Relative study between anti-EGFR and GE-11 peptide conjugated gold nanoparticles for in vivo targeting in pancreatic cancer [abstract]

Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States due to its severe aggressiveness and lethal malignancy. Epidermal Growth Factor Receptor (EGFR) is over expressed in more than 95% of human pancreatic cancer patients. A number of peptides and monoclonal antibodies have been developed to target the EGFR in pancreatic cancer. Our research has focused on developing EGFR targeting biomolecule conjugated gold nanoparticles for the diagnosis and staging of various cancers. In this study, we have synthesized a series of Antibody EGFR and EGFR-peptide (GE-11) conjugated AuNPs. We investigated the in vivo EGFR targeting characteristics of these conjugates in pancreatic tumor bearing SCID mice models. Our investigation has provided evidence that the peptide conjugated AuNPs have high in vivo mobility and targets pancreatic tumor effectively. We have also established that the EGFR-peptide-AuNP conjugates serve as better X-ray contrast agents for early detection of pancreatic cancer in mice models. The details of this comparative study will be presented in this poster

A Comparative Study between Antibody and Peptide Conjugated Gold Nanoparticles for In Vivo Targeting of EGFR in Pancreatic Cancer Bearing Mice Models [abstract]

Nanoscience Poster SessionPancreatic cancer is the fourth leading cause of cancer related deaths in the United States due to its severe aggressiveness and lethal malignancy. Epidermal Growth Factor Receptor (EGFR) is over expressed in more than 95% of human pancreatic cancer patients. A number of peptides and monoclonal antibodies have been developed to target the EGFR in pancreatic cancer. Our research has focused on developing EGFR targeting biomolecule conjugated gold nanoparticles for the diagnosis and staging of various cancers. In this study, we synthesized a series of Antibody EGFR and EGFR-peptide conjugated AuNPs. We investigated the in vivo EGFR targeting characteristics of these conjugates in pancreatic tumor bearing SCID mice models. Our investigation establishes that the peptide conjugated AuNPs have high in vivo mobility and targets pancreatic tumor effectively. We have also established that EGFR-peptide -AuNP conjugates act as better X-ray contrast agents for early detection of pancreatic cancer in mice models. The details of this comparative study will be presented in this poster

Working with patients and members of the public: informing health economics in child health research

This paper considers patient and public involvement (PPI) in health economics research and how this might be facilitated. PPI refers to research carried out ‘with’ or ‘by’ members of the public and is now an important aspect of health research policies internationally. Patients and members of the public can be involved in all stages of the research cycle, from establishing whether the topic is important to influencing details of study design, wording of patient-facing documentation and interpretation and dissemination of findings. PPI has become commonplace in health services research. In the context of clinical trials, it has become imperative, with, for example, patients and members of the public informing the selection of outcome measures and recruitment methods, and qualitative research is frequently steered by PPI input regarding the content of interview topic guides and the interpretation of study findings. It is less common for PPI to be explicitly reported in the economic components of health services research. However, we argue that involvement is no less important in this area. The fundamental rationale for involving people in research is that it promotes democratic principles, research quality and relevance to service users. These arguments equally apply to health economics as to other health research disciplines. Our overarching aim in this paper is to show how health economic research might be informed by PPI. We report our experiences of PPI via case studies in child health, reflect on our learnings, and make suggestions for future research practice

Combining PPI with qualitative research to engage ‘harder-to-reach’ populations: service user groups as co-applicants on a platform study for a trial

Abstract Background: Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing. complex intervention trials. Combining both together might enable inclusion of ‘harder-to-reach’ perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. Methods: In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. Results: We engaged with ‘harder-to-reach’ women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. 21 women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. 19 participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Conclusions: Combining and overlapping PPI and qualitative research added ‘harder-to-reach’ contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone. (350/350

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

Selecting and implementing overview methods: implications from five exemplar overviews

