Superoxide is produced by a NADPH oxidase of phagocytic cells and contributes to their microbicidal activities. The oxidase is activated when receptors in the neutrophil plasma membrane bind to the target microbe. These receptors recognise antibodies and complement fragments which coat the target cell. The oxidase electron transport chain, located in the plasma membrane, comprises a low potential cytochrome b heterodimer (gp 91‐phox and p22‐phox) associated with FAD. It is non‐functional until at least three proteins, p67‐phox, p47‐phox and p21rac (and (...) possibly others), move from the cytosol to dock on the cytochrome b. The docking involves the interaction of SH3 domains may become exposed follwoing phosphorylation of p47‐phox by protein kinase C or, in model systems, by addition of arachidonic acid to reconstitution mixtures. Following the docking process the electron‐transporting component is able to transfer electrons from NADPH to oxygen. This electrogenic event is charge‐compensated by the opening of a prton channel. Components of the oxidase are expressed in non‐phagocytes, where their function is uncretain but could be related to some signal function of superoxide. (shrink)

During the past decade and a half, the field of family literacy has gone from its infancy on the educational periphery toward a position closer to the mainstream. Characteristic ofthe field’s growth is the nation’s largest endeavor in family literacy, the federal Even Start program, which began from scratch in the late 1980s and now claims more than 800 local programs in 50 states and Puerto Rico.Despite several national evaluations of Even Start, no comprehensive study in the family literacy literature (...) specifically focuses on this quarter-billion dollar program’s attempts to measure the progress of its adult students. Accordingly, this study sought to discover the ways in which adult assessment is performed by Even Start programs.This essay emphasizes critical thinking with regards to assessment in Even Start programs Critical thought and reflection drive the exploration of several themes in the study’s data that carry itnplications for the families served by Even Start. These implications, gleaned from what Brookfield (1987) calls “reflective skepticism” and careful study of the data, bring the survey’s numbers to life and ultimately yield useful, potentially program-enhancing information.The article offers background on family literacy and Even Start programs and briefly illustrates the study’s methodology. Then follows a discourse that views the study’s findings through the lens of critical thought, drawing meaning from selected findings that contain repercussions for Even Start families. The piece concludes with recommendations for the improvement of Even Start programs through enhanced assessment and continued study. (shrink)

Heidegger’s position on the relation of the holy and the divine to the truth of being and the possible signification of the word ‘God’ is internally related to his understanding of truth as a double-concealment. Formal indication holds the key to this internal relation. The question of how the deity enters into philosophy forms the framework within which these thoughts are developed.

Futile medical interventions have virtually no chance of success. Doctors might perform such procedures because of pressure from families or patients. The doctor might also have an ulterior motive of gain or prefer to do it rather than take time to communicate with the patient about a poor prognosis. Established ways to communicate bad news to patients are not always used by managing physicians with time constraints. The SPIKES protocol method is outlined to assist in sensitive communication where further intervention (...) is futile. This review primarily explores various aspects of medical futility. It also explores strategies for effectively communicating with patients and their families regarding futility interventions. A side-effect of futile interventions is burnout in doctors and other health practitioners (HPs). The complex relationship between futility and burnout is described. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

In addition to considering sociocultural, political, economic, and ethical factors, effectively engaging socioscientific issues requires that students understand and apply scientific explanations and the nature of science. Promoting such understandings can be achieved through immersing students in authentic real-world contexts where the SSI impacts occur and teaching those students about how scientists comprehend, research, and debate those SSI. This triangulated mixed-methods investigation explored how 60 secondary students’ trophic cascade explanations changed through their experiencing place-based SSI instruction focused on the Yellowstone (...) wolf reintroduction, including scientists’ work and debates regarding that issue. Furthermore, this investigation determined the association between the students’ post place-based SSI instruction trophic cascade explanations and NOS views. Findings from this investigation demonstrate that through the place-based SSI instruction students’ trophic cascade explanations became significantly more accurate and complex and included more ecological causal mechanisms. Also, significant and moderate to moderately large correlations were found between the accuracy and contextualization of students’ post place-based SSI instruction NOS views and the complexity of their trophic cascade explanations. Empirical substantiation of the association between the complexity of students’ scientific explanations and their NOS views responds to an understudied area in the science education research. It also encourages the consideration of several implications, drawn from this investigation’s findings and others’ prior work, which include the need for NOS to be forefront alongside and in connection with science content in curricular standards and through instruction focused on relevant and authentic place-based SSI. (shrink)

The increasing availability of passively observed data has yielded a growing interest in “data fusion” methods, which involve merging data from observational and experimental sources to draw causal conclusions. Such methods often require a precarious tradeoff between the unknown bias in the observational dataset and the often-large variance in the experimental dataset. We propose an alternative approach, which avoids this tradeoff: rather than using observational data for inference, we use it to design a more efficient experiment. We consider the case (...) of a stratified experiment with a binary outcome and suppose pilot estimates for the stratum potential outcome variances can be obtained from the observational study. We extend existing results to generate confidence sets for these variances, while accounting for the possibility of unmeasured confounding. Then, we pose the experimental design problem as a regret minimization problem subject to the constraints imposed by our confidence sets. We show that this problem can be converted into