Definition of the problem: Recent progress in the pharmacological sciences provides a first glimpse of the development of an individual, genotype-based drug therapy in order to improve the efficiency of drug utilization. Genotyping of genetic polymorphisms in genes involved in drug response promises to optimize drug therapy fundamentally by identifying patients for whom a pharmaceutical agent may be effective and safe or contraindicated because of expected adverse drug reactions. Arguments: The new pharmacogenomic treatment strategies raise complex bioethical issues, (...) because genetic screening for drug therapy may identify asymptomatic patients who are at risk for a particular adverse outcome. Thus, pharmacogenomics will affect the relationship between the treating physician and the patient which is traditionally based on privacy, confidentiality, beneficience and non-maleficience. Conclusion: In the article presented some ethical aspects of these new pharmacogenomic approaches concerning the physician-patient relationship are discussed. (shrink)

Contemporary medicine views health as the individual’s physical, mental, and social well-being. Oral health plays a crucial role in one’s well-being, as the oral cavity and its surrounding regions execute essential functions in verbal and nonverbal communication, sensing, digestion, and significantly contribute to aesthetic appearance. The multifaceted nature of the notion of oral health, as well as the patient’s needs and autonomous will result in various treatment options for the same oral state, favouring often contrasting ethical values and different (...) aspects of oral health. The objective of this article is to suggest alternative treatment strategies in dentistry with respect to the following factors: extent of rehabilitation, preserving one’s anatomical structures, aesthetic outcome, number of sessions, patient autonomy. Additionally, this article describes the suggested treatment strategies in an ethical context and determines the conditions of their employment. The suggested treatment strategies are divided in two categories, extensive treatment strategies focusing on the patient’s entire craniofacial complex, while specific treatment strategies focus on specific paramount issues. (shrink)

New neural models for anorexia nervosa are emerging as a result of increased research on the neurobiology of AN, and these offer a rationale for the development of new treatment technologies such as neuromodulation. The emergence of such treatment technologies raises new ethical questions; however these have been little discussed for AN. In this article, I take an empirical approach and explore how young women who suffer from AN perceive treatment technologies in light of the concept of (...) authenticity. Interview data showed that participants in this study did not seem to unconditionally adhere to treatment modalities that only imply laborious self-work, such as therapy. The data also showed that they were willing to accept new treatment possibilities such as pharmacological or brain-directed treatment strategies, which they view as having potential instrumental value in coping with certain symptoms of the illness. However, such modalities can pose threats to patients’ authenticity, especially with regard to self-discovery. I argue that, in a context where there is an increased interest in brain-directed treatment strategies for AN, studies should continue to explore the ethical and psychological impact of such treatment technologies on individuals. (shrink)

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties (...) of drugs in adolescents are expected to be similar to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention and treatment research can be considered adults, based on US Food and Drug Administration regulations and the appropriate application of state law. The FDA permits local jurisdictions to apply state and local HIV/sexually transmitted infection minor treatment laws so that adolescents who are HIV-positive or at risk of contracting HIV may be enrolled in therapeutic or prevention trials without obtaining parental permission. (shrink)

Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood (...) stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. (shrink)

(2010). Resuscitation Strategies in the United States: Realities of Hospital and Prehospital Treatment. The American Journal of Bioethics: Vol. 10, No. 1, pp. 72-73.

Current treatments for chronic pain have limited benefit. We describe a resilience intervention for individuals with chronic pain which is based on a model of viewing chronic pain as dysregulated homeostasis and which seeks to restore homeostatic self-regulation using strategies exemplified by survivors of extreme environments. The intervention is expected to have broad effects on well-being and positive emotional health, to improve cognitive functions, and to reduce pain symptoms thus helping to transform the suffering of pain into self-growth. A (...) total of 88 Veterans completed the pre-assessment and were randomly assigned to either the treatment intervention or control. Fifty-eight Veterans completed pre- and post-testing. The intervention covered resilience strengths organized into four modules: engagement, social relatedness, transformation of pain and building a good life. A broad set of standardized, well validated measures were used to assess three domains of functioning: health and well-being, symptoms, and cognitive functions. Two-way Analysis of Variance was used to detect group and time differences. Broadly, results indicated significant intervention and time effects across multiple domains: Pain decreased in present severity [F = 5.02, p < 0.05, η2p = 0.08], total pain over six domains [F = 14.52, p < 0.01, η2p = 0.21], and pain interference [F = 6.82, p < 0.05, η2p = 0.11]; Affect improved in pain-related negative affect [F = 7.44, p < 0.01, η2p = 0.12], fear [F = 7.70, p < 0.01, η2p = 0.12], and distress [F = 10.87, p < 0.01, η2p = 0.16]; Well-being increased in pain mobility [F = 5.45, p < 0.05, η2p = 0.09], vitality [F = 4.54, p < 0.05, η2p = 0.07], and emotional well-being [F = 5.53, p < 0.05, η2p = 0.09] Mental health symptoms and the cognitive functioning domain did not reveal significant effects. This resilience intervention based on homeostatic self-regulation and survival strategies of survivors of extreme external environments may provide additional sociopsychobiological tools for treating individuals with chronic pain that may extend beyond treating pain symptoms to improving emotional well-being and self-growth.Clinical Trial Registration: Registered with ClinicalTrials.gov. (shrink)

