Relationship between infarct tissue characteristics and left ventricular remodeling in patients with versus without early revascularization for acute myocardial infarction as assessed with contrast-enhanced cardiovascular magnetic resonance imaging

Left ventricular (LV) remodeling following myocardial infarction (MI) is the result of complex interactions between various factors, including presence or absence of early revascularization. The impact of early revascularization on the relationship between infarct tissue characteristics and LV remodeling is incompletely known. Therefore, we investigated in patients with versus without successful early revascularization for acute MI potential relations between infarct tissue characteristics and LV remodeling with contrast-enhanced (CE) cardiovascular magnetic resonance (CMR). Patients with versus without successful early revascularization underwent CE-CMR for tissue characterization and assessment of LV remodeling including end-diastolic and end-systolic volumes, LV ejection fraction, and wall motion score index (WMSI). CE-CMR images were analyzed for infarct tissue characteristics including core-, peri- and total-infarct size, transmural extent, and regional scar scores. In early revascularized patients (n = 46), a larger area of infarct tissue correlated significantly with larger LV dimensions and a more reduced LV function (r = 0.39-0.68; all P ≤ 0.01). Multivariate analyses identified peri-infarct size as the best predictor of LV remodeling parameters (R2 = 0.44-0.62). In patients without successful early revascularization (n = 47), there was no correlation between infarct area and remodeling parameters; only peri-infarct size versus WMSI (r = 0.33; P = 0.03) and transmural extent versus LVEF (r = -0.27; P = 0.07) tended to be related. A correlation between infarct tissue characteristics and LV remodeling was found only in patients with early successful revascularization. Peri-infarct size was found to be the best determinant of LV remodeling. Our findings stress the importance of taking into account infarct tissue characteristics and success of revascularization when LV remodeling is studie

Infarct tissue characterization in implantable cardioverter-defibrillator recipients for primary versus secondary prevention following myocardial infarction: a study with contrast-enhancement cardiovascular magnetic resonance imaging

Knowledge about potential differences in infarct tissue characteristics between patients with prior life-threatening ventricular arrhythmia versus patients receiving prophylactic implantable cardioverter-defibrillator (ICD) might help to improve the current risk stratification in myocardial infarction (MI) patients who are considered for ICD implantation. In a consecutive series of (ICD) recipients for primary and secondary prevention following MI, we used contrast-enhanced (CE) cardiovascular magnetic resonance (CMR) imaging to evaluate differences in infarct tissue characteristics. Cine-CMR measurements included left ventricular end-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and mass. CE-CMR images were analyzed for core, peri, and total infarct size, infarct localization (according to coronary artery territory), and transmural extent. In this study, 95 ICD recipients were included. In the primary prevention group (n = 66), LVEF was lower (23 ± 9 % vs. 31 ± 14 %; P < 0.01), ESV and WMSI were higher (223 ± 75 ml vs. 184 ± 97 ml, P = 0.04, and 1.89 ± 0.52 vs. 1.47 ± 0.68; P < 0.01), and anterior infarct localization was more frequent (P = 0.02) than in the secondary prevention group (n = 29). There were no differences in infarct tissue characteristics between patients treated for primary versus secondary prevention (P > 0.6 for all). During 21 ± 9 months of follow-up, 3 (5 %) patients in the primary prevention group and 9 (31 %) in the secondary prevention group experienced appropriate ICD therapy for treatment of ventricular arrhythmia (P < 0.01). There was no difference in infarct tissue characteristics between recipients of ICD for primary versus secondary prevention, while the secondary prevention group showed a higher frequency of applied ICD therapy for ventricular arrhythmia.\u

A Ring of Peace around the Oslo Synagogue: Muslims and Jews Expressing Interfaith Solidarity in Response to the Paris and Copenhagen Attacks

This chapter stresses the importance of a material approach to the study of peace and conflict, by means of a case study of the Ring of Peace: an interreligious public event that was organized by young Muslims in Oslo, Norway, in response to terrorist attacks in Paris and Copenhagen in 2015. It brings together insights from the fields of material religion and affect studies to explore the relationship between materiality, sensorial experiences, and affects in this performance of ‘peaceful togetherness’. I argue that combining Birgit Meyer’s concept of the “sensational form” with Sara Ahmed’s notion of “affective economies” creates a fruitful ground to analyze how communities are made and remade in relation to violent conflicts, and how unequal power relationships between people of different origins and beliefs are challenged as well as reproduced through efforts for peaceful interfaith coexistence

