For medical interventions there is a gap between what clinical scientific research has established as likely to carry clinical benefit and what the National Institute for Clinical Excellence (NICE) has judged as cost-effective. This gap is the affordability gap. It is created by a value judgement made by NICE and affirmed by the Secretary of State for Health. This value judgement operates to affect other value judgements made in actual clinical situations where at least one choice of treatment falls into (...) the affordability gap. This paper considers how the creation of this affordability gap impacts upon actual clinical decisions. It explores these issues in the context of the choice between a drug-eluting stent and a bare metal stent for elective coronary angioplasty. It also argues that the option of an NHS procedure with a top-up fee to cover the cost of the affordability gap is a genuine one; that this option could improve clinical outcomes; that it is morally acceptable; and that the rules that prevent the utilization of this option should be relaxed. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics andin vivonanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

This personal account traces a series of studies that led from DNA physical chemistry to anticancer drug mechanisms. Chemical crosslinking as a basis for anticancer drug actions had been suspected since the time of the first clinical reports of the effectiveness of nitrogen mustard in 1946. After the elucidation of the DNA helix‐coil transition, several nearly concurrent findings in the early 1960s established the paradigm of DNA interstrand crosslinking. The DNA filter elution phenomenon was discovered in the early 1970s, and (...) lent itself to the development of practical assays for DNA crosslinks and other DNA lesions in mammalian cells. The assays allowed studies of the effects of DNA damaging agents at pharmacologically or toxicologically relevant doses, and have been widely applied in studies of mutagenic and chemotherapeutic agents. During the period 1979–1986, DNA filter elution studies led to the paradigm of DNA topoisomerases as targets of anticancer drug action, and this has become one of the most active areas of anticancer drug development. (shrink)

The monist approach to the ancient mind-body problem styled "neurophilosophy" put forward recently by Patricia Smith Churchland on the basis of latter-day advances in the neurosciences is philosophically inadequate because it does not deal with the ethical dimension of the mind. Keywords: brain, complementarity, free will, mind-body problem, neuroscience, reductionism CiteULike Connotea Del.icio.us What's this?

I was surprised to note the critical tone of the discussion which my friend Leonard B. Meyer recently devoted in these pages to an article on the relation of art and science that I wrote for a popular scientific magazine. For I had believed all the while that in my article I was merely presenting to a general scientific audience a watered-down version of what I thought were Meyer's own views. Evidently I was mistaken in that belief, though I have (...) been unable to fathom just where I went wrong in interpreting Meyer's earlier writings, which, more than any other source, are the provenance of my ideas about the nature of art. Gunther S. Stent, professor of molecular biology at the University of California, Berkeley, is the author of Molecular Biology of Bacterial Viruses, Phage and the Origin of Molecular Biology, Molecular Genetics: An Introductory Narrative, The Coming of the Golden Age: A View of the End of Progress, and many important scientific papers. In Concerning the Sciences, the Arts—AND the Humanities" , Leonard B. Meyer took issue with views expressed by Professor Stent in "Prematurity and Uniqueness in Scientific Discovery," published in Scientific American. (shrink)

In this 2002 J.F. Lewis Award-winning monograph, Gunther Stent traces the origins and development of the paradoxes of free will in this well-crafted ...

When people engage in conversation, they tailor their utterances to their conversational partners, whether these partners are other humans or computational systems. This tailoring, or adaptation to the partner takes place in all facets of human language use, and is based on a mental model or a user model of the conversational partner. Such adaptation has been shown to improve listeners' comprehension, their satisfaction with an interactive system, the efficiency with which they execute conversational tasks, and the likelihood of achieving (...) higher level goals such as changing the listener's beliefs and attitudes. We focus on one aspect of adaptation, namely the tailoring of the content of dialogue system utterances for the higher level processes of persuasion, argumentation and advice‐giving. Our hypothesis is that algorithms that adapt content for these processes, according to a user model, will improve the usability, efficiency, and effectiveness of dialogue systems. We describe a multimodal dialogue system and algorithms for adaptive content selection based on multi‐attribute decision theory. We demonstrate experimentally the improved efficacy of system responses through the use of user models to both tailor the content of system utterances and to manipulate their conciseness. (shrink)

