The controversy over the prescription drug, alosetron, is examined in order to investigate what is permitted to count as ‘therapeutic advance’ and ‘therapeutic breakthrough’ within pharmaceutical innovation and regulation. It is argued that those official accounting categories can mask very modest efficacy of some drugs by reference to the official techno-scientific evidence, thus leading to questionable acceptance of risks to public health. This is explained by: the drug availability options set by the commercial interests of manufacturers; the FDA (...) management's need to demonstrate rapid approval of therapeutic advances to their budgetary masters, especially in the context of patient demands for access to new drugs; and the increasing capacity of patient groups, sometimes in collaboration with pharmaceutical manufacturers, to challenge techno-scientific expertise and evidence with experiential testimony. It is concluded that regulatory policy-makers need much more sophisticated accounting systems for differentiating between drugs defined as significant therapeutic advances, and between drugs (‘therapeutic breakthroughs’ fast-tracked to treat serious or life-threatening conditions. Contrary to some STS analyses, the desirability of an ascendancy of patients’ anecdotal evidence in regulatory decisions for public health is questioned. (shrink)

This paper explores the use of advance directives in clinical dementia research. The focus is on advance consent to participation of demented patients in non-therapeutic research involving more than minimal risks and/or burdens. First, morally relevant differences between advance directives for treatment and care, and advance directives for dementia research are discussed. Then attention is paid to the philosophical issue of dementia and personal identity, and the implications for the moral authority of research advance directives. Thirdly, a number of (...) practical shortcomings of advance directives for non-therapeutic dementia research are explored and attention is paid to the role of proxies. It is concluded that upon a closer look the initial attractiveness of advance directives for dementia research is lessened, and that it is doubtful whether these instruments can compensate for the lack of subject consent in case of non-therapeutic dementia research involving more than minimal risks and/or burdens for the incompetent demented subject. (shrink)

\noindent\textbf{Introduction} Online interventions hold great potential for Therapeutic Change Process Research (TCPR), a field that aims to relate in-therapeutic change processes to the outcomes of interventions. Online a client is treated essentially through the language their counsellor uses, therefore the verbal interaction contains many important ingredients that bring about change. TCPR faces two challenges: how to derive meaningful change processes from texts, and secondly, how to assess these complex, varied and multi-layered processes? We advocate the use text mining (...) and multi-level models (MLMs): the former offers tools and methods to discovers patterns in texts; the latter can analyse these change processes as outcomes that vary at multiple levels. \noindent\textbf{Method} We (re-)used the data from \cite{Lamers2015} because it includes outcomes and the complete online intervention for clients with mild depressive symptoms. We used text mining to obtain basic text-variables from e-mails, that we analysed through MLMs. \noindent\textbf{Results} We found that we could relate outcomes of interventions to variables containing text-information. We conclude that we can indeed bridge text mining and MLMs for TCPR as it was possible to relate text-information (obtained through text mining) to multi-levelled TCPR outcomes (using a MLM). \noindent\textbf{Discussion} Text mining can be helpful to obtain change processes, which is also the main challenge for TCPR. We showed how MLMs and text mining can be combined, but our proposition leaves open how to obtain the most relevant textual operationalization of TCPR concepts. That requires interdisciplinary collaboration and discussion. The future does look bright: based on our proof-of-concept study we conclude that MLMs and text mining can indeed advance TCPR. (shrink)

This paper develops and defends a new account of therapeutic trust, its nature and its constitutive norms. Central to the view advanced is a distinction between two kinds of therapeutic trust – default therapeutic trust and overriding therapeutic trust – each which derives from a distinct kind of trusting competence. The new view is shown to have advantages over extant accounts of therapeutic trust, and its relation to standard (non-therapeutic) trust, as defended by Hieronymi, (...) Frost-Arnold, and Jones. (shrink)

The transcription factor Nrf2 is the master regulator of cellular stress response, facilitating the expression of cytoprotective genes, including those responsible for drug detoxification, immunomodulation, and iron metabolism. FDA‐approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non‐specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease and other neurodegenerative diseases with Bach1 dysregulation, excessive Bach1 accumulation interferes with Nrf2 activation. Bach1 (...) is a heme sensor protein, which, upon heme binding, is targeted for proteasomal degradation, relieving the repression of Nrf2 target genes. Ideally, a combination of Nrf2 stabilization and Bach1 inhibition is necessary to achieve the full therapeutic benefits of Nrf2 activation. Here, we discuss recent advances and future perspectives in developing small molecule inhibitors of Bach1, highlighting the significance of the Bach1/Nrf2 signaling pathway as a promising neurotherapeutic strategy. (shrink)

Non-therapeutic ventilation of potential organ donors would increase the supply of kidneys for transplantation. There are no major ethical objections to it. The means of permitting it are forbidden by laws with an ethical basis. A law permitting it would need an ethical basis. Introducing a third legal method of diagnosing death would be unethical. Expanding the power of the advance directive to permit procedures involving minimal harm would be ethical but not helpful. Extending the power of proxies to (...) permit specific non-therapeutic procedures which caused or risked minimal harm to incompetent patients is the best way forward. (shrink)

