An Effective Strategy for the Synthesis of Biocompatible Gold Nanoparticles Using Cinnamon Phytochemicals for Phantom CT Imaging and Photoacoustic Detection of Cancerous Cells

This is a post-print version of the Pharmaceutical Research Article. The original publication is available at www.springerlink.com. DOI 10.1007/s11095-010-0276-6Purpose: The purpose of the present study was to explore the utilization of cinnamon coated gold nanoparticles (Cin-AuNPs) as CT/optical contrast enhancement agent for detection of cancer cells. Methods: Cin-AuNPs were synthesized by a “Green” procedure and the detailed characterization has been performed by physic-chemical analysis. Cytotoxicity and cellualar uptake studies were carried out in normal human fibroblast and cancerous (PC-3 and MCF-7) cells respectively. The efficacy of detecting cancerous cells was monitored using photoacoustic technique. In vivo biodistribution was studied after IV injection of Cin-AuNPs in mice and a CT phantom model was generated. Results: Biocompatible Cin-AuNPs were synthesized with high purity. Significant uptake of these gold nanoparticles was observed in PC-3 and MCF-7 cells. Cin-AuNPs internalized in cancerous cells facilitate detectable photoacoustic signals. In vivo biodistribution in normal mouse shows steady accumulation of gold nanoparticles in lungs and rapid clearance from blood. Quantitative analysis of CT values in phantom model reveals that the cinnamon phytochemicals coated AuNPs has reasonable attenuation efficiency. Conclusions: The results indicate that these non-toxic Cin-AuNPs can serve as excellent CT/ photoacoustic contrast enhancement agents and may provide a novel approach toward the tumor detection through nanopharmaceuticals.This work has been supported by grants from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program (grant number: 5R01CA119412-01), NIH - 1R21CA128460-01; NIH-SBIR-Contract no. 241, and University of Missouri-Research Board - Program C8761 RB 06-030

Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers

Regional disparities in the beneficial effects of rising CO2 concentrations on crop water productivity

Rising atmospheric CO2 concentrations ([CO2]) are expected to enhance photosynthesis and reduce crop water use1. However, there is high uncertainty about the global implications of these effects for future crop production and agricultural water requirements under climate change. Here we combine results from networks of field experiments1, 2 and global crop models3 to present a spatially explicit global perspective on crop water productivity (CWP, the ratio of crop yield to evapotranspiration) for wheat, maize, rice and soybean under elevated [CO2] and associated climate change projected for a high-end greenhouse gas emissions scenario. We find CO2 effects increase global CWP by 10[0;47]%–27[7;37]% (median[interquartile range] across the model ensemble) by the 2080s depending on crop types, with particularly large increases in arid regions (by up to 48[25;56]% for rainfed wheat). If realized in the fields, the effects of elevated [CO2] could considerably mitigate global yield losses whilst reducing agricultural consumptive water use (4–17%). We identify regional disparities driven by differences in growing conditions across agro-ecosystems that could have implications for increasing food production without compromising water security. Finally, our results demonstrate the need to expand field experiments and encourage greater consistency in modelling the effects of rising [CO2] across crop and hydrological modelling communities

Uncertainty in Simulating Wheat Yields Under Climate Change

Projections of climate change impacts on crop yields are inherently uncertain1. Uncertainty is often quantified when projecting future greenhouse gas emissions and their influence on climate2. However, multi-model uncertainty analysis of crop responses to climate change is rare because systematic and objective comparisons among process-based crop simulation models1,3 are difficult4. Here we present the largest standardized model intercomparison for climate change impacts so far. We found that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient. However, simulated climate change impacts vary across models owing to differences in model structures and parameter values. A greater proportion of the uncertainty in climate change impact projections was due to variations among crop models than to variations among downscaled general circulation models. Uncertainties in simulated impacts increased with CO2 concentrations and associated warming. These impact uncertainties can be reduced by improving temperature and CO2 relationships in models and better quantified through use of multi-model ensembles. Less uncertainty in describing how climate change may affect agricultural productivity will aid adaptation strategy development and policymaking

