Philosophical discussion of the topic of intentional agency has often focused on questions about the nature of the events which are intentional actions. This event-oriented approach cannot yield an adequate account of human agency because it cannot accommodate negative acts, or acts of omission. Agents may act intentionally by omitting to act, but many such acts of omission cannot be identified with any event consisting of a bodily movement. This dissertation is an attempt to develop an account of agency which (...) can accommodate acts of omission. In the course of this, generally accepted views about the causal powers of agents, the ontology of action, the relation between an intention and the act which realizes it and the abilities exercised in acting are challenged. In Chapter One it is argued that causation by acts of omission cannot be explicated in terms of event causation and that the abilities which an agent exercises in intentionally omitting must be analyzed as second order abilities. Views according to which acts of omission are in some way constituted by positive actions are surveyed and criticized in Chapter Two. It is claimed that an agent omits to act by forming a negative intention, but this mental act is not identical to the act of omission. Acts of omission are states of affairs which obtain or facts and are not events. In Chapter Three it is shown that certain positive non-basic acts like killings also cannot be identified with any event because no event could have the requisite temporal and causal properties. Two important differences between positive and negative acts are identified in Chapter Four. The relation between a positive intention and behavior which realizes it is a causal one, but negative intentions do not cause the behavior which realizes them. A person may perform a positive action and may be responsible for this even though he lacks the ability to refrain from doing so, but to omit to perform some action and to be responsible for this, a person must have the ability to perform it. (shrink)

Fluorescence imaging has become an indispensable tool in cell and molecular biology. GFP‐like fluorescent proteins have revolutionized fluorescence microscopy, giving experimenters exquisite control over the localization and specificity of tagged constructs. However, these systems present certain drawbacks and as such, alternative systems based on a fluorogenic interaction between a chromophore and a protein have been developed. While these systems are initially designed as fluorescent labels, they also present new opportunities for the development of novel labeling and detection strategies. This review (...) focuses on new labeling protocols, actuation methods, and biosensors based on fluorogenic protein systems. (shrink)

John Fischer and Mark Ravizza defend in this book a painstakingly constructed analysis of what they take to be a core condition of moral responsibility: the notion of guidance control. The volume usefully collects in one place ideas and arguments the authors have previously published in singly or jointly authored works on this and related topics, as well as various refinements to those views and some suggestive discussions that aim to show how their account of guidance control might fit into (...) a more comprehensive account of moral responsibility. (shrink)

The doctrine (or principle) of double effect is often invoked to explain the permissibility of an action that causes a serious harm, such as the death of a human being, as a side effect of promoting some good end. According to the principle of double effect, sometimes it is permissible to cause a harm as a side effect (or “double effect”) of bringing about a good result even though it would not be permissible to cause such a harm as a (...) means to bringing about the same good end. Does the principle of double effect play the important explanatory role that has been claimed for it? To consider this question, one must be careful to clarify just what the principle is supposed to explain. Three misinterpretations of the principle’s force or range of application are common. 1. To ensure that Double Effect is not misunderstood as principle issuing a blanket permission on causing any unintended harm that yields a benefit, applications must require that the agent seek to minimize the harm involved. 2. Since it is widely accepted that it is wrong to aim to produce harm to someone as an end, to rule this out is not part of double effect’s distinctive content. 3. Harms that were produced regretfully and only for the sake of producing a good end may be prohibited by double effect because they were brought about as part of the agent’s means to realizing the good end. (shrink)

I will introduce six constraints that should guide the formulation and use of DE. One goal in listing them is to engage in dialectical fair play by ruling out criticisms of the doctrine that are directed at misformulations of DE or that result from misapplications of it. Each of these constraints should be acceptable to any proponent of DE. Yet when these constraints on the application of DE are respected, it becomes clear that many of the examples provided as illustrations (...) of DE actually illustrate other, more interesting uses of the contrast between intention and foresight. (shrink)

Many would say that unlike other failures of practical rationality, which can be difficult to recognize, weakness of will wears its rational defect on its sleeve. Whenever we judge that it would be best not to do x, while intentionally doing x without relinquishing this judgment, we condemn quite explicitly the intention on which we act. This observation gives rise to the attractive idea that weak-willed agents indict themselves of irrationality as they fail to comply with their own practical judgments. (...) Weakness of will is often treated as the paradigm of practical irrationality just because of the explicit and quasi-logical form of incoherence in the weak-willed or akratic agent’s attitudes. Underpinning this idea is the assumption that practical rationality can be characterized as a kind of executive capacity that produces congruence between judgment and action by ensuring that practical judgments are faithfully enacted. Some are happy to call this capacity the will, so that the label “weakness of will” is literally true. I will argue against both of these assumptions. (shrink)

