Iron oxide particles for atheroma imaging

The selection of patients for vascular interventions has been solely based on luminal stenosis and symptomatology. However, histological data from both the coronary and carotid vasculature suggest that other plaque features such as inflammation may be more important in predicting future thromboembolic events. Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents have been used for noninvasive MRI assessment of atherosclerotic plaque inflammation in humans. It has reached the stage of development to have been recently used in an interventional drug study to not only assess inflammatory progression but also select patients at high risk. This article reviews the basic science behind the use of USPIO contrast agents in atheroma MR imaging, experimental work in animals, and how this has led to the emergence of this promising targeted imaging platform for assessment of high risk carotid atherosclerosis in humans.

The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease

Objectives: The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. Background: Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. Methods: Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (ΔSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. Results: Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (ΔSI 0.13; p = 0.0003) and at 12 weeks (ΔSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. Conclusions: Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: An ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study

Introduction: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). Methods: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. Results: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p < 0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p < 0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p = 0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p < 0.001). Conclusions: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

In vivo positive contrast IRON sequence and quantitative T2* measurement confirms inflammatory burden in a patient with asymptomatic carotid atheroma after USPIO-enhanced MR Imaging

The authors report an in vivo human examination of carotid atheroma by using the inversion-recovery ON resonance (IRON) sequence, which is able to produce positive contrast after the infusion of an ultrasmall super paramagnetic iron oxide (USPIO) contrast medium. This technique provides a method of potentially identifying inflammatory burden within carotid atheroma. This may be particularly useful in patients who currently do not meet criteria for intervention (ie, moderate symptomatic stenosis or <70% asymptomatic stenosis) to further risk-stratify this important patient cohort. A 63-year-old man was imaged at 1.5 T before and 36 hours after USPIO infusion by using the IRON sequence. Regions of interest showing profound signal loss at T2*-weighted imaging corresponded well with regions of positive contrast at IRON imaging after the administration of USPIO. These regions also showed a profound decrease in T2* measurements after USPIO infusion, whereas surrounding tissue did not. It has been shown that such strong signal loss on T2*-weighted images after USPIO infusion is indicative of USPIO uptake.

Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI

BACKGROUND AND PURPOSE It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. METHODS Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. RESULTS There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). CONCLUSIONS - This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Using global formulary apportionment for international profit allocation: The case of Indonesia's mining industry

My thesis examined an alternative approach, referred to as the unitary taxation approach to the allocation of profit, which arises from the notion that as a multinational group exists as a single economic entity, it should be taxed as one taxable unit. The plausibility of a unitary taxation regime achieving international acceptance and agreement is highly contestable due to its implementation issues, and economic and political feasibility. Using a case-study approach focusing on Freeport-McMoRan and Rio Tinto's mining operations in Indonesia, this thesis compares both tax regimes against the criteria for a good tax system - equity, efficiency, neutrality and simplicity. This thesis evaluates key issues that arise when implementing a unitary taxation approach with formulary apportionment based on the context of mining multinational firms in Indonesia.

Aging-in-place: Perspectives from the construction industry

Older adults report a desire to remain within the preferred environment for as long as possible. This desire is referred to as aging-in-place. Aging-in-place integrates housing and care options. Factors affecting the ability to remain within the preferred environment include current home designs, access to housing choices, social support networks, and community services, to name a few. Research supports physical and psychosocial benefits of aging-in-place for the individual. Home modifications have the potential to influence the quality of life in a number of positive directions that range from personal mobility to community engagement. Modifications range from minor to significant. Financial resources, contractor interest and expertise, consumer awareness and consumer opportunity affect the degree of change. Increasingly, construction professionals express an interest in learning more about aging-in place. Queries ranged from obtaining a greater understanding of the meaning of the concept, impact of demographic change on housing stock, and increased awareness of universal design features. This paper presents findings from a survey administered to current members of the Canadian Home Builders’ Association – Calgary Regional Office. Within this presentation, we report findings on members understanding of demographic change and the effect of this change on the current and future housing stock. We discuss perceived barriers and benefits of the development of business models to support aging-in-place. Finally, we conclude with discussion of educational support to enhance the understanding of aging-in-place.

Job-related diversity and team performance: An empirical analysis of the US music industry

A significant amount of research has been carried out to investigate the existing bonds between team characteristics and team outcomes in contexts of social creativity. Specifically, how work group diversity affects its performance is of great relevance but unfortunately, there is no clear understanding of the diversity-performance relationship. Therefore, to improve our understanding of this phenomenon, it would be worthwhile to investigate further empirical settings. For this reason, we decided to study the music industry that, to our knowledge, has never been chosen as empirical setting for the application of the theoretical constructs linked to the topic of team diversity and performance. Our research aims at analyze the US music industry to study the relationship between job-related characteristics of team diversity and team performances.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Comparative study on green building supportive policies of pacific-rim countries most vulnerable to climate change

