Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base. Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design. Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up. Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events). Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3. Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D. Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively. Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level. Copyright © 2012 by The Endocrine Society.

An in-vitro 3-D cell culture model for studying pathomechanisms in AMD

Purpose To develop a novel 3-D cell culture model with the view to studying the pathomechanisms underlying the development of age-related macular degeneration (AMD). Our central hypothesis is that the silk structural protein fibroin used in conjunction with cultured human cells can be used to mimic the structural relationships between the RPE and choriocapillaris in health and disease. Methods Co-cultures of human RPE cells (ARPE-19 cells grown in Miller’s medium) and microvascular endothelial cells (HMEC-1 cells grown in endothelial culture medium) were established on opposing sides of a synthetic Bruch’s membrane (3 microns thick) constructed from B mori silk fibroin. Cell attachment was facilitated by pre-coating the fibroin membrane with vitronectin (for ARPE-19 cells) and gelatin (for HMEC-1 cells) respectively. The effects of tropoelastin on attachment of ARPE-19 cells was also examined. Barrier function was examined by measurement of trans-epithelial resistance (TER) using a voltohmmeter (EVOM-2). The phagocytic activity of the synthetic RPE was tested using vitronectin-coated microspheres (2 micron diameter FluoSpheres). In some cultures, membrane defects were created by puncturing within a 24 G needle. The architecture of the synthetic tissue before and after wounding was examined by confocal microscopy after staining for ZO-1 and F-actin. Results The RPE layer of the 3D model developed a cobblestoned morphology (validated by staining for ZO-1 and F-actin), displayed barrier function (validated by measurement of TER) and demonstrated cytoplasmic uptake of vitronectin-coated microspheres. Attachment of ARPE-19 cells to fibroin was unaffected by tropoelastin. Microvascular endothelial cells attached well to the gelatin-coated surface of the fibroin membrane and remained physically separated from the overlaying RPE layer. The fibroin membranes were amenable to puncturing without collapse thus providing the opportunity to study transmembrane migration of the endothelial cells. Conclusions Synthetic Bruch’s membranes constructed from silk fibroin, vitronectin and gelatin, support the co-cultivation of RPE cells and microvascular endothelial cells. The resulting RPE layer displays functions similar to that of native RPE and the entire tri-layered structure displays potential to be used as an in vitro model of choroidal neovascularization.

Fast exact nearest neighbour matching in high dimensions using d-D Sort

Data structures such as k-D trees and hierarchical k-means trees perform very well in approximate k nearest neighbour matching, but are only marginally more effective than linear search when performing exact matching in high-dimensional image descriptor data. This paper presents several improvements to linear search that allows it to outperform existing methods and recommends two approaches to exact matching. The first method reduces the number of operations by evaluating the distance measure in order of significance of the query dimensions and terminating when the partial distance exceeds the search threshold. This method does not require preprocessing and significantly outperforms existing methods. The second method improves query speed further by presorting the data using a data structure called d-D sort. The order information is used as a priority queue to reduce the time taken to find the exact match and to restrict the range of data searched. Construction of the d-D sort structure is very simple to implement, does not require any parameter tuning, and requires significantly less time than the best-performing tree structure, and data can be added to the structure relatively efficiently.

Design approaches for promoting beneficial indoor environments in healthcare facilities : a review

As a result of growing evidence regarding the effects of environmental characteristics on the health and wellbeing of people in healthcare facilities (HCFs), more emphasis is being placed on, and more attention being paid to, the consequences of design choices in HCFs. Therefore, we have critically reviewed the implications of key indoor physical design parameters, in relation to their potential impact on human health and wellbeing. In addition, we discussed these findings within the context of the relevant guidelines and standards for the design of HCFs. A total of 810 abstracts, which met the inclusion criteria, were identified through a Pubmed search, and these covered journal articles, guidelines, books, reports and monographs in the studied area. Of these, 231 full publications were selected for this review. According to the literature, the most beneficial design elements were: single-bed patient rooms, safe and easily cleaned surface materials, sound-absorbing ceiling tiles, adequate and sufficient ventilation, thermal comfort, natural daylight, control over temperature and lighting, views, exposure and access to nature, and appropriate equipment, tools and furniture. The effects of some design elements, such as lighting (e.g. artificial lighting levels) and layout (e.g. decentralized versus centralized nurses’ stations), on staff and patients vary, and “the best design practice” for each HCF should always be formulated in co-operation with different user groups and a multi-professional design team. The relevant guidelines and standards should also be considered in future design, construction and renovations, in order to produce more favourable physical indoor environments in HCFs.