After years of failure, in November 2007 primate embryonic stem cells were derived by somatic cellular nuclear transfer, also known as therapeutic cloning. The first embryo transfer for human reproductive cloning purposes was also attempted in 2006, albeit with negative results. These two events force us to think carefully about the possibility of human cloning which is now much closer to becoming a reality. In this paper we tackle this issue from two sides, first summarising what scientists have achieved (...) so far, then discussing some of the ethical arguments in favour and against human cloning which are debated in the context of policy making and public consultation. Therapeutic cloning as a means to improve and save lives has uncontroversial moral value. As to human reproductive cloning, we consider and assess some common objections and failing to see them as conclusive. We do recognise, though, that there will be problems at the level of policy and regulation that might either impair the implementation of human reproductive cloning or make its accessibility restricted in a way that could become difficult to justify on moral grounds. We suggest using the time still available before human reproductive cloning is attempted successfully to create policies and institutions that can offer clear directives on its legitimate applications on the basis of solid arguments, coherent moral principles, and extensive public consultation. (shrink)

The aim of this paper is to discuss monastic paideia in the context of providing shelter for ASD individuals in the High Middle Ages. Firstly, we will canvas the historical and conceptual shift from Ancient Greek paideitic ideas to their Christian counterparts. Then, by drawing on the recent literature in the history of medicine that traces the signs and symptoms of autism spectrum disorder (ASD) in Hildegard of Bingen, a German abbess in the 12th century, we will turn to her (...) invented language Lingua Ignota as a source of both her diagnosis and a manner of dealing with her disability. This, in turn, could be further advanced by identifying monasteries as therapeutic loci for neuroatypical individuals who had trouble finding their place within the arid and somewhat monochromatic medieval society. (shrink)

The British Parliament legalized therapeutic cloning in December 2000 despite opposition from the European Union. The watershed event in Parliament's move was the active and unprecedented government support for the generation and destruction of human embryonic life merely as a means of medical advancement. This article contends that the utilitarian analysis of this procedure is necessary to identify the real world risks of therapeutic cloning but insufficient to identify the breach of defensible ethical limits that this procedure represents. (...) A value-oriented approach to Kantian ethics demonstrates that the utilitarian endorsement of therapeutic cloning entails a contradiction of the necessity of human vulnerability and a faulty valuation of the human embryo. The concern is that a narrow utilitarian focus ultimately commodifies human embryonic life and preferences outcomes as the sole determinant of moral value. (shrink)

La comprensión de la muerte varía según la época, la cultura, la religión y la edad. Con anterioridad al desarrollo que la ciencia médica ha experimentado desde finales del siglo XIX, en la mayoría de las culturas y religiones había una aceptación de la muerte y se consideraba como parte del ciclo vital de la persona donde se trascendía a una forma celestial y puramente sobrenatural. Los avances científicos de la medicina han venido a cambiar esta situación. La muerte se (...) empezó a ver como un enemigo y dio comienzo a una lucha encarnizada entre ambas. El concepto de "muerte natural" se sustituyó por el de "muerte intervenida," dando origen a numerosas cuestiones relacionadas con la toma de decisiones y actuaciones a realizar en pacientes ingresados y en situación terminal. En este trabajo se realiza una reflexión teórica que tiene como objetivo el análisis bioético acerca de las diferencias entre los aspectos religiosos y culturales relacionados con la práctica de la limitación del esfuerzo terapéutico. The understanding of death varies according to time, culture, religion, and age. Previous to the development that medical sciences has undergone since the end of the XIX Century, in most cultures and religions there have been an acceptation of death and considered as part of the person vital cycle in which one would transcend to a celestial and purely supernatural form. The scientific advances in medicine have emerged to change this situation. Death began to be seen as an enemy and gave rise to an enraged struggle between both of them. The concept of natural death was changed into intervened death, which originated numerous related questions with decision and action taking to be performed in hospitalized patients and those in terminal situation. In this work a theoretical reflection is performed whose objective is the bioethical analysis on the differences among religious and cultural aspects related to the practice of therapeutic effort limitation. (shrink)

Non-therapeutic research with imminently dying patients in intensive care presents complex ethical issues. The vulnerabilities of the imminently dying, together with societal disquiet around death and dying, contribute to an intuition that such research is beyond the legitimate scope of scientific inquiry. Yet excluding imminently dying patients from research hinders the advancement of medical science to the detriment of future patients. Building on existing ethical guidelines for research, we propose a framework for the ethical design and conduct of research (...) involving the imminently dying. To enable rapid translation to practice, we frame the approach in the form of eight ethical questions that researchers and research ethics committees ought to answer prior to conducting any research with this patient population. (1) Does the study hypothesis require the inclusion of imminently dying patients? (2) Are non-therapeutic risks and burdens minimised consistent with sound scientific design? (3) Are the risks of these procedures no more than minimal risk? (4) Are these non-therapeutic risks justified insofar as they are reasonable in relation to the anticipated benefits of the study? (5) Will valid informed consent be obtained from an authorised surrogate decision maker? (6) How will incidental findings be handled? (7) What additional steps are in place to protect families and significant others of research participants? (8) What additional steps are in place to protect clinical staff and researchers? Several ethical challenges hinder research with imminently dying patients. Nonetheless, provided adequate protections are in place, non-therapeutic research with imminently dying patients is ethically justifiable. Applying our framework to an ongoing study, we demonstrate how our question-driven approach is well suited to guiding investigators and research ethics committees. (shrink)

