Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Margaret Cavendish's prolific and wide-ranging contributions to seventeenth-century intellectual culture are impossible to contain within the discrete confines of modern academic disciplines. Paying attention to the innovative uses of genre through which she enhanced and complicated her writings both within literature and beyond, this collection addresses her oeuvre and offers the most comprehensive and multidisciplinary resource on Cavendish's works to date. The astonishing breadth of her varied intellectual achievements is reflected through elegantly arranged sections on History of Science, Philosophy, Literature, (...) Politics and Reception, and New Directions, together with an Afterword by award-winning novelist Siri Hustvedt. The first book to cover nearly all of Cavendish's major works in a single volume, this collection brings together a variety of expert perspectives to illuminate the remarkable ideas and achievements of one of the most fascinating and prolific figures of the early modern period. (shrink)

This book compares two competing theories of human nature: the more traditional theory espoused in different forms by centuries of western philosophy and the newer, Darwinian model. In the traditional view, the human being is a hybrid being, with a lower, animal nature and a higher, rational or “spiritual” component. The competing Darwinian account does away with the idea of a higher nature and attempts to provide a complete reduction of human nature to the evolutionary goals of survival and reproduction. (...) Whitley Kaufman presents the case that the traditional conception, regardless of one's religious views or other beliefs, provides a superior account of human nature and culture. We are animals, but we are also rational animals. Kaufman explores the most fundamental philosophical questions as they relate to this debate over human nature—for example: Is free will an illusion? Is morality a product of evolution, with no objective basis? Is reason merely a tool for promoting reproductive success? Is art an adaptation for attracting mates? Is there any higher meaning or purpose to human life? Human Nature and the Limits of Darwinism aims to assess the competing views of human nature and present a clear account of the issues on this most pressing of questions. It engages in a close analysis of the numerous recent attempts to explain all human aims in terms of Darwinian processes and presents the arguments in support of the traditional conception of human nature. (shrink)

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of anylackofmemoryofpastlives,the lack of proportionality between wrongdoing (...) and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide (it is argued) sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

The vast network of Drosophila geneticists spawned by Thomas Hunt Morgan's fly room in the early 20th century has justifiably received a significant amount of scholarly attention. However, most accounts of the history of Drosophila genetics focus heavily on the "boss and the boys," rather than the many other laboratory groups which also included large numbers of women. Using demographic information extracted from the Drosophila Information Service directories from 1934 to 1970, we offer a profile of the gendered division of (...) labor within Drosophila genetics in the United States during the middle decades of the 20th century. Our analysis of the gendered division of labor supports a reconsideration of laboratory practices as different forms of work. (shrink)

It is widely held by moral philosophers that J.J. Thomson’s “Loop Variant,” a version of the Trolley Problem first presented by her in 1985, decisively refutes the Doctrine of Double Effect as the right explanation of our moral intuitions in the various trolley-type cases.See Bruers and Brackman, “A Review and Systematization of the Trolley Problem,” Philosophia 42:2 : 251–269; T. Scanlon, Moral Dimensions: Permissibility, Meaning, Blame ; Peter Singer, “Ethics and Intuitions,” Journal of Ethics 9:314 : 331–352, p. 340; Matthew (...) Liao, “The Loop Case and Kamm’s Doctrine of Triple Effect,” Philosophical Studies 146:2 : 223–231; H. Sauer, “Morally Irrelevant Factors: What’s Left of the Dual Process Model of Moral Cognition?,” Philosophical Psychology 25:6 : 783–811, p. 797. Frances Kamm suggests the DDE can be saved from the objection, but only by radically revising it into a doctrine of “Triple Effect” (In .. (shrink)

The problem of punishment -- Punishment as crime prevention -- Can retributive punishment be justified? -- The mixed theory of punishment -- Retribution and revenge -- What is the purpose of retribution? -- Making sense of honor -- Is punishment justified?

In Justified Killing, Whitley R. P. Kaufman argues that none of the leading theories adequately explains why it is permissible even to kill an innocent attacker in self-defense, given the basic moral prohibition against killing the innocent. Kaufman suggests that such an explanation can be found in the traditional Doctrine of Double Effect, according to which self-defense is justified because the intention of the defender is to protect himself rather than harm the attacker.

