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.

An historical analysis of the development of thinking in the principal writings of Malcolm Knowles

Malcolm Shepherd Knowles was a key writer and theorist in the field of adult education in the United States. He died in 1997 and left a large legacy of books and journal articles. This thesis traced the development of his thinking over the 46-year period from 1950 to 1995. It examined the 25 works authored, co-authored, edited, reissued and revised by him during that period. The writings were scrutinised using a literature research methodology to expose the theoretical content, and a history of thought lens to identify and account for the development of major ideas. The methodology enabled a gradual unfolding of the history. A broadly-consistent and sequential pattern of thought focusing on the notion of andragogy emerged. The study revealed that after the initial phases of exploratory thinking, Knowles developed a practical-theoretical framework he believed could function as a comprehensive theory of adult learning. As his thinking progressed, his theory developed into a unified framework for human resource development and, later, into a model for the development of self-directed lifelong learners. The study traced the development of Knowles’ thinking through the phases of thought, identified the writings that belonged within each phase and produced a series of diagrammatic representations showing the evolution of his conceptual framework. The production of a history of the development of Knowles’ thought is the major outcome of the study. In addition to plotting the narrative sequence of thought-events, the history helps to explicate the factors and conditions that influenced Knowles’ thinking and to show the interrelationships between ideas. The study should help practitioners in their use and appreciation of Knowles’ works.

The historical understandings : an overview

This chapter will explore some of the pioneering ideas about adolescence. It begins with origin of the word 'adolescence,' before probing into various perspectives related to the emergence of modern day adolescent. It then offers a look at the theoretical models of adolescence. Finally, it looks at the evolution of an adolescent in the school...

Adiabatic compression testing - part I : historical development and evaluation of fluid dynamic processes including shock-wave considerations

Adiabatic compression testing of components in gaseous oxygen is a test method that is utilized worldwide and is commonly required to qualify a component for ignition tolerance under its intended service. This testing is required by many industry standards organizations and government agencies. This paper traces the background of adiabatic compression testing in the oxygen community and discusses the thermodynamic and fluid dynamic processes that occur during rapid pressure surges. This paper is the first of several papers by the authors on the subject of adiabatic compression testing and is presented as a non-comprehensive background and introduction.

Disclosure in insurance law : contemporary and historical economic considerations

This article examines the importance of accurate classification and identification of risk with particular reference to the problem of adverse selection. It is argued that, historically, this concern was the paramount consideration influencing standard form contract formation and disclosure laws. The scope of its relevance today however is less apparent in that contemporary insurance contracting is conducted in a vastly different environment from that which prevailed at the time Lloyd's was better known as a coffee house. Accordingly, the second part of this article looks at the contemporary framework of information disclosure and those dynamics within it designed to elicit information weighing on risk forecasting : specifically, (a) direct inquiry and testing requirements; (b) signaling - or incentive based structuring of insurance contractual and (c) bargaining in the shadow of the utmost good faith doctrine. Finally, certain conclusions arising out of contemporary and historical economic considerations underpinning disclosure in insurance law are outlined.

A secure framework and related protocols for ubiquitous access to electronic health records using Java sim cards

Ubiquitous access to patient medical records is an important aspect of caring for patient safety. Unavailability of sufficient medical information at the point-ofcare could possibly lead to a fatality. The U.S. Institute of Medicine has reported that between 44,000 and 98,000 people die each year due to medical errors, such as incorrect medication dosages, due to poor legibility in manual records, or delays in consolidating needed information to discern the proper intervention. In this research we propose employing emergent technologies such as Java SIM Cards (JSC), Smart Phones (SP), Next Generation Networks (NGN), Near Field Communications (NFC), Public Key Infrastructure (PKI), and Biometric Identification to develop a secure framework and related protocols for ubiquitous access to Electronic Health Records (EHR). A partial EHR contained within a JSC can be used at the point-of-care in order to help quick diagnosis of a patient’s problems. The full EHR can be accessed from an Electronic Health Records Centre (EHRC) when time and network availability permit. Moreover, this framework and related protocols enable patients to give their explicit consent to a doctor to access their personal medical data, by using their Smart Phone, when the doctor needs to see or update the patient’s medical information during an examination. Also our proposed solution would give the power to patients to modify the Access Control List (ACL) related to their EHRs and view their EHRs through their Smart Phone. Currently, very limited research has been done on using JSCs and similar technologies as a portable repository of EHRs or on the specific security issues that are likely to arise when JSCs are used with ubiquitous access to EHRs. Previous research is concerned with using Medicare cards, a kind of Smart Card, as a repository of medical information at the patient point-of-care. However, this imposes some limitations on the patient’s emergency medical care, including the inability to detect the patient’s location, to call and send information to an emergency room automatically, and to interact with the patient in order to get consent. The aim of our framework and related protocols is to overcome these limitations by taking advantage of the SIM card and the technologies mentioned above. Briefly, our framework and related protocols will offer the full benefits of accessing an up-to-date, precise, and comprehensive medical history of a patient, whilst its mobility will provide ubiquitous access to medical and patient information everywhere it is needed. The objective of our framework and related protocols is to automate interactions between patients, healthcare providers and insurance organisations, increase patient safety, improve quality of care, and reduce the costs.