[Excerpted From Editor's Introduction] Matthew Crippen takes this up in a Marcusian critique of Wittgenstein that attends, among other things, to the place of silence in that discourse. Referring to Horkheimer’s citation of the Latin aphorism that silence is consent, Crippen is critical of Wittgenstein’s admonition that we must pass over in silence those matters of which we cannot speak. This raises fascinating questions for critical theory that Crippen explores particularly with reference to Marcuse’s concept of one-dimensionality. To the extent (...) that Wittgenstein’s philosophy is “therapeutic,” it may effectively contain dissent by “helping” dissenters become “well-adjusted.” Marcuse, of course, was particularly concerned with the power of Total States— and particularly those engendered by advanced industrial capitalism—to contain dissent precisely by using therapeutic techniques to maintain adjustment. Bringing Marcuse and Wittgenstein together here has particularly explosive possibilities. In the context of a Total State, transformation depends on the possibility of calling the State into question from the inside (since “total” States systematically eliminate “outsides”). This is the point at which Wittgenstein’s silence becomes most intriguing. What is it, we must ask, that we cannot say? Silence may be (as Martin Luther King, Jr. said) more than consent: there comes a time when silence is betrayal. But this is one of many places where it pays to look at what is done as much as what is said. What game, we might ask, is Wittgenstein playing? And, more to the point, what is the field of play that joins Wittgenstein and Marcuse? John Cage famously said “I have nothing to say and I am saying it and that is poetry as I need it...” Crippen begins a process (via Wittgenstein) of putting poetry into play that has important implications for the public work of philosophers. (shrink)

In spite of the advances in our knowledge of cancer biology, most cancers remain not curable with present therapies. Current treatments consider cancer as resulting from uncontrolled proliferation and are non‐specific. Although they can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but recent developments indicate that different types of cells contribute to the tumour structure, and that the tumour's cellular organization would be analogous to that of a normal tissue, with (...) a main mass of differentiating cells sensitive to anti proliferative agents, together with a small percentage of quiescent, resistant stem cells responsible for replenishing the tumour: the Cancer Stem Cells (CSCs). Anti‐CSCs targeted therapeutic agents would prevent tumour regeneration. New mouse models tailored to exploit this novel concept will be critical to develop CSC‐based anti‐cancer therapies. Here we review the biological basis and the therapeutic implications of the stem‐cell model of cancer. BioEssays 29:1269–1280, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The term “therapeutic misconception” was coined in 1982 by Paul Appelbaum, Loren Roth, and Charles Lidz. Appelbaum and his colleagues interviewed participants in several psychiatric studies, including a drug trial with a placebo control arm. Appelbaum's group found that many people were unaware of the differences between participating in a study and receiving treatment in the clinical setting. Rather than understanding these differences, study participants tended to believe that therapy and research were governed by the same primary goal: to (...) advance the individual patient's best interests. Appelbaum's group labeled this mistaken belief the therapeutic misconception. (shrink)

This book explores the impact of developments in pharmaceutical medicine in the twentieth century on a Christian ethical evaluation of transhumanism and future 'hi tech' medical enhancement technologies. It suggests that the Christian ethical assessment of proposed future radical transhumanist biomedical technologies should be conducted in the light of responses to past medical advances. Two specific case studies are featured, focusing on the oral contraceptive pill and on Prozac and SSRI antidepressants. Whilst future biomedical technologies may have therapeutic (...) benefits for the relief of disease and contribute to improving human health and welfare, the book considers the implications for society and their acceptability as therapies from a Christian perspective. Stressing the inadequacy of natural law alone, the author proposes an ethical framework for assessing novel biomedical technologies according to the effects on personal autonomy, embodiment and bodily life, and on the Imago Dei. (shrink)

Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease‐related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from (...) combining ‘protect and repair’ strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site‐specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long‐term therapies for many brain diseases in human patients. (shrink)

Advanced Cell Technology's Ethics Advisory Board has been called window dressing for a corporate marketing plan. But the scientists and managers have paid attention, and the lawyers have gone along.

The continuing debate about the use of human embryonic stem cell researchThere is a growing consensus among scientists worldwide that embryonic stem cell research will lead to the development of therapies for common diseases or conditions that affect millions of people, including neurological disease or injury, diabetes, and myocardial infarction. HES cells are also valuable tools in understanding early human developmental processes, cell division and differentiation mechanisms, drug discovery and toxicity testing, and for developing models of human diseases. At the (...) same time many individuals profess to be outraged by the prospect of using human embryos for research and therapeutic purposes and some countries or states have declared such research to be unethical and have banned it. Many people also think it would be immoral to benefit from what they consider to be evil.Obviously all those who think HES cell research is immoral will wish to ensure not only that no HES cell therapies are developed but that they will not openly or inadvertently benefit from such therapies when they can avoid it. I have accordingly designed the following Advance Directive and here offer it as a service to all those offended by therapeutic and research use of human embryos.The design of this advance directive to protect embryos highlights an important point that is often overlooked, namely that those who object to HES cell research as unethical and block such research are committed in consistency to the rejection of any benefits or therapies, which may flow from such research. It is questionable whether these people will fully accept this consequence of opposition to HES cell research, and whether this rejection of HES cell research will be practically possible. (Once …. (shrink)