Hume’s discussion of pride and sympathy in the _Treatise_ shows direct engagement with Malebranche’s discussion of ‘imitation’ in the _Search_. For Malebranche, imitation—both of passions and belief—and our tendency to judge ourselves by comparison, generate the passion of pride or grandeur, which plays a useful social role. However, as both cause and effect of the admiration of others, grandeur is ungrounded and thus imaginary. Hume disagrees. He invokes the principle of sympathy to explain how the evaluations of others can support (...) pride by indicating, without constituting, grounds for pride. Hume’s argument depends on his underappreciated claim that sympathy can communicate the evaluative opinions as well as the passions of others. Working with the Malebranchean inventory of principles—sympathy and comparison—Hume refines their characterization, thereby redeeming the human tendency to feel pride and humility by characterizing it as corrigible and subject to social regulation. (shrink)

Familiarity with the doctrines presented in Richard Allestree’s devotional work The Whole Duty of Man (1658), which Hume reported having read as a boy, can illuminate the strategy of argument Hume employs in Treatise 2.1.6–2.1.8 to undermine views he attributes to “the vulgar systems of ethicks.” Hume’s explicit critique of the view that pride is a sin and humility a virtue in Treatise 2.1.7 relies on assumptions that are already present in Allestree’s account of pride and humility and are described (...) using similar language. Sections 6–8 of Treatise 2.1 also provide an implicit critique of Allestree’s attempts to induce a general stance of humility based on mortifying considerations about human nature and to inspire episodes of penitential humility for the sins of the day. I argue that the “limitations to this account” gathered together in 2.1.6 are placed there to set up this critique. Together, the limitations imply that defects in our personal character are sufficiently close to us, peculiar to us, discernible to others, of appropriate duration, and supported by general rules to generate the passion of humility when we reflect on them, while reflection on human nature in general and particular episodes of sin are not. (shrink)

Public disclosure of industry payments to physicians is one way to address financial conflicts of interest in medicine. As part of the Patient Protection and Affordable Care Act, the Physician Payment Sunshine Act requires pharmaceutical, medical device, and biologics manufacturers who have at least one product reimbursed by Medicare or Medicaid to disclose payments to physicians and teaching hospitals on a public website starting in 2014. The physician payment data will contain individual physician names, monetary values, and specific products connected (...) to payments.According to the Final Regulations issued by the Centers for Medicare and Medicaid Services in February 2013, the law will make transparent the extent and nature of relationships between physicians, teaching hospitals, and manufacturers. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

IntroductionThe pelvic floor muscles are active during motor tasks that increase intra-abdominal pressure, but little is known about how the PFM respond to dynamic activities, such as gait. The purpose of this study was to characterize and compare PFM activity during walking and jogging in continent adults across the entire gait cycle.Methods17 able-bodied individuals with no history of incontinence participated in this study. We recorded electromyography from the abdominal muscles, gluteus maximus, and PFM while participants performed attempted maximum voluntary contractions (...) of all muscles and completed 60–70 strides in four gait conditions: slow walk ; regular walk ; transition walk ; jog. We quantified activity throughout the whole gait cycle and during periods of bursting for each participant, and analyzed the timing of PFM bursting periods to explore when the PFM were most active in the gait cycle. We also conducted a phase metric analysis on the PFM and GM burst timings. We performed a Spearman's rank-order correlation to examine the effect of speed on %aMVCGC, %aMVCBR, and phase metric score, and used the Wilcoxon Signed-Rank test to evaluate the effect of gait modality, matched for speed, on these variables.ResultsThe PFM were active throughout the gait cycle, with bursts typically occurring during single-leg support. The PFM and GM were in phase for 44–69% of the gait cycle, depending on condition. There was a positive correlation between gait speed and both %aMVCGC and %aMVCBR. Phase metric scores were significantly higher during jogging than transition walking, but there was no difference between gait modality on %aMVCGC or %aMVCBR. Where possible we disaggregated data by sex, although were unable to make statistical comparisons due to low sample sizes.ConclusionThe PFM are active during walking and jogging, with greater activity at faster speeds and with bursts in activity around single-leg support. The PFM and GM co-activate during gait, but are not completely in phase with each other. (shrink)

Book 1 of Hume’s A Treatise of Human Nature was reshaped into the first Enquiry, while the second Enquiry further develops some themes from Book 3. What became of Book 2, “Of the Passions”? Did Hume never extend his thinking in that area? Amyas Merivale notes that the standard answer to that question is that Hume did not do much in the way of rethinking T2 beyond selecting a few passages to excerpt, almost verbatim, in his “Dissertation on the Passions.” (...) In this fine, wide-ranging, scrupulously researched and carefully argued book, Merivale offers a more intriguing and satisfying answer: the essays collected in the Four Dissertations, “The Natural History of Religion”, “Of the Passions”... (shrink)

BackgroundMulti-centre studies generally cost more than single-centre studies because of larger sample sizes and the need for multiple ethical approvals. Multi-centre studies include clinical trials, clinical quality registries, observational studies and implementation studies. We examined the costs of two large Australian multi-centre studies in obtaining ethical and site-specific approvals.MethodsWe collected data on staff time spent on approvals and expressed the overall cost as a percent of the total budget.ResultsThe total costs of gaining approval were 38 % of the budget for (...) a study of 50 centres (mean cost AUD $6960 per site) and 2 % for a study of 11 centres (mean cost AUD $2300 per site). Seventy-five and 90 % of time was spent on repeated tasks, respectively, and many time-consuming tasks, such as reformatting documents, did nothing to improve the study design or participant safety.ConclusionsImprovements have been made to the ethical approval application system, but more gains could be made without increasing risks of harm to research participants. We propose that ethical review bodies and individual sites publish statistics on how long they take to process approvals which could then be nationally benchmarked. (shrink)

This collection, the first of its kind, brings together specially commissioned academic essays to mark fifty years since the death of John Kennedy Toole.

