Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats

Background: Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas. Methods: No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant. Results: The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, nocarrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions. Conclusion: This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Measurement, Verification and Additionality of Electricity Demand Reductions : Final report – recast

This project supports the Electricity Demand Reduction (EDR) project in the Department of Energy and Climate Change (DECC). It was commissioned to explore the needs and requirements for a robust approach to measurement, verification and additionality (M&V and additionality) of electricity demand reduction projects in the context of providing financial incentives for electricity efficiency. DECC defines financial incentives as incentives that provide direct payment to electricity efficiency projects in exchange for demand reduction (i.e. kWh saved). The focus of the financial incentive considered in this M&V and additionality advice is on large efficiency projects or efficiency programmes (aggregation of small projects) in order to reduce the administrative burden of the scheme. The purpose of an M&V and additionality approach is to filter the efficiency projects in order to pay only for permanent (long-term kWh saved) and additional (compared to a baseline) electricity demand savings. Main issues 1. Needs and requirements for a robust approach to M&V and additionality in the context of a financial incentive for electricity efficiency 2. Risks of failure to address the M&V and additionality issues 3. Lessons from international comparators for feasibility of UK M&V and additionality 4. Key challenges for identifying an M&V and additionality approach in the context of a financial incentive for efficiency in the UK 5. Suitability of the International Performance Measurement and Verification Protocol (IPMVP) for the Electricity Demand Reduction Project

Measurement, Verification and Additionality of Electricity Demand Reductions : Final report – recast

This project supports the Electricity Demand Reduction (EDR) project in the Department of Energy and Climate Change (DECC). It was commissioned to explore the needs and requirements for a robust approach to measurement, verification and additionality (M&V and additionality) of electricity demand reduction projects in the context of providing financial incentives for electricity efficiency. DECC defines financial incentives as incentives that provide direct payment to electricity efficiency projects in exchange for demand reduction (i.e. kWh saved). The focus of the financial incentive considered in this M&V and additionality advice is on large efficiency projects or efficiency programmes (aggregation of small projects) in order to reduce the administrative burden of the scheme. The purpose of an M&V and additionality approach is to filter the efficiency projects in order to pay only for permanent (long-term kWh saved) and additional (compared to a baseline) electricity demand savings. Main issues 1. Needs and requirements for a robust approach to M&V and additionality in the context of a financial incentive for electricity efficiency 2. Risks of failure to address the M&V and additionality issues 3. Lessons from international comparators for feasibility of UK M&V and additionality 4. Key challenges for identifying an M&V and additionality approach in the context of a financial incentive for efficiency in the UK 5. Suitability of the International Performance Measurement and Verification Protocol (IPMVP) for the Electricity Demand Reduction Project

Convolutional neural networks for PET functional volume fully automatic segmentation : development and validation in a multi-center setting

Purpose: In this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics. Methods: In cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing). Results: The model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training. Conclusion: The proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context