Evaluation of PSA and PSA Density in a Multiparametric Magnetic Resonance Imaging-Directed Diagnostic Pathway for Suspected Prostate Cancer: The INNOVATE Trial

OBJECTIVES: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. METHODS: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. RESULTS: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. CONCLUSIONS: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing

Applying Bayesian model averaging for uncertainty estimation of input data in energy modelling

Background Energy scenarios that are used for policy advice have ecological and social impact on society. Policy measures that are based on modelling exercises may lead to far reaching financial and ecological consequences. The purpose of this study is to raise awareness that energy modelling results are accompanied with uncertainties that should be addressed explicitly. Methods With view to existing approaches of uncertainty assessment in energy economics and climate science, relevant requirements for an uncertainty assessment are defined. An uncertainty assessment should be explicit, independent of the assessor&#8217;s expertise, applicable to different models, including subjective quantitative and statistical quantitative aspects, intuitively understandable and be reproducible. Bayesian model averaging for input variables of energy models is discussed as method that satisfies these requirements. A definition of uncertainty based on posterior model probabilities of input variables to energy models is presented. Results The main findings are that (1) expert elicitation as predominant assessment method does not satisfy all requirements, (2) Bayesian model averaging for input variable modelling meets the requirements and allows evaluating a vast amount of potentially relevant influences on input variables and (3) posterior model probabilities of input variable models can be translated in uncertainty associated with the input variable. Conclusions An uncertainty assessment of energy scenarios is relevant if policy measures are (partially) based on modelling exercises. Potential implications of these findings include that energy scenarios could be associated with uncertainty that is presently neither assessed explicitly nor communicated adequately

Research and Development Actions to Reduce CO2 Emissions Within the European Union

This paper describes the research actions put in place by the Directorate General of Research of the European Commission (EC) in the field of the mitigation of CO2 emissions. Global policy for climate change mitigation and the associated energy policy considerations are presented. The use of renewables and fossil fuels within the overall energy mix are discussed, leading to European Union research policy for fossil fuel carbon management options. The European Union's (EU) current and proposed RTD project portfolio for CO2 capture and sequestration is then given. An overview of the involvement by the EC in complementary international cooperation and coordination activities is also presented

An expert system concept for diagnosis and monitoring of gas turbine combustion chambers.&quot; Applied Thermal Engineering 26

Abstract In this paper, the main principles of operation, the conceptual design and the development of an expert system for fault diagnosis and monitoring of gas turbine combustion chambers are presented. The concept of the gas turbine chamber expert system is based on the monitoring of the spatial and temporal distribution of the heat flux inside the combustion chamber and the simultaneous comparison of respective readings of diagnostic variables with values obtained through numerical model simulation of different situations which lead to the malfunction of combustion chamber and deterioration of its performance. The demonstration of the expert system will be performed at the VTI (All Union Energy Institute, Russia) gas turbine combustion chamber test facility

Inference of conversion and purity for ETBE reactive distillation

Reactive distillation (RD), an unconventional and attractive technique, has been applied in fuel ether production. A typical application of RD is the synthesis of the widely used methyl tert-butyl ether (MTBE). RD has also been found to have potential to produce high quality ethyl tert-butyl ether (ETBE), a potential alternative to MTBE. A RD process integrates conventional reaction and separation into a single unit, resulting in extra complexity and dual process objectives, i.e. maximization of reactant conversion and purity of products. The conversion and the purity are thus important variables to be controlled in RD of ETBE. Unfortunately, both of them are not economically and reliably available for closed-loop control. This study aims to develop an effective method to infer the conversion and the purity from multiple temperature measurements that are easily available on-line and in real time. Nonlinear inferential models are recommended for ETBE synthesis with a ten-stage pilot scale RD column. The models are two-variable third-order regressive models, in which the temperature measurements of the reboiler and the bottom reactive section are employed. Experimental design, model identification, and model testing are also investigated

Multi-criteria evaluation for CHP system options

Several Combined Heat and Power (CHP) system options have been considered for evaluation with respect to the end-user requirements. These included Internal Combustion Engines (Otto and Diesel), Gas Turbines, Steam Turbines and Combined Cycles covering a wide range of electrical output. Data have been obtained from literature and the CHP systems have been evaluated using different criteria such as overall efficiency, investment cost, fuel cost, electricity cost, heat cost, CO2 production and footprint. A multi-criteria method is used with an agglomeration function based on the statistical evaluation of weight factors. The technical, economic and social aspects of each system have been evaluated in an integrated manner and the results have been compared by means of the Sustainability Index. Based on the above criteria and depending on the user requirements, the best CHP system options have been established. (c) 2006 Elsevier Ltd. All rights reserved