There are five ways in which shame might negatively impact upon our attempts to combat and treat HIV. Shame can prevent an individual from disclosing all the relevant facts about their sexual history to the clinician. Shame can be a motivational factor in people living with HIV not engaging with or being retained in care. Shame can prevent individuals from presenting at clinics for STI and HIV testing. Shame can prevent an individual from disclosing their HIV status to new sexual (...) partners. Shame can serve to psychologically imprison people, it makes the task of living with HIV a far more negative experience than it should, or needs to, be. Drawing on recent philosophical work on shame, and more broadly on work in the philosophy and psychology of emotion, we propose a framework for understanding how shame operates upon those who experience the emotion, propose a strategy for combatting the negative role shame plays in the fight against HIV, and suggest further study so as to identify the tactics that might be employed in pursuing the strategy here proposed. (shrink)

BackgroundPrognostic uncertainty is a challenge for physicians in the neuro intensive care field. Questions about whether continued life-sustaining treatment is in a patient’s best interests arise in different phases after a severe traumatic brain injury. In-depth information about how physicians deal with ethical issues in different contexts is lacking. The purpose of this study was to seek insight into clinicians’ strategies concerning unresolved prognostic uncertainty and their ethical reasoning on the issue of limitation of life-sustaining treatment in (...) patients with minimal or no signs of neurological improvement after severe traumatic brain injury in the later trauma hospital phase.MethodsInterviews with 18 physicians working in a neurointensive care unit in a large Norwegian trauma hospital, followed by a qualitative thematic analysis focused on physicians’ strategies related to treatment-limiting decision-making.ResultsA divide between proactive and wait-and-see strategies emerged. Notwithstanding the hospital’s strong team culture, inter-physician variability with regard to ethical reasoning and preferred strategies was exposed. All the physicians emphasized the importance of team—family interactions. Nevertheless, their strategies differed: (1) The proactive physicians were open to consider limitations of life-sustaining treatment when the prognosis was grim. They initiated ethical discussions, took leadership in clarification and deliberation processes regarding goals and options, saw themselves as guides for the families and believed in the necessity to prepare families for both best-case and worst-case scenarios. (2) The “wait-and-see” physicians preferred open-ended treatment (no limitations). Neurologically injured patients need time to uncover their true recovery potential, they argued. They often avoided talking to the family about dying or other worst-case scenarios during this phase.ConclusionsDepending on the individual physician in charge, ethical issues may rest unresolved or not addressed in the later trauma hospital phase. Nevertheless, team collaboration serves to mitigate inter-physician variability. There are problems and pitfalls to be aware of related to both proactive and wait-and-see approaches. The timing of best-interest discussions and treatment-limiting decisions remain challenging after severe traumatic brain injury. Routines for timely and open discussions with families about the range of ethically reasonable options need to be strengthened. (shrink)

Weight-gain in psychiatric populations is a common clinical challenge. Many patients suffering from mental disorders, when exposed to psychotropic medications, gain significant weight with or without other side-effects. In addition to reducing the patients' willingness to comply with treatment, this weight-gain may create added psychological or physiological problems that need to be addressed. Thus, it is critical that clinicians take precautions to monitor and control weight-gain and take into account and treat all problems facing an individual. In this review, (...) we examine some of the key issues surrounding weight-gain in individuals suffering from mental disorders for contemporary practitioners in community clinics. We describe some factors known to make certain patients more susceptible to treatment-induced weight-gain and mechanisms implicated in this process. We also highlight a few psychological and pharmacological interventions that have proven effective in weight management. Importantly, we provide critical steps for management and prevention of weight-gain and related issues in the clinical practice of psychopharmacology. (shrink)

Treatment pressures are communicative strategies that mental health professionals use to influence the decision-making of mental health service users and improve their adherence to recommended treatment. Szmukler and Appelbaum describe a spectrum of treatment pressures, which encompasses persuasion, interpersonal leverage, offers and threats, arguing that only a particular type of threat amounts to informal coercion. We contend that this account of informal coercion is insufficiently sensitive to context and fails to recognize the fundamental power imbalance in (...) mental healthcare. Based on a set of counterexamples, we argue that what makes a proposal coercive is not whether service users will actually be made worse off if they reject the proposal, but rather whether they have the justified belief that this is the case. Whether this belief is justified depends on the presence of certain contextual factors, such as strong dependency on professionals and the salient possibility of formal coercion. (shrink)

