Over the past decade, the number of clinical trials registered with the Food and Drug Administration has increased dramatically. The business of clinical research has become more diverse, involving academic institutions, clinician-researchers in community settings, pharmaceutical companies, and contract research organizations. This growth has been accompanied by increasing concerns about the ethical conduct of research. Much of this concern has been directed to procedural issues including institutional review board review, data monitoring, and informed consent forms. However, the protection of human (...) subjects cannot be achieved by relying solely on procedural safeguards. There are more nuanced issues related to recruitment and retention of subjects, and to the process of informed consent, that are generated during the interaction between study staff and subjects. It is only through an examination of these relationships that one can more fully define and understand the challenges of protecting subjects in research. (shrink)

Large-scale sequencing tests, including whole-exome and whole-genome sequencing, are rapidly moving into clinical use. Sequencing is already being used clinically to identify therapeutic opportunities for cancer patients who have run out of conventional treatment options, to help diagnose children with puzzling neurodevelopmental conditions, and to clarify appropriate drug choices and dosing in individuals. To evaluate and support clinical applications of these technologies, the National Human Genome Research Institute and National Cancer Institute have funded studies on clinical and research sequencing under (...) the Clinical Sequencing Exploratory Research program as well as studies on return of results. Most of these studies use sequencing in real-world clinical settings and collect data on both the application of sequencing and the impact of receiving genomic findings on study participants. They are occurring in the context of controversy over how to obtain consent for exome and genome sequencing. (shrink)

'Ugly as sin', 'ugly duckling', 'rear its ugly head'. The word 'ugly' is used freely, yet it is a loaded term: from the simply plain and unsightly to the repulsive and even offensive, definitions slide all over the place. Hovering around 'feared and dreaded', ugliness both repels and fascinates. But the concept of ugliness has a lineage that has long haunted our cultural imagination. Gretchen E. Henderson explores perceptions of ugliness through history, from ancient Roman feasts to medieval grotesque (...) gargoyles, from Mary Shelley's monster cobbled from corpses to the Nazi Exhibition of Degenerate Art. Covering literature, art, music and even Uglydolls, Henderson reveals how ugliness has long posed a challenge to aesthetics and taste. Henderson digs into the muck of ugliness, moving beyond the traditional philosophic argument or mere opposition to beauty, and emerges with more than a selection of fascinating tidbits. Following ugly bodies and dismantling ugly senses across periods and continents, [this book] draws on a wealth of fields to cross cultures and times, delineating the changing map of ugliness as it charges the public imagination. Illustrated with a range of artefacts, this book offers a refreshing perspective that moves beyond the surface to ask what 'ugly' truly is, even as its meaning continues to shift. (shrink)

Reliablists have argued that the important evaluative epistemic concept of being justified in holding a belief, at least to the extent that that concept is associated with knowledge, is best understood as concerned with the objective appropriateness of the processes by which a given belief is generated and sustained. In particular, they hold that a belief is justified only when it is fostered by processes that are reliable (at least minimally so) in the believer’s actual world.[1] Of course, reliablists typically (...) recognize other concepts of justification--typically subjective notions--which are given a noncompeting sort of epistemic legitimacy. However, they have tended to focus on the epistemically central notion of "strong justification," and have come to settle on this familiar reliablist analysis, supposing that it pretty much exhausts what there is to say about "objective justification.". (shrink)

Striking similarities across ape gestural repertoires suggest shared phylogenetic origins that likely provided a foundation for the emergence of language. We pilot a novel approach for exploring possible semantic universals across human and nonhuman ape species. In a forced‐choice task, n = 300 participants watched 10 chimpanzee gesture forms performed by a human and chose from responses that paralleled inferred meanings for chimpanzee gestures. Participants agreed on a single meaning for nine gesture forms; in six of these the agreed form‐meaning (...) pair response(s) matched those established for chimpanzees. Such shared understanding suggests apes' (including humans') gesturing shares deep evolutionary origins. (shrink)

In much the same way that genomic technologies are changing the complexion of biomedical research, the issues they generate are changing the agenda of IRBs and research ethics. Many of the biggest challenges facing traditional research ethics today — privacy and confidentiality of research subjects; ownership, control, and sharing of research data; return of results and incidental findings; the relevance of group interests and harms; the scope of informed consent; and the relative importance of the therapeutic misconception — have become (...) important policy issues over the last 20 years because of the ways they have been magnified by genomic research efforts. Research that examines the ethical, legal, and social implications of human genomics research has become a burgeoning international field of scholarship over the last 20 years, thanks in part to its support first by the genome research funding bodies in the U.S. and then by national science agencies in other countries. (shrink)

A paradigmatic aspect of a paradigmatic kind of right is that the rights holder is the only one who can alienate it. When individuals waive rights, the normative source of that waiving is normally taken to be the individual herself. This moral feature?immunity?is usually in the background of discussions about rights. We bring it into the foreground here, with specific attention to a recent U.S. Supreme Court decision, Kentucky v. King (2011), concerning search and seizure rights. An entailment of the (...) Court's decision is that, at least in some cases, a right can be removed by the intentional actions of the very party against whom the right supposedly protects the rights holder. We argue that the Court's decision is mistaken. The police officers in the case were not morally permitted, and should not be legally permitted, to intentionally create the very circumstances that result in the removal of an individual's right against forced, warrantless search and seizure. (shrink)

In this target article by Morain and Largent (2023), the authors focus on an investigator’s duty to patient-subjects specifically regarding incidental or collateral findings within the context of e...