When people engage in conversation, they tailor their utterances to their conversational partners, whether these partners are other humans or computational systems. This tailoring, or adaptation to the partner takes place in all facets of human language use, and is based on a mental model or a user model of the conversational partner. Such adaptation has been shown to improve listeners' comprehension, their satisfaction with an interactive system, the efficiency with which they execute conversational tasks, and the likelihood of achieving (...) higher level goals such as changing the listener's beliefs and attitudes. We focus on one aspect of adaptation, namely the tailoring of the content of dialogue system utterances for the higher level processes of persuasion, argumentation and advice-giving. Our hypothesis is that algorithms that adapt content for these processes, according to a user model, will improve the usability, efficiency, and effectiveness of dialogue systems. We describe a multimodal dialogue system and algorithms for adaptive content selection based on multi-attribute decision theory. We demonstrate experimentally the improved efficacy of system responses through the use of user models to both tailor the content of system utterances and to manipulate their conciseness. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

Despite their centrality to medicine, drugs are not easily defined. We introduce two desiderata for a basic definition of medical drugs. It should: (a) capture everything considered to be a drug in medical contexts and (b) rule out anything that is not considered to be a drug. After canvassing a range of options, we find that no single definition of drugs can satisfy both desiderata. We conclude with three responses to our exploration of the drug concept: maintain a monistic concept, (...) or choose one of two pluralistic outcomes. Notably, the distinction between drugs and other substances is placed under pressure by the most plausible of the options available. (shrink)

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a “necessary” prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of “drug instrumentalization.” Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn (...) that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific “instrumentalization goals” and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. (shrink)

This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, (...) social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on the prospects for a reasonable profit and the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry’s efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade‐Related Aspects of Intellectual Property Rights agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and bulk buying. (shrink)

Drug exceptional access programs (DEAPs) exist across Canada to address gaps in access to pharmaceuticals. These programs circumvent standard procedures, raising epistemic, economic, social and political issues. This commentary provides insights into these issues by revealing the context and procedures on which these programs depend.

Periodic and unexpected shortages of drugs, biologics, and even medical devices have become commonplace in the United States. When shortages occur, hospitals and clinics need to decide how to ration their available stock. When such situations arise, institutions can choose from several different allocation schemes, such as first-come, first-served, a lottery, or a more rational and calculated approach. While the first two approaches sound reasonable at first glance, there are a number of problems associated with them, including the inability to (...) make fine, individual patient-centered decisions. They also do not discriminate between what kinds of patients and what types of uses may be more deserving or reasonable than others. In this article I outline an ethically acceptable procedure for rationing drugs during a shortage in which demand outstrips supply. (shrink)

We often get evidence concerning the reliability of our own thinking about some particular matter. This “higher-order evidence” can come from the disagreement of others, or from information about our being subject to the effects of drugs, fatigue, emotional ties, implicit biases, etc. This paper examines some pros and cons of two fairly general models for accommodating higher-order evidence. The one that currently seems most promising also turns out to have the consequence that epistemic akrasia should occur more frequently than (...) is sometimes supposed. But it also helps us see why this might not be a bad thing. (shrink)

Promotion of prescription drugs may appear to be severely limited in some jurisdictions due to restrictions on direct-to-consumer advertising. However, in most jurisdictions, strategies exist to raise consumer awareness about prescription drugs, notably through the deployment of direct-to-consumer information campaigns that encourage patients to seek help for particular medical conditions. In Canada, DTCI is presented by industry and regulated by Health Canada as being purely informational activities, but their design and integration in broader promotional campaigns raise very similar ethical concerns (...) as those associated with DTCA. Specifically, DTCI can be an effective means of familiarizing the public with the scope and benefits of a particular prescription drug and so, like DTCA, can promote increased patient-consumer demand and thus a problematic rise in the prescribing and use of medications that may be neither the most appropriate nor the most cost-effective. Yet, with DTCI the industry is playing within the existing rules and regulations set by health regulators. To respond appropriately to this regulatory incoherence, we argue that DTCI should be regulated as a type of direct-to-consumer indirect advertising. Even if the case and specific regulations presented here are Canadian, the implications extend to every country that has a partial or total prohibition on DTCA. (shrink)

Drugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the safety and efficacy of (...) the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions. (shrink)