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of any lack of memory of past (...) lives, the lack of proportionality between wrongdoing and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide (it is argued) sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

In a recent edition of the journal Philosophy, Sophie Botros asserts that modern ethical theorists have badly misunderstood the role of the Doctrine of Double Effect, turning it into a device by which to prohibit actions which are deemed impermissible; whereas the true function of the Doctrine is rather one of justifying actions. In my reply, I argue that Dr Botros has misunderstood the Doctrine: that its ‘prohibitive’ and its ‘justificatory’ roles are merely two sides of the same coin, since (...) its function is to decide for a given action whether it is permissible or impermissible. Furthermore, Dr Botros has misconstrued the essential contribution of the DDE is not the balancing of good results against bad ones, but the quite different position that the crucial moral distinction is between intended and merely foreseen results. (shrink)

It is an assumption widely shared by both retributivists and anti-retributivists that revenge is a morally impermissible basis for inflicting harm. Retributivists have thus exercised great ingenuity in demonstrating that retribution is fundamentally different from revenge. But this is, I argue, to misconstrue the problem. The problem is rather to recognize the essential continuity between revenge and retribution, and to address the question whether there is a moral basis for the very idea of inflicting harm in response to moral wrongdoing. (...) I argue that the only plausible such moral justification is the defense of honor, and that the debate needs to be focused on the legitimacy of honor as a moral basis for punishment. (shrink)

Sam Harris’ new book “The Moral Landscape” is the latest in a series of attempts to provide a new “science of morality.” This essay argues that such a project is unlikely to succeed, using Harris’ text as an example of the major philosophical problems that would be faced by any such theory. In particular, I argue that those trying to construct a scientific ethics need pay far more attention to the tradition of moral philosophy, rather than assuming the debate is (...) simply between a scientific ethics and a “supernatural” ethics provided by religion. (shrink)

A frequent argument is that Darwin’s theory of evolution has or should revolutionize our conception of the relation between humans and animals, though society has yet to take account of that revolution in our treatment of animals. On this view, after Darwin demonstrated the essential continuity of humans and animals, traditional morality must be rejected as speciesist in seeing humans as fundamentally distinct from other animals. In fact, the argument is of dubious merit. While there is plenty of room for (...) improving our treatment of animals, it is unlikely that these shortcomings can be blamed on scientific ignorance, or that knowledge of the theory of evolution has any clear moral implications for our treatment of animals. (shrink)

Introduction -- The principles of self-defense -- The leading theories of self-defense -- The doctrine of double effect -- Double effect and common sense morality -- Can double effect justify self-defense? -- Conclusion: Justifying self-defense.

In this essay I analyze and defend the common sense moral conviction that terrorism, i.e., the use of violence against civilians for political or military purposes, is always morally impermissible. Terrorism violates the fundamental moral prohibition against harming the innocent, even to produce greater overall good. It is therefore just the sort of case that serves as a refutation of consequentialist moral theories. From a deontological perspective, the only remotely plausible forms of justification for a terrorist act would be that (...) it constitutes a form of justifiable punishment of the guilty, or that it is legitimate self-defense against an aggressor. But an examination of the fundamental moral and legal principles of punishment and self-defense demonstrates that neither of these claims can succeed. Since terrorism cannot be justified either as punishment or as self-defense, it cannot be morally justified at all. (shrink)

In this essay I analyze and defend the common sense moral conviction that terrorism, i.e., the use of violence against civilians for political or military purposes, is always morally impermissible. Terrorism violates the fundamental moral prohibition against harming the innocent, even to produce greater overall good. It is therefore just the sort of case that serves as a refutation of consequentialist moral theories. From a deontological perspective, the only remotely plausible forms of justification for a terrorist act would be that (...) it constitutes a form of justifiable punishment of the guilty, or that it is legitimate self-defense against an aggressor. But an examination of the fundamental moral and legal principles of punishment and self-defense demonstrates that neither of these claims can succeed. Since terrorism cannot be justified either as punishment or as self-defense, it cannot be morally justified at all. (shrink)