The HealthyFood program offers members up to 25% cash back monthly on healthy food purchases. In this randomized controlled trial, we tested the efficacy of financial incentives combined with text messages in increasing healthy food purchases among HF members. Members receiving the lowest cash back level were randomized to one of six arms: Arm 1 : 10% cash back, no weekly text, standard monthly text; Arm 2: 10% cash back, generic weekly text, standard monthly text; Arm 3: 10% cash back, (...) personalized weekly text, standard monthly text; Arm 4: 25% cash back, personalized weekly text, standard monthly text; Arm 5: 10 + 15%NET cash back, personalized weekly text, standard monthly text; and, Arm 6: 10 + 15%NET cash back, personalized weekly text, unbundled monthly text. In the 10 + 15%NET cash back, the cash back amount was the baseline 10% plus 15% of the net difference between healthy and unhealthy spending. The generic text included information on HF and healthy eating, while the personalized text had individualized feedback on purchases. The standard monthly text contained the cash back amount. The unbundled monthly text included the amount lost due to unhealthy purchases. The primary outcome was the average monthly percent healthy food spending. Secondary outcomes were the percent unhealthy food spending, and the percent healthy and unhealthy food items. Of the members contacted, 20 opted out, and 2841 met all inclusion criteria. There were no between-arm differences in the examined outcomes. The largest mean difference in percent healthy spending was between Arm 1 and Arm 2, and the largest mean difference in percent unhealthy spending was also between Arm 1 and Arm 2, but no differences were statistically significant after correction for multiple comparisons. None of the tested financial incentive structures or text strategies differentially affected food purchasing. Notably, more than doubling the cash back amount and introducing a financial disincentive for unhealthy purchases did not affect purchasing. These findings speak to the difficulty of changing shopping habits and to the need for innovative strategies to shift complex health behaviors. NCT02486588 Increasing Engagement with a Healthy Food Benefit. The trial was prospectively registered on July 1, 2015. (shrink)

A collection of personal narratives and essays, Living Professionalism is designed to help medical students and residents understand and internalize various aspects of professionalism. These essays are meant for personal reflection and above all, for thoughtful discussion with mentors, with peers, with others throughout the health care provider community who care about acting professionally.

Three major aspects of G1 regulation acting at START in fission yeast are discussed in this review. Firstly, progression towards S phase in the mitotic cycle. This is controlled by the activation of transcription complexes at START which cause cell cycle‐dependent activation of genes required for DNA synthesis. The second aspect is the regulation of developmental fate occurring during G1. Passage through START appears to inhibit sexual differentiation because the meiotic and mitotic pathways are mutually exclusive. This is brought about (...) because the meiotic pathway is inhibited by the same gene functions that are required for S phase onset. Thirdly, distinct checkpoint, or dependency, controls operate both pre‐ and post‐START in the mitotic cycle to inhibit mitosis in the absence of replicated DNA, and also to limit rounds of DNA replication to one per cell cycle. (shrink)

Intermediate filaments (IFs) formed by vimentin are less understood than their cytoskeletal partners, microtubules and F‐actin, but the unique physical properties of IFs, especially their resistance to large deformations, initially suggest a mechanical function. Indeed, vimentin IFs help regulate cell mechanics and contractility, and in crowded 3D environments they protect the nucleus during cell migration. Recently, a multitude of studies, often using genetic or proteomic screenings show that vimentin has many non‐mechanical functions within and outside of cells. These include signaling (...) roles in wound healing, lipogenesis, sterol processing, and various functions related to extracellular and cell surface vimentin. Extracellular vimentin is implicated in marking circulating tumor cells, promoting neural repair, and mediating the invasion of host cells by viruses, including SARS‐CoV, or bacteria such as Listeria and Streptococcus. These findings underscore the fundamental role of vimentin in not only cell mechanics but also a range of physiological functions. Also see the video abstract here https://youtu.be/YPfoddqvz-g. (shrink)

George G. Simpson (1902–1984) and Stephen J. Gould (1941–2002) were both engaged with the normative – i.e., social, cultural, political, and even ethical – consequences of their evolutionary theorizing. However, there is a normative point of departure between Simpson and Gould’s work in that regard that has received little attention. Yet, their motivations converge into a larger program of resistance and social protection from misconstrued and illegitimate overreaches of the biological sciences leading up to and after the peak of the (...) modern synthesis. (shrink)