Exploring the challenge of health research priority setting in partnership: reflections on the methodology used by the James Lind Alliance Pressure Ulcer Priority Setting Partnership

Background: Studies identifying a mismatch between the priorities of academics and clinicians and those of people with direct experience of a health condition pose a challenge to the assumption that professional researchers can represent the interests of patients and the public in setting priorities for health research. The James Lind Alliance (JLA) brings patients, carers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritise shared uncertainties about the effects of treatment. There is no formal evaluation yet to examine the different approaches used by individual PSPs and the impact these methods have on the quality of the partnership and subsequent outputs. There is no gold standard method for health research topic identification and priority setting and reporting on public involvement in this area is predominantly descriptive rather than evaluative. Methods and Findings: The JLA Pressure Ulcer PSP (JLAPUP) was developed and worked between 2009 and 2013 to identify and prioritise the top 10 ‘uncertainties’, or ‘unanswered questions’, about the effects of pressure ulcer interventions. JLAPUP identified a mismatch between the nature and quality of RCTs in pressure ulcer prevention and treatment and the kind of research evidence desired by patients or service users, carers and health professionals. Results and methods have been reported fully elsewhere. The consultative and deliberative methods used to establish health research priorities in PSPs are fundamentally interpretive. PSPs are therefore an arena in which ‘hard’ evidence-informed ideals meet ‘soft’ participatory practices. This article provides an account of the challenges faced in one particular PSP. We explain the rationale for the approaches taken, difficulties faced and the limitations at each stage, because these aspects are particularly under-reported. The JLAPUP case is used to identify possible areas for evaluation and reporting across PSPs. Conclusion: Engaging people with very different health and life experiences in the complexities of health science based discussions of uncertainty is challenging. This is particularly the case when engaging groups routinely excluded from participating in health research, for example, older people with multiple comorbidities. The JLA principles of transparency, inclusivity and avoiding waste in research require paying close critical attention to PSP methodology, including full evaluation and reporting of PSP processes and outcomes. Assessing the impact of PSPs is contingent on the decision making processes of commissioners and funders

Imaging shear stress distribution and evaluating the stress concentration factor of the human eye.

Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future

Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials

Background Despite the promising benefits of adaptive designs (ADs), their routine use, especially in confirmatory trials, is lagging behind the prominence given to them in the statistical literature. Much of the previous research to understand barriers and potential facilitators to the use of ADs has been driven from a pharmaceutical drug development perspective, with little focus on trials in the public sector. In this paper, we explore key stakeholders’ experiences, perceptions and views on barriers and facilitators to the use of ADs in publicly funded confirmatory trials. Methods Semi-structured, in-depth interviews of key stakeholders in clinical trials research (CTU directors, funding board and panel members, statisticians, regulators, chief investigators, data monitoring committee members and health economists) were conducted through telephone or face-to-face sessions, predominantly in the UK. We purposively selected participants sequentially to optimise maximum variation in views and experiences. We employed the framework approach to analyse the qualitative data. Results We interviewed 27 participants. We found some of the perceived barriers to be: lack of knowledge and experience coupled with paucity of case studies, lack of applied training, degree of reluctance to use ADs, lack of bridge funding and time to support design work, lack of statistical expertise, some anxiety about the impact of early trial stopping on researchers’ employment contracts, lack of understanding of acceptable scope of ADs and when ADs are appropriate, and statistical and practical complexities. Reluctance to use ADs seemed to be influenced by: therapeutic area, unfamiliarity, concerns about their robustness in decision-making and acceptability of findings to change practice, perceived complexities and proposed type of AD, among others. Conclusions There are still considerable multifaceted, individual and organisational obstacles to be addressed to improve uptake, and successful implementation of ADs when appropriate. Nevertheless, inferred positive change in attitudes and receptiveness towards the appropriate use of ADs by public funders are supportive and are a stepping stone for the future utilisation of ADs by researchers