Background: Clinical research nurses experience unique challenges in the context of their role that can lead to conflict and moral distress. Although examined in many areas, moral distress has not been studied in clinical research nurses. Research aim: The aim of this study was to examine moral distress in clinical research nurses and the relationship between moral distress scores and demographic characteristics of clinical research nurses. Research design: This was a descriptive quantitative study to measure moral distress in clinical research (...) nurses using the Measure of Moral Distress – Healthcare Professionals (MMD-HP) administered electronically. Demographic data were also collected. Participants and research context: Registered nurses working in the clinical research nurse role ( N = 322) were recruited through use of social media, emails, digital flyers, and snowball recruitment. Data was analyzed using SPSS. Pearson’s correlation, independent t-test, and one-way ANOVA were performed to explore differences among the demographic variables. Ethical considerations: This study was approved by the Institutional Review Board at Texas Woman’s University. A consent statement was included, and completion of the questionnaire was construed as consent. Findings/results: Analysis revealed a mean overall moral distress score of 79.58 (SD = 64.27) and median of 67, with a range of 0–354. Moral distress scores were negatively correlated with clinical research nurse age ( r = 0-.156, p < 0.05). Reliability of the MMD-HP was demonstrated with a Cronbach’s alpha of 0.93. Conclusions: The findings demonstrate that clinical research nurses do experience moral distress and revealed a wide range of scores. Further research is necessary to determine potential patient impact due to moral distress and to develop processes to minimize moral distress in the clinical research setting. This study was conducted during the COVID-19 pandemic, and the digital recruitment methods proved effective in recruiting a wide range of clinical research nurses, both nationally and internationally. (shrink)

Excerpt from Uebersicht ber das Aristotelische Lehrgeb ude und Er rterung der Lehren Seiner N chsten Nachfolger: Als Uebergang zur Dritten Entwickelungsperiode der Griechischen Philosophie Sci) bergebe hie $erbattnifie 111e cbe hie @d einnng biefe8 %anbe8 meiner (R)efcbicbte n1eljr brei Sabre lang ber3ogert haben; bie @1'm bnnng befiel en m rbe mir fcbn1er3; I11I) unb fiir ben 8efer ohne 8'nterefie fein. S'huen finh fie befannt nnb (c)ie werben ben (c)pnren ber (R)tin1n1nngen, 111 Innen MB 931119 gefcf;rieben ift, 351e 9tacbficbt nicht (...) verfagen. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

Tato studie pojednává o rané fázi mikroskopického zkoumání přírody, které ve svém díle Micrographia představil Robert Hooke. Vzhledem k obsáhlosti díla se zaměřuje na pasáže, které Hooke věnoval výzkumu hmyzu. Předmětem analýzy je především metodologie Hookova výzkumu: způsob, jakým tento experimentátor využíval mikroskop ke zkoumání mravenců, much, komárů a jiného hmyzu. Dále je pozornost věnována způsobu, jakým Hooke představoval výsledky svého pozorování, tedy popisům a ilustracím hmyzu. A konečně, příspěvek se také pokouší vyložit vybrané záznamy mikroskopických pozorování v Micrographii a (...) objasnit jejich vazbu na filosofickou a náboženskou interpretaci přírody sedmnáctého století. (shrink)

Academic dishonesty among students is not confined to the dynamics of the classrooms in which it occurs. The institution has a major role in fostering academic integrity. Ways that institutions can have a significant impact on attitudes toward and knowledge about academic integrity as well as reducing the incidence of academic dishonesty are described. These include the content of an effective academic honesty policy, campus-wide programs designed to foster integrity, and the development of a campus-wide ethos that encourages integrity.

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of anylackofmemoryofpastlives,the lack of proportionality between wrongdoing (...) and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

Authentic objects are those that have a historical link to a person, event, time, or place of some significance. The current study examines everyday beliefs about authentic objects, with three primary goals: to determine the scope of adults' evaluation of authentic objects, to examine such evaluation in two distinct cultural settings, and to determine whether a person's attachment history predicts evaluation of authentic objects. We found that college students in the UK and the USA consistently evaluate a broad range of (...) authentic items as more valuable than matched control objects, more desirable to keep, and more desirable to touch, though only non-personal authentic items were judged to be more appropriate for display in a museum. These patterns were remarkably similar across the two cultural contexts. Additionally, those who had an attachment object as a child evaluated objects more favorably, and in particular judged authentic objects to be more valuable. Altogether, these results demonstrate broad endorsement of "positive contagion" among college-educated adults. (shrink)

Розкрито сутність поняття «рейтинг». Доведено значущість рейтингової оцінки для суб’єктів фінансового ринку, зокрема для страхових компаній, потенційних страхувальників, інвесторів та кредиторів.

