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• Practical E-MPC scheme for space heating demand response was developed. • The scheme relies on dwelling-level heat metering and simple thermal zoning. • Co-simulation of a case study was used to test the scheme. • The scheme yields the same load shifting as when using room-level heat measurements. • The scheme eliminates the need for investments in room heat meters. Recent research has indicated a significant potential for providing demand response using Economic Model Predictive Control (E-MPC) of radiators in residential space heating systems. Previous studies indicate the need for distinct temperatures in different rooms, which would require an E-MPC with different temperature constraints across the dwelling. Studies on E-MPC concepts for this purpose often assume that it is possible to measure the heating power delivered to each room separately. However, this assumption is not valid in typical existing residential buildings heated by hydronic radiators; they only have one heat meter measuring the heating use of the entire housing unit. This study presents a simulation-based study of a novel dual-zone E-MPC scheme that relies on indoor air temperature measurements in individual rooms of the housing unit, and only one heat meter measuring the total heating use for space heating and domestic hot water. The results indicate that the proposed scheme has the same load shifting potential as an E-MPC using room-level heat metering. The proposed scheme thus reduces the additional hardware and data infrastructure needed for the practical realization of E-MPC of residential space heating systems for demand response purposes. [ABSTRACT FROM AUTHOR]

• Load shifting experiments were performed in a single-family inhabited house. • Room radiators were controlled with variable set-point schedules. • Heat consumption was successfully shifted from the controlled rooms. • The total load shifting on a building level was limited. • A list of challenges for developing E-MPC in real buildings was identified. Recent simulation-based studies have indicated that load shifting using Economic Model Predictive Control (E-MPC) of radiators for residential space heating can be utilized for demand response purposes in energy systems. However, there is a lack of studies on whether this load shift potential can be realized in real, inhabited buildings. This paper reports on a field experiment aiming at realizing load shifting of space heating in a single-family house with a hydronic radiator system connected to the local district heating. Radiators in a limited number of 'active' rooms were controlled using set-point schedules mimicking the typical behavior of E-MPC. The results indicate that it was possible to load shift heating consumption in the 'active' rooms but that the load shift for the building as a whole was limited due to the hydronics of the radiator system. The paper also reports on the several practical issues encountered during the experiments – issues that in different ways are barriers to the practical realization of demand response from E-MPC of hydronic space heating systems. [ABSTRACT FROM AUTHOR]

Abstract: Several boreholes were studied in detail through different analytical methods in order to highlight the Holocene relative sea-level changes and the paleogeographical evolution of the southern sector of the Sele river coastal plain (Tyrrhenian Sea, southern Italy). Stratigraphic and paleontological analyses identified a transition from floodplain strata to brackish water, lagoon and upper shoreface deposits. The present setting of the outermost plain strip was interpreted as the result of a barrier-lagoon system which first migrated landward and then seaward during the Holocene. After being exposed to continental conditions during the Last Glacial regression, the study area gradually reached brackish water conditions at the beginning of the Holocene. Shortly before 6.7 ka cal BP the coastline reached its maximum retreat, reaching 1.6 km inland from the present shore. Subsequently, the barrier-lagoon system mainly prograded until marshy conditions were established, which partially persisted until very recent times. Four biological sea-level markers were sampled, and their ages, constrained by AMS 14C dating, span between 6.77 and 7.98 ka cal BP. Altitudes (m above mean sea level) of the collected samples were corrected taking into account the uncertainties of the vertical position with respect to the palaeo sea level. Vertical tectonic displacements were evaluated through the comparison between relative sea-level data and the Holocene predicted sea-level curve, as well as with the available morphotectonic and stratigraphic data. The results suggest negligible rates of vertical tectonic displacements during the Holocene, at least along the southern sector of the Sele river coastal plain. [Copyright &y& Elsevier]