Leveraging R&D Investment for the Australian Built Environment : Industry Report

The overarching goal of this project is to better match funding strategies to industry needs to maximise the benefits of R&D to Australia’s infrastructure and building industry. Project partners are: Queensland Department of Public Works; Queensland Transport and Main Roads; Western Australian Department of Treasury and Finance; John Holland; Queensland University of Technology; Swinburne University of Technology; and VTT Technical Research Centre of Finland (Prof Göran Roos). This project has been endorsed by the Australian Built Environment Industry Innovation Council (BEIIC) with Council member Prof Catherin Bull serving on this project’s Steering Committee. This project seeks to: (i) maximise the value of R&D investment in this sector through improved understanding of future industry research needs; and (ii) address the perceived problem of a disproportionately low R&D investment in this sector, relative to the size and national importance of the sector. This research will develop new theory built on open innovation, dynamic capabilities and absorptive capacity theories in the context of strategic foresighting and roadmapping activities. Four project phases have been designed to address this research: 1: Audit and analysis of R&D investment in the Australian built environment since 1990 - access publically available data relating to R&D investments across Australia from public and private organisations to understand past trends. 2: Examine diffusion mechanisms of research and innovation and its impact on public and private organisations – investigate specific R&D investments to determine the process of realising research support, direction-setting, project engagement, impacts and pathways to adoption. 3: Develop a strategic roadmap for the future of this critical Australian industry - assess the likely future landscapes that R&D investment will both respond to and anticipate. 4: Develop policy to maximise the value of R&D investments to public and private organisations – through translating project learnings into policy guidelines.

Brave new green world : consequences of a carbon economy for the conservation of Australian biodiversity

Pricing greenhouse gas emissions is a burgeoning and possibly lucrative financial means for climate change mitigation. Emissions pricing is being used to fund emissions-abatement technologies and to modify land management to improve carbon sequestration and retention. Here we discuss the principal land-management options under existing and realistic future emissions-price legislation in Australia, and examine them with respect to their anticipated direct and indirect effects on biodiversity. The main ways in which emissions price-driven changes to land management can affect biodiversity are through policies and practices for (1) environmental plantings for carbon sequestration, (2) native regrowth, (3) fire management, (4) forestry, (5) agricultural practices (including cropping and grazing), and (6) feral animal control. While most land-management options available to reduce net greenhouse gas emissions offer clear advantages to increase the viability of native biodiversity, we describe several caveats regarding potentially negative outcomes, and outline components that need to be considered if biodiversity is also to benefit from the new carbon economy. Carbon plantings will only have real biodiversity value if they comprise appropriate native tree species and provide suitable habitats and resources for valued fauna. Such plantings also risk severely altering local hydrology and reducing water availability. Management of regrowth post-agricultural abandonment requires setting appropriate baselines and allowing for thinning in certain circumstances, and improvements to forestry rotation lengths would likely increase carbon-retention capacity and biodiversity value. Prescribed burning to reduce the frequency of high-intensity wildfires in northern Australia is being used as a tool to increase carbon retention. Fire management in southern Australia is not readily amenable for maximising carbon storage potential, but will become increasingly important for biodiversity conservation as the climate warms. Carbon price-based modifications to agriculture that would benefit biodiversity include reductions in tillage frequency and livestock densities, reductions in fertiliser use, and retention and regeneration of native shrubs; however, anticipated shifts to exotic perennial grass species such as buffel grass and kikuyu could have net negative implications for native biodiversity. Finally, it is unlikely that major reductions in greenhouse gas emissions arising from feral animal control are possible, even though reduced densities of feral herbivores will benefit Australian biodiversity greatly.