La especulación filosófica suele observar que lo feo y el mal carecen de entidad y que sólo pueden ser considerados como una belleza y bondad menguadas. Sin embargo, esta disminución entitativa no constituye sólo una carencia, sino que además puede ofrecer en sí la posibilidad de una belleza y un bien mayores. En este sentido, pensar la belleza del mal no ha constituido para muchos autores antiguos y medievales una imposibilidad lógica, sino por el contrario una nueva manera de hablar (...) de la Belleza del Universo. Este ha sido el parecer agustino y dionisiano, y es también el que asume la conocida Summa Halensis, aunque desde una óptica cuya originalidad radica en la integración de esas tradiciones. Analizar cómo la Summa Halensis entiende que la belleza es capaz de integrar a lo malo, es la intención del presente trabajo. (shrink)

No hay duda que la cuestión de los trascendentales y su posible distinción atrajo la atención de los pensadores del siglo XIII. Sin embargo, este tema siguió caminos diversos. En tal sentido, la Summa Halensis propone un abordaje que no sólo delimita cada transcendental en sí, sino que además los incorpora al plano soteriológico humano. Así, el presente trabajo se ocupará de ambos aspectos.

This essay explores the relationship between nature and grace and the theological impact of this relationship on feminist anthropological debates. Engaging this debate through an examination and critique of Serene Jones’ ‘eschatological essentialism’, this essay suggests that Jones mistakenly characterizes constructivism, and thus turns too quickly to an essentialist paradigm without considering its risks. Using Judith Butler and Karl Barth, this essay proposes an account of identity that the author calls a ‘Christological constructivism’. Suggesting that the person and work of (...) Christ instantiates a grace that disrupts nature, Daniels argues for an account of identity as ‘more-than’, suggesting that this anthropology engenders healing for women, and men, within communities religious and otherwise. (shrink)

Ecclesial practices have long served as a resource in and for Christian ethical scholarship; drawing on both the postliberal tradition and critical identity studies, a number of contemporary theologians and ethicists have turned to ecclesial practices as a liberative resource for marginalized identities and oppressed communities. Through a close reading of two contemporary examples of this ethical approach, this essay outlines and critically examines how Christian identity, belonging, and practice function discursively, subsuming difference into religious sameness, in ways that perpetuate (...) the systemic and social injustices they aim to address and combat. Drawing on recent critiques of the theo-ethical turns to practice by Katie Grimes and Lauren Winner, and on feminist philosopher Lynne Huffer’s ethics of narrative performance, this essay proposes a more critical attention to difference for and within ethical turns to Christian practices, and begins to outline potential paths forward. (shrink)

Review of Joel Faflak. Romantic Psychoanalysis: The Burden of the Mystery. Albany: State University of New York Press, 2008. 333 pages; paper $29.95. ISBN 978-0-7914-7269-0.

When I was a 7 months pregnant medical student, an attending surgeon asked me to which specialty I would be applying. When I replied that I was hoping to match in general surgery, he touched my pregnant abdomen and said, “Not with that you’re not.” I am not alone. Gender bias and discrimination have been shown to negatively impact women surgeons throughout their careers and deter women from even applying in surgical fields.1 Bias against female surgical trainees leads to less (...) operative autonomy and higher dropout rates.2 3 Once faculty, women surgeons are less likely to reach leadership roles.4 Recent studies confirm the author’s assertion that implicit biases create substantial harm. The author has undertaken an important study, conducting in-depth interviews with 46 women surgeons in Australia that identifies four distinct types of bias causing cumulative harm. In all four types of biases: Workplace factors including leave policies and mentorship. Epistemic injustices, or unfair assessments of women surgeons’ credibility by patients and colleagues. Stereotyped expectations. Objectification, implicit biases were seen. While many of the broad factors impeding women in surgery are well known, the author argues that these subtler factors, including both implicit bias and epistemic injustice, have a large impact. The …. (shrink)

Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description (...) of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death. (shrink)

Within the deep philosophical reflection of the thirteenth century are commonly heard names such as Albertus Magnus, Thomas Aquinas and Bonaventure. However, little is said of those disciples of lesser brilliance who spread the thought of their teachers. Such is the case of Ulrich of Strasbourg. This Dominican friar, a fellow student of Thomas Aquinas in Cologne, studied under Albertus Magnus the De Divinis nominibus of Pseudo-Dionysius. Years later, Ulrich wrote a work called Summa de bono where, in dealing with (...) beauty, a unique Neoplatonic synthesis operates, but from the original perspective of his master. This paper analyses the concept of beauty present in Ulrich of Strasbourg to show how there is as much clear dependence on Albertian Neoplatonism as there is originality in the presentation of the topic. (shrink)