- Problem Climate change is affecting the world in numerous ways such as increased temperatures, sea level rise, and increased droughts and floods. Governments worldwide, especially in the most vulnerable countries, are urged to seek better solutions for sustainable development. The construction industry and buildings have enormous impacts on humans and the environment, meaning green building must be one of the solutions. Government involvement is widely considered as one of the essential and most effective ways to promote green building and drive the construction market towards sustainability. This paper will review green building policy of the Pacific-Rim countries that are most vulnerable to climate change according to the recent Standard and Poor’s ranking, including: Cambodia, Vietnam, Fiji, Philippines, Papua New Guinea and Indonesia. Methodology: This paper will review policy related publications including journal and conference papers, portal websites of governments, legislation documents and reports of international organisations. It will focus on the policies and governmental instruments that support the adoption of green building practices. - Findings All six governments have launched climate change adaptation policies, showing a great concern regarding the damages caused by the phenomenon. All countries except Papua New Guinea have promulgated energy efficiency policy and programs which indirectly promote the adoption of green building practices. The comparison study shows that Philippines and Indonesia motivate the adoption of renewable energy generation, energy efficiency and green building through either financial or advocacy instruments, while other four countries tend to implement regulatory tools to mandate energy conservation. Through comparison, Cambodia and Vietnam – the two countries providing vision to develop green building - can learn from Philippines and Indonesia’s policy and instruments. - Research limitations Language differences between the countries and limit of formal sources may pose difficulties in searching for information. While much English language literature exists, sources from Cambodia, Philippines and Indonesia are less accessible. - Takeaway for practice As the paper provides more understanding about the supportive policy of those countries, it will introduce more opportunities for green property developers to invest in construction markets of those Pacific-Rim countries. - Originality There is little research reviewing green building supportive policies of developing and less-wealthy countries that are forecasted to be most vulnerable and most impacted by climate change. The originality of this paper lies in its investigation on how those countries intend to respond to this phenomenon and whether and to what extent they support the green building market by using policy tools.

A design approach to innovation in the Australian energy industry

Electricity businesses across Australia are facing many market disruptions, such as the increasing demand from the rapid uptake of domestic air conditioners and the contrasting problematic generation from solar power connections to the grid. In this context, the opportunity to proactively leverage forthcoming technological advances in battery storage and electric vehicles to address the steeply rising cost of electricity supply has emerged. This research explores a design approach to support a business to navigate such disruptions in the current market.This study examines a design-led approach to innovation conducted over a ten month action research study within a large, risk-averse firm in the Australian energy sector. This article presents results describing a current foresight gap within the business; the response of the business to using design-led innovation to address this issue; and the tools, approaches and processes used. The business responses indicate their perception of the value of qualitative customer engagement as a path to addressing, and potentially benefiting from, disruptive innovation. It is anticipated that these results will further business model development within the company, and assist in leveraging disruptive innovations for this industry participant, thus limiting future increases in the cost of electricity supply for customers in Australia.

Australian feature films and distribution: Industry or cottage industry?

Feature films remain critical flagships to any national film industry. Australian feature films can be highly commercial endeavours that also perform symbolic functions by embodying the national imaginary in big screen based sound and imagery. They conduct a dialogue with domestic audiences as well as showcase key aspects of Australia in the global film festival circuit. As the pre-eminent filmmaking form, feature films also serve as important launchpads for the careers of many Australian writers, directors, actors and technical crew. In the wake of over a decade of diminished share of local box office obtained by Australian feature films, Australian Feature Films and Distribution: Industry or cottage industry, examines issues in the production sector affecting the performance of Australian feature films and some responses by the central funding and support screen agency, Screen Australia.

Using Big Data to manage safety-related risk in the upstream oil and gas industry: A research agenda

Despite considerable effort and a broad range of new approaches to safety management over the years, the upstream oil & gas industry has been frustrated by the sector’s stubbornly high rate of injuries and fatalities. This short communication points out, however, that the industry may be in a position to make considerable progress by applying “Big Data” analytical tools to the large volumes of safety-related data that have been collected by these organizations. Toward making this case, we examine existing safety-related information management practices in the upstream oil & gas industry, and specifically note that data in this sector often tends to be highly customized, difficult to analyze using conventional quantitative tools, and frequently ignored. We then contend that the application of new Big Data kinds of analytical techniques could potentially reveal patterns and trends that have been hidden or unknown thus far, and argue that these tools could help the upstream oil & gas sector to improve its injury and fatality statistics. Finally, we offer a research agenda toward accelerating the rate at which Big Data and new analytical capabilities could play a material role in helping the industry to improve its health and safety performance.

Knowledge management research in the construction industry: a review

Purpose: Knowledge management (KM) is important to the knowledge-intensive construction industry. The diversified and changing nature of works in this field warrants us to stocktake, identify changes and map out KM research framework for future exploration. Design/methodology/approach: The study involves three aspects. First, three stages of KM research in construction were distinguished in terms of the time distribution of 217 target publications. Major topics in the stages were extracted for understanding the changes of research emphasis from evolutionary perspective. Second, the past works were summed up in a three-dimensional research framework in terms of management organization, managerial methodology and approach, and managerial objective. Finally, potential research orientations in the future were predicted to expand the existing research framework. Findings: It was found that (1) KM research has significantly blossomed in the last two decades with a great potential; (2) major topics of KM were changing in terms of technology, technique, organization, attribute of knowledge and research objectives; (3) past KM studies centred around management organization, managerial methodology and approach, and managerial objective thus a three-dimensional research framework was proposed; (4) within the research framework, team-level, project-level and firm-level KM were studied to achieve project, organizational and competitive objectives by integrated methodologies of information technology, social technique and KM process tool; and (5) nine potential research orientations were predicted corresponding to the three dimensions. Finally, an expanded research framework was proposed to encourage and guide future research works in this field. Research limitations/implications: The paper only focused on the construction industry. The findings need further exploration in order to discover any possible missing important research works which were not published in English or not included in the time period. Originality/value: The paper formed a systematic framework of KM research in construction and predicted the potential research orientations. It provides much value for the researchers who want to understand the past and the future of global KM research in the construction industry.

Molecular and biochemical characterisation of transgenic banana lines containing iron uptake and storage enhancing genes

This thesis investigated the basis for availability of iron (Fe) and zinc (Zn) content in different banana fruits grown in Uganda and Australia. Rather than micronutrient content levels in different banana cultivar, genotype and environment interactions explained much of the differences. Such information should provide important insights for future developments in the biofortification of banana. Bananas consumed in Uganda did not contain sufficient levels of Fe and Zn that meet the nutrient requirements for vulnerable groups.