Many measures can control lipid risk factors for atherosclerosis. Yet, even with excellent control of dyslipidemia, other sources of risk remain. Hence, we must look beyond lipids to address residual ...risk. Lifestyle measures should form the foundation of cardiovascular risk control. Many pharmacological interventions targeting oxidation have proven disappointing. A large program tested inhibition of a LpPLA2 (lipoprotein-associated phospholipase A2), culminating in 2 large-scale clinical trials that did not meet their primary end points. A variety of antioxidants have not shown benefit in clinical trials. Numerous laboratory and clinical studies have inculpated inflammatory pathways in the pathogenesis of atherosclerotic events. The p38 MAPK (mitogen-activated protein kinase) inhibitor losmapimod and an inhibitor of a leukocyte adhesion molecule, P-selectin, did not alter adverse events in trials. Low-dose methotrexate, despite the promising observational studies, did not lower biomarkers of inflammation or alter cardiovascular outcomes in the CIRT (cardiovascular inflammation reduction trial). Four large-scale investigations underway will determine colchicine’s ability to reduce recurrent events in secondary prevention. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed that an antibody that neutralizes IL (interleukin)-1β can reduce recurrent cardiovascular events in secondary prevention. The success of CANTOS points to the pathway that leads from the NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) inflammasome through IL-1β to IL-6 as an attractive target for further study and clinical development beyond lipid therapies to address the unacceptable burden of risk that remains despite our best current care in secondary prevention.
A new system for CO2 reduction to methanol has been demonstrated using homogeneous ruthenium catalysts with a range of amine auxiliaries. Modification of this amine has a profound effect on the yield ...and selectivity of the reaction. A TON of 8900 and TOF of 4500 h-1 is achieved using a RuCl2(Ph2PCH2CH2NHMe)2 catalyst with a diisopropylamine auxiliary.
A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ...ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8
T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate-cystine antiporter xc
, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy. SIGNIFICANCE: This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy.
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Patients with coronary artery disease were randomly assigned to either methotrexate (15 to 20 mg weekly) or placebo. At a median of 2.3 years, there was no difference between the two groups in the ...rate of myocardial infarction, stroke, or cardiovascular death.
Background Inflammation plays a fundamental role in atherothrombosis. Yet, whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known. Design ...The Cardiovascular Inflammation Reduction Trial (CIRT) ( ClinicalTrials.gov NCT01594333 ) will randomly allocate 7,000 patients with prior myocardial infarction (MI) and either type 2 diabetes or the metabolic syndrome to low-dose methotrexate (target dose 15-20 mg/wk) or placebo over an average follow-up period of 3 to 5 years. Low-dose methotrexate is a commonly used anti-inflammatory regimen for the treatment of rheumatoid arthritis and lacks significant effects on lipid levels, blood pressure, or platelet function. Both observational and mechanistic studies suggest that low-dose methotrexate has clinically relevant antiatherothrombotic effects. The CIRT primary end point is a composite of nonfatal MI, nonfatal stroke, and cardiovascular death. Secondary end points are all-cause mortality, coronary revascularization plus the primary end point, hospitalization for congestive heart failure plus the primary end point, all-cause mortality plus coronary revascularization plus congestive heart failure plus the primary end point, incident type 2 diabetes, and net clinical benefit or harm. CIRT will use standardized central methodology designed to ensure consistent performance of all dose adjustments and safety interventions at each clinical site in a manner that protects the blinding to treatment but maintains safety for enrolled participants. Summary CIRT aims to test the inflammatory hypothesis of atherothrombosis in patients with prior MI and either type 2 diabetes or metabolic syndrome, conditions associated with persistent inflammation. If low-dose methotrexate reduces cardiovascular events, CIRT would provide a novel therapeutic approach for the secondary prevention of heart attack, stroke, and cardiovascular death.
We present results from high-resolution, optical to near-IR imaging of host stars of Kepler Objects of Interest (KOIs), identified in the original Kepler field. Part of the data were obtained under ...the Kepler imaging follow-up observation program over six years (2009-2015). Almost 90% of stars that are hosts to planet candidates or confirmed planets were observed. We combine measurements of companions to KOI host stars from different bands to create a comprehensive catalog of projected separations, position angles, and magnitude differences for all detected companion stars (some of which may not be bound). Our compilation includes 2297 companions around 1903 primary stars. From high-resolution imaging, we find that ∼10% (∼30%) of the observed stars have at least one companion detected within 1″ (4″). The true fraction of systems with close ( 4″) companions is larger than the observed one due to the limited sensitivities of the imaging data. We derive correction factors for planet radii caused by the dilution of the transit depth: assuming that planets orbit the primary stars or the brightest companion stars, the average correction factors are 1.06 and 3.09, respectively. The true effect of transit dilution lies in between these two cases and varies with each system. Applying these factors to planet radii decreases the number of KOI planets with radii smaller than 2 by ∼2%-23% and thus affects planet occurrence rates. This effect will also be important for the yield of small planets from future transit missions such as TESS.
