A catalogue of works devoted to end-of-life themes. The volume consists of eleven articles arranged in four parts corresponding to a broad range of issues: law, ethics, philosophy, and cultural ...studies. The arrangement of the book is thus constructed around various perspectives upon which any reflection on death and dying must be based.
Recent studies show that cancer cells are sometimes able to evade the host immunity in the tumor microenvironment. Cancer cells can express high levels of immune inhibitory signaling proteins. One of ...the most critical checkpoint pathways in this system is a tumor‐induced immune suppression (immune checkpoint) mediated by the programmed cell death protein 1 (PD‐1) and its ligand, programmed death ligand 1 (PD‐L1). PD‐1 is highly expressed by activated T cells, B cells, dendritic cells, and natural killer cells, whereas PD‐L1 is expressed on several types of tumor cells. Many studies have shown that blocking the interaction between PD‐1 and PD‐L1 enhances the T‐cell response and mediates antitumor activity. In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD‐1 and PD‐L1 interaction in various cancers.
In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD‐1 and PD‐L1 interaction in various cancers.
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Taking as her focus a body of writings in poetic, didactic, and legal modes that circulated in England's capital between the 1380sjust a generation after the Black Deathand the first decade of the ...English reformation in the 1530s, Amy Appleford offers the first full-length study of the Middle English "art of dying" (ars moriendi). An educated awareness of death and mortality was a vital aspect of medieval civic culture, she contends, critical not only to the shaping of single lives and the management of families and households but also to the practices of cultural memory, the building of institutions, and the good government of the city itself.
In fifteenth-century London in particular, where an increasingly laicized reformist religiosity coexisted with an ambitious program of urban renewal, cultivating a sophisticated attitude toward death was understood as essential to good living in the widest sense. The virtuous ordering of self, household, and city rested on a proper attitude toward mortality on the part both of the ruled and of their secular and religious rulers. The intricacies of keeping death constantly in mind informed not only the religious prose of the period, but also literary and visual arts. In London's version of the famous image-text known as the Dance of Death, Thomas Hoccleve's poetic collectionThe Series, and the early sixteenth-century prose treatises of Tudor writers Richard Whitford, Thomas Lupset, and Thomas More, death is understood as an explicitly generative force, one capable (if properly managed) of providing vital personal, social, and literary opportunities.
From economist Anne Case and Nobel Prize winner Angus Deaton, a groundbreaking account of how the flaws in capitalism are fatal for America's working class
Life expectancy in the United States has ...recently fallen for three years in a row—a reversal not seen since 1918 or in any other wealthy nation in modern times. In the past two decades, deaths of despair from suicide, drug overdose, and alcoholism have risen dramatically, and now claim hundreds of thousands of American lives each year—and they're still rising. Anne Case and Angus Deaton, known for first sounding the alarm about deaths of despair, explain the overwhelming surge in these deaths and shed light on the social and economic forces that are making life harder for the working class. They demonstrate why, for those who used to prosper in America, capitalism is no longer delivering.
Deaths of Despair and the Future of Capitalism paints a troubling portrait of the American dream in decline. For the white working class, today's America has become a land of broken families and few prospects. As the college educated become healthier and wealthier, adults without a degree are literally dying from pain and despair. In this critically important book, Case and Deaton tie the crisis to the weakening position of labor, the growing power of corporations, and, above all, to a rapacious health-care sector that redistributes working-class wages into the pockets of the wealthy. Capitalism, which over two centuries lifted countless people out of poverty, is now destroying the lives of blue-collar America.
This book charts a way forward, providing solutions that can rein in capitalism’s excesses and make it work for everyone.