The explanatory/pragmatic-trial distinction enjoys a burgeoning philosophical and medical literature and a significant contingent of support among philosophers and healthcare stakeholders as an important way to assess the design and results of randomized controlled trials. A major motivation has been the need to provide relevant, generalizable data to drive healthcare decisions. While talk of pragmatic and explanatory trials could be seen as convenient shorthand, the distinction can also be seen as harboring deeper issues related to inferential strategies used to (...) evaluate causal claims regarding medical treatments. A comprehensive, critical analysis of the distinction and underlying epistemological framework upon which the distinction is based, particularly with respect to treatment effectiveness, has yet to be forthcoming. I provide this, analyzing the distinction’s relationship to generalizability and cognate distinctions between ideal conditions and real-world practice, internal and external validity, and efficacy and effectiveness. I also analyze recent philosophical work that relies on the explanatory/pragmatic-trial distinction and that advocates for more pragmatic trials. I conclude that as an organizing principle for trial-design decisions and trial evaluation, the explanatory/pragmatic-trial distinction is conceptually problematic and not as useful as its proponents seem to think. Since some pragmatic-trial features can be inimical to establishing treatment effectiveness, pragmatic-trial features should not be conflated with pragmatic trials’ avowed goals. If the distinction is to be useful, it and some associated concepts, including generalizability, should be reformulated, lest they continue to underlie a medical epistemology that could contribute to methodologically flawed and potentially unethical advice for the design and interpretation of trials. (shrink)

The article examines the process of niche standardization in medical research as an example of democratizing strategies implemented in industry-funded science. I argue that niche standardization can lead to undesirable epistemic and ethical consequences, if the various goals of research are not properly aligned. I examine two examples: the case of Sarafem, approved for the treatment of premenstrual dysphoric disorder in women, and the case of BiDil, approved for exclusive use in African Americans for the treatment of (...) congestive heart failure. I conclude by cautioning against the unqualified support of democratizing strategies in industry-funded research. (shrink)

This paper explores the justifications and impression management strategies that industrial companies use to rationalize their impacts on climate change. These strategies influence the perceptions of stakeholders through the use of techniques of neutralization intended to legitimize the impacts of corporate operations in the area of climate change. Based on a qualitative and inductive approach, 10 case studies were conducted of large Canadian industrial emitters. Interviews were conducted with managers and environmental specialists. Public documentation was also collected when (...) available. This study identifies six main neutralization techniques that industrial emitters use to rationalize their impacts: self-proclaimed excellence, promotion of a systemic view, denial and minimization, denouncing unfair treatment and deceptive appearances, economic and technological blackmail, and blaming others. The paper develops a better understanding of corporate arguments and strategies aimed at influencing the perceptions of stakeholders, including policymakers. The study also contributes to the literature on impression management by shedding light on new strategies and techniques of neutralization used by managers to shape the perceptions of stakeholders on socially sensitive issues. (shrink)

The goal of referent tracking is to create an ever-growing pool of data relating to the entities existing in concrete spatiotemporal reality. In the context of Electronic Healthcare Records (EHRs) the relevant concrete entities are not only particular patients but also their parts, diseases, therapies, lesions, and so forth, insofar as these are salient to diagnosis and treatment. Within a referent tracking system, all such entities are referred to directly and explicitly, something which cannot be achieved when familiar concept-based (...) systems are used in what is called “clinical coding”. In this paper we describe the components of a referent tracking system in an informal way and we outline the procedures that would have to be followed by healthcare personnel in using such a system. We argue that the referent tracking paradigm can be introduced with only minor – though nevertheless ontologically important – technical changes to existing EHR infrastructures, but that it will require a radically different mindset on the part of those involved in clinical coding and terminology development from that which has prevailed hitherto. (shrink)

Gerd Buchdahl’s international reputation rests on his masterly writings on Kant. In them he showed how Kant transformed the philosophical problems of his predecessors and he minutely investigated the ways in which Kant related his critical philosophy to the contents and methods of natural science. Less well known, if only because in large part unpublished, are the writings in which Buchdahl elaborated his own views on the methods and status of the sciences. In this paper I examine the roles of (...) hermeneutics in Buchdahl’s reconstruction of Kant’s philosophical system and in his own ‘transcendental methodological’ approach to the philosophy of science. The first section looks at Buchdahl’s views on the theory and practice of historical interpretation and at the Husserlian hermeneutic scheme of reduction and realisation that he used in his later accounts of the philosophies of science of Kant and himself. The second section concentrates on Buchdahl’s treatment of the grounds of science in Kant; and the third on the hermeneutic strategies Buchdahl employed in articulating and justifying his own views. The paper closes with reflections on the impact and importance of Buchdahl’s interpretation of Kant’s critical philosophy in relation to the sciences and of his own hermeneutically based philosophy of science.Author Keywords: Buchdahl; Kant; Hermeneutics; Methodology; Transcendental philosophy. (shrink)

