Identification of Nanotechnology skill shortages in Ireland’s Agri-food sector: Towards the safe, innovative and sustainable development of nano-food technology

The purpose of this research was to assess the nanotechnology skill and capacity shortages in Irelands Agri-food sector. In 2008 the Food Safety Authority of Ireland (FSAI) published its statement on ‘The Relevance for Food Safety of Applications of Nanotechnology in the Food and Feed Industries’. The importance of the food sector to the Irish economy was clearly emphasised by the FSAI’s statement. The report identified the urgent need for focused research programs into the potential of nanotechnology in the agri-food sector and it highlighted the need for a multi-organisation approach between state agencies, industry and academia to ensure safe innovations of nanotechnology are applied in the sector. This concept was first proposed by the FSAI more than ten years ago, however to date no attempt has been made to quantify the precise role or contribution each organisation could play in closing knowledge gaps. A review of Ireland’s nanofood and agriculture research expenditure over the period 2008 - date revealed that almost €29 billion was invested into nano related activities. Only a fraction of that investment was directed towards nanofood i.e. \u3c 5%. Additionally a survey of the academic community revealed that almost 50% had not actually received exchequer funding for nano-food or agriculture related activities. Despite the lack of funding 40% of academic respondents indicated that they had suitable analytical infrastructure in their home institute to fully characterise food related nanomaterials. In addition more than 60% are confident that the infrastructure was available nationally as well. In contrast the regulatory and enforcement community where not as confident that such infrastructure was accessible to them and more than half of enforcement officers indicated that they would need significant upskilling and training. Interestingly interaction between the regulatory bodies and academia also seems to be quite limited with academics indicating that collaboration with industry was more valuable i.e. 95% of academics did not consider collaboration with competent authorities as being of primary importance. This may be reflective of the fact that the competent authority for food safety does not appear to have a strong research arm nor the available resources to fund research in a similar manner to the EPA. A brief overview of suitable tools and techniques for the determination and the characterisation of nanomaterials is presented, and an example of a collaborative approach taken by a regulatory control agency and an academic institution is given as evidence of the potential to capitalise on the skillset and analytical infrastructure which is currently available. A potential roadmap for Ireland is presented, involving further engagement between all stakeholders, from academia through to the competent risk assessment bodies, at national, and subsequently at EU level. This research builds upon the recommendations of previous national reports and it delivers a fresh quantitative look at nanotechnology in the agrifood sector in Ireland. It presents the ‘state of the art’ and it establishes baseline data of the current national capacity to assist the development of safe nano-food technology, and to fully implement any potential nano-legislation arising from an informed regulatory process

Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles

Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles

Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.

OBJECTIVE: Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC. DESIGN: Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025). CONCLUSION: The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.This work was supported by the Gastrointestinal Cancer Research Charitable Fund administered by the Belfast Health and Social Care Trust, the Cancer Research UK Experimental Cancer Medicine Centre Initiative, Invest Northern Ireland and Almac Diagnostics. Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) was funded by a programme grant from Cancer Research UK (RG66287). We would like to thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre from Addenbrooke’s Hospital. Additional infrastructure support was provided from the CRUK funded Experimental Cancer Medicine Centre. RF has programmatic funding from the Medical Research Council and infrastructure support from the NIHR Biomedical Research Centre and the Cambridge Experimental Medicine Centre. Tissue samples used in this research were received from the Northern Ireland Biobank, which is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast Cancer Research UK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from the Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory has received funding from Cancer Research UK, the Friends of the Cancer Centre and the Sean Crummey Foundation. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no 721906. The OCCAMS Study Group is a multicentre UK collaboration

Workshop on Regulatory Preparedness for Innovation in Nanotechnology

This report summarises the presentations and discussions at the first NanoReg2 Workshop on Regulatory Preparedness for Innovation in Nanotechnology held in Ispra, Italy 5 to 6 October 2017 and attended by approximately 60 regulators, industry representatives and other stakeholders. NanoReg2 is a European Union (EU) Horizon 2020 project. At the workshop, Regulatory Preparedness was defined as the regulators' timely awareness of innovations and the regulator's actions to check whether present legislation covers all safety aspects of each innovation, including initiating revision of the legislation as appropriate. Regulatory Preparedness, and Safe-by-Design (SbD) jointly constitute the NanoReg2 Safe Innovation Approach (SIA) for developing innovative products based on nanotechnology. The workshop aimed to gather views and identify current practices in regulatory work on safety of innovative products, tools already in use or needed, and potential difficulties in implementing Regulatory Preparedness in the EU. Presentations addressed the current state of the safety of nanotechnology innovation. The viewpoints included the regulatory framework, the principles behind it and the agencies and authorities enforcing it; nanosafety research projects and their support system (e.g. the current EU Horizon 2020 Framework Programme); national nanosafety initiatives; and the development of tools, such as foresight tools and harmonised test guidelines by the OECD for data generation. The workshop served to generate ideas for achieving Regulatory Preparedness. The participants recognised that while regulators deal with the safety of innovations, only few systematic approaches to this work exist. Some innovative products may reach the market before their safety has been appropriately assessed, as illustrated by RAPEX, the Rapid Exchange of Information System. A continuous and proactive combination of interconnected activities was considered to be required for ensuring Regulatory Preparedness. Thus, anticipation, e.g. horizon scanning, was seen as important, as was communication between regulators, innovators (industry) and other stakeholders. Regulators need to become aware of innovative products under development to ensure that the legislation and methods for safety assessment are available and adequate. Innovators must be aware of regulatory requirements and their likely development. This mutual awareness helps to develop safe products and to avoid delays or other problems in obtaining market approval. Awareness can be achieved through communication, which requires trust, e.g. promoted via "trusted environments" for confidential inquiries and information sharing. Furthermore, regulators need early access to the existing information and data relevant to safety assessment of innovative products to provide timely guidance and advice to Industry as well as to develop strategies for dealing with uncertainty, e.g. by applying the precautionary principle. Regulatory Preparedness was discussed as part of the SIA, and a "road map" of actions was suggested and outlined. The workshop has thus contributed towards acceptance of implementing Regulatory Preparedness for innovation in nanotechnology through the participation of a variety of stakeholders. This paves the way for a better dialogue among stakeholders in a fast economic development cycle, where it is even more important to quickly identify emerging needs for new approaches to regulatory issues for innovationJRC.F.2-Consumer Products Safet

Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study.

PURPOSE: To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. METHODS: A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. RESULTS: In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13-3.38) but not adjusted (HR 1.70 95% CI 0.95-3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. CONCLUSIONS: In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study.

PURPOSE To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. METHODS A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. RESULTS In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13-3.38) but not adjusted (HR 1.70 95% CI 0.95-3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. CONCLUSIONS In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival