Uraemic vascular damage and calcification in children with chronic kidney disease

Summary of thesis: Cardiovascular disease is the most common cause of death in patients with chronic kidney disease. Structural and functional vascular abnormalities and arterial calcification begins early in the course of renal decline and can be found even in children, contributing to their high mortality risk. Through clinical and laboratory studies, this thesis sought to investigate the causes of uraemic vascular damage and calcification in children with chronic kidney disease and on dialysis. Dysregulated mineral metabolism, manifested by hyperparathyroidism and high phosphate, in association with low vitamin D levels, is key to the pathophysiology of ectopic vascular and soft tissue calcification. In addition, a number of treatment- related factors can potentially lead to a high calcium load, contributing to an increased risk of calcification. Importantly, these are modifiable risk factors and have been associated with an increased mortality risk in adult dialysis patients. Using established surrogate measures of vascular damage, carotid artery intima media thickness, pulse wave velocity and multi-slice CT scan, I have studied a cohort of children on chronic dialysis, and shown that those with mean parathyroid hormone levels above twice the upper limit of normal had increased vascular thickness, stiffer vessels and a higher prevalence of coronary artery calcification, whereas those with lower levels had vascular measures that were similar to age-matched controls. Also, a higher vitamin D dosage was associated with thicker vessels and coronary calcification. To explore this association, in a further study I have measured the levels of 25-hydroxy and 1,25-dihydroxy vitamin D and shown that both low and high levels of 1,25-dihydroxy vitamin D are associated with thicker vessels and calcification. Also, 1,25-dihydroxy vitamin D showed a strong inverse association with high sensitivity CRP, and we speculate that vitamin D’s influence on calcium-phosphate homeostasis and inflammation may be lead to this bimodal effect. Levels of the circulating calcification inhibitors, fetuin-A, osteoprotegerin and Matrix Gla-protein, may influence an individual patients’ susceptibility to calcify, and but have not been described in children. I found that these levels influenced vascular stiffness and calcification, and that there may be a protective upregulation of fetuin-A in the early stages of exposure to a pro-calcific and pro-inflammatory uraemic environment. In a subsequent translational study I have sought to find direct evidence of vascular damage and calcification in the vessels. Using intact human arteries removed at the time of routine surgery, I have shown that calcium accumulation begins pre-dialysis, but dialysis induced vascular smooth muscle cell apoptosis coupled with osteo/chondrocytic transformation and a loss of the normal calcification inhibitors leads to overt calcification. Our currently available clinical measures are not sensitive enough to detect the earliest stages of calcification. On in vitro culture in calcifying media, dialysis but not control vessels showed accelerated time-dependent calcification, suggesting that these vessels had lost their smooth muscle cell defence mechanisms and were primed to undergo rapid calcification. Apoptotic cell death was a key event that triggerred calcification, and this was a vesicle mediated process, possibly involving oxidative DNA damage. This thesis investigates the role of modifiable risk factors in uraemic vascular damage and calcification in children with CKD and explores the earliest changes in the pathophysiology of uraemic medial calcification in intact human vessels

Surprising differences, hidden difficulties: findings from a teacher education pilot

Conference Theme: Education for a Global Networked SocietyPaper PresentationIn the last several years, Hong Kong has undergone significant changes in quality assurance and enhancement at the tertiary level. Within this context, the Hong Kong Institute of Education, the region's largest teacher education provider has conducted an exploration of an outcome-based approach to course design, implementation and assessment within teacher education programs. This paper reports findings from an institute-wide pilot study on OBL ...postprin

Achieving Optimal Throughput and Near-Optimal Asymptotic Delay Performance in Multi-Channel Wireless Networks with Low Complexity: A Practical Greedy Scheduling Policy

In this paper, we focus on the scheduling problem in multi-channel wireless networks, e.g., the downlink of a single cell in fourth generation (4G) OFDM-based cellular networks. Our goal is to design practical scheduling policies that can achieve provably good performance in terms of both throughput and delay, at a low complexity. While a class of $O(n^{2.5} \log n)$-complexity hybrid scheduling policies are recently developed to guarantee both rate-function delay optimality (in the many-channel many-user asymptotic regime) and throughput optimality (in the general non-asymptotic setting), their practical complexity is typically high. To address this issue, we develop a simple greedy policy called Delay-based Server-Side-Greedy (D-SSG) with a \lower complexity $2n^2+2n$, and rigorously prove that D-SSG not only achieves throughput optimality, but also guarantees near-optimal asymptotic delay performance. Specifically, we show that the rate-function attained by D-SSG for any delay-violation threshold $b$, is no smaller than the maximum achievable rate-function by any scheduling policy for threshold $b-1$. Thus, we are able to achieve a reduction in complexity (from $O(n^{2.5} \log n)$ of the hybrid policies to $2n^2 + 2n$) with a minimal drop in the delay performance. More importantly, in practice, D-SSG generally has a substantially lower complexity than the hybrid policies that typically have a large constant factor hidden in the $O(\cdot)$ notation. Finally, we conduct numerical simulations to validate our theoretical results in various scenarios. The simulation results show that D-SSG not only guarantees a near-optimal rate-function, but also empirically is virtually indistinguishable from delay-optimal policies.Comment: Accepted for publication by the IEEE/ACM Transactions on Networking, February 2014. A preliminary version of this work was presented at IEEE INFOCOM 2013, Turin, Italy, April 201

