While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application (...) process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic. (shrink)

Background Equal access to healthcare is a core principle in Norway’s public healthcare system. The COVID-19 pandemic challenged healthcare systems in the early phase – in particular, related to testing and hospital capacity. There is little knowledge on how older people experienced being infected with an unfamiliar and severe disease, and how they experienced the need for healthcare early in the pandemic Aim To explore the experiences of older people infected by COVID-19 and their need for testing and hospitalisation. Research (...) design An explorative and descriptive approach, with qualitative interviews conducted in October 2020. Participants and research context Seventeen participants above 60 years of age hospitalised due to COVID-19 during spring 2020 were recruited 6 months after discharge. Ethical considerations Ethical approval was granted by the Regional Committee for Medical and Health Research Ethics in South-Eastern Norway (155425). Findings The main finding was that the informants experienced vulnerability and arbitrariness. This finding was supported by three sub-themes: experiences with a severe and unfamiliar disease, the strict criteria and the importance of someone advocating needs. Discussion Participants described varying access to healthcare. Those who did not meet the national criteria to be tested or hospitalised struggled against the system. Findings reveal arbitrary access to healthcare, in contrast to Norway’s ethical principle of fair and just access to health services. Moreover, to access and receive necessary healthcare, informants were dependent on their next-of-kin’s advocacy. Conclusion Even when dealing with an unfamiliar disease, health professionals’ assessments of symptoms must be performed with an ethical obligation to applicate competent appraisal and the exercise of discernment; this is in line with care ethics and ethical standards for nurses. These perspectives are a significant part of caring and the intension of doing good. (shrink)

While information technologies present organizations with opportunities to become more competitive, unsettled social norms and lagging legislation guiding the use of these technologies present organizations and individuals with ethical dilemmas. This paper presents two studies investigating the relationship between intellectual property and privacy attitudes, Machiavellianism and Ethical Ideology, and working in R&D and computer literacy in the form of programming experience. In Study 1, Machiavellians believed it was more acceptable to ignore the intellectual property and privacy rights of others. Programmers (...) and R&D workers considered violating intellectual property rights more acceptable. Programmers did not consider violating privacy rights more acceptable, but R&D workers did. Finally, there was an interaction between Machiavellianism, programming and R&D. Machiavellians who also had programming experience or worked in R&D found violations of intellectual property much more acceptable. The effect of Machiavellianism on attitudes toward violations of privacy was enhanced by working in R&D, but not by programming experience. In Study 2, idealists believed it was less acceptable to ignore the intellectual property and privacy rights of others. Relativists found it more acceptable to violate intellectual property rights, though they did not consider it more acceptable to violate privacy rights. Those with programming experience were more accepting of intellectual property rights violations, but not of privacy violations. Finally, programming experience moderated the relationship between idealism, relativism and attitudes toward these unethical information practices. Implications for diminishing unethical behavior among Machiavellians, Relativists, programmers and those in R&D are discussed. (shrink)

In recent years, there has been a proliferation of neuroscientific theories of consciousness. These include theories which explicitly point to EM fields, notably Operational Architectonics and, more recently, the General Resonance Theory. In phenomenological terms, human consciousness is a unified composition of contents. These contents are specific and meaningful, and they exist from a subjective point of view. Human conscious experience is temporally continuous, limited in content, and coherent. Based upon those phenomenal observations, pre-existing theories of consciousness, and a large (...) body of experimental evidence, I derived the Temporally-Integrated Causality Landscape. In brief, the TICL proposes that the neural correlate of consciousness is a structure of temporally integrated causality occurring over a large portion of the thalamocortical system. This structure is composed of a large, integrated set of neuronal elements, which contains some subsystems, defined as having a higher level of temporally-integrated causality than the System as a whole. Each Subsystem exists from the point of view of the System, in the form of meaningful content. In this article, I review the TICL and consider the importance of EM forces as a mechanism of neural causality. I compare the fundamentals of TICL to those of several other neuroscientific theories. Using five major characteristics of phenomenal consciousness as a standard, I compare the basic tenets of Integrated Information Theory, Global Neuronal Workspace, General Resonance Theory, Operational Architectonics, and the Temporo-spatial Theory of Consciousness with the framework of the TICL. While the literature concerned with these theories tends to focus on different lines of evidence, there are fundamental areas of agreement. This means that, in time, it may be possible for many of them to converge upon the truth. In this analysis, I conclude that a primary distinction which divides these theories is the feature of spatial and temporal nesting. Interestingly, this distinction does not separate along the fault line between theories explicitly concerned with EM fields and those which are not. I believe that reconciliation is possible, at least in principle, among those theories that recognize the following: just as the contents of consciousness are distinctions within consciousness, the neural correlates of conscious content should be distinguishable from but fall within the spatial and temporal boundaries of the full neural correlates of consciousness. (shrink)