Decision-making about hormone replacement therapy by women in England and Scotland

OBJECTIVE: The aim of this study was to explore women's decision-making about the balance of risks and benefits of taking hormone replacement therapy (HRT) based on the latest evidence from the Women's Health Initiative (WHI) trial of combined HRT. METHODS: Women aged 50-69 years, who were eligible for the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) trial, were invited to participate in one of eight focus groups. Participants were asked to discuss their views about taking HRT based on the latest international evidence. RESULTS AND CONCLUSIONS: Eighty-two women participated overall. Qualitative content analysis was applied to the discussion transcripts. Women regarded the decisions they make about taking HRT as highly personal, and, for women currently taking HRT, the overwhelming reason for continuation was perceived improvement in quality of life regardless of either the risks or the benefits in the longer term.

Vitamin D status and skin cancer risk independent of time outdoors : 11-year prospective study in and Australian community

Vitamin D may have anti-skin cancer effects, but population-based evidence is lacking. We therefore assessed associations between vitamin D status and skin cancer risk in an Australian subtropical community. We analyzed prospective skin cancer incidence for 11 years following baseline assessment of serum 25(OH)-vitamin D in 1,191 adults (average age 54 years) and used multivariable logistic regression analysis to adjust risk estimates for age, sex, detailed assessments of usual time spent outdoors, phenotypic characteristics, and other possible confounders. Participants with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) versus those below 75 nmol  l(-1) more often developed basal cell carcinoma (odds ratio (OR)=1.51 (95% confidence interval (CI): 1.10-2.07, P=0.01) and melanoma (OR=2.71 (95% CI: 0.98-7.48, P=0.05)). Squamous cell carcinoma incidence tended to be lower in persons with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) compared with those below 75 nmol  l(-1) (OR=0.67 (95% CI: 0.44-1.03, P=0.07)). Vitamin D status was not associated with skin cancer incidence when participants were classified as above or below 50 nmol  l(-1) 25(OH)-vitamin D. Our findings do not indicate that the carcinogenicity of high sun exposure can be counteracted by high vitamin D status. High sun exposure is to be avoided as a means to achieve high vitamin D status.

Sunlight and other determinants of circulating 25-hydroxyvitamin D levels in black and white participants in a nationwide U.S. study

Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n 842), blacks (n 646), and people of other races/ethnicities (n 12). Participants were recruited monthly (20082009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25 of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.

Predicting vitamin D deficiency in older Australian adults

OBJECTIVE There has been a dramatic increase in vitamin D testing in Australia in recent years, prompting calls for targeted testing. We sought to develop a model to identify people most at risk of vitamin D deficiency. DESIGN AND PARTICIPANTS This is a cross-sectional study of 644 60- to 84-year-old participants, 95% of whom were Caucasian, who took part in a pilot randomized controlled trial of vitamin D supplementation. MEASUREMENTS Baseline 25(OH)D was measured using the Diasorin Liaison platform. Vitamin D insufficiency and deficiency were defined using 50 and 25 nmol/l as cut-points, respectively. A questionnaire was used to obtain information on demographic characteristics and lifestyle factors. We used multivariate logistic regression to predict low vitamin D and calculated the net benefit of using the model compared with 'test-all' and 'test-none' strategies. RESULTS The mean serum 25(OH)D was 42 (SD 14) nmol/1. Seventy-five per cent of participants were vitamin D insufficient and 10% deficient. Serum 25(OH)D was positively correlated with time outdoors, physical activity, vitamin D intake and ambient UVR, and inversely correlated with age, BMI and poor self-reported health status. These predictors explained approximately 21% of the variance in serum 25(OH)D. The area under the ROC curve predicting vitamin D deficiency was 0·82. Net benefit for the prediction model was higher than that for the 'test-all' strategy at all probability thresholds and higher than the 'test-none' strategy for probabilities up to 60%. CONCLUSION Our model could predict vitamin D deficiency with reasonable accuracy, but it needs to be validated in other populations before being implemented.

A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P= 0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 μg/week ( ≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).

The changing role of copyright in China’s emergent media economy

This chapter introduces the changing role of copyright in China from a historical perspective. It begins by briefly tracing the history of copyright, from a censorship-related system associated with the emergence of the printing press in imperial China, through modernisation during the Republican period, abolition under communism and finally to the introduction of the People's Republic of China's (PRC) first copyright law in 1990 and the nation's entry into the World Trade Organisation (WTO) in 2001.