Energy End-Use : Industry

The industrial sector accounts for about 30% of the global final energy use and accounts for about 115 EJ of final energy use in 2005. 1Cement, iron and steel, chemicals, pulp and paper and aluminum are key energy intensive materials that account for more than half the global industrial use. There is a shift in the primary materials production with developing countries accounting for the majority of the production capacity. China and India have high growth rates in the production of energy intensive materials like cement, fertilizers and steel (12–20%/yr). In different economies materials demand is seen to grow initially with income and then stabilize. For instance in industrialized countries consumption of steel seems to saturate at about 500 kg/capita and 400–500 kg/capita for cement. The aggregate energy intensities in the industrial sectors in different countries have shown steady declines – due to an improvement in energy efficiency and a change in the structure of the industrial output. As an example for the EU-27 the final energy use by industry has remained almost constant (13.4 EJ) at 1990 levels. Structural changes in the economies explain 30% of the reduction in energy intensity with the remaining due to energy efficiency improvements. In different industrial sectors adopting the best achievable technology can result in a saving of 10–30% below the current average. An analysis of cost cutting measures for motors and steam systems in 2005 indicates energy savings potentials of 2.2 EJ for motors and 3.3 EJ for steam. The payback period for these measures range from less than 9 months to 4 years. A systematic analysis of materials and energy flows indicates significant potential for process integration, heat pumps and cogeneration for example savings of 30% are seen in kraft, sulfite, dairy, chocolate, ammonia, and vinyl chloride. An exergy analysis (second law of thermodynamics) reveals that the overall global industry efficiency is only 30%. It is clear that there are major energy efficiency improvements possible through research and development (R&D) in next generation processes. A comparison of energy management policies in different countries and a summary of country experiences, program impacts for Brazil, China, India, South Africa shows the features of successful policies. Energy management International Organization for Standardization (ISO) standards are likely to be effective in facilitating industrial end use efficiency. The effective use of demand side management can be facilitated by combination of mandated measures and market strategies. A frozen efficiency scenario is constructed for industry in 2030. This implies a demand of final energy of 225 EJ in 2030. This involves an increase of the industrial energy output (in terms of Manufacturing Value Added (MVA)) by 95% over its 2005 value. Due to normal efficiency improvements the Business as Usual scenario results in a final energy demand of 175 EJ. The savings possibilities in motors and steam systems, process improvements, pinch, heat pumping and cogeneration have been computed for the existing industrial stock and for the new industries. An energy efficient scenario for 2030 has been constructed with a 95% increase in the industrial output with only a 17% increase in the final energy demand (total final energy demand for industry (135 EJ)). The total direct and indirect carbon dioxide emissions from the industry sector in 2005 is about 9.9 GtCO 2 . Assuming a constant carbon intensity of energy use, the business as usual scenario results in carbon dioxide (CO 2 ) emissions increasing to 17.8 GtCO 2 annually in 2030. In the energy efficient scenario this reduces to 11.6 GtCO 2 . Renewables account for 9% of the final energy of industry (10 EJ in 2005). If an aggressive renewables strategy resulting in an increase in renewable energy supply to 23% in 2030 is targeted (23 EJ), it is possible to have a scenario of constant greenhouse gas (GHG) emissions by the industrial sector (at 2005 levels) with a 95% increase in the industrial output. Several interventions will be required to achieve the energy efficient or constant GHG emission scenario. For the existing industry measures include developing capacity for systems assessment for motors, steam systems and pinch analysis, sharing and documentation of best practices, benchmarks and roadmaps for different industry segments, access to low interest finance etc. A new energy management standard has been developed by ISO for energy management in companies. Its adoption will enable industries to systematically monitor and track energy efficiency improvements. In order to level the playing field for energy efficiency a paradigm shift is required with the focus on energy services not on energy supply per se. This requires a re-orientation of energy supply, distribution companies and energy equipment manufacturing companies. Planning for next generation processes and systems needs the development of long term research agenda and strategic collaborations between industry, academic and research institutions and governments

TRICALS: creating a highway toward a cure

A change in our current approach toward drug development is required to improve the likelihood of finding effective treatment for patients with amyotrophic lateral sclerosis (ALS). The aim of the Treatment Research Initiative to Cure ALS (TRICALS) is to extend the collective effort with industry and consolidate drug development paths. TRICALS has begun a series of meetings on how to best move the field forward collaboratively, thereby addressing five major topics in ALS clinical trials: (1) preclinical research, (2) biomarker development, (3) eligibility criteria, (4) efficacy endpoints and (5) innovative trial design. There is an appetite for ongoing discussions of these major topics in clinical trials between representatives from academia, patient advocacy groups, industry partners and funding bodies. Industry is open to fundamentally change drug development for ALS and shorten the time to effective therapy for patients by implementing promising innovations in biomarker development, trial design, and patient selection. There is however, a pressing need from all stakeholders for regulatory discussions and amendments of current guidelines to successfully adopt innovation in future clinical development lines

Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma:A nationwide case series of 35 patients in The Netherlands

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT). Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P=.02). Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit

Design and pharmacological profile of a novel covalent partial agonist for the adenosine A1 receptor

Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. Accordingly, the design and profiling of novel hA1AR partial agonists has become an important research focus. In this study, we report on LUF7746, a capadenoson derivative bearing an electrophilic fluorosulfonyl moiety, as an irreversibly binding hA1AR modulator. Meanwhile, a nonreactive ligand bearing a methylsulfonyl moiety, LUF7747, was designed as a control probe in our study.In a radioligand binding assay, LUF7746’s apparent affinity increased to nanomolar range with longer pre-incubation time, suggesting an increasing level of covalent binding over time. Moreover, compared to the reference full agonist CPA, LUF7746 was a partial agonist in a hA1AR-mediated G protein activation assay and resistant to blockade with an antagonist/inverse agonist. An in silico structure-based docking study combined with site-directed mutagenesis of the hA1AR demonstrated that amino acid Y2717.36 was the primary anchor point for the covalent interaction. Additionally, a label-free whole-cell assay was set up to identify LUF7746’s irreversible activation of an A1 receptor-mediated cell morphological response.These results led us to conclude that LUF7746 is a novel covalent hA1AR partial agonist and a valuable chemical probe for further mapping the receptor activation process. It may also serve as a prototype for a therapeutic approach in which a covalent partial agonist may cause less on-target side effects, conferring enhanced safety compared to a full agonist.Toxicolog