The idea of dignity is often taken to be a foundation for principles of justice and democracy. In the West it has numerous formulations and conceptualisations. Within the capabilities approach to justice theorists have expanded the concept of dignity to encompass animals and ecological communities. In this article I rework the idea of dignity to include the Māori philosophical concepts of Mauri, tapu and mana – something I argue is necessary if the capabilities approach is to decolonise in the Aotearoa (...) context. Furthermore, the article links the nation’s recognition of three extensive geographical regions – Te Awa Tupua, Te Urewera and Mt Taranaki – as legal persons to Mātauranga Māori and nonhuman dignity. In doing so, I identify the potential that this understanding of dignity and these legal moves have to decolonise democracy within the settler state. (shrink)

In this paper, the authors describe an aspect of a program of research around grief and clinical practice. The first phase of the study involves examination of experiences of grief with attention to troublesome or problematic beliefs that fuel the extent of suffering in the bereaved. The data, obtained from a review of videotaped clinical interviews with families seen in the Family Nursing Unit at the University of Calgary, were analyzed according to philosophical hermeneutic tradition. Findings suggest that grief is (...) an experience that is ongoing, that changes in nature over time, but that involves a continuing relationship with the deceased; it is a graceful, periodic, deliberate walk backwards while keeping a sure foot in living forward. (shrink)

In A Climate of History Dipesh Chakrabarty locates Kant’s speculative reading of Genesis as “the Enduring Fable” furnishing the background for human domination and earthly destruction. Writing from the fable’s “ruins,” Chakrabarty urges the elaboration of new fables that provide the background ethics and meanings required to recast relations between humans and the natural world. Responding to Chakrabarty’s challenge, we outline two “fables” based first in the oft ignored Genesis 2, and second, in Matauranga Māori. Although marginalised, these extant fables (...) provide the imaginary for radically other ways of being human in a more-than-human world in turmoil. (shrink)

Originally published in German, Christoph Wulf’s _Anthropology_ sets its sights on a topic as ambitious as its title suggests: anthropology itself. Arguing for an interdisciplinary and intercultural approach to anthropology that incorporates science, philosophy, history, and many other disciplines, Wulf examines—with breathtaking scope—all the ways that anthropology has been understood and practiced around the globe and through the years. Seeking a central way to understand anthropology in the midst of many different approaches to the discipline, Wulf concentrates on the human (...) body. An emblem of society, culture, and time, the body is also the result of many mimetic processes—the active acquisition of cultural knowledge. By examining the role of the body in the performance of rituals, gestures, language, and other forms of imagination, he offers a bold new look at how culture is produced, handed down, and transformed. Drawing such examinations into a comprehensive and sophisticated assessment of the discipline as a whole, _Anthropology_ looks squarely at the mystery of humankind and the ways we have attempted to understand it. (shrink)

This article presents a case for thinking that moral principles within Aristotle's ethical theory can be both codifiable and action-guiding without minimizing the role of practical reason in determining what should be done. I argue that McDowell dismisses this possibility too hastily. Much of the force of this case rests on my interpretation of "for the most part" relationships in Aristotle.

Introduction Perhaps more than any other member of the Frankfurt School, Herbert Marcuse articulated a hope for a radically transfigured world. He imagined a world characterized by receptive, generous relationships rather than domination and violence. Yet Marcuse's philosophy of liberation has been placed on trial within various critical circles. Michel Foucault's rejection of the “repressive hypothesis” and his concomitant analysis of power as generative is typically interpreted as an indirect response to Marcuse's tendency to treat the social order as a (...) primarily repressive force vis-à-vis our instincts and desires.1 Martin Jay has expressed concerns about the…. (shrink)

Brexit activists demonstrating outside the British Houses of Parliament were studied in situ to examine their potential for pro-group extreme behavior. This involved activists of two polarized, opposing views; those of Leave and Remain. The research engaged concepts linking the different theoretical perspectives of identity fusion and personal construct psychology. The study measured participants' degree of fusion to their group using a verbal measure. Willingness to undertake extreme acts was assessed in several ways: a measure of willingness to fight for (...) the group, adaptations of the trolley dilemma and questions regarding political violence. Individual construing was examined using repertory grid technique and a semi-structured interview. Results were similar for both Leave and Remain participants. The majority of activists identified as “fused” to their group and, if so, were more likely to undertake hypothetical extreme behavior compared to those who did not identify as “fused.” Repertory grid technique indicated that becoming an activist provided individuals with a clearer and more positive view of themselves. Opposition activists were construed more negatively and extremely than fellow activists, and this construal was associated with an increased willingness to undertake extreme pro-group behavior. This was consistent with the personal construct model of radicalization and was heightened in those who were “fused.” Interview data provided support for the constructivist model and revealed characteristics and concerns of the two groups. Overall, the findings indicate that campaigning organizations contain fused individuals, who are more likely to undertake hypothetical pro-group violence including self-sacrifice. This has broader implications which may be particularly pertinent, given the violent impact of extremist activists around the globe. (shrink)