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)

One dark and rainy night, Yuso sexually assaults and tortures Zelan. In escaping from the scene of his crime, he falls heavily and becomes an impotent paraplegic. Instead of treating his fate as divine retribution for his wicked acts, Yuso sees it as sheer bad luck. He shows no remorse for what he has done, and vainly hopes that he will recover his powers, which he now treats as involuntarily hoarded resources to be used on less rainy days. In the (...) presence of others, he pretends that he has turned over a new leaf. He asks for religious and educational books, hoping to make up for his poor education and deprived social background. But he immediately discards them when he is alone in favor of the pornographic magazines which he has bribed a nurse to smuggle in for him. His deception and various obscene acts committed in the hospital are exposed; by the time he comes up for trial, everyone knows that he is still a lustful, sadistic, and unrepentant man. Most retributivists have a sufficient justification for punishing Yuso independently of the social consequences of his punishment. Two features of the case might cause some difficulties. First, Yuso has already experienced considerable suffering and deprivation both before and after his crime, and retributivists might disagree about the relevance of the suffering to his punishment. Secondly, Yuso is unrepentant, and it is unlikely that punishment will change him. This might, as we shall see, create a problem for those who think that the justifying aim of punishment is the moral reform of the offender. (shrink)

The need for informed analyses of health policy is now greater than ever. The twelve essays in this volume show that public debates routinely bypass complex ethical, sociocultural, historical, and political questions about how we should address ideals of justice and equality in health care. Integrating perspectives from the humanities, social sciences, medicine, and public health, this volume illuminates the relationships between justice and health inequalities to enrich debates. Understanding Health Inequalities and Justice explores three questions: How do scholars approach (...) relations between health inequalities and ideals of justice? When do justice considerations inform solutions to health inequalities, and how do specific health inequalities affect perceptions of injustice? And how can diverse scholarly approaches contribute to better health policy? From addressing patient agency in an inequitable health care environment to examining how scholars of social justice and health care amass evidence, this volume promotes a richer understanding of health and justice and how to achieve both. -/- The contributors are Judith C. Barker, Paula Braveman, Paul Brodwin, Jami Suki Chang, Debra DeBruin, Leslie A. Dubbin, Sarah Horton, Carla C. Keirns, J. Paul Kelleher, Nicholas B. King, Eva Feder Kittay, Joan Liaschenko, Anne Drapkin Lyerly, Mary Faith Marshall, Carolyn Moxley Rouse, Jennifer Prah Ruger, and Janet K. Shim. (shrink)

In Defense of Utilitarianism, C.L. Sheng provides a more intensive study of the Unified Utilitarian Theory , which he proposed in his previous work A New Approach to Utilitarianism . Sheng defends utilitarianism, particularly UUT, against the objections and attacks raised by nonutilitarians, showing it to be a viable ethical theory.

“Career value” is the name of a kind of value I used (or perhaps I coined) in my classification of value according to good things in life based on the law of nonreplaceability. I classify value into seven classes: (1) health value, (2) sentimental value, (3) economic value1, (4) belief value, (5) environmental value, (6) social value, and (7) career value. Career value refers to the extra value of the most important work, which one wants to do and actually does (...) in one’s life time, for oneself. In Section 2, I explain the nature of career value, which is different from the natures of all other values. In Section 3, I discuss various career values themselves. Career value has several different forms, depending on the nature and size of career. Finally, I conclude that, except for economic value3, which isunsuitable and unreasonable to be a career value, the pursuit of any kind of a nonmaterial career value is a good thing and conforms to the maximization of social utility in utilitarianism. (shrink)

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called ‘smart’, ‘lifelike’ materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology are still unclear (...) and a clear conceptual understanding of the notions ‘smart' and ‘lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered ‘smart’ because they can communicate with human tissues, and ‘lifelike’ because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants. (shrink)

All students of the classical languages are aware that, in referring to intervals of time, the Greeks and Romans often employed a method of reckoning which was inclusive and consequently different from our own. The Greeks, for example, refer to the period between two celebrations of the Olympic games as a though we should call it a four-year interval. One instance of this kind of usage in Latin is the stereotyped formula employed in expressing a date: ante diem quintum Id. (...) Mai. is 11 May, though we should say that there was an interval of four days only between 11 and 15 May. Another instance is the use of tertiana and quartana as applied to fevers which recur on alternate days and on every third day respectively. The ramifications of this mode of expression are extensive, but I am only concerned here with one, namely the use of quisque with ordinals. (shrink)

This volume in the Routledge History of Philosophy series discusses the philosophers belonging to both the `analytical' and `continental' traditions, as well as the now influential American pragmatists. Each chapter is written by a different author who presents the issues in the context of the period when they arose, while also keeping an eye on their relevance to current philosophical interests. A few philosophers are discussed in multiple chapters in different but mutually illuminating contexts.

Organisational change is one of the most frequently recurring organisational phenomena of our time, yet despite this, organisations are not succeeding in instituting change processes effectively; dismal "change success rates" are recorded. Van Tonder and Van Vuuren (2004) have argued that the adoption of an ethical framework from within which change practices are to be approached and "managed", would significantly reduce the negative consequences of change initiatives. As a first step in this direction, the current study set out to establish (...) the meaning that employees attribute to "ethical" and "unethical" change. Data obtained from a sample of 111 respondents from seven companies were subjected to basic content analysis and key themes extracted. The results indicate a limited understanding of ethics concepts among employees. A clear need for both intensified education and research is indicated. (shrink)

This detailed and sympathetic, but not uncritical, study of On Liberty' argues for the general consistency and coherence of Mill's defence of individual liberty, but maintains that there are significant non-utilitarian elements in his arguments.