To compare the efficacy and safety of sotalol and quinidine after conversion of atrial fibrillation (AF) of <6 months, a prospective multicenter trial enrolled 121 patients who were randomized to receive dl-sotalol (160 to 320 mg/day, 58 patients) or quinidine sulfate (600 to 800 mg/day, 63 patients). Patients with left ventricular ejection fraction of <0.40 or left atrial diameter >5.2 cm were excluded. After 6 months of follow-up, using the Kaplan-Meier method, the probabilities of success were comparable between sotalol (74%) and quinidine (68%), but recurrences occurred later with sotalol than with quinidine (69 vs 10 days, p <0.05). Four patients developed proarrhythmic events, 3 (5%) with sotalol and 1 (2%) with quinidine, which were all associated with diuretic therapy. In patients converted from recent-onset AF (< or = 72 hours), sotalol was more effective than quinidine (93% vs 64%, p = 0.01), whereas in chronic AF (> 72 hours), quinidine was more effective than sotalol (68% vs 33%, p <0.05). During recurrences, the ventricular rate was significantly reduced in patients taking sotalol (98 to 82 beats/min, p <0.05). Independent predictors of therapeutic success were recent-onset AF in the sotalol group (p <0.001) and absence of hypertension in the quinidine group (p <0.05). In conclusion, sotalol and quinidine have comparable efficacy and safety for the maintenance of sinus rhythm in the overall group. In recent-onset AF, sotalol was more effective, whereas in chronic AF, quinidine had a better result. Recurrences occurred later with sotalol when compared with quinidine. Because of proarrhythmia, these drugs should be used judiciously in patients on diuretic therapy. [ABSTRACT FROM AUTHOR]

Background: The EGFR tyrosine kinase inhibitors gefitinib and erlotinib are first-line therapy for NSCLCs harbouring EGFR-activating mutations. The intrinsic and acquired resistance to these agents is a relevant clinical issue. Although Src tyrosine kinase has been involved in such resistance in preclinical models, clinical development of these agents has been so far limited. Methods: We used a panel of human NSCLC cell lines: PC9 and HCC827 (EGFR-activating mutation; highly sensitive to erlotinib), Calu3 (EGFR/Ras wild-type, wt; moderately sensitive), Calu3-ER (with acquired resistance), H1299 and A549 (Ras mutant; resistant), H1975 (EGFR T790M mutant; resistant). In these models, we tested three different Src inhibitors (saracatinib, dasatinib, and bosutinib), both in vitro and in vivo. Findings: NSCLC cell lines showed different activation of EGFR-dependent and Src-dependent pathways and variable sensitivity to Src inhibitors. A kinase assay demonstrated that all the compounds are able to directly inhibit EGFR tyrosine kinase variants. In cell lysates only saracatinib and bosutinib efficiently reduced EGFR activation, while dasatinib was the more effective agent in inhibiting Src tyrosine kinase. Consistently, in EGFR-activating mutant, erlotinib sensitive cells, saracatinib and bosutinib showed anti-proliferative effects related to simultaneous EGFR/Src inhibition. In EGFR wt/Ras mutant cells Src inhibition by dasatinib interfered with cell proliferation and signal transduction. Since Src inhibitors had only moderate effects as single agents we tested the combination of saracatinib with EGFR inhibitors (erlotinib or cetuximab) in EGFR-addicted cells, and of dasatanib with MEK inhibitors (selumetinib) in Ras mutant, erlotinib resistant models. These combinations were effective both in vitro and in nude mice, inhibiting tumour growth, prolonging mice survival, and interfering with signal transduction. Importantly, the combination of saracatanib and cetuximab was effective also in the erlotinib resistant, EGFR T790M mutant model. Interpretation: Src inhibitors may act with different mechanisms in NSCLC cell lines, depending on EGFR/Ras mutational profile. Integration of anti-Src agents with EGFR or MEK inhibitors could represent effective therapeutic options for different cohorts of NSCLC patients. [ABSTRACT FROM AUTHOR]