This article explores traditional views of advance care planning in the broader context of advance personal planning, which also accounts for legal and financial matters. Criticisms of existing processes are noted, while the significance of interprofessional collaboration is highlighted. Reframing the purpose of advance personal planning as planning for the rest of life, rather than the end-of-life, and adopting a more holistic perspective informed by theory may help individuals to view advance personal planning as a routine, preventative exercise that safeguards (...) their autonomy and well-being. Both lawyers and healthcare providers have an important role to play in reframing the purpose of advance personal planning. This revised approach is underpinned by the unification of two separate theoretical lenses: Preventive Law Theory and Therapeutic Jurisprudence. This combination enhances our understanding of what it means for people to truly achieve “the good result” (Holtz 2017) when planning ahead for their future legal, financial, health, and personal interests. Preventive Law Theory encourages an ongoing, collaborative relationship between lawyers and their clients, or healthcare providers and their patients, while Therapeutic Jurisprudence ensures an ethical approach to advance personal planning that accounts for all aspects of the individual’s well-being, including consideration of vulnerability, autonomy, and empowerment. (shrink)

The author presents a varied menu of ideas and experiences in many areas - in research, in diagnosis, and in psychotherapy, each using art media with patients of all ages. She integrates art, phenomenology and gestalt psychology, describing specific techniques and findings. Part I of the book lays out the theoretical foundations and the techniques; Part II addresses the formal components used in art therapy - line, shape and colour in their interrelated dynamics and discusses other aspects and modes of (...) symbolic expression found in clients' work. Part III looks at symbolic expression through the scribble, offering a system of classification, diagnostic possibilities and case studies of work with eating disorders. Part IV focuses on art expression for art therapy diagnostics, including a method for qualitative diagnostics, and a first full diagnostic battery for adolescents. Part V is devoted to Holocaust children's art expressions, highlighting the power of art expression in children under ultimate stress, the intensity of their inner experience, and its visualization in the structure of the pictures. The book is for art therapists and advanced students. It can be used as a textbook on phenomenological art therapy; for therapeutically-oriented art teachers, educators and social workers; and for practicing psychotherapists, to see that art is a source of expression demonstrating how a person is. (shrink)

Background Non-therapeutic trials in which terminally ill cancer patients are asked to undergo procedures such as biopsies or venipunctures for research purposes, have become increasingly important to learn more about how cancer cells work and to realize the full potential of clinical research. Considering that implementing non-therapeutic studies is not likely to result in direct benefits for the patient, some authors are concerned that involving patients in such research may be exploitive of vulnerable patients and should not occur (...) at all, or should be greatly restricted, while some proponents doubt whether such restrictions are appropriate. Our objective was to explore clinician-researcher attitudes and concerns when recruiting patients who are in advanced stages of cancer into non-therapeutic research. Methods We conducted a qualitative exploratory study by carrying out open-ended interviews with health professionals, including physicians, research nurses, and study coordinators. Interviews were audio-recorded and transcribed. Analysis was carried out using grounded theory. Results The analysis of the interviews unveiled three prominent themes: 1) ethical considerations; 2) patient-centered issues; 3) health professional issues. Respondents identified ethical issues surrounding autonomy, respect for persons, beneficence, non-maleficence, discrimination, and confidentiality; bringing to light that patients contribute to science because of a sense of altruism and that they want reassurance before consenting. Several patient-centered and health professional issues are having an impact on the recruitment of patients for non-therapeutic research. Facilitators were most commonly associated with patient-centered issues enhancing communication, whereas barriers in non-therapeutic research were most often professionally based, including the doctor-patient relationship, time constraints, and a lack of education and training in research. Conclusions This paper aims to contribute to debates on the overall challenges of recruiting patients to non-therapeutic research. This exploratory study identified general awareness of key ethical issues, as well as key facilitators and barriers to the recruitment of patients to non-therapeutic studies. Due to the important role played by clinicians and clinician-researchers in the recruitment of patients, it is essential to facilitate a greater understanding of the challenges faced; to promote effective communication; and to encourage educational research training programs. (shrink)

The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the neocortex and, (...) more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the differentiation of CSMN for therapeutic benefit. (shrink)

Some authors have advanced a contractual model to protect patient autonomy within the therapeutic relationship. Such a conception of the physician–patient relationship is intended to serve both parties by respecting patients' choices and preserving physician integrity. I critique this contractual view and offer an alternative, feminist contextualized approach to autonomy within the therapeutic relationship. This approach places the physician-patient relationship within a larger social context, and indicates the many social inequalities that render insupportable the notion of physicians and (...) patients as contracting equals. (shrink)

Worldwide populations are aging with economic development as a result of public health initiatives and advances in therapeutic discoveries. Since 1850, life expectancy has advanced by 1 year for every four. Accompanying this change is the rapid development of anti‐aging science. There are three schools of thought in the field of aging science. One perspective is the life course approach, which considers that aging is a good and natural process to be embraced as a necessary and positive aspect (...) of life, where the aim is to improve the quality of existing lifespan and “compress” morbidity. Another view is that aging is undesirable, and that rejuvenation and indeed immortality are possible since the biological basis of aging is understood, and therefore, strategies are possible for engineering negligible senescence. Finally, a hybrid approach is that life span can be extended by anti‐aging medicines but with uncertain effects on health. While these advances offer much promise, the ethical perspectives are seldom discussed in cross‐disciplinary settings. This article discusses some of the key ethical issues arising from recent advances in biogerontology. (shrink)