Painters are the experts in colour phenomenology. Their business is to use colour to affect our feelings. Psychophysicists are expert in making experimental inferences from behavioural responses to the functional mechanisms of perception. The varying aims of these two groups of people mean that much that is of interest to the one is of little concern to the other. However, in recent times several prominent psychophysicists, such as Floyd Ratliff , Jack Werner and Dorothea Jameson , have thrown much light (...) on painterly practice. Following their lead, I would like to sketch some of the mechanisms that are responsible for many of the features of colour appearance important to the work of visual artists. I will begin with some phenomena that can be accounted for by mechanisms that are reasonably well understood, and then move to phenomena whose underlying basis is less well established. I will conclude with a suggestive experiment and, true to my calling as a philosopher, a piece of downright speculation. (shrink)

On July 3, 1996, in Jones v. United States), the United States District Court for the Northern District of California held that plaintiffs in a wrongful birth action cannot recover costs or damages associated with the birth and upbringing of their daughter absent evidence of causation and proof to satisfy liability requirements. Plaintiffs scientific evidence regarding the alleged interaction between antibiotics and oral contraceptives did not satisfy the Daubertstandard, cert. denied,116 S. Ct. 189 )) for admissibility developed by the Supreme (...) Court. In addition, the plaintiffs failed to meet their burden of persuasion on duty of care and causation.On January 16, 1992, Karyn Jones went to a U.S. Army gynecologist, Dr. James Murphy, to obtain a prescription for birth control pills. (shrink)

Taking organs from dead people seems, prima facie, to raise fewer ethical complications than taking organs from other sources. There are, however, serious ethical problems in taking organs from the dead unless there is premortem evidence that this is what the deceased would have wanted, or at least, not have objected to. In this paper we will look at a “strong” opting out policy as proposed by John Harris. We will argue that people can be harmed after their death and (...) that the posthumous removal of organs against their expressed wishes is one form that such harm might take. We also argue that Harris’s claim that we show “equality of concern” between the donor and recipient requires too much. (shrink)

In the essay On Liberty , Mill put forward his famous principle that society may only interfere with those actions of an individual which concern others and not with actions which merely concern himself. The validity of this principle depends on there being a distinction between self-regarding and other-regarding actions. But the concept of self-regarding actions has been severely criticised on the ground that all actions affect others in some way and are therefore other-regarding. The notion of self-regarding actions appears (...) to be completely discredited. Very recently, however, there has been some dissatisfaction with the traditional debunking of Mill on this score. Two serious and important attempts to reinterpret the principle were made by Mr J. C. Rees in an article entitled ‘A Re-Reading of Mill on Liberty’, and by Mr Alan Ryan in two brief but extremely useful contributions. My aim is to discuss these reinterpretations of Mill, and on the basis of this, build up what I think is the correct account of Mill's notion of self-regarding actions. (shrink)

This work has been selected by scholars as being culturally important and is part of the knowledge base of civilization as we know it. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and (...) made generally available to the public. To ensure a quality reading experience, this work has been proofread and republished using a format that seamlessly blends the original graphical elements with text in an easy-to-read typeface. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

Objective: To examine current research payment practices and to inform development of clearer guidelines for researchers and ethics committees.Design: Exploratory email based questionnaire study of current research participant reimbursement practices. A diverse sample of organisations and individuals were targeted.Setting: Australia.Participants: Contacts in 84 key research organisations and select electronic listservers across Australia. A total of 100 completed questionnaires were received with representations from a variety of research areas .Main measurements: Open-ended and fixed alternative questions about type of research agency; type (...) of research; type of population under study; whether payment is standard; amounts and mechanisms of payment; factors taken into account when deciding on payment practices; and whether payment policies exist.Results: Reimbursement practice is highly variable. Where it occurs it is largely monetary and is for time and out-of-pocket expenses. Ethics committees were reported to be often involved in decision making around reimbursement.Conclusions: Research subject payment practices vary in Australia. Researchers who do provide payments to research participants generally do so without written policy and procedures. Ethics committees have an important role in developing guidelines in this area. Specific guidelines are needed considering existing local policies and procedures; payment models and their application in diverse settings; case study examples of types and levels of reimbursement; applied definitions of incentive and inducement; and the rationale for diverse payment practices in different settings. (shrink)

The legal requirements and justifications for collecting patient-identifiable data without patient consent were examined. The impetus for this arose from legal and ethical issues raised during the development of a population-based disease register. Numerous commentaries and case studies have been discussing the impact of the Data Protection Act 1998 and Caldicott principles of good practice on the uses of personal data. But uncertainty still remains about the legal requirements for processing patient-identifiable data without patient consent for research purposes. This is (...) largely owing to ignorance, or misunderstandings of the implications of the common law duty of confidentiality and section 60 of the Health and Social Care Act 2001. The common law duty of confidentiality states that patient-identifiable data should not be provided to third parties, regardless of compliance with the DPA1998. It is an obligation derived from case law, and is open to interpretation. Compliance with section 60 ensures that collection of patient-identifiable data without patient consent is lawful despite the duty of confidentiality. Fears regarding the duty of confidentiality have resulted in a common misconception that section 60 must be complied with. Although this is not the case, section 60 support does provide the most secure basis in law for collecting such data. Using our own experience in developing a disease register as a backdrop, this article will clarify the procedures, risks and potential costs of applying for section 60 support. (shrink)