•A thermo-economic analysis of natural gas/biomass fired microturbine is proposed.•Energy efficiency, capex, opex and electricity revenues trade-offs are assessed.•The optimal biomass energy input is ...70% of total CHP consumption.•Industrial/tertiary heat demand and baseload/heat driven operation is assessed.•The main barriers of small scale CHP systems in Italy are overviewed.
This paper proposes a thermo-economic assessment of small scale (100kWe) combined heat and power (CHP) plants fired by natural gas and solid biomass. The focus is on dual fuel gas turbine cycle, where compressed air is heated in a high temperature heat exchanger (HTHE) using the hot gases produced in a biomass furnace, before entering the gas combustion chamber. The hot air expands in the turbine and then feeds the internal pre-heater recuperator, Various biomass/natural gas energy input ratios are modeled, ranging from 100% natural gas to 100% biomass. The research assesses the trade-offs between: (i) lower energy conversion efficiency and higher investment cost of high biomass input rate and (ii) higher primary energy savings and revenues from bio-electricity feed-in tariff in case of high biomass input rate. The influence of fuel mix and biomass furnace temperature on energy conversion efficiencies, primary energy savings and profitability of investments is assessed. The scenarios of industrial vs. tertiary heat demand and baseload vs. heat driven plant operation are also compared. On the basis of the incentives available in Italy for biomass electricity and for high efficiency cogeneration (HEC), the maximum investment profitability is achieved for 70% input biomass percentage. The main barriers of these embedded cogeneration systems in Italy are also discussed.
The wider adoption of organic Rankine cycle (ORC) technology for power generation or cogeneration from renewable or recovered waste-heat in many applications can be facilitated by improved ...thermodynamic performance, but also reduced investment costs. In this context, it is suggested that the further development of ORC power systems should be guided by combined thermoeconomic assessments that can capture directly the trade-offs between performace and cost with the aim of proposing solutions with high resource-use efficiency and, importantly, improved economic viability. This paper couples, for the first time, the computer-aided molecular design (CAMD) of the ORC working-fluid based on the statistical associating fluid theory (SAFT)-γ Mie equation of state with thermodynamic modelling and optimisation, in addition to heat-exchanger sizing models, component cost correlations and thermoeconomic assessments. The resulting CAMD-ORC framework presents a novel and powerful approach with extended capabilities that allows the thermodynamic optimisation of the ORC system and working fluid to be performed in a single step, thus removing subjective and pre-emptive screening criteria that exist in conventional approaches, while also extending to include cost considerations relating to the resulting optimal systems. Following validation, the proposed framework is used to identify optimal cycles and working fluids over a wide range of conditions characterised by three different heat-source cases with temperatures of 150 °C, 250 °C and 350 °C, corresponding to small- to medium-scale applications. In each case, the optimal combination of ORC system design and working fluid is identified, and the corresponding capital costs are evaluated. It is found that fluids with low specific-investment costs (SIC) are different to those that maximise the power output. The fluids with the lowest SIC are isoheptane, 2-pentene and 2-heptene, with SICs of £5620, £2760 and £2070 per kW respectively, and corresponding power outputs of 32.9 kW, 136.6 kW and 213.9 kW.
•Thermoeconomic CAMD-ORC framework developed with component sizing and cost correlations.•Validated for novel cycles (partial evaporation, mixtures) and applied to 150, 250, 350 °C heat sources.•Minimising SIC identifies different fluids compared to thermodynamic optimisation.•Optimal SICs of £5620, £2760 and £2070 per kW are identified for 150, 250 and 350 °C, respectively.•Optimal fluids correspond to power outputs of 32.9, 136.6 and 213.9 kW.
•Two-stage screw expanders offer highest power and efficiency.•Piston expanders found to deliver the lowest specific investment costs.•Project viability sensitive to the heat demand intensity and ...electricity price.
The high cost of organic Rankine cycle (ORC) systems is a key barrier to their implementation in waste-heat recovery (WHR) applications. In particular, the choice of the expansion device has a significant influence on this cost, strongly affecting the economic viability of an installation. In this work, numerical simulations and optimisation strategies are used to compare the performance and profitability of small-scale ORC systems using reciprocating-piston or single/two-stage screw expanders when recovering heat from the exhaust gases of a 185-kW internal combustion engine operating in baseload mode. The study goes beyond previous work by directly comparing these small-scale expanders for a broad range of working fluids, and by exploring the sensitivity of project viability to key parameters such as electricity price and onsite heat demand. For the piston expander, a lumped-mass model and optimisation based on artificial neural networks are used to generate performance maps, while performance and cost correlations from the literature are used for the screw expanders. The thermodynamic analysis shows that two-stage screw expanders typically deliver more power than either single-stage screw or piston expanders due to their higher conversion efficiency at the required pressure ratios. The best fluids for the proposed application are acetone and ethanol, as these provide a compromise between the exergy losses in the condenser and in the evaporator. The maximum net power output is found to be 17.7 kW, from an ORC engine operating with acetone and a two-stage screw expander. On the other hand, the thermoeconomic optimisation shows that reciprocating-piston expanders show a potential for lower specific costs, and since piston-expander technology is not mature, especially at these scales, this finding motivates further consideration of this component. A minimum specific investment cost of 1630 €/kW is observed for an ORC engine with a piston expander, again with acetone as the working fluid. This system, optimised for minimum cost, gives the shortest payback time of 4 years at an avoided electricity cost of 0.13 €/kWh. Finally, financial appraisals show a high sensitivity of the investment profitability to the value of produced electricity and to the heat-demand intensity.