This article explores parallel tendencies in Ludwig Wittgenstein’s and Ernst Gombrich’s thinking that aimed to dissolve misconceptions about mind, culture, and art that emerged in modernity but that continue to influence current art education. Section one gives an overview of Wittgenstein’s and Gombrich’s therapeutic projects, which drew on perspicuity and genealogy to eliminate confusions in thinking, rather than advance new theories. The second section illustrates Wittgenstein’s and Gombrich’s curative response to modern misconceptions about mind and culture. The analysis is (...) extended in a thematic way to dissolve similar misconceptions that prevail in current art education. The aim of the article is to provide conditions for sustaining better practices of art education. (shrink)

To date, ethics discussions about stem cell research overwhelmingly have centered on the morality and acceptability of using human embryonic stem cells. Governments in many jurisdictions have now answered these “first-level questions” and many have now begun to address ethical issues related to the donation of cells, gametes, or embryos for research. In this commentary, we move beyond these ethical concerns to discuss new themes that scientists on the forefront of NRM development anticipate, providing a preliminary framework for further discussion (...) between scientists and ethicists. Fostering strong partnerships between neuroscientists and ethicists that operate and collaborate within this evolving framework will maximize the translation of NRM discoveries on the brain into cures that are safe and address the needs of science and society. (shrink)

The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various (...) types of Leukemia/Blood malignancies. (shrink)

Despite the long history of beliefs about the therapeutic properties of work for people with mental ill health, rarely has therapeutic work itself been a focus for historical analysis. In this article, the development of a therapeutic work ethic (1813—1979) is presented, drawing particular attention to the changing character and quality of beliefs about therapeutic work throughout time. From hospital factories to radical ‘antipsychiatric’ communities, the article reveals the myriad forms of activities that have variously been (...) considered fit work for people with mental health problems. While popular stereotypes of basket-weaving paint a hapless portrait of institutional work, a more nuanced reading of therapeutic work and its political and philosophical commitments is advanced. The article concludes by arguing that the non-linear and inherently contested development of therapeutic work is less the effect of paradigmatic shifts within the therapeutic professions, but rather evidence of a broader human struggle with work. (shrink)

We live in an era that often described as 'therapeutic.' Our culture is suffused with unconscious fantasies and psychoanalytic ways of thinking about self, other, and society. Aspects of the Freudian cultural universe have also had an impact on how we think about religion. In this volume, William Parsons explores the relationship between religion and psychoanalysis through multiple, linked investigations. Why did Freud write about religion and what did he say? What were the multiple critiques levelled at his work? (...) What were the post-Freudian psychoanalytic advances? How can we still apply psychoanalytic ideas going forward? In answering these and related questions, Parsons distinguishes between classic-reductive, adaptive, and transformational psychoanalytic models. He also argues that the psychoanalytic theory of religion needs to integrate reflexive, dialogical, and inclusive elements as part of its toolkit. Offering illustrations and applications of such revisions, Parsons creates new capacities for thinking psychologically and critically about religion. (shrink)

Pancreatic β‐cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in β‐cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential β‐cell factors have been identified that are required for normal β‐cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that control expression of MODY (...) and other factors continue to be revealed. Post‐transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T‐cells (NFAT) may be required for β‐cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the β‐cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed. BioEssays 29:1011–1021, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The need to better balance the promotion of scientific and technological innovation with risk management for consumer protection has inspired several recent reforms attempting to make regulations more flexible and adaptive. The pharmaceutical sector has a long, established regulatory tradition, as well as a long history of controversies around how to balance incentives for needed therapeutic innovations and protecting patient safety. The emergence of disruptive biotechnologies has provided the occasion for regulatory innovation in this sector. This article investigates the (...) regulation of advanced biotherapeutics in the European Union and shows that it presents several defining features of an adaptive regulation regime, notably institutionalized processes of planned adaptation that allow regulators to gather, generate, and mobilize new scientific and risk evidence about innovative products. However, our in-depth case analysis highlights that more attention needs to be paid to the consequences of the introduction of adaptive regulations, especially for critical stakeholders involved in this new regulatory ecosystem, the capacity and resource requirements placed on them to adapt, and the new tradeoffs they face. In addition, our analysis highlights a deficit in how we currently evaluate the performance and public value proposition of adaptive regulations vis-à-vis their stated goals and objectives. (shrink)

In this article, Charlotte Blease argues that patient access to online shared clinical notes (also called ‘open notes’) may cause or exacerbate nocebo effects in two ways. 1 First, open notes may enhance patient understanding about the adverse effects of medications and treatments. However, reading information about adverse effects may lead patients to form negative expectations that, in turn, may cause or worsen symptoms via nocebo mechanisms. Second, open notes may paradoxically lower the quality of the therapeutic relationship by (...) allowing patients to detect signs of discrimination and stigma in clinical notes. By accessing their shared notes, patients may identify (or think that they are identifying) signs of stigmatisation and discrimination in clinicians’ words. This may diminish their trust while increasing their anxieties and fears, all factors that have been associated with enhanced nocebo effects. The article then suggests different strategies to mitigate nocebo effects while using open... (shrink)