Privacy and trust management for electronic health records

Establishing a nationwide Electronic Health Record system has become a primary objective for many countries around the world, including Australia, in order to improve the quality of healthcare while at the same time decreasing its cost. Doing so will require federating the large number of patient data repositories currently in use throughout the country. However, implementation of EHR systems is being hindered by several obstacles, among them concerns about data privacy and trustworthiness. Current IT solutions fail to satisfy patients’ privacy desires and do not provide a trustworthiness measure for medical data. This thesis starts with the observation that existing EHR system proposals suer from six serious shortcomings that aect patients’ privacy and safety, and medical practitioners’ trust in EHR data: accuracy and privacy concerns over linking patients’ existing medical records; the inability of patients to have control over who accesses their private data; the inability to protect against inferences about patients’ sensitive data; the lack of a mechanism for evaluating the trustworthiness of medical data; and the failure of current healthcare workflow processes to capture and enforce patient’s privacy desires. Following an action research method, this thesis addresses the above shortcomings by firstly proposing an architecture for linking electronic medical records in an accurate and private way where patients are given control over what information can be revealed about them. This is accomplished by extending the structure and protocols introduced in federated identity management to link a patient’s EHR to his existing medical records by using pseudonym identifiers. Secondly, a privacy-aware access control model is developed to satisfy patients’ privacy requirements. The model is developed by integrating three standard access control models in a way that gives patients access control over their private data and ensures that legitimate uses of EHRs are not hindered. Thirdly, a probabilistic approach for detecting and restricting inference channels resulting from publicly-available medical data is developed to guard against indirect accesses to a patient’s private data. This approach is based upon a Bayesian network and the causal probabilistic relations that exist between medical data fields. The resulting definitions and algorithms show how an inference channel can be detected and restricted to satisfy patients’ expressed privacy goals. Fourthly, a medical data trustworthiness assessment model is developed to evaluate the quality of medical data by assessing the trustworthiness of its sources (e.g. a healthcare provider or medical practitioner). In this model, Beta and Dirichlet reputation systems are used to collect reputation scores about medical data sources and these are used to compute the trustworthiness of medical data via subjective logic. Finally, an extension is made to healthcare workflow management processes to capture and enforce patients’ privacy policies. This is accomplished by developing a conceptual model that introduces new workflow notions to make the workflow management system aware of a patient’s privacy requirements. These extensions are then implemented in the YAWL workflow management system.

A secure framework and related protocols for ubiquitous access to electronic health records using Java SIM cards

Ubiquitous access to patient medical records is an important aspect of caring for patient safety. Unavailability of sufficient medical information at the patient point-of-care could possibly lead to a fatality. In this paper we propose employing emergent technologies such as Java SIM Cards (JSC),Smart Phones (SP), Next Generation Networks (NGN), Near Field Communications (NFC), Public Key Infrastructure (PKI), and Biometric Identification to develop a secure framework and related protocols for ubiquitous access to Electronic Health Records (EHRs). A partial EHR contained within a JSC can be used at the patient point-of-care in order to help quick diagnosis of a patient’s problems. The full EHR can be accessed from an Electronic Healthcare Records Centre (EHRC).

Influence of historical landscapes, drainage evolution and ecological traits on patterns of genetic diversity in Southeast Asian freshwater snakehead fishes