Abstract Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, ...strengthening what initially observed in two cases. Patients and methods From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib. Results Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2–28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1 – NR4A3 fusion, while refractory cases carried the alternative TAF15 – NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples. Conclusions This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1 – NR4A3 fusion. Involvement of RET deserves further investigation.
Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have ...a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1–negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01–7.76). Moreover, membrane hENT-1–positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.
•Human equilibrative nucleoside transporter 1 (hENT-1) regulates intrahepatic cholangiocarcinoma (iCC) growth.•The mechanism relies on hENT-1 localisation on tumour cell membrane.•Membrane hENT-1 positive patients have higher Ki67-positive tumour cells and worse survival than membrane hENT-1 negative.
The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon ...18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility.
VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes.
A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib.
ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment.
•This study comprehensively documents the landscape of KIT and PDGFRA mutations in metastatic, imatinib-resistant GIST.•Selective pressure exerted with prior lines promotes a shift toward increased resistant subpopulations in the KIT A-loop.•Individual mutations in KIT/PDGFRA determine TKI sensitivity and resistance in metastatic GIST.•ctDNA-detected KIT/PDGFRA mutations in imatinib-resistant GIST prognosticate third- or fourth-line TKI treatment outcomes.
The genetic background and the antigenic landscape of cancer cells play a critical role in the response to immunotherapies. A high tumor antigenicity, together with an increased adjuvanticity ...potentially induced by a peculiar type of cell death, namely immunogenic cell death (ICD), could foster the response to immunogenic therapies. The gestational trophoblastic neoplasm (GTN) is a one-of-a-kind cancer in the oncological landscape due to its exclusive genomic makeup. The prognosis of GTN is significantly better than non-gestational trophoblastic neoplasm (nGTN). Due to its peculiar genetic inheritance, GTN potentially constitutes a singular archetype in the immuno-oncological field.
Current risk models in solitary fibrous tumour (SFT) were developed using cohorts with short follow-up and cannot reliably identify low-risk patients. We recently developed a novel risk model ...(G-score) to account for both early and late recurrences. Here, we aimed to validate the G-score in a large international cohort with long-term follow-up.
Data were collected from nine sarcoma referral centres worldwide. Recurrence-free interval (RFi) was the primary endpoint.
The cohort comprised 318 patients with localised extrameningeal SFTs. Disease recurrence occurred in 96 patients (33%). The estimated 5-year RFi rate was 72%, and the 10-year RFi rate was 52%. G-score precisely predicted recurrence risk with estimated 10-year RFi rate of 84% in low risk, 54% in intermediate risk and 36% in high risk (p < 0.001; C-index 0.691). The mDemicco (p < 0.001; C-index 0.749) and Salas
(p < 0.001; C-index 0.674) models also predicted RFi but identified low-risk patients less accurate with 10-year RFi rates of 72% and 70%, respectively.
G-score is a highly significant predictor of early and late recurrence in SFT and is superior to other models to predict patients at low risk of relapse. A less intensive follow-up schedule could be considered for patients at low recurrence risk according to G-score.
About 15 million people live in rural communities in the Russian Federation. Most of them are not energetically supplied from the main national infrastructures (electric and gas). People living in ...such isolated communities use diesel engines for generating electricity and heat. In many cases, diesel is supplied using rail tracks, boats or even helicopters. Consequently, the generation of electricity has very high costs and very low reliability. For this reason, more and more rural isolated communities are using renewable energy sources to decrease their dependency on diesel sources. This study deals with the concept of net-zero multi-energy systems in rural and stand-alone areas. A methodology, based on economical, ecological, technical and social criteria, has been developed for planning the generation capacity and sizing the energy storage units. In addition, controlling algorithms have been developed to deal with the volatility of renewable energy sources (wind and sun) and integrate heat/electricity energy systems. The proposed methodology has been applied to the design of a net-zero energy system for a Siberian rural energy community.
•Designing Energy Storage Systems within rural Net-Zero Energy Systems.•Multi-Criteria Approach to size energy storage systems.•Exploitation of RES in remote Siberian areas.
•This Clinical Practice Guideline provides key recommendations on the management of soft tissue and visceral sarcomas.•Recommendations have been agreed following a consensus meeting of ...representatives from ESMO, EURACAN and GENTURIS.•Authorship includes a multidisciplinary group of experts from several European institutions, India and Japan.
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