In the UK, female genital mutilation is unlawful, not only when performed on minors, but also when performed on adult women. The aim of our paper is to examine several arguments which have been advanced in support of this ban and to assess whether they are sufficient to justify banning female genital mutilation for competent, consenting women. We proceed by comparing female genital mutilation, which is banned, with cosmetic surgery, towards which the law has taken a very permissive stance. We (...) then examine the main arguments for the prohibition of the former, assessing in each case both (a) whether the argument succeeds in justifying the ban and, if so, (b) whether a parallel argument would not also support a ban on the latter. We focus on the following arguments. Female genital mutilation should be unlawful because: (1) no woman could validly consent to it; (2) it is an oppressive and sexist practice; (3) it involves the intentional infliction of injury; (4) it causes offence. Our view is that arguments (3) and (4) are unsound and that, although arguments (1) and (2) may be sound, they support not only a ban on female genital mutilation, but also one on (some types of) costmetic surgery. Hence, we conclude that the present legal situation in the UK is ethically unsustainable in one of the following ways. Either the ban on female genital mutilation is unjustified because arguments (1) and (2) are not in fact successful; or the law's permissive attitude towards cosmetic surgery is unjustified because arguments (1) and (2) are in fact successful and apply equally to female genital mutilation and (certain forms of) cosmetic surgery. The people of the countries where female genital mutilation is practised resent references to ‘barbaric practices imposed on women by male‐dominated primitive societies’, especially when they look at the Western world and see women undergoing their own feminization rites intended to increase sexual desirability: medically dangerous forms of cosmetic plastic surgery, for instance …. (shrink)

Background: The Albanian medical system and Albanian health legislation have adopted a paternalistic position with regard to individual decision making. This reflects the practices of a not-so-remote past when state-run facilities and a totalitarian philosophy of medical care were politically imposed. Because of this history, advance directives concerning treatment refusal and do-not-resuscitate decisions are still extremely uncommon in Albania. Medical teams cannot abstain from intervening even when the patient explicitly and repeatedly solicits therapeutic abstinence. The Albanian law on health (...) care has no provisions regarding limits or withdrawal of treatment. This restricts the individual's healthcare choices.DiscussionThe question of 'medically futile' interventions and pointless life-prolonging treatment has been discussed by several authors. Dutch physicians call such interventions 'medisch zinloos' (senseless), and the Netherlands, as one of the first states to legislate on end-of-life situations, actually regulates such issues through appropriate laws. In contrast, leaving an 'advance directive' is not a viable option for Albanian ailing individuals of advanced age. Verbal requests are provided during periods of mental competence, but unfortunately such instructions are rarely taken seriously, and none of them has ever been upheld in a legal or other official forum.SummaryEnd-of-life decisions, treatment refusal and do-not-resuscitate policies are hazardous options in Albania, from the legal point of view. Complying with them involves significant risk on the part of the physician. Culturally, the application of such instructions is influenced from a mixture of religious beliefs, death coping-behaviors and an immense confusion concerning the role of proxies as decision-makers. Nevertheless, Albanian tradition is familiar with the notion of 'amanet', a sort of living will that mainly deals the property and inheritance issues. Such living wills, verbally transmitted, may in certain cases include advance directives regarding end-of-life decisions of the patient including refusal or termination of futile medical treatments. Since these living wills are never formally and legally validated, their application is impossible and treatment refusal remains still non practicable. Tricks to avoid institutional treatment under desperate conditions are used, aiming to provide legal coverage for medical teams and relatives that in extreme situations comply with the advice of withholding senseless treatment. (shrink)

Is it ever permissible to publish a patient’s confidences without permission? I investigate this question for the field of psychoanalysis. Whereas most medical fields adopted a 1995 recommendation for consent requirements, psychoanalysis continues to defend the traditional practice of nonconsensual publication. Both the hermeneutic and the scientific branches of the field justify the practice, arguing that it provides data needed to help future patients, and both branches advance generalizations and causal claims. However the hermeneutic branch embraces methods tending to undermine (...) the reliability of such claims, while the scientific branch aims to improve the field’s empirical base – in their words, to advance psychoanalysis as a science. The scientific branch therefore has the stronger claim to the traditional practice, and it their claim that I consider. An immediate concern arises. We seem unable to answer the applied ethical question without first determining which ethical theory is correct; for defenders of the practice appeal variously to therapeutic privilege, principlism, and utilitarianism, while opponents wage autonomy-based arguments. The concern turns out to be unfounded, however, because all of these ethical approaches fail to justify the traditional practice. The more promising defenses fail partly because even the scientific branch of the field lacks empirically sound methods for establishing its causal claims and generalizations, often appealing to authority instead. I conclude that it is currently unethical for analysts to continue publishing their patients’ confidences without permission, and I suggest that the field help future patients by attending to its methodological problems. (shrink)

