Hypnotics' association with mortality or cancer: a matched cohort study

Objectives: An estimated 6%e10 % of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality. Setting: A large integrated health system in the USA. Design: Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis. Subjects: Subjects (mean age 54 years) were 10 529 patients who received hypnotic prescriptions and 23 676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 year

Proving Craig and Lyndon Interpolation Using Labelled Sequent Calculi

We have recently presented a general method of proving the fundamental logical properties of Craig and Lyndon Interpolation (IPs) by induction on derivations in a wide class of internal sequent calculi, including sequents, hypersequents, and nested sequents. Here we adapt the method to a more general external formalism of labelled sequents and provide sufficient criteria on the Kripke-frame characterization of a logic that guarantee the IPs. In particular, we show that classes of frames definable by quantifier-free Horn formulas correspond to logics with the IPs. These criteria capture the modal cube and the infinite family of transitive Geach logics

Teleological Essentialism

Placeholder essentialism is the view that there is a causal essence that holds category members together, though we may not know what the essence is. Sometimes the placeholder can be filled in by scientific essences, such as when we acquire scientific knowledge that the atomic weight of gold is 79. We challenge the view that placeholders are elaborated by scientific essences. On our view, if placeholders are elaborated, they are elaborated Aristotelian essences, a telos. Utilizing the same kinds of experiments used by traditional essentialists—involving superficial change (study 1), transformation of insides (study 2), acquired traits (study 3) and inferences about offspring (study 4)—we find support for the view that essences are elaborated by a telos. And we find evidence (study 5) that teleological essences may generate category judgments

Cd40–Cd40 Ligand Interactions in Vivo Regulate Migration of Antigen-Bearing Dendritic Cells from the Skin to Draining Lymph Nodes

Whereas CD40–CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand −/− mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand −/− mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand −/− mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-α production and was corrected by injecting recombinant TNF-α or an agonistic anti-CD40 monoclonal antibody. Thus, CD40–CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-α production and play a vital role in the initiation of acquired T cell–mediated immunity

The Explication Defence of Arguments from Reference

In a number of influential papers, Machery, Mallon, Nichols and Stich have presented a powerful critique of so-called arguments from reference, arguments that assume that a particular theory of reference is correct in order to establish a substantive conclusion. The critique is that, due to cross-cultural variation in semantic intuitions supposedly undermining the standard methodology for theorising about reference, the assumption that a theory of reference is correct is unjustified. I argue that the many extant responses to Machery et al.’s critique do little for the proponent of an argument from reference, as they do not show how to justify the problematic assumption. I then argue that it can in principle be justified by an appeal to Carnapian explication. I show how to apply the explication defence to arguments from reference given by Andreasen (for the biological reality of race) and by Churchland (against the existence of beliefs and desires)

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p < 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival

How to find an attractive solution to the liar paradox

The general thesis of this paper is that metasemantic theories can play a central role in determining the correct solution to the liar paradox. I argue for the thesis by providing a specific example. I show how Lewis’s reference-magnetic metasemantic theory may decide between two of the most influential solutions to the liar paradox: Kripke’s minimal fixed point theory of truth and Gupta and Belnap’s revision theory of truth. In particular, I suggest that Lewis’s metasemantic theory favours Kripke’s solution to the paradox over Gupta and Belnap’s. I then sketch how other standard criteria for assessing solutions to the liar paradox, such as whether a solution faces a so-called revenge paradox, fit into this picture. While the discussion of the specific example is itself important, the underlying lesson is that we have an unused strategy for resolving one of the hardest problems in philosophy

A Functional Naturalism

I provide two arguments against value-free naturalism. Both are based on considerations concerning biological teleology. Value-free naturalism is the thesis that both (1) everything is, at least in principle, under the purview of the sciences and (2) all scientific facts are purely non-evaluative. First, I advance a counterexample to any analysis on which natural selection is necessary to biological teleology. This should concern the value-free naturalist, since most value-free analyses of biological teleology appeal to natural selection. My counterexample is unique in that it is likely to actually occur. It concerns the creation of synthetic life. Recent developments in synthetic biology suggest scientists will eventually be able to develop synthetic life. Such life, however, would not have any of its traits naturally selected for. Second, I develop a simple argument that biological teleology is a scientific but value-laden notion. Consequently, value-free naturalism is false. I end with some concluding remarks on the implications for naturalism, the thesis that (1). Naturalism may be salvaged only if we reject (2). (2) is a dogma that unnecessarily constrains our conception of the sciences. Only a naturalism that recognizes value-laden notions as scientifically respectable can be true. Such a naturalism is a functional naturalism