, and (iii) achieving good academic grades. Their reasoned response therefore, was simply to resist engagement with the digital learning innovation. Second, a small minority of students seemed dispositionally inclined to negotiate the learning affordances and performance constraints of digital learning and traditional schooling more effectively than others. These students were able to engage more frequently and meaningfully with the SMC in school. Their ability to adapt and traverse seemingly incommensurate social and institutional identities and norms is theorised as cultural agility – a dispositional construct that comprises personal innovativeness, cognitive playfulness and learning goals orientation. The logic then is ‘both and’ rather than ‘either or’ for these individuals with a capacity to accommodate both learning and performance in school, whether in terms of digital engagement and academic excellence, or successful brokerage across multiple social identities and institutional affiliations within the school. In sum, this study takes us beyond the familiar terrain of deficit discourses that tend to blame institutional conservatism, lack of resourcing and teacher resistance for low uptake of digital technologies in schools. It does so by providing an empirical base for the development of a ‘third way’ of theorising technological and pedagogical innovation in schools, one which is more informed by students as critical stakeholders and thus more relevant to the lived culture within the school, and its complex relationship to students’ lives outside of school. It is in this relationship that we find an explanation for how these individuals can, at the one time, be digital kids and analogue students.

Granule-based knowledge representation for intra and inter transaction association mining

Abstract With the phenomenal growth of electronic data and information, there are many demands for the development of efficient and effective systems (tools) to perform the issue of data mining tasks on multidimensional databases. Association rules describe associations between items in the same transactions (intra) or in different transactions (inter). Association mining attempts to find interesting or useful association rules in databases: this is the crucial issue for the application of data mining in the real world. Association mining can be used in many application areas, such as the discovery of associations between customers’ locations and shopping behaviours in market basket analysis. Association mining includes two phases. The first phase, called pattern mining, is the discovery of frequent patterns. The second phase, called rule generation, is the discovery of interesting and useful association rules in the discovered patterns. The first phase, however, often takes a long time to find all frequent patterns; these also include much noise. The second phase is also a time consuming activity that can generate many redundant rules. To improve the quality of association mining in databases, this thesis provides an alternative technique, granule-based association mining, for knowledge discovery in databases, where a granule refers to a predicate that describes common features of a group of transactions. The new technique first transfers transaction databases into basic decision tables, then uses multi-tier structures to integrate pattern mining and rule generation in one phase for both intra and inter transaction association rule mining. To evaluate the proposed new technique, this research defines the concept of meaningless rules by considering the co-relations between data-dimensions for intratransaction-association rule mining. It also uses precision to evaluate the effectiveness of intertransaction association rules. The experimental results show that the proposed technique is promising.