Based on therapeutic meetings with individuals who have experienced sexual violence and abuse, the challenge is how do we help these couples to establish sexual relationships on their own terms, without interference of defence or coping strategies they have used to protect themselves against the overwhelming experiences of violence or abuse in the past? This article will focus on therapeutic work with such couples and how to interact with them and support their efforts to establish satisfying sexual relationships, based (...) on sexological experience as well as experience from work with traumatisation. The basis for our treatment is a modified version of William Masters and Virginia Johnson’s approach. The technique of sensate focus is central, modified by trauma theory, including the understanding of dissociation, and the need to integrate memories from different levels: somatic, emotional, and cognitive. The traumatised client needs special attention to the experiences of predictability and safety and respect due to their history of being transgressed against. The therapists must be aware of the issue of dissociation; different dissociated inner parts can play different roles in the interaction between client and therapist. While couples therapy is a necessary frame for this therapy, the therapist often needs to work with issues unique to each individual. Each partner must be able to identify their own responses and their own sexual needs and preferences. It may therefore be valuable to have a co-therapist. The central goal is for the clients to identify responses to stimulation as a here and now experience in a setting that feels safe and welcome. (shrink)

Recent studies have shown that self‐explanation is an effective metacognitive strategy, but how can it be leveraged to improve students' learning in actual classrooms? How do instructional treatments that emphasizes self‐explanation affect students' learning, as compared to other instructional treatments? We investigated whether self‐explanation can be scaffolded effectively in a classroom environment using a Cognitive Tutor, which is intelligent instructional software that supports guided learning by doing. In two classroom experiments, we found that students who explained their steps during problem‐solving (...) practice with a Cognitive Tutor learned with greater understanding compared to students who did not explain steps. The explainers better explained their solutions steps and were more successful on transfer problems. We interpret these results as follows: By engaging in explanation, students acquired better‐integrated visual and verbal declarative knowledge and acquired less shallow procedural knowledge. The research demonstrates that the benefits of self‐explanation can be achieved in a relatively simple computer‐based approach that scales well for classroom use. (shrink)

The ArgumentEuropean ethology and North American comparative psychology have been the two most prominent approaches to the study of animal behavior through most of the twentieth century. In this paper I analyze sets of popular articles by ethologist Nikolaas Tinbergen and psychologist Frank Beach, in an effort to understand the contrasting rhetorical styles of the two. Among the numerous ways in which Tinbergen and Beach differed were with respect to expressing the joy of research, the kind of scientific approach adopted, (...) their treatment of animals, their sense of history, and the types of illustrations they chose. In general, Tinbergen‘s articles placed him closer to nature and Beach‘s more in the tradition of dispassionate scientific inquiry. These differences in rhetoric may have been one factor in the greater success of ethology after World War II. (shrink)

The key claims of left accelerationism are grounded upon a network of concepts. Crucial here have been the notions of hegemony ; strategy ; and rationality. Though the concepts of hegemony–strategy and strategy–rationality have received wide treatment, the hegemony and rationality pair has received minimal attention. Yet to render the core arguments of left accelerationism explicable requires that these three ideas are placed in some concrete relation. To put the issue another way: what is the relationship between power and (...) rationality? This article will argue that many of the critiques which the left accelerationist position has received are bound up in misunderstanding this relationship. To remedy such misnomers, we will argue that it is a more sophisticated understanding of strategy that can help bridge these two domains. This leads us to delineate a form of strategy-without-a-strategiser, a distributed and emergent strategic orientation which mediates the power/rationality binary. (shrink)

What if neurofeedback or other types of neurotechnological treatment, by itself or in combination with behavioral treatment, could achieve a successful “rewiring” of the psychopath’s brain? Imagine that such treatments exist and that they provide a better long-term risk-minimizing strategy compared to imprisonment. Would it be ethical to offer such treatments as a condition of probation, parole, or prison release? In this paper, I argue that it can be ethical to offer effective, non-invasive neurotechnological treatments to offenders as (...) a condition of probation, parole, or prison release provided that: the status quo is in no way cruel, inhuman, degrading, or in some other way wrong, the treatment option is in no way cruel, inhuman, degrading, or in some other way wrong, the treatment is in the best interests of the offender, and the offender gives his/her informed consent. (shrink)

Light and Kennison found that bias effects in the forced-choice perceptual identification of words occurred only in a subset of participants, those who claimed on a strategy questionnaire to be deliberately guessing words they had studied previously. McKoon and Ratcliff raised a number of objections to the proposal that bias effects are due to guessing strategies, citing difficulties in our statistical treatment of data, our use of subjective reports to classify participants, and our approach to the general problem (...) of separating implicit from explicit influences on performance. This article responds to these objections. (shrink)

To date, the effective management of HIV‐1 infection by anti‐retroviral drugs has proved remarkably difficult to achieve. This is primarily due to the ease with which HIV‐1 becomes resistant to drugs which initially may be very effective at blocking viral replication. In a recent issue of Science, two promising new AIDS treatments were reported. The first described the use of retroviral‐type zinc finger structures found in the HIV‐1 nucleocapsid protein as targets for anti‐retroviral drugs(1). The second demonstrated the feasibility of (...) the reverse transcriptase inhibitor (R)‐9‐(2‐phosphonylmethoxypropyl) adenine as a postexposure prophylaxis in blocking HIV‐1 infection(2). (shrink)