Objective: This study examined whether patients who were randomly assigned to their preferred therapy arm had stronger engagement with their treatment than those who were randomly assigned to a non-preferred therapy arm.Method: Data were drawn from a RCT comparing Individual Meaning-Centered Psychotherapy, with Individual Supportive Psychotherapy, in patients with advanced cancer. Treatment engagement was operationalized as patients' perceptions of the therapeutic alliance with their therapist and therapy sessions attended. Two 2 by 2 Analysis of Variance models were used, with (...) treatment preference and treatment assignment as the independent variables and working alliance and number of sessions attended as outcome variables.Results: Patients who preferred and were assigned to IMCP reported a significantly stronger alliance than those who preferred IMCP but were assigned to ISP.Conclusions: The findings from this study have broader implications for research on psychotherapy beyond the appeal of IMCP in advanced cancer patients. Patients who prefer a novel psychotherapy that they cannot engage in elsewhere, but receive the standard treatment may experience weaker alliance than patients who prefer the standard but receive the novel therapy.Trial registration:Clinicaltrial.gov ID: NCT01323309. (shrink)

Is it ever permissible to publish a patient’s confidences without permission? I investigate this question for the field of psychoanalysis. Whereas most medical fields adopted a 1995 recommendation for consent requirements, psychoanalysis continues to defend the traditional practice of nonconsensual publication. Both the hermeneutic and the scientific branches of the field justify the practice, arguing that it provides data needed to help future patients, and both branches advance generalizations and causal claims. However the hermeneutic branch embraces methods tending to undermine (...) the reliability of such claims, while the scientific branch aims to improve the field’s empirical base – in their words, to advance psychoanalysis as a science. The scientific branch therefore has the stronger claim to the traditional practice, and it their claim that I consider. An immediate concern arises. We seem unable to answer the applied ethical question without first determining which ethical theory is correct; for defenders of the practice appeal variously to therapeutic privilege, principlism, and utilitarianism, while opponents wage autonomy-based arguments. The concern turns out to be unfounded, however, because all of these ethical approaches fail to justify the traditional practice. The more promising defenses fail partly because even the scientific branch of the field lacks empirically sound methods for establishing its causal claims and generalizations, often appealing to authority instead. I conclude that it is currently unethical for analysts to continue publishing their patients’ confidences without permission, and I suggest that the field help future patients by attending to its methodological problems. (shrink)

There are two main paradigms for brain-related science, with different implications for brain-focused intervention or advancement. The paradigm of homeostasis (“stability through constancy,” Walter Cannon), originating from laboratory-based experimental physiology pioneered by Claude Bernard, shows that living systems tend to maintain system functionality in the direction of constancy (or similitude). The aim of physiology is elucidate the factors that maintain homeostasis, and therapeutics aim to correct abnormal factor functions. The homeostasis paradigm does not formally recognize influences outside its controlled experimental (...) frames and it is variable in its modelling of neural contributions. The paradigm of allostatic orchestration (PAO) extends the principle of allostasis (“stability through change”) as originally put forth by Peter Sterling. The PAO originates from an evolutionary perspective and recognizes that biological set points change in anticipation of changing environments. The brain is the organ of central command, orchestrating cross-system operations to support optimal behavior at the level of the whole organism. Alternative views of blood pressure regulation and posttraumatic stress disorder illustrate differences between the paradigms. For the PAO, complexities of top-down neural effects and environmental context are foundational (not to be “factored out”), and anticipatory regulation is the principle of their interface. The allostatic state represents the integrated totality of brain-body interactions. Health itself is an allostatic state of optimal anticipatory oscillation, hypothesized to relate to the state of criticality, a mathematical point of poise between phases, on the border between order and disorder (or the “edge of chaos”). Diseases are allostatic states of impaired anticipatory oscillations, demonstrated as rigidifications of set points across the brain and body (disease comorbidity). Conciliation of the paradigms is possible, with “reactive homeostasis” resolved as an illusion stemming from anticipation of environmental monotony. Considerations are presented with respect to implications of the two paradigms for brain-focused intervention or advancement; the hypothesis that the state of criticality is a vehicle for evolutionary processes; concordance with a philosophy of freedom based on ethical individualism as well as self-creativity, non-obsolescence, empowerment, and citizenship; and concluding reflections on the science and ethics of the placebo, and the potential for virtuous cycles of brain-Anthropocene interactions. (shrink)

Is it ever permissible to publish a patient’s confidences without permission? I investigate this question for the field of psychoanalysis. Whereas most medical fields adopted a 1995 recommendation for consent requirements, psychoanalysis continues to defend the traditional practice of nonconsensual publication. Both the hermeneutic and the scientific branches of the field justify the practice, arguing that it provides data needed to help future patients, and both branches advance generalizations and causal claims. However the hermeneutic branch embraces methods tending to undermine (...) the reliability of such claims, while the scientific branch aims to improve the field’s empirical base – in their words, to advance psychoanalysis as a science. The scientific branch therefore has the stronger claim to the traditional practice, and it their claim that I consider. An immediate concern arises. We seem unable to answer the applied ethical question without first determining which ethical theory is correct; for defenders of the practice appeal variously to therapeutic privilege, principlism, and utilitarianism, while opponents wage autonomy-based arguments. The concern turns out to be unfounded, however, because all of these ethical approaches fail to justify the traditional practice. The more promising defenses fail partly because even the scientific branch of the field lacks empirically sound methods for establishing its causal claims and generalizations, often appealing to authority instead. I conclude that it is currently unethical for analysts to continue publishing their patients’ confidences without permission, and I suggest that the field help future patients by attending to its methodological problems. (shrink)