           Eliminative materialism, as William Lycan (this volume) tells us, is materialism plus the claim that no creature has ever had a belief, desire, intention, hope, wish, or other “folk-psychological†state. Some contemporary philosophers claim that eliminative materialism is very likely true. They sketch certain potential scenarios, for the way theory might develop in cognitive science and neuroscience, that they claim are fairly likely; and they maintain that if such scenarios (...) turned out to be the truth about humans, then eliminative materialism would be true.            Broadly speaking, there are two ways to reply to such arguments, for those who maintain that eliminative materialism is false (or that the likelihood of its being true is very low). One way is to argue that the scenarios the eliminativists envision are themselves extremely unlikely—that we can be very confident, given what we now know (including nontendentious scientific knowledge), that those scenarios will not come to pass. The other is to argue that even if they did come to pass, this would not undermine common-sense psychology anyway. People would still have beliefs, etc. The two strategies are not incompatible; one could pursue them both. But the second strategy attacks eliminativism at a more fundamental level. And if it can be successfully carried out, then the dialectical state of play will be strikingly secure for folk psychology. For, then it will turn out that folk psychology simply is not hostage to the kinds of potential empirical-theoretical developments that the eliminativists envision. It doesn’t matter, as far as the integrity of folk psychology is concerned, whether or not such scenarios are likely to come to pass. Eliminativist arguments inevitably rely, often only implicitly, on certain assumptions about what it takes for a creature to have beliefs, desires, and other folk-psychological states—assumptions about some alleged necessary condition(s) for being a true believer (to adapt this colorful usage from Dennett 1987). (shrink)

Determination of the structure of the nucleic acids involved inter alia identification of the ring atom of the purines to which ribose or deoxyribose was attached. This in turn depended on knowledge of the ring atoms that could be so substituted and hence that were bonded to replaceable hydrogens. In 1897 E. Fischer adopted a convention of depicting this hydrogen at position 7 of the purine ring, although he was aware that it was equally correct to depict it at position (...) 9. Many later workers apparently came to believe that the 7H structure was more than just a convention, and considered that the sugar was attached solely at position 7 and could not be attached to position 9. When evidence was presented in 1933 that the sugar was in fact attached to position 9, the force of this convention apparently was so strong that many were reluctant to accept this evidence. More than 20 years was required for complete acceptance of the new view, and Fischer's convention was still being used in other contexts until at least 1967. (shrink)

Potts (2005) and many subsequent works have argued that the semantic content of appositive (non-restrictive) relative clauses, e.g., the underlined material in John, who nearly killed a woman with his car, visited her in the hospital, must be in some way separate from the content of the rest of the sentence, i.e., from at-issue content. At the same time, there is mounting evidence from various anaphoric processes that the two kinds of content must be integrated into a single, incrementally evolving (...) semantic representation. The challenge is how to reconcile this informational separation with these pervasive anaphoric connections. We propose a dynamic semantic account that accomplishes this by taking appositive and at-issue content to involve two different kinds of updates to the Context Set (CS). Treating the context set as a distinguished propositional variable, pcs, we argue that appositives directly impose their content on the CS by eliminating possible values assigned to pcs. In contrast, we treat at-issue assertions as introducing a new propositional dref and proposing that pcs be updated with its content, subject to addressee's response. In addition to capturing the behavior of appositives in discourse, we show that the account can be extended to capture the projection of appositive content past various sentential operators. (shrink)

We propose an approach to epistemic justification that incorporates elements of both reliabilism and evidentialism, while also transforming these elements in significant ways. After briefly describing and motivating the non-standard version of reliabilism that Henderson and Horgan call “transglobal” reliabilism, we harness some of Henderson and Horgan’s conceptual machinery to provide a non-reliabilist account of propositional justification (i.e., evidential support). We then invoke this account, together with the notion of a transglobally reliable belief-forming process, to give an account (...) of doxastic justification. (shrink)

I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University (...) (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

THE PASSAGE CITED IN THE TITLE IS commonly said to deal with puzzles or paradoxes about size and other measurable attributes of bodies. Nearly all recent commentators seek to interpret this portion of the dialogue as supporting or otherwise cohering with the Protagorean position Socrates expounds in the Theaetetus. On the present analysis, however, the support or harmony is mere appearance. The puzzles Socrates brings up are indeed associated with entities rejected by Protagoras. Socrates certainly uses the puzzles to foster (...) Theaetetus's trust in Protagorean doctrine. All the same, Socrates' procedure should not be taken at face value. The passage, which is an important digression, is fundamentally quite critical of the Protagorean position. (shrink)

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 1242-1701 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 1702-2198 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 2199-2664 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 2665-3286 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 3287-3648 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

The foundation of the Christian counselling movement -- Christian counselling in the UK -- The aims of Christian counselling -- Integrating psychological and biblical truth -- Sigmund Freud--the founding father of psychotherapy -- The individual psychology of Alfred Adler -- Abraham Maslow--the man with new age tendencies -- Carl Rogers--a man who believed in himself -- Albert Ellis--the aggressive atheist -- The Bible's verdict on psychological 'truth' -- The case against Larry Crabb -- Self-esteem: the secular foundation -- Self-esteem and (...) the Christian counselling movement -- Self-esteem dogma in the light of scripture. (shrink)

An introductory work on the various school of Indian philosophy.

On the life of Mādhava, d. 1386, exponent of Dvaita philosophy.