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Overviews of systematic reviews are an increasingly popular method of evidence synthesis; there is a lack of clear guidance for completing overviews and a number of methodological challenges. At the UK Cochrane Symposium 2016, methodological challenges of five overviews were explored. Using data from these five overviews, practical implications to support methodological decision making of authors writing protocols for future overviews are proposed. Methods Methods, and their justification, from the five exemplar overviews were tabulated and compared with areas of debate identified within current literature. Key methodological challenges and implications for development of overview protocols were generated and synthesised into a list, discussed and refined until there was consensus. Results Methodological features of three Cochrane overviews, one overview of diagnostic test accuracy and one mixed methods overview have been summarised. Methods of selection of reviews and data extraction were similar. Either the AMSTAR or ROBIS tool was used to assess quality of included reviews. The GRADE approach was most commonly used to assess quality of evidence within the reviews. Eight key methodological challenges were identified from the exemplar overviews. There was good agreement between our findings and emerging areas of debate within a recent published synthesis. Implications for development of protocols for future overviews were identified. Conclusions Overviews are a relatively new methodological innovation, and there are currently substantial variations in the methodological approaches used within different overviews. There are considerable methodological challenges for which optimal solutions are not necessarily yet known. Lessons learnt from five exemplar overviews highlight a number of methodological decisions which may be beneficial to consider during the development of an overview protocol.The overview conducted by Pollock [19] was supported by a project grant from the Chief Scientist Office of the Scottish Government. The overview conducted by McClurg [21] was supported by a project grant by the Physiotherapy Research Foundation. The overview by Hunt [22] was supported as part of doctoral programme funding by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC). The overview conducted by Estcourt [20] was supported by an NIHR Cochrane Programme Grant for the Safe and Appropriate Use of Blood Components. The overview conducted by Brunton [23] was commissioned by the Department of Health as part of an ongoing programme of work on health policy research synthesis. Alex Pollock is employed by the Nursing, Midwifery and Allied Health Professions (NMAHP) Research Unit, which is supported by the Chief Scientist Office of the Scottish Government. Pauline Campbell is supported by the Chief Nurses Office of the Scottish Government

Testing of crop Models for Accurate Predictions of Evapotranspiration and crop Water Use

All crop models, whether site-specific or global-gridded and regardless of crop, simulate daily crop transpiration and soil evaporation during the crop life cycle, resulting in seasonal crop water use. Modelers use several methods for predicting daily potential evapotranspiration (ET), including FAO-56, Penman-Monteith, Priestley-Taylor, Hargreaves, full energy balance, and transpiration water efficiency. They use extinction equations to partition energy to soil evaporation or transpiration, depending on leaf area index. Most models simulate soil water balance and soil-root water supply for transpiration, and limit transpiration if water uptake is insufficient, and thereafter reduce dry matter production. Comparisons among multiple crop and global gridded models in the Agricultural Model Intercomparison and Improvement Project (AgMIP) show surprisingly large differences in simulated ET and crop water use for the same climatic conditions. Model intercomparisons alone are not enough to know which approaches are correct. There is an urgent need to test these models against field-observed data on ET and crop water use. It is important to test various ET modules/equations in a model platform where other aspects such as soil water balance and rooting are held constant, to avoid compensation caused by other parts of models. The CSM-CROPGRO model in DSSAT already has ET equations for Priestley-Taylor, Penman-FAO-24, Penman-Monteith-FAO-56, and an hourly energy balance approach. In this work, we added transpiration-efficiency modules to DSSAT and AgMaize models and tested the various ET equations against available data on ET, soil water balance, and season-long crop water use of soybean, fababean, maize, and other crops where runoff and deep percolation were known or zero. The different ET modules created considerable differences in predicted ET, growth, and yield

Quantifying potential benefits of drought and heat tolerance in rainy season sorghum for adapting to climate change

Maintaining high levels of productivity under climate change will require developing cultivars that are able to perform under varying drought and heat stresses and with maturities that match water availability. The CSM-CERES-Sorghum model was used to quantify the potential benefits of altering crop life cycle, enhancing yield potential traits, and incorporating drought and heat tolerance in the commonly grown cultivar types at two sites each in India (cv. CSV 15 at both Akola and Indore) and Mali (cv. CSM 335 at Samanko and cv. CSM 63E at Cinzana), West Africa. Under current climate CSV 15 on average matured in 108 days and produced 3790 kg ha−1 grain yield at Akola; whereas at Indore it matured in 115 days and produced 3540 kg ha−1 grain yield. Similarly under current climate, CSM 335 matured in 120 days and produced 2700 kg ha−1 grain yield at Samanko; whereas CSM 63E matured in 85 days at Cinzana and produced 2210 kg ha−1 grain yield. Decreasing crop life cycle duration of cultivars by 10% decreased yields at all the sites under both current and future climates. In contrast, increasing crop life cycle by 10% increased yields up to 12% at Akola, 9% at Indore, 8% at Samanko and 33% at Cinzana. Enhancing yield potential traits (radiation use efficiency, relative leaf size and partitioning of assimilates to the panicle each increased by 10%) in the longer cycle cultivars increased the yields by 11–18% at Akola, 17–19% at Indore, 10–12% at Samanko and 14–25% at Cinzana under current and future climates of the sites. Except for the Samanko site, yield gains were larger by incorporating drought tolerance than heat tolerance under the current climate. However, under future climates yield gains were higher by incorporating heat tolerance at Akola, Samanko and Cinzana, but not at Indore. Net benefits of incorporating both drought and heat tolerance increased yield up to 17% at Akola, 9% at Indore, 7% at Samanko and 16% at Cinzana under climate change. It is concluded that different combinations of traits will be needed to increase and sustain productivity of sorghum in current and future climates at these target sites and that the CSM-CERES-Sorghum model can be used to quantify benefits of incorporating certain traits

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