As therapeutic advances in the treatment of AIDS began to emerge in the late 1980s and public health began to have more to offer than just the threat, or the perceived threat, of quarantine or partner notification, fissures began to appear in the alliance against named HIV reporting that had emerged a few years earlier. In 1989, New York City’s Health Commissioner stated that the prospects of early clinical intervention warranted “a shift toward a disease-control approach to HIV (...) infection along the lines of classic tuberculosis practices,” including the “reporting of seropositives.”Although his proposal met with fierce and effective resistance, it is now clear that his call represented part of a national trend. The CDC continued to press for cases of HIV to he reported by name to health departments, an effort that assumed the dimensions of a campaign. It was supported by a growing number of public health officials. (shrink)

As therapeutic advances in the treatment of AIDS began to emerge in the late 1980s and public health began to have more to offer than just the threat, or the perceived threat, of quarantine or partner notification, fissures began to appear in the alliance against named HIV reporting that had emerged a few years earlier. In 1989, New York City’s Health Commissioner stated that the prospects of early clinical intervention warranted “a shift toward a disease-control approach to HIV (...) infection along the lines of classic tuberculosis practices,” including the “reporting of seropositives.”Although his proposal met with fierce and effective resistance, it is now clear that his call represented part of a national trend. The CDC continued to press for cases of HIV to he reported by name to health departments, an effort that assumed the dimensions of a campaign. It was supported by a growing number of public health officials. (shrink)

It may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. Because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. The eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. Currently, adenovirus, adeno‐associated virus and lentivirus have been used (...) to successfully transfer genetic material to retinal pigment epithelium and photoreceptor cells. By harnessing therapeutic genes to these viruses, researchers have been able to demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence that this form of therapy can be effective in delaying photoreceptor cell death. Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long‐term rescue with minimal toxicity. BioEssays 23:662–668, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

How can one investigate phenomenal consciousness? As in other areas of science, the investigation of consciousness aims for a more precise knowledge of its phenomena, and the discovery of general truths about their nature. This requires the development of appropriate first-person, second-person, and third-person methods. This book introduces some of the creative ways in which these methods can be applied to different purposes, e.g. to understand the relation of consciousness to brain, to examining or changing consciousness as such, and to (...) the way consciousness is influenced by social, clinical and therapeutic contexts. To clarify the strengths and weaknesses of different methods and to demonstrate the interplay of methodology and epistemology, the book also suggests a number of "maps" of the consciousness studies terrain that places different approaches to the study of consciousness into a broader, interdisciplinary context. (shrink)

Research that involves the creation of animals with human-derived parts opens the door to potentially valuable scientific and therapeutic advances, yet invokes unsettling moral questions. Critics and champions alike stand to gain from clear identification and careful consideration of the strongest ethical objections to this research. A prevailing objection argues that crossing the human/nonhuman species boundary introduces inexorable moral confusion (IMC) that warrants a restriction to this research on precautionary grounds. Though this objection may capture the intuitions of (...) many who find this research unsettling, it relies on mistaken views of both biology and moral standing, ultimately distorting the morally relevant facts. We critically examine IMC, identify mistaken essentialist assumptions, and reframe ethical concerns. The upshot is a stronger line of objection that encourages a more inclusive and productive ethical discourse. (shrink)

The human body is becoming hot property, a resource to be “mined,” “harvested,” patented, and traded commercially for profit as well as scientific and therapeutic advances. Under the new entrepreneurial approach to the body old tensions take on new dimensions—about consent, the fair distribution of tissues and products developed from them, the individual and cultural values represented by the body, and public policy governing the use of organs and tissues.

Without exaggeration, it could be said that we are entering a golden age of neuroscience. Informed by recent developments in neuroimaging that allow us to peer into the working brain at both a structural and functional level, neuroscientists are beginning to untangle mechanisms of recovery after brain injury and grapple with age-old questions about brain and mind and their correlates neural mechanisms and consciousness. Neuroimaging, coupled with new diagnostic categories and assessment scales are helping us develop a new diagnostic nosology (...) about disorders of consciousness which will likely improve prognostication and suggest therapeutic advances. Historically such diagnostic refinement has yield therapeutic advances in medicine and there is no reason to doubt that this will be the case for disorders of consciousness, perhaps bringing relief to a marginalized population now on the periphery of the therapeutic agenda. In spite of this promise, the translation of research findings into the clinical context will be difficult. As we move from descriptive categories about disorders of consciousness, like the vegetative or minimally conscious states, to ones further specified by integrating behavioral and neuroimaging findings, humility not hubris should be the virtue that guides the ethical conduct of research and practice. (shrink)

Enhancing research and development and ensuring equitable pricing and access to cutting-edge treatments are both vital to a biopharmaceutical innovation system that works in the public interest. However, despite delivering numerous therapeutic advances, the existing system suffers from major problems: a lack of directionality to meet key needs, inefficient collaboration, high prices that fail to reflect the public contribution, and an overly-financialized business model.

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non‐coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the in‐depth (...) molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome‐editing techniques including CRISPR/Cas9. These approaches are also applicable to low‐frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. (shrink)