A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.

Search for Low-Molecular-Weight Biomarkers in Plant Tissues and Seeds Using Metabolomics: Tools, Strategies, and Applications

This chapter summarises the metabolomic strategies currently in force used in plant science and describes the methods used. The metabolite profiling and fingerprinting of plant tissues through MS- and/or NMR-based approaches and the subsequent identification of biomarkers is detailed. Strategies for the microisolation and de novo identification of unknown biomarkers are also discussed. The various approaches are illustrated by a metabolomic study of the maize response to herbivory. A review of recent metabolomic studies performed on seed and crop plant tissues involving various analytical strategies is provided.

Linking livelihood strategies with a regional level landscape mosaic to explore trade-offs between forest conservation and human wellbeing in a Madagascar biodiversity hotspot

The north-eastern escarpment of Madagascar contains the island’s last remaining large-scale humid forest massifs surrounded by diverse small-scale agricultural mosaics. There is high deforestation mainly caused by shifting cultivation practiced by local land users to produce upland rice for subsistence. Today, large protected areas restrict land users’ access to forests to collect wood and other forest products. Moreover, they are no more able to expand their cultivated land, which leads to shorter shifting cultivation cycles and decreasing plot sizes for irrigated rice and cash crop cultivation. Cash crop production of clove and vanilla is exposed to risks such as extreme inter-annual price fluctuations, pests and cyclones. In the absence of work opportunities, agricultural extension services and micro-finance schemes people are stuck in a poverty trap. New development strategies are needed to mitigate the trade-offs between forest conservation and human well-being. As landscape composition and livelihood strategies vary across the region, these strategies need to be spatially differentiated to avoid implementing generic solutions, which do not fit the local context. However, up to date, little is known about the spatial patterns of shifting cultivation and other land use systems at the regional level. This is mainly due to the high spatial and temporal dynamics inherent to shifting cultivation, which makes it difficult to monitor the dynamics of this land use system with remote sensing methods. Furthermore, knowledge about land users’ livelihood strategies and the risks and opportunities they face stems from very few local case studies. To overcome this challenge, firstly, we used remote sensing data and a landscape mosaic approach to delineate the main landscape types at the regional level. Secondly, we developed a land user typology based on socio-ecological data from household surveys in 45 villages spread throughout the region. Combining the land user typology with the landscape mosaic map allowed us to reveal spatial patterns of the interaction between landscapes and people and to better understand the trade-offs between forest conservation and local wellbeing. While shifting cultivation systems are being transformed into more intensive permanent agricultural systems in many countries around the globe, Madagascar seems to be an exception to this trend. Linking land cover information to human-environmental interactions over large areas is crucial to designing policies and to inform decision making for a more sustainable development of this resource-rich but poverty-prone context.

The SOLUTIONS project: challenges and responses for present and future emerging pollutants in land and water resources management.

SOLUTIONS (2013 to 2018) is a European Union Seventh Framework Programme Project (EU-FP7). The project aims to deliver a conceptual framework to support the evidence-based development of environmental policies with regard to water quality. SOLUTIONS will develop the tools for the identification, prioritisation and assessment of those water contaminants that may pose a risk to ecosystems and human health. To this end, a new generation of chemical and effect-based monitoring tools is developed and integrated with a full set of exposure, effect and risk assessment models. SOLUTIONS attempts to address legacy, present and future contamination by integrating monitoring and modelling based approaches with scenarios on future developments in society, economy and technology and thus in contamination. The project follows a solutions-oriented approach by addressing major problems of water and chemicals management and by assessing abatement options. SOLUTIONS takes advantage of the access to the infrastructure necessary to investigate the large basins of the Danube and Rhine as well as relevant Mediterranean basins as case studies, and puts major efforts on stakeholder dialogue and support. Particularly, the EU Water Framework Directive (WFD) Common Implementation Strategy (CIS) working groups, International River Commissions, and water works associations are directly supported with consistent guidance for the early detection, identification, prioritisation, and abatement of chemicals in the water cycle. SOLUTIONS will give a specific emphasis on concepts and tools for the impact and risk assessment of complex mixtures of emerging pollutants, their metabolites and transformation products. Analytical and effect-based screening tools will be applied together with ecological assessment tools for the identification of toxicants and their impacts. The SOLUTIONS approach is expected to provide transparent and evidence-based candidates or River Basin Specific Pollutants in the case study basins and to assist future review of priority pollutants under the WFD as well as potential abatement options.

Edge caching with mobility prediction in virtualized LTE mobile networks

Abstract Mobile Edge Computing enables the deployment of services, applications, content storage and processing in close proximity to mobile end users. This highly distributed computing environment can be used to provide ultra-low latency, precise positional awareness and agile applications, which could significantly improve user experience. In order to achieve this, it is necessary to consider next-generation paradigms such as Information-Centric Networking and Cloud Computing, integrated with the upcoming 5th Generation networking access. A cohesive end-to-end architecture is proposed, fully exploiting Information-Centric Networking together with the Mobile Follow-Me Cloud approach, for enhancing the migration of content-caches located at the edge of cloudified mobile networks. The chosen content-relocation algorithm attains content-availability improvements of up to 500 when a mobile user performs a request and compared against other existing solutions. The performed evaluation considers a realistic core-network, with functional and non-functional measurements, including the deployment of the entire system, computation and allocation/migration of resources. The achieved results reveal that the proposed architecture is beneficial not only from the users’ perspective but also from the providers point-of-view, which may be able to optimize their resources and reach significant bandwidth savings.