In November 1998, millions of television viewers watched as Thomas Youk died. Suffering from the late stages of Lou Gehrig's disease, Youk had called upon infamous Michigan pathologist Dr. Jack ...Kevorkian to help end his life on his own terms. After delivering the videotape to60 Minutes, Kevorkian was arrested and convicted of manslaughter, despite the fact that Youk's family firmly believed that the ending of his life qualified as a good death. Death is political, as the controversies surrounding Jack Kevorkian and, more recently, Terri Schiavo have shown. While death is a natural event, modern end-of-life experiences are shaped by new medical, demographic, and cultural trends. People who are dying are kept alive, sometimes against their will or the will of their family, with powerful medications, machines, and "heroic measures." Current research on end-of-life issues is substantial, involving many fields.Beyond the Good Deathtakes an anthropological approach, examining the changes in our concept of death over the last several decades. As author James W. Green determines, the attitudes of today's baby boomers differ greatly from those of their parents and grandparents, who spoke politely and in hushed voices of those who had "passed away." Dr. Elisabeth Kübler-Ross, in the 1960s, gave the public a new language for speaking openly about death with her "five steps of dying." If we talked more about death, she emphasized, it would become less fearful for everyone. The term "good death" reentered the public consciousness as narratives of AIDS, cancer, and other chronic diseases were featured on talk shows and in popular books such as the best-sellingTuesdays with Morrie. Green looks at a number of contemporary secular American death practices that are still informed by an ancient religious ethos. Most important,Beyond the Good Deathprovides an interpretation of the ways in which Americans react when death is at hand for themselves or for those they care about.
Lifeling by Kirsty Applebaum (review) Spisak, April
Bulletin of the Center for Children's Books,
02/2022, Volume:
75, Issue:
6
Journal Article, Book Review
Neurology ethics at the end of life Mazzola, Maria Antonietta; Russell, James Adams
Handbook of clinical neurology,
2023, Volume:
191
Journal Article
Peer reviewed
Ethical challenges in medical decision making are commonly encountered by clinicians caring for patients afflicted by neurological injury or disease at the end of life (EOL). In many of these cases, ...there are conflicting opinions as to what is right and wrong originating from multiple sources. There is a particularly high prevalence of impaired patient judgment and decision-making capacity in this population that may result in a misrepresentation of their premorbid values and goals. Conflict may originate from a discordance between what is legal or from stakeholders who view and value life and existence differently from the patient, at times due to religious or cultural influences. Promotion of life, rather than preservation of existence, is the goal of many patients and the foundation on which palliative care is built. Those who provide EOL care, while being respectful of potential cultural, religious, and legal stakeholder perspectives, must at the same time recognize that these perspectives may conflict with the optimal ethical course to follow. In this chapter, we will attempt to review some of the more notable ethical challenges that may arise in the neurologically afflicted at the EOL. We will identify what we believe to be the most compelling ethical arguments both in support of and opposition to specific EOL issues. At the same time, we will consider how ethical analysis may be influenced by these legal, cultural, and religious considerations that commonly arise.
The Routledge History of Death Since 1800 looks at how death has been treated and dealt with in modern history – the history of the past 250 years – in a global context, through a mix of definite, ...often quantifiable changes and a complex, qualitative assessment of the subject.
The book is divided into three parts, with the first considering major trends in death history and identifying widespread patterns of change and continuity in the material and cultural features of death since 1800. The second part turns to specifically regional experiences, and the third offers more specialized chapters on key topics in the modern history of death. Historical findings and debates feed directly into a current and prospective assessment of death, as many societies transition into patterns of ageing that will further alter the death experience and challenge modern reactions. Thus, a final chapter probes this topic, by way of introducing the links between historical experience and current trajectories, ensuring that the book gives the reader a framework for assessing the ongoing process, as well as an understanding of the past.
Global in focus and linking death to a variety of major developments in modern global history, the volume is ideal for all those interested in the multifaceted history of how death has been dealt with in different societies over time and who want access to the rich and growing historiography on the subject.
PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, ...incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC′ sheet, which is flexible and completely lacks a C″ strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC′ sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1·ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3–4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors.
Background: The inhibitory leukocyte receptor PD-1 binds two ligands, PD-L1 and PD-L2.
Results: Nuclear magnetic resonance analysis and rigorous binding and thermodynamic measurements reveal the structure of, and the mode of ligand recognition by, PD-1.
Conclusion: PD-L1 and PD-L2 bind differently to PD-1 and much more weakly than expected.
Significance: Potent inhibitory signaling can be initiated by weakly interacting receptors.
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