Aims Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma ...concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization. Methods and results We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture. Conclusion Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.
The Road to Nowhere Hacker, Jacob S
2020, 1996, 2020-11-10, 19960101, Letnik:
69
eBook
During the 1992 presidential campaign, health care reform became a hot issue, paving the way for one of the most important yet ill-fated social policy initiatives in American history: Bill Clinton's ...1993 proposal for comprehensive coverage under "managed competition." Here Jacob Hacker not only investigates for the first time how managed competition became the president's reform framework, but also illuminates how issues and policies emerge. He follows Clinton's policy ideas from their initial formulation by policy experts through their endorsement by medical industry leaders and politicians to their inclusion--in a new and unexpected form--in the proposal itself. Throughout he explores key questions: Why did health reform become a national issue in the 1990s? Why did Clinton choose managed competition over more familiar options during the 1992 presidential campaign? What effect did this have on the fate of his proposal? Drawing on records of the President's task force, interviews with a wide range of key policy players, and many other sources, Hacker locates his analysis within the context of current political theories on agenda setting. He concludes that Clinton chose managed competition partly because advocates inside and outside the campaign convinced him that it represented a unique middle road to health care reform. This conviction, Hacker maintains, blinded the president and his allies to the political risks of the approach and hindered the development of an effective strategy for enacting it.
Two decades ago, the idea that a “radical right” could capture and drive Israeli politics seemed highly improbable. While it was a boisterous faction and received heavy media coverage, it constituted ...a fringe element. Yet by 2009, Israel’s radical right had not only entrenched itself in mainstream Israeli politics, it was dictating policy in a wide range of areas. The government has essentially caved to the settlers on the West Bank, and restrictions on non-Jews in Israel have increased in the past few years. Members of the radical right have assumed prominent positions in Israel’s elite security forces. The possibility of a two state solution seems more remote than ever, and the emergence of ethnonationalist politician Avigdor Lieberman suggests that its power is increasing. Quite simply, if we want to understand the seemingly intractable situation in Israel today, we need a comprehensive account of the radical right. This book provides an analysis of its ascendance to the heights of Israeli politics. After analyzing what, exactly, they believe in, the book explains how mainstream Israeli policies like “the right of return” have served as unexpected foundations for their nativism and authoritarian tendencies. It then traces the right’s steady rise, from the first intifada to the “Greater Israel” movement that is so prominent today. Throughout, the book focuses on the radical right’s institutional networks and how the movement has been able to expand its constituency. The closing chapter is grim yet realistic: the book contends that a two state solution is no longer viable and that the vision of the radical rabbi Meir Kahane, who was a fringe figure while alive, has triumphed.
The Tsunami-HySEA model is used to perform some of the numerical benchmark problems proposed and documented in the “Proceedings and results of the 2011 NTHMP Model Benchmarking Workshop”. The final ...aim is to obtain the approval for Tsunami-HySEA to be used in projects funded by the National Tsunami Hazard Mitigation Program (NTHMP). Therefore, this work contains the numerical results and comparisons for the five benchmark problems (1, 4, 6, 7, and 9) required for such aim. This set of benchmarks considers analytical, laboratory, and field data test cases. In particular, the analytical solution of a solitary wave runup on a simple beach, and its laboratory counterpart, two more laboratory tests: the runup of a solitary wave on a conically shaped island and the runup onto a complex 3D beach (Monai Valley) and, finally, a field data benchmark based on data from the 1993 Hokkaido Nansei-Oki tsunami.
An insider's account of the origins of the Middle East peace process at the Madrid Peace Conference in 1991. Bentsur sheds new light on the leading personalities and ideas that made the conference a ...success and a foundation for future progress.
Pitches the ideas and aspirations of people on the ground against the theory and assumptions often made by the international development and peace-building agencies and organisations. This book ...discusses about conflict and society in Africa.
This book presents a comprehensive history of the modern Middle East and Arab-Israeli conflict through the Cold War, focusing on relations between the region and the two superpowers.
Ambient or ground-level ozone (O3), a key player in atmospheric chemistry, has been studied extensively throughout the world in recent decades due to its harmful effects on human health and the ...environment. The aim of this study is to examine in detail the time patterns of O3 in the Czech Republic, a Central European country with a long–term history of ambient air pollution. We have examined the interplay between annual trends and within-a-year seasonality in daily O3 concentrations at twelve stations representing different environments, geographical regions and altitudes in the Czech Republic in 1993–2018. We base our analysis on a generalised additive model (GAM) framework as a modern regression approach suitable for addressing non-linear trend shapes in a formalised and unified way. In particular, we use penalised splines. The inconsistent behaviour of the stations prior to 1998, two local maxima around 2003 and 2006 and a steady increase in O3 at all sites from 2014 to the present are the main features of our study. A seasonality O3 pattern with a clear maximum in May–June is similar for all stations. In parallel with the O3 concentration changes over the years, the deformation of seasonality profiles over a long period of time occurs, resulting in a shift of the peak O3 concentrations towards later days in the year. Our statistical modelling offers a detailed view of both long-term trend and seasonality components separately. Additionally, in a model with trend*seasonality interaction, we are able to study the gradual deformation of the seasonality profile over the years.
Capsule: Our analysis of daily mean O3 concentrations at twelve Czech sites in 1993–2018 revealed a steady increase in O3 from 2014 and deformation of the seasonality O3 profiles over the year.
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•O3 time trends and seasonality at 12 sites in 1993–2018 were examined using GAM.•Inconsistent behaviour of the stations prior to 1998 was detected.•An increase in O3 concentrations is apparent at all sites from 2014.•Deformation of seasonal profiles over a long period was detected.•Shift of the peak O3 concentrations towards later days in the year was found.
The Dark Eclipseis a book of personal essays in which author A.W. Barnes seeks to come to terms with the suicide of his older brother, Mike. Using source documentation-police report, autopsy, suicide ...note, and death certificate-the essays explore Barnes' relationship with Mike and their status as gay brothers raised in a large conservative family in the Midwest. In addition, the narrative traces the brothers' difficult relationship with their father, a man who once studied to be a Trappist monk before marrying and fathering eight children. Because of their shared sexual orientation, Andrew hoped he and Mike would be close, but their relationship was as fraught as the author's relationship with his other brothers and father. While the rest of the family seems to have forgotten about Mike, who died in 1993, Barnes has not been able to let him go. This book is his attempt to do so. Published by Bucknell University Press. Distributed worldwide by Rutgers University Press.
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