Rid and Wendler propose the development of a Patient Preference Predictor (PPP), an actuarial model for predicting incapacitated patient’s life-sustaining treatment preferences across a wide range of end-of-life scenarios. An actuarial approach to end-of-life decision making has enormous potential, but transferring the logic of actuarial prediction to end-of-life decision making raises several conceptual complexities and logistical problems that need further consideration. Actuarial models have proven effective in targeted prediction tasks, but no evidence supports their effectiveness in the kind of (...) broad spectrum prediction task that is the proposed goal of the PPP. We argue that a more focused approach, targeting specific medical conditions and generating treatment predictions based on the preferences of individuals with actual disease experience, is both more firmly grounded in past research and is a more prudent initial strategy for exploring the efficacy of actuarial prediction in end-of-life decision making. (shrink)

The paper discusses inappropriate (futile) treatment by analyzing the casuistics of palliative patients in the terminal stage of illness who are hospitalized at the Department of Internal Medicine and Geriatrics of the Faculty hospital with policlinic (FNsP). Our research applies the principles of palliative care in the context of bioethics. The existing clinical conditions of healthcare in Slovakia are characteristic of making a taboo of the issues of inappropriate treatment of palliative patients. Inductive-deductive and normative clinical bioethics methods (...) of palliative care and ethical strategy are applied for defining issues found in inappropriate hemodialysis treatment. An algorithm of hemodialysis treatment requires the definition of those lege artis criteria which, in the context of a patient’s autonomy and his/her decision, precondition the avoidance of the situation in which hemodialysis treatment is inappropriate (futile). Futile treatment in a terminal condition is ethically inappropriate medical treatment that extends the suffering of patients and their relatives. Its definition is determined by the relevant legislation and the methods of bioethics. An active palliative strategy is aimed at managing the process of incurable diseases in the patient’s bio-psycho-socio-spiritual continuity in the process of special bioethics. The global bioethical objective of general bioethics for palliative care is based on the paradigm of social harmony and solidarity in the context of an authentic modus of the patient’s existence as a constitutive principle for the phenomenon of the patient’s being to finite being (death). (shrink)

The aim of the present study was to describe how registered nurses in nursing homes ensure legal security, good and safe nursing care and uphold the dignity of nursing home residents with severe dementia without violating residents’ integrity. Semi-structured interviews were conducted with 10 charge nurses in a county in central Sweden. The transcribed interviews were examined using manifest and latent content analyses. The manifest analysis identified actual local routines involving coercive treatment and registered nurses’ descriptions of complications and (...) alternative measures. The latent analysis resulted in three themes describing nursing strategies: one with coercive treatment, one with coercive treatment under specific circumstances and one to prevent coercive treatment. Interpretations of legal terms regarding coercive treatment and inadequate gerontological nursing training and understaffing seem to preserve the use of coercive treatment. (shrink)

Access to treatment, in HIV vaccine trials (HVTs), remains ethically controversial. In most prevention trials, including in South Africa, participants who seroconvert are referred to publicly funded programmes for treatment. This strategy is problematic when there is inadequate and uneven access to public sector antiretroviral therapy (ART) and support resources. The responsibilities, if any, of researchers, sponsors and public health authorities involved in HVTs has been hotly debated among academics, scholars, representatives of international organizations and sponsors. However, there (...) is little published on community perceptions. Recent guidance asserts that communities should make inputs into treatment and care decisions. This qualitative study explored a South African community's perceptions of who should provide what to HVT participants as well as how and why this should be done. Twenty-nine adults working at or attending five primary health care clinics in two rural areas in KwaZulu-Natal participated in in-depth interviews. Respondents expressed that researchers should ‘help participants to access’ treatment and care ‘because they are in a position to do so’ and ‘are in a relationship with’ trial participants. Respondents suggested that researchers could help by ‘facilitating referral’ until such time that participants can access care and treatment on their own. We highlight a series of implications for researchers in HVTs, including their need to be aware of prospective participants' considerable trust in and respect for researchers, the responsibility that this places on them, and the need for clear communication with communities so as not to erode community trust. (shrink)

Despite the remarkable achievements of novel targeted anti‐cancer drugs, most therapies only produce remission for a limited time, resistance to treatment, and relapse, often being the ultimate outcome. Drug resistance is due to highly efficient adaptive strategies utilized by cancer cells. Exogenous and endogenous stress stimuli are known to induce first‐line responses, capable of re‐establishing cellular homeostasis and determining cell fate decisions. Cancer cells may also mount second‐line adaptive strategies, such as the mutator response. Hypermutable subpopulations of (...) cells may expand under severe selective stress, thereby accelerating the emergence of adapted clones. As with first‐line protective responses, these strategies appear highly conserved, and are found in yeasts and bacteria. We hypothesize that evolutionarily conserved programs rheostatically regulate mutability in fluctuating environments, and contribute to drug resistance in cancer cells. Elucidating the conserved genetic and molecular mechanisms may present novel opportunities to increase the effectiveness of cancer therapies. (shrink)

