This paper presents Integrated Information Theory (IIT) 4.0. IIT aims to account for the properties of experience in physical (operational) terms. It identifies the essential properties of experience (axioms), infers the necessary and sufficient properties that its substrate must satisfy (postulates), and expresses them in mathematical terms. In principle, the postulates can be applied to any system of units in a state to determine whether it is conscious, to what degree, and in what way. IIT offers a parsimonious explanation of (...) empirical evidence, makes testable predictions, and permits inferences and extrapolations. IIT 4.0 incorporates several developments of the past ten years, including a more accurate translation of axioms into postulates and mathematical expressions, the introduction of a unique measure of intrinsic information that is consistent with the postulates, and an explicit assessment of causal relations. By fully unfolding a system's irreducible cause-effect power, the distinctions and relations specified by a substrate can account for the quality of experience. (shrink)

The faults of logical empiricist accounts of metascientific discourse are examined through a study of the modifications Carnap makes to his version of the program over four decades. As empiricists acquiesced on the distinction between theory and observation, Carnap attempted to retain and insulate an equally suspect sharp distinction between the theoretic and the pragmatic. Carnap's later philosophy was understood as a modification of the program in the direction of pragmatism. But neither the key notion of "external questions" nor an (...) instrumentalist understanding of "pragmatic utility" are genuinely compatible with pragmatism. This underlines the need to clarify what is unique to pragmatic views of cognitive evaluation and normative discourse as they affect scientific reasoning. I conclude by suggesting how pragmatic conceptions of metascientific discourse can work to correct misconceptions about norm generation and governance that are shared in logicist and historicist accounts. (shrink)

Context The attitudes of medical professionals towards physician assisted dying have been widely discussed. Less explored is the level of agreement among physicians on the possibility of ‘rational suicide’—a considered suicide act made by a sound mind and a precondition of assisted dying legislation. Objective To assess attitudes towards rational suicide in a representative sample of senior doctors in England and Wales. Methods A postal survey was conducted of 1000 consultants and general practitioners randomly selected from a commercially available database. (...) The main outcome of interest was level of agreement with a statement about rational suicide. Results The corrected participation rate was 50%; 363 questionnaires were analysed. Overall 72% of doctors agreed with the possibility of rational suicide, 17% disagreed, and 11% were neutral. Doctors who identified themselves as being more religious were more likely to disagree. Some doctors who disagreed with legalisation of physician assisted suicide nevertheless agreed with the concept of rational suicide. Conclusions Most senior doctors in England and Wales feel that rational suicide is possible. There was no association with specialty. Strong religious belief was associated with disagreement, although levels of agreement were still high in people reporting the strongest religious belief. Most doctors who were opposed to physician assisted suicide believed that rational suicide was possible, suggesting that some medical opposition is best explained by other factors such as concerns of assessment and protection of vulnerable patients. (shrink)

This book traces the intellectual revolution initiated by Thales in the sixth century BC to its culmination in the metaphysics of Parmenides.

Koonin, in an article in this issue, claims that CRISPR–Cas systems are mechanisms for the inheritance of acquired adaptive characteristics, and that the operation of such systems comprises a “Lamarckian mode of evolution.” We argue that viewing the CRISPR–Cas mechanism as facilitating a form of “directed mutation” more accurately represents how the system behaves and the history of neoDarwinian thinking, and is to be preferred.

BackgroundThe proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children.MethodsWe conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following (...) electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report.ResultsOf the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in researchConclusionResearchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV. (shrink)

This Is A New Release Of The Original 1922 Edition.

Drug Safety Communications are used by the Food and Drug Administration to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone (...) between July 1, 2012 and June 30, 2013. Among the 594 respondents, two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited. Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep and seek out more information about the safety of their specific sleeping pill. Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications. (shrink)

Aims: To describe individuals’ perceptions of the activities that take place within the cancer genetics clinic, the relationships between these activities and how these relationships are sustained. Design: Qualitative interview study. Participants: Forty individuals involved in carrying out cancer genetics research in either a clinical (n = 28) or research-only (n = 12) capacity in the UK. Findings: Interviewees perceive research and clinical practice in the subspecialty of cancer genetics as interdependent. The boundary between research and clinical practice is described (...) as vague or blurred, and this ambiguity is regarded as being sustained by a range of methodological, ethical and economic factors. The implications of these findings for the “therapeutic misconception” are explored. It is argued that while research participation is seen as having therapeutic benefit for individual patients, the interviewees are not labouring under any misconceptions about the relationship between research and clinical care. It is suggested that concepts such as the “therapeutic misconception” may have less relevance in highly technological specialities that are characterised by a developing evidence base. (shrink)