Dietary calcium intake does not meet the nutritional requirements of children with chronic kidney disease and on dialysis

Background: Adequate calcium (Ca) intake is required for bone mineralization in children. We assessed Ca intake from diet and medications in children with CKD stages 4–5 and on dialysis (CKD4–5D) and age-matched controls, comparing with the UK Reference Nutrient Intake (RNI) and international recommendations. Methods: Three-day prospective diet diaries were recorded in 23 children with CKD4–5, 23 with CKD5D, and 27 controls. Doses of phosphate (P) binders and Ca supplements were recorded. Results: Median dietary Ca intake in CKD4–5D was 480 (interquartile range (IQR) 300–621) vs 724 (IQR 575–852) mg/day in controls (p = 0.00002), providing 81% vs 108% RNI (p = 0.002). Seventy-six percent of patients received  200% RNI. Three children (6%) exceeded the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) upper limit of 2500 mg/day. None with a total Ca intake  2 × RNI was hypercalcemic. Conclusions: Seventy-six percent of children with CKD4–5D had a dietary Ca intake < 100% RNI. Restriction of dairy foods as part of a P-controlled diet limits Ca intake. Additional Ca from medications is required to meet the KDOQI guideline of 100–200% normal recommended Ca intake

Assessing Individual-level Factors Supporting Student Intrinsic Motivation in Online Discussions: A Qualitative Study

Research has established that intrinsic motivation has a positive effect on learning and academic achievement. However, little is known about the impact of different technology-supported learning activities on student intrinsic motivation or whether such learning activities significantly enhance student intrinsic motivation compared to traditional classroom environments without technological support. In order to investigate the phenomenon of intrinsic motivation in technology-supported learning environments, this paper examines factors that support individual student intrinsic motivation in online discussions. A research model is presented based on research into motivation, and the specific areas of self-determination and curiosity provide a framework for the model. A qualitative research methodology is used to validate the model. Results from the study indicate that five factors; perceived competence, perceived challenge, feedback, perceived interest and perceived curiosity, were strongly supported, with partial support for the construct of perceived choice

Sociocultural Learning: A Perspective on GSS-Enabled Global Education

Virtual teams are rapidly developing in organisations of the new economy. As educators, we have a responsibility to ensure that our students are appropriately prepared for work in the virtual workspace, where teams may cross time, geographical, and cultural boundaries. In this article, the culturally sensitive theory of sociocultural learning is combined with GSS (Group Support Systems) in an illustration of how cross-cultural, globally distributed virtual teams of students located in The Netherlands, Greece, and Hong Kong work on vested interest projects. Finally, a set of critical success factors that inform virtual learning contexts is derived from our findings and recommendations are made for operational practice in the virtual work space

Child Nutritional Status, Feeding Practices and Women's Autonomy in Rural Andhra Pradesh, India

Childhood under-nutrition is a prevalent public health issue through out the developing world. In recent surveys, such as the one carried out by the National Nutrition Monitoring Bureau, India, poor dietary intakes (energy, protein and micro-nutrients) and nutrition status was evident among 0-3 year old children, even in families where the adults meet their daily dietary requirements (NNMB, 2001). This indicates that availability of food may not be the only necessarily cause of under-nutrition among the under three-year-olds in such families. Further, recent research postulates the linkage between women's autonomy and child health, particularly in countries such as India where mothers play a vital role in childcare. This dissertation investigates the influence of maternal autonomy on child feeding and child nutritional status in a sequence of three essays. In the first essay, using logistic regression, we examine the overall effect of mother's autonomy on child stunting using a secondary dataset from the state of Andhra Pradesh (AP) in India. In particular we examine the influence of indicators of autonomy on child stunting. Our results show financial independence and not needing permission to go to the local market have a positive impact in reducing child stunting. In the second essay, we further investigate the role of woman's autonomy on feeding behavior through a set of qualitative interviews, conducted among a sample of 43 mothers in 3 rural villages of Andhra Pradesh, India. In particular, we explored the perception and beliefs regarding women's autonomy and environmental factors such as income and family structure and their influence on infant feeding practices. We find that not only does mother's autonomy play a role in the woman seeking information through formal health care system for a her to introduce foods and liquids to the infant, but the family structure and the cultural norms surrounding the mother-child environment also plays an important role in child feeding practices. In our third essay, using structural equation modeling approach, we examine the impact of seven latent dimensions of maternal autonomy on infant feeding practice. Our results indicate that mothers with higher autonomy [indicated by financial autonomy and decrease experience of domestic violence] are more likely to breastfeed 3-5 month old infants. Mothers in joint family households are more likely to have infants with poor growth. Overall, these results suggest that improving certain dimensions of maternal autonomy will have a positive impact on infant care and growth outcomes in rural settings of India. Future research should consider autonomy as a multi-dimensional concept to examine the influence of individual dimension of autonomy on health behaviors and health outcomes