Uncertainty is pervasive in ecology where the difficulties of dealing with sources of uncertainty are exacerbated by variation in the system itself. Attempts at classifying uncertainty in ecology have, for the most part, focused exclusively on epistemic uncertainty. In this paper we classify uncertainty into two main categories: epistemic uncertainty (uncertainty in determinate facts) and linguistic uncertainty (uncertainty in language). We provide a classification of sources of uncertainty under the two main categories and demonstrate how each impacts on applications in (...) ecology and conservation biology. In particular, we demonstrate the importance of recognizing the effect of linguistic uncertainty, in addition to epistemic uncertainty, in ecological applications. The significance to ecology and conservation biology of developing a clear understanding of the various types of uncertainty, how they arise and how they might best be dealt with is highlighted. Finally, we discuss the various general strategies for dealing with each type of uncertainty and offer suggestions for treating compounding uncertainty from a range of sources. (shrink)

would like for them to know that I am in pain or this part of my body hurts or the other part hurts — that I am not lying about it. To examine me and to cut down on the pain….And help me out.Patient with Sickle Cell Disease, Focus Group ParticipantPain in the United States is widely recognized to be undertreated; however, the capacity to treat pain has never been greater. The causes of this undertreatment are varied. As we focus (...) on pain and why it is too often ineffectively treated, we also discover that this undertreatment afflicts some more than others. What divides the some from the others isn't limited to one factor, but one particularly disturbing factor is race and ethnicity. Racial and ethnic minority populations are at higher risk for oligoanalgesia, or the ineffective treatment of pain. Only through further study of the differences in pain treatment based on race and ethnicity can we develop strategies to reduce the disparities in care. (shrink)

The compassionate treatment of animals has been the focal point of speeches and writings by one of the most influential Buddhist cleric-scholars on the Tibetan plateau today, Khenpo Tsultrim Lodrö of Larung Buddhist Academy. This essay surveys the Khenpo's broad-based advocacy for animal welfare and details his discrete appeals to nomads in eastern Tibet to forgo selling livestock for slaughter, to eat a vegetarian diet on religious holidays, to relinquish wearing animal fur, to protect wildlife habitat, and to liberate (...) the lives of animals. I focus on the modernist “this worldly” dimension of his advocacy, calling attention to how Tsultrim Lodrö goes beyond traditional scare tactics that emphasize the karmic effects of negative deeds in future lives and instead invokes compassion by attending to the lived experience and suffering of animals. In doing so, the Khenpo positions Buddhism as a civilizing force in order to reform certain Tibetan customs and mitigate the influence of Chinese modernity and state marketization policies. I argue that his strategy of “reverse orientalism” appropriates state civilizational discourse and reverses its terms. (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)

The involuntary admission or treatment of a mentally ill individual is highly controversial, as it may be argued that such intervention infringes on individual autonomy and the right to choose a particular treatment. However, this argument must be balanced with the need to provide immediate healthcare services to a vulnerable person who cannot or will not make a choice in his or her own best interests at a particular time. A study carried out in Gauteng Province, South Africa, (...) highlighted the fact that the annual rate of involuntary admissions increased by almost double from 2007 to 2008. This could indicate that healthcare providers are not treating patients without their consent only when this is absolutely necessary. Alternatively, it could indicate that healthcare professionals are more aware of the provisions of the Mental Health Care Act and relevant national policy guidelines. Or it could suggest that more patients are presenting with mental illnesses or disorders that require their involuntary admission. It remains for strategies to be developed that change negative perceptions and inequities for individuals with mental illness. Above all, the strategies should be underpinned by inalienable respect for mentally ill individuals – a concept that was blatantly disregarded in the Life Esidimeni case. In this article, we highlight the functions of mental health review boards and their accountability where involuntary admissions are concerned, while emphasising the protections for mentally ill persons as a vulnerable population group, as set out in the SA Constitution. (shrink)

The current spread of democracy has not enabled the poor to use rights to win equity, raising questions about whether the poor and weak can use liberal democratic freedoms to address inequality. An oft-cited model of success, however, is the Treatment Action Campaign ’s campaign to press the South African government into distributing anti-retroviral medication to people living with HIV/aids. This article finds that TAC’s strategy of using the rights and rules of constitutional democracy to win gains may offer (...) an exemplar for forms of collective action which can win substantive equality, but that the model remains of limited application. (shrink)

Informed by interviews conducted with members of a local research ethics committee, this article reflects upon how RECs can act to improve the quality of patient consent to clinical trials. Two emergent narratives which trial participants have drawn upon to account for their experiences are explored: the narrative of the clinical trial itself and a narrative of individualized treatment. Informed consent requires participants to recognize that only the first of these narratives is relevant to the design, and their experience, (...) of randomized controlled trials. Improving the clarity of patient information is argued to be a relevant, but insufficient, strategy for increasing patient familiarity with the methodology of clinical trials. In the concluding sections of the article, other approaches, and the role of RECs, are considered. (shrink)