One of the curious things about Homeric studies is the way in which, although opinions in this field fluctuate violently, from time to time certain among them tend to become crystallized for no particular reason and are then accepted as something approaching orthodoxy. It is to try to delay such a crystallization, if it is not already too late, that I direct this brief coup d'ail at some current opinions on whether Homer—for the sake of clarity I apply this name (...) in the first instance to the monumental composer of the Iliad—used the aid of writing, and in general at the value of comparative inferences based on the heroic poetry of modern Yugoslavia. (shrink)

Logopenic variant primary progressive aphasia is a neurodegenerative language disorder primarily characterized by impaired phonological processing. Sentence repetition and comprehension deficits are observed in lvPPA and linked to impaired phonological working memory, but recent evidence also implicates impaired speech perception. Currently, neural encoding of the speech envelope, which forms the scaffolding for perception, is not clearly understood in lvPPA. We leveraged recent analytical advances in electrophysiology to examine speech envelope encoding in lvPPA. We assessed cortical tracking of the speech envelope (...) and in-task comprehension of two spoken narratives in individuals with lvPPA and age-matched controls. Despite markedly reduced narrative comprehension relative to controls, individuals with lvPPA had increased cortical tracking of the speech envelope in theta oscillations, which track low-level features, but not delta oscillations, which track speech units that unfold across a longer time scale. This neural signature was highly correlated across narratives. Results indicate an increased reliance on acoustic cues during speech encoding. This may reflect inefficient encoding of bottom-up speech cues, likely as a consequence of dysfunctional temporoparietal cortex. (shrink)

“Nocebo,” a term coined in the mid-twentieth century, refers to the onset of negative side effects in individuals who anticipate harm from biomedical treatment. Sylvia Wynter invokes nocebo effects as racializing phenomena that demonstrate the injurious impact of colonial practices. By soliciting insights from Nocebo Studies, as well as Wynter and Achille Mbembe, this article explores decolonial philosophies of selfhood, especially in terms of the meaning-making expressivity of selves. This conversation between Nocebo Studies and Wynter proffers ways to engage with (...) nocebo effects as mani-festations of the structures of colonial violence, while undercutting biomedical accounts of nocebos that presuppose an overly generic human body. (shrink)

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits (...) can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w. (shrink)

In [10] Friedman showed that is a conservative extension of <ε0for-sentences wherei= min, i.e.,i= 2, 3, 4 forn= 0, 1, 2 +m. Feferman [5], [7] and Tait [11], [12] reobtained this result forn= 0, 1 and even with instead of. Feferman and Sieg established in [9] the conservativeness of over <ε0for-sentences for alln. In each paper, different methods of proof have been used. In particular, Feferman and Sieg showed how to apply familiar proof-theoretical techniques by passing through languages with Skolem (...) functionals.In this paper we study the same choice principles in the presence of theBar Rule, which permits one to infer the scheme of transfinite induction on a primitive recursive relation ≺ when it has been proved that ≺ is wellfounded. The main result characterizes + as a conservative extension of a system of the autonomously iterated-comprehension axiom for-sentences. Forn= 0 this has been proved by Feferman in the form that + is a conservative extension of <Γ0; this was first done in [8] by use of the Gödel functional interpretation for the stronger systemZω+μ+ + and then more recently by the simpler methods of [9]. Jäger showed how the latter methods could also be used to obtain the general result of Theorem 1 below. (shrink)

It seems very commonly agreed that Sappho's wedding-songs display none of the ritual obscenity so frequent in the genre. Thus D. L. Page wrote of fr. i ioa that ‘There is no trace here or elsewhere in Sappho of that ribaldry which was characteristic of the songs recited at this and other stages of Greek wedding-ceremonies’. Similarly Sir Maurice Bowra asserted of fr. 111 that it is ‘neither bawdy nor exalted, but playful. If the humour is a bit primitive, that (...) is due to tradition, which expected jokes at this level’. On the next page he writes of the songs sung outside the bridal chamber, as distinct from those sung in the procession thither, that ‘Here too Sappho seems to avoid bawdry but is not averse from rather elementary jokes’. (shrink)