Stress cardiomyopathy (SCM) is a syndrome of transient ventricular dysfunction triggered by severe emotional or physical stress, likely resulting from catecholamine-mediated myocardial toxicity. ...Repolarization abnormalities associated with other hyperadrenergic states can cause QT prolongation and lethal arrhythmia including torsades de pointes (TdP). Despite the development of repolarization abnormalities and QT prolongation in SCM, little is known about the risk of ventricular fibrillation (VF) and TdP.
The aim of this study was to assess the prevalence and clinical predictors of ventricular arrhythmias in a cohort of patients with SCM.
Data from a registry of consecutive patients with SCM from 2 institutions were reviewed. Patients who developed VF or TdP were identified. Clinical characteristics and outcomes were analyzed and compared with a control group of patients with SCM without VF/TdP.
Of 93 patients with SCM, 8 (8.6%) experienced VF/TdP. Of these 8 patients, 2 presented with VF and were subsequently diagnosed with SCM. Six other patients experienced pause-dependent TdP or VF after SCM diagnosis in the setting of substantial QT prolongation. Prolongation of the corrected QT interval (QTc) was significantly associated with the occurrence of ventricular arrhythmia (odds ratio 1.28 for each 10 ms increase in QTc, 95% confidence interval 1.10 to 1.50).
SCM can be associated with life-threatening ventricular arrhythmia in over 8% of cases. SCM should be recognized among the causes of acquired long QT syndrome and can be associated with a risk of TdP.
Research Synthesis Baker, Reg; Blumberg, Stephen J.; Brick, J. Michael ...
Public opinion quarterly,
01/2010, Letnik:
74, Številka:
4
Journal Article
Recenzirano
In September 2008, the AAPOR Executive Council established an Opt-In Online Panel Task Force and charges it with "reviewing the current empirical findings related to opt-in online panels utilized for ...data collection and developing recommendations for AAPOR members." The council further specified that the charge did not include development of best practices, but rather would "provide key information and recommendations about whether and when opt-in panels might be best utilized and how best to judge their quality." The task force was formed in October 2008. This is its report. Adapted from the source document.
This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that ...observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 Å, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected. These Akt inhibitors potently inhibit intracellular Akt activation and its downstream target (PRAS40) in vitro. In vivo pharmacodynamic and pharmacokinetic studies with two examples, 12e and 12j, showed the series to be similarly effective at inhibiting the activation of Akt and an additional downstream effector (p70S6) following oral dosing in mice.
Holistic Engineering Education: Beyond Technology is a compilation of coordinated and focused essays from world leaders in the engineering profession who are dedicated to a transformation of ...engineering education and practice. The contributors define a new and holistic approach to education and practice that captures the creativity, interdisciplinarity, complexity, and adaptability required for the profession to grow and truly serve global needs. With few exceptions today, engineering students and professionals continue to receive a traditional, technically-based education and training using curriculum models developed for early 20th century manufacturing and machining. While this educational paradigm has served engineering well, helping engineers create awe-inspiring machines and technologies for society, the coursework and expectations of most engineering programs eschew breadth and intellectual exploration to focus on consistent technological precision and study. Why this dichotomy? While engineering will always need precise technological skill, the 21st century innovation economy demands a new professional perspective that recognizes the value of complex systems thinking, cross-disciplinary collaborations, economic and environmental impacts (sustainability), and effective communication to global and community leaders, thus enabling engineers to consider "the whole patient" of society`s needs. The goal of this book is to inspire, lead, and guide this critically needed transformation of engineering education. "Holistic Engineering Education: Beyond Technology points the way to a transformation of engineering education and practice that will be sufficiently robust, flexible, and systems-oriented to meet the grand challenges of the 21st century with their ever-increasing scale, complexity, and transdisciplinary nature." -- Charles Vest, President, National Academy of Engineering, President Emeritus, MIT "This collection of essays provides compelling arguments for the need of an engineering education that prepares engineers for the problems of the 21st century. Following the National Academy`s report on the Engineer of 2020, this book brings together experts who make the case for an engineering profession that looks beyond developing just cool technologies and more into creating solutions that can address important problems to benefit real people." -- Linda Katehi, Chancellor, University of California at Davis "This superb volume offers a provocative portrait of the exciting future of engineering education...A dramatically new form of engineering education is needed that recognizes this field as a liberal art, as a profession that combines equal parts technical rigor and creative design...The authors challenge the next generation to engineering educators to imagine, think and act in new ways. " -- Lee S. Shulman, President Emeritus, The Carnegie Foundation for the Advancement of Teaching and Charles E. Ducommun Professor of Education Emeritus, Stanford University TOC:FOREWORDS: C. Judson King, Provost and Senior Vice President - Academic Affairs, Emeritus, Director, Center for Studies in Higher Education, Professor of Chemical Engineering, Emeritus, University of California-Berkeley. Rick Miller, President, Franklin W. Olin College of Engineering. Maria Klawe, President, Harvey Mudd College.- Beyond Technology: The Holisitic Advantage: Domenico Grasso, Vice President for Research and Dean of the Graduate College, College of Engineering and Mathematical Sciences, The University of Vermont, Melody Brown Burkins, Senior Director for Research and Strategic Initiatives, The University of Vermont.