This article offers a critical discourse analysis of the Israeli television series In Treatment. The series unfolds the therapy sessions of a 40-year-old single female attorney with her therapist. The main objective of the study was to identify the scripted tactics or narrative strategies that establish and maintain singlehood. The findings indicate that the therapeutic discourse plays a central role in the construction and interpretation of single women’s subjectivities, prompting a narrative that encourages the ‘discarding’ of singlehood as (...) well as therapeutic work slanted towards a more familial and maternally oriented subjectivity. This narrative unfolds through two dominant scripted tactics: the symbolic annihilation of singlehood and the construction of feminine identity hierarchies. Moreover, it is also prompted by the discursive alliance between the therapeutic discourse and the postfeminist discourse. Consequently, long-term singlehood is portrayed as an unnatural and pathological life script characterized by its lack and deficiency. Furthermore, as opposed to childless singlehood, single motherhood by choice emerges as a preferred and desirable life option. The category of single motherhood is endowed with new forms of legitimacy, reinforcing new-old patriarchal and postfeminist conceptions of women’s reproductive potential and what is considered to be women’s primary life purpose. (shrink)

Ethical analyses, professional guidelines and legal decisions support the equivalence thesis for life-sustaining treatment: if it is ethical to withhold treatment, it would be ethical to withdraw the same treatment. In this paper we explore reasons why the majority of medical professionals disagree with the conclusions of ethical analysis. Resource allocation is considered by clinicians to be a legitimate reason to withhold but not to withdraw intensive care treatment. We analyse five arguments in favour of non-equivalence, (...) and find only relatively weak reasons to restrict rationing to withholding treatment. On the contrary, resource allocation provides a strong argument in favour of equivalence: non-equivalence causes preventable death in critically ill patients. We outline two proposals for increasing equivalence in practice: (1) reduction of the mortality threshold for treatment withdrawal, (2) time-limited trials of intensive care. These strategies would help to move practice towards more rational treatment limitation decisions. (shrink)

This article investigates Abelard’s defence of the compatibility between universal bivalence and the existence of future contingent events. It first considers the standard strategy put forward by twelfth-century commentators to solve Aristotle’s dilemma in De Interpretatione 9, which fundamentally relies on Boethius’ distinction between definite and indefinite truth values. Abelard’s own position on the dilemma is then introduced, focusing on a specific deterministic argument considered in his logical works that aims to demonstrate that, given the determinacy of present-tense propositions such (...) as ‘“that Socrates will eat tomorrow” is true’, future contingent events such as that Socrates will eat tomorrow are determinate in advance. In addition to presenting Abelard’s reply to the argument, the article offers an analysis of his notions of contingency, determinacy, and future events, and a comparison between Abelard’s position and other twelfth-century discussions on future contingents. (shrink)

Eighteenth-century disputes in moral theory seem to offer an opportunity to scepticism about moral theory and about morality. Twentieth-century theorists have tried to forestall a sceptical argument from disagreement in moral theory to doubts about morality, by appeal to a division between first-order and second-order questions. This division, however, does not answer the sceptical argument. A better reply appears in Butler's treatment of disagreement through his strategies of consensus and comprehension. These strategies are illustrated by his discussion (...) of utilitarianism and of the relation between conscience and self-love. (shrink)

This article deals with optimal control applied to vaccination and treatment strategies for an SIRS epidemic model with logistic growth and delay. The delay is incorporated into the model in order to modeled the latent period or incubation period. The existence for the optimal control pair is also proved. Pontryagin’s maximum principle with delay is used to characterize these optimal controls. The optimality system is derived and then solved numerically using an algorithm based on the forward and backward (...) difference approximation. (shrink)

Stein & Glasier suggest embryonic neural tissue grafts as a potential treatment strategy for Alzheimer's and Parkinson's disease. As an alternative, we suggest that the family of nerve growth factor-related neurotrophins and their trk (tyrosine kinase) receptors underlie cholinergic basal forebrain (CBF) and dopaminergic substantia nigra neuron degeneration in these diseases, respectively. Therefore, treatment approaches for these disorders could utilize neurotrophins.

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences (...) of parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

Heterogeneous treatment effects represent a major issue for medicine as they undermine reliable inference and clinical decision-making. To overcome the issue, the current vision of precision and personalized medicine acknowledges the need to control individual variability in response to treatment. In this paper, we argue that gene-treatment-environment interactions (G × T × E) undermine inferences about individual treatment effects from the results of both genomics-based methodologies—such as genome-wide association studies (GWAS) and genome-wide interaction studies (GWIS)—and randomized (...) controlled trials (RCTs). Then, we argue that N-of-1 trials can be a solution to overcome difficulties in handling individual variability in treatment response. Although this type of trial has been suggested as a promising strategy to assess individual treatment effects, it nonetheless has limitations that limit its use in everyday clinical practice. We analyze the existing variability within the designs of N-of-1 trials in terms of a continuum where each design prioritizes epistemic and pragmatic considerations. We then support wider use of the designs located at the pragmatic end of the explanatory-pragmatic continuum. (shrink)

Relationships, jobs, and health behaviors-these are what New Year's resolutions are made of. Every year millions resolve to adopt a better diet, exercise more, become fit, or lose weight but few put into practice the health behaviors they aspire to. For those who successfully begin, the likelihood that they will maintain these habits is low. Healthcare professionals recognize the importance of these, and other, health behaviors but struggle to provide their patients with the tools necessary for successful maintenance of their (...) medical regimens. The thousands of research papers that exist on patient adherence and health behavior change can leave professionals overwhelmed. This book synthesizes the results from more than 50 years of empirical research, resulting in simple, powerful, and practical guidance for health professionals who want to know the most effective strategies for helping their clients to put long-term health-relevant behavior changes into practice. It advocates a straightforward 3-ingredient model: Before a person can change, they must know what change is necessary ; desire the change ; and then have the tools to achieve and maintain the change. This book is designed to be informative and compelling, but its numerous anecdotes and examples render it engaging and entertaining, as well. Written for a practitioners and students of medicine, chiropractic, osteopathy, nursing, health education, physician assistant programs, dentistry, clinical and health psychology, marriage and family counseling, social work, school psychology, and care administrators -- and for lay persons who wish to take an active role in their health, this book brings together major empirically-based findings within the field and provides succinct, evidence-based recommendations and strategies for using these findings to make real changes. (shrink)

Borderline Personality disorder is a severe personality dysfunction characterized by behavioural features such as impulsivity, identity disturbance, suicidal behaviour, emptiness, and intense and unstable relationships. Approximately 2% of the population are thought to meet the criteria for BPD. The authors of this volume - Anthony Bateman and Peter Fonagy - have developed a psychoanalytically oriented treatment to BPD known as mentalization treatment. With randomised controlled trials having shown this method to be effective, this book presents the first account (...) of mentalization treatment for BPD. The first section gives an overview of BPD, including discussion of nosology, epidemiology, natural history, and psychosocial aetiology. It additionally summarises the present state of our research knowledge about effective psychotherapeutic treatments and use of medication. The second section outlines the authors' theoretical approach and contrasts it with other well known methods, including DBT, CAT, and CBT. In the extensive final section, the authors outline their clinical approach starting with how treatment is organised. A detailed account of the transferable features of the model is provided along with the main strategies and techniques of treatment. Numerous clinical examples are given to illustrate the core techniques and detailed information provided about how to apply aspects of the mentalization based treatment approach in everyday practice. Aimed at mental health professionals, along with counsellors, psychotherapists, and psychoanalysts, the book will be a valuable tool, providing an effective means of treating those suffering from Borderline Personality Disorder. (shrink)

In the first half of this dissertation, I develop a heuristic methodology for analyzing scientific solutions to the problem of underdetermination. Heuristics are rough-and-ready procedures used by scientists to construct models, design experiments, interpret evidence, etc. But as powerful as they are, heuristics are also error-prone. Therefore, I argue that they key to prudently using a heuristic is the articulation of meta-heuristics---guidelines to the kinds of problems for which a heuristic is well- or ill-suited. Given that heuristics will introduce certain (...) errors into our scientific investigations, I emphasize the importance of a particular category of meta-heuristics involving the search for robust evidence. Robustness is understood to be the epistemic virtue bestowed by agreement amongst multiple modes of determination. The more modes we have at our disposal, and the more these confirm the same result, the more confident can we be that a result is not a mere artifact of some heuristic simplification. Through an analysis of case-studies in the philosophy of biology and clinical trials, I develop a principled method for modeling and evaluating heuristics and robustness claims in a qualitative problem space. The second half of the dissertation deploys the heuristic methodology to address ethical and epistemological issues in the science of clinical trials. To that end, I develop a network model for the problem space of clinical research, capable of representing the various kinds of experiments, epistemic relationships, and ethical justifications intrinsic to the domain. I then apply this model to ongoing research with the antibacterial agent, moxifloxacin, for the treatment of tuberculosis, tracking its development from initially successful and promising in vitro and animal studies to its disappointing and discordant performance across five human efficacy trials. Given this failure to find a robust result with moxifloxacin across animal and human studies, what should researchers now do? While my final analysis of this case does not definitively answer that question, I demonstrate how my methodology, unlike a statistical meta-analysis, helps to clarify the directions for further research. (shrink)

Recent evidence confirming that the administration of antiretroviral drugs (ARVs) to HIV-infected persons may effectively reduce their risk of transmission has revived the discussion about priority setting in the fight against HIV/AIDS. The fact that the very same drugs can be used both for treatment purposes and for preventive purposes (Treatment as Prevention) has been seen as paradigm-shifting and taken to spark a new controversy: In a context of scarce resources, should the allocation of ARVs be prioritized based (...) on the goal of providing treatment, or on the goal of preventing the spread of the HIV epidemic? Contributions to this discussion tend to assume that treatment and prevention constitute two divergent goals that entail conflicting priorities. We challenge that assumption on the basis of both conceptual and empirical examination. We argue that, as far as the provision of ARVs to HIV-infected persons is concerned, the goals of treatment and prevention do not entail conflicting priorities; to the contrary, they dictate converging strategies for the optimal allocation of ARVs. In light of the current evidence, the concept of Treatment as Prevention can indeed be seen as paradigm-shifting, yet in a novel way: Rather than extending the tension between the goals of treatment and prevention to the level of drug-allocation, it dissolves this tension by providing a rationale for a unified strategy for allocating ARVs. (shrink)