Seismic observations in volcanically active calderas are challenging. A new cabled observatory atop Axial Seamount on the Juan de Fuca ridge allows unprecedented real-time monitoring of a submarine ...caldera. Beginning on 24 April 2015, the seismic network captured an eruption that culminated in explosive acoustic signals where lava erupted on the seafloor. Extensive seismic activity preceding the eruption shows that inflation is accommodated by the reactivation of an outward-dipping caldera ring fault, with strong tidal triggering indicating a critically stressed system. The ring fault accommodated deflation during the eruption and provided a pathway for a dike that propagated south and north beneath the caldera's east wall. Once north of the caldera, the eruption stepped westward, and a dike propagated along the extensional north rift.
Entertainment-Education and Social Change introduces readers to entertainment-education (E-E) literature from multiple perspectives. This distinctive collection covers the history of ...entertainment-education, its applications in the United States and throughout the world, the multiple communication theories that bear on E-E, and a range of research methods for studying the effects of E-E interventions. The editors include commentary and insights from prominent E-E theoreticians, practitioners, activists, and researchers, representing a wide range of nationalities and theoretical orientations.
Examples of effective E-E designs and applications, as well as an agenda for future E-E initiatives and campaigns, make this work a useful volume for scholars, educators, and practitioners in entertainment media studies, behavior change communications, public health, psychology, social work, and other arenas concerned with strategies for social change. It will be an invaluable resource book for members of governmental and non-profit agencies, public health and development professionals, and social activists.
Contents: Preface. Part I: History and Theory. A. Singhal, E.M. Rogers, The Status of Entertainment-Education Worldwide. D. Poindexter, A History of Entertainment-Education, 1958-2000. P.T. Poitrow, E. de Fossard, Entertainment-Education as a Public Health Intervention. M. Sabido, The Origins of Entertainment-Education. A. Bandura, Social Cognitive Theory for Personal and Social Change by Enabling Media. W.J. Brown, B.P. Fraser, Celebrity Identification in Entertainment-Education. S. Sood, T. Menard, K. Witte, The Theory Behind Entertainment-Education. Part II: Research and Implementation. S. Usdin, A. Singhal, T. Shongwe, S. Goldstein, A. Shabalala, No Short Cuts in Entertainment-Education: Designing Soul City Step-by-Step. W.N. Ryerson, N. Teffera, Organizing a Comprehensive National Plan for Entertainment-Education in Ethiopia. B.S. Greenberg, C.T. Salmon, D. Patel, V. Beck, G. Cole, Evolution of an E-E Research Agenda. V. Beck, Working With Daytime and Prime-Time Television Shows in the United States to Promote Health. M. Bouman, Entertainment-Education Television Drama in the Netherlands. M.J. Cody, S. Fernandes, H. Wilkin, Entertainment-Education Programs of the BBC and BBC World Service Trust. A.C. La Pastina, D.S. Patel, M. Schiavo, Social Merchandizing in Brazilian Telenovelas. E.M. Rogers, Delivering Entertainment-Education Health Messages Through the Internet to Hard-to-Reach U.S. Audiences in the Southwest. Part III: Entertainment-Education Interventions and Their Outcomes. R.A. Abdulla, Entertainment-Education in the Middle East: Lessons From the Egyptian Oral Rehydration Campaign. Y. Yaser, The Turkish Family Health and Planning Foundation's Entertainment-Education Campaign. N. McKee, M. Aghi, R. Carnegie, N. Shahzadi, Cartoons and Comic Books for Changing Social Norms: Meena, the South Asian Girl. A. Singhal, D. Sharma, M.J. Papa, K. Witte, Air Cover and Ground Mobilization: Integrating Entertainment-Education Broadcasts With Community Listening and Service Delivery in India. A. Singhal, Entertainment-Education Through Participatory Theater: Freirean Strategies for Empowering the Oppressed. T. Tufte, Soap Operas and Sense-Making: Mediations and Audience Ethnography. J.D. Storey, T.L. Jacobson, Entertainment-Education and Participation: Applying Habermas to a Population Program in Nepal. Epilogue.
Among patients with diabetes and stable heart disease, those with troponin T levels of 14 ng per liter or more had a 5-year rate of cardiovascular death, MI, or stroke of 27%, versus 13% in those ...with lower levels, but received no benefit from prompt revascularization.
Cardiac troponin concentration is the preferred marker of myocardial necrosis.
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Elevated concentrations of cardiac troponin have a strong association with an adverse prognosis in patients with acute coronary syndromes and are used to identify patients who are likely to benefit from an early invasive management strategy.
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High-sensitivity assays that allow the measurement of very low cardiac troponin levels in patients with stable heart disease are now available for clinical and research use. These low, previously undetectable troponin concentrations have shown strong associations with myocardial infarction, stroke, and death in a variety of primary and secondary prevention populations, including in . . .
► Full structural information of two mode network data is nearly always contained in the projections. ► Using both projections together usually means there is no loss of structural information. ► ...Projections have the potential to allow us to use methods which uncover additional structural information in two mode data.
There have been two distinct approaches to two-mode data. The first approach is to project the data to one-mode and then analyze the projected network using standard single-mode techniques, also called the conversion method. The second approach has been to extend methods and concepts to the two-mode case and analyze the network directly with the two modes considered jointly. The direct approach in recent years has been the preferred method since it is assumed that the conversion method loses important structural information. Here we argue that this is not the case, provided both projections are used together in any analysis. We illustrate how this approach works using core/periphery, structural equivalence and centrality as examples.
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