- Holistic Engineering: Domenico Grasso and David Martinelli, Chairman, Department of Civil and Environmental Engineering, West Virginia University.- Engineering for a Changing World: A Roadmap to the Future of American Engineering Practice, Research, and Education: James J. Duderstadt, President Emeritus and University Professor of Science and Engineering, The University of Michigan.- K-12 Engineering, The Missing Core Discipline: Ioannis Miaoulis, President and Director, Museum of Science, Boston.- Liberal Arts and Engineering: Catherine P. Koshland, Vice Provost, Academic Planning Facilities, Wood-Calvert Professor in Engineering, University of California-Berkeley.- What Is Happening In Liberal Education?: Carol T. Christ, President, Smith College.- Holistic Engineering and Educational Reform: Domenico Grasso and Joseph J. Helble, Dean and Professor of Engineering, Thayer School of Engineering, Dartmouth College.- Beyond Systems Engineering - Educational Approaches for the 21st Century: Priscilla Guthrie, Associate Director of National Intelligence and Intelligence Community Chief Information Officer, Office of Director of National Intelligence.- The Education of an Engineer in a Holistic Age: A Latin American Perspective: Hector Gallegos, President of the Peruvian College of Engineering.- On the Cultivation of Innovative Engineering Talent: Pan Yunhe, Vice President, Chinese Academy of Engineering.- International Education and Holistic Thinking for Engineers: Dennis D. Berkey, President, Worcester Polytechnic Institute.- Engineering Value Propositions: Professional and Personal Needs: Gary E. Wnek and Suzette Williamson, The Institute for Management and Engineering (TiME), Case Western Reserve University.- The Missing Basics Other Philosophical Reflections for the Transformation of Engineering Education: David E. Goldberg, Illinois Foundry for Innovation in Engineering Education (iFoundry), University of Illinois at Urbana-Champaign.- Dispelling the Myths of Holistic Engineering: Domenico Grasso, Melody Brown Burkins, Joseph Helble, and David Martinelli.- The Practice of Systems Engineering: A Foundation for Technical Leadership: Dr. Wanda Austin, et al, The Aerospace Corporation.- Holistic Systems Integration: Al Grasso et al, President CEO, MITRE Corporation.- Engineers of Tomorrow: Holistic-Thinking System Engineers: Charla K. Wise, Vice President - Program Excellence and Operations, Energy and Security Services, Lockheed Martin.- Collaborative Innovation and Service Systems: Implications for Institutions and Disciplines: Nicholas Donofrio, Executive Vice President, IBM.- Technology and Policy: M. Granger Morgan, Head, Department of Engineering and Public Policy, Carnegie-Mellon University.-
Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML).
This analysis included 272 ...5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age < or =21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed.
The average follow-up was 20.5 years (range, 5-33 years). The overall survival rate was 97% at 10 years (95% confidence interval 95%CI, 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%-7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged > or =25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively).
Long-term survival from childhood AML > or =5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population.
Immune editing is a major mechanism used by tumors to promote their survival. We have previously reported the presence of immunosuppressive monocytes (CD14+HLA-DR low/neg) in a number of cancers. ...Increased presence of these cells was associated with decreased treatment response and OS. Here we report an in vitro model to examine tumor monocyte cross talk and demonstrate that these monocytes may directly promote tumor cells' resistance to chemotherapy.
Monocytes from healthy donors were co-cultured with lymphoma cell lines (OCI-Ly1, OCI-Ly3, OCI-Ly7, OCI-Ly10, Su-DHL2, Su-DHL6, Jeko-1, Granta-519) with or without doxorubicin (DOX). Cultured cells were assessed for phenotype, viability, proliferation, and induced protein expression. Changes in vitro were confirmed in primary tissue by gene expression profile from 48 primary diffuse large B cell (DLBCL) lymphoma tumors.
Monocytes converted CD14+HLA-DR+ to the CD14+HLA-DRlow/neg phenotype by co-culture with 5 of the 8 B cell lymphoma cell lines. The HLA-DR suppression was not due to the known regulatory effects of IL-10 nor was the effect seen in co-culture using B cells from healthy donors. Thus, the magnitude of DR loss is mediated by a yet undetermined mechanism. DOX incubation induced apoptosis in all of the cell lines. Co-culture with monocytes improved lymphoma cell survival in 3 of the 4 lymphoma cell lines. For example, untreated OCI-Ly3 had a 1.3±0.2 fold expansion that was reduced to 0.6±0.1 when treated with DOX (p<0.0001, n=13). However, when the cells were treated with DOX and co-cultured with monocytes the survival improved to 0.8±0.2 (p<0.0001, n=13). Having previously shown that CD14+HLA-DRlow/neg were capable of suppressing patient immunity, partially through arginase I, we determined if co-culture of monocytes with tumor cells increased arginase I expression in either monocytes or tumor cells. Not only did we see arginase I expression increases during co-culture(n=10, p<0.01), but surprisingly, the greatest increases were seen during co-culture and DOX treatment (n=10, p=0.01). To determine if our in vitro observations reflect human tumors, we used gene expression data obtained from 48 DLBCL tumors and found that increased CD14 gene expression was positively correlated with increased arginase I expression (n=48, p=0.02).
We have demonstrated that certain tumor cells induced phenotype changes in monocytes in an IL-10 independent and a tumor specific way. In those cells where tumors factors mediate monocyte phenotype, the monocytes can promote tumor cell resistance to cytotoxic killing by DOX, thus demonstrating a cross-talk between monocyte and tumor function. We found that in an environment of monocyte/tumor cross talk, arginase I expression is further increased in a cytotoxic environment. Together, this data demonstrates an active cross talk between monocytes and tumors resulting in multiple mechanisms of tumor resistance to chemotherapy.
No relevant conflicts of interest to declare.
PDF