Snakehead fishes in the family Channidae are obligate freshwater fishes represented by two extant genera, the African Parachannna and the Asian Channa. These species prefer still or slow flowing water bodies, where they are top predators that exercise high levels of parental care, have the ability to breathe air, can tolerate poor water quality, and interestingly, can aestivate or traverse terrestrial habitat in response to seasonal changes in freshwater habitat availability. These attributes suggest that snakehead fishes may possess high dispersal potential, irrespective of the terrestrial barriers that would otherwise constrain the distribution of most freshwater fishes. A number of biogeographical hypotheses have been developed to account for the modern distributions of snakehead fishes across two continents, including ancient vicariance during Gondwanan break-up, or recent colonisation tracking the formation of suitable climatic conditions. Taxonomic uncertainty also surrounds some members of the Channa genus, as geographical distributions for some taxa across southern and Southeast (SE) Asia are very large, and in one case is highly disjunct. The current study adopted a molecular genetics approach to gain an understanding of the evolution of this group of fishes, and in particular how the phylogeography of two Asian species may have been influenced by contemporary versus historical levels of dispersal and vicariance. First, a molecular phylogeny was constructed based on multiple DNA loci and calibrated with fossil evidence to provide a dated chronology of divergence events among extant species, and also within species with widespread geographical distributions. The data provide strong evidence that trans-continental distribution of the Channidae arose as a result of dispersal out of Asia and into Africa in the mid–Eocene. Among Asian Channa, deep divergence among lineages indicates that the Oligocene-Miocene boundary was a time of significant species radiation, potentially associated with historical changes in climate and drainage geomorphology. Mid-Miocene divergence among lineages suggests that a taxonomic revision is warranted for two taxa. Deep intra-specific divergence (~8Mya) was also detected between C. striata lineages that occur sympatrically in the Mekong River Basin. The study then examined the phylogeography and population structure of two major taxa, Channa striata (the chevron snakehead) and the C. micropeltes (the giant snakehead), across SE Asia. Species specific microsatellite loci were developed and used in addition to a mitochondrial DNA marker (Cyt b) to screen neutral genetic variation within and among wild populations. C. striata individuals were sampled across SE Asia (n=988), with the major focus being the Mekong Basin, which is the largest drainage basin in the region. The distributions of two divergent lineages were identified and admixture analysis showed that where they co-occur they are interbreeding, indicating that after long periods of evolution in isolation, divergence has not resulted in reproductive isolation. One lineage is predominantly confined to upland areas of northern Lao PDR to the north of the Khorat Plateau, while the other, which is more closely related to individuals from southern India, has a widespread distribution across mainland SE Asian and Sumatra. The phylogeographical pattern recovered is associated with past river networks, and high diversity and divergence among all populations sampled reveal that contemporary dispersal is very low for this taxon, even where populations occur in contiguous freshwater habitats. C. micropeltes (n=280) were also sampled from across the Mekong River Basin, focusing on the lower basin where it constitutes an important wild fishery resource. In comparison with C. striata, allelic diversity and genetic divergence among populations were extremely low, suggesting very recent colonisation of the greater Mekong region. Populations were significantly structured into at least three discrete populations in the lower Mekong. Results of this study have implications for establishing effective conservation plans for managing both species, that represent economically important wild fishery resources for the region. For C. micropeltes, it is likely that a single fisheries stock in the Tonle Sap Great Lake is being exploited by multiple fisheries operations, and future management initiatives for this species in this region will need to account for this. For C. striata, conservation of natural levels of genetic variation will require management initiatives designed to promote population persistence at very localised spatial scales, as the high level of population structuring uncovered for this species indicates that significant unique diversity is present at this fine spatial scale.

Sustainable fashion textiles design : value adding through technological enhancement

A key concern in the field of contemporary fashion/textiles design is the emergence of ‘fast fashion’: best explained as "buy it Friday, wear it Saturday and throw it away on Sunday" (O'Loughlin, 2007). In this contemporary retail atmosphere of “pile it high: sell it cheap” and “quick to market”, even designer goods have achieved a throwaway status. This modern culture of consumerism is the antithesis of sustainability and is proving a dilemma surrounding sustainable practice for designers and producers in the disciplines (de Blas, 2010). Design researchers including those in textiles/fashion have begun to explore what is a key question in the 21st century in order to create a vision and reason for their disciplines: Can products be designed to have added value to the consumer and hence contribute to a more sustainable industry? Fashion Textiles Design has much to answer for in contributing to the problems of unsustainable practices on a global scale in design, production and waste. However, designers within this field also have great potential to contribute to practical ‘real world’ solutions. ----- ----- This paper provides an overview of some of the design and technological developments from the fashion/textiles industry, endorsing a model where designers and technicians use their transferrable skills for wellbeing rather than desire. Smart materials in the form of responsive and adaptive fibres and fabrics combined with electro active devices, and ICT are increasingly shaping many aspects of society particularly in the leisure industry and interactive consumer products are ever more visible in healthcare. Combinations of biocompatible delivery devices with bio sensing elements can create analyse, sense and actuate early warning and monitoring systems which can be linked to data logging and patient records via intelligent networks. Patient sympathetic, ‘smart’ fashion/textiles applications based on interdisciplinary expertise utilising textiles design and technology is emerging. An analysis of a series of case studies demonstrates the potential of fashion textiles design practitioners to exploit the concept of value adding through technological garment and textiles applications and enhancement for health and wellbeing and in doing so contribute to a more sustainable future fashion/textiles design industry.

The influence of underreported crashes on hotspot identification

Hot spot identification (HSID) plays a significant role in improving the safety of transportation networks. Numerous HSID methods have been proposed, developed, and evaluated in the literature. The vast majority of HSID methods reported and evaluated in the literature assume that crash data are complete, reliable, and accurate. Crash under-reporting, however, has long been recognized as a threat to the accuracy and completeness of historical traffic crash records. As a natural continuation of prior studies, the paper evaluates the influence that under-reported crashes exert on HSID methods. To conduct the evaluation, five groups of data gathered from Arizona Department of Transportation (ADOT) over the course of three years are adjusted to account for fifteen different assumed levels of under-reporting. Three identification methods are evaluated: simple ranking (SR), empirical Bayes (EB) and full Bayes (FB). Various threshold levels for establishing hotspots are explored. Finally, two evaluation criteria are compared across HSID methods. The results illustrate that the identification bias—the ability to correctly identify at risk sites--under-reporting is influenced by the degree of under-reporting. Comparatively speaking, crash under-reporting has the largest influence on the FB method and the least influence on the SR method. Additionally, the impact is positively related to the percentage of the under-reported PDO crashes and inversely related to the percentage of the under-reported injury crashes. This finding is significant because it reveals that despite PDO crashes being least severe and costly, they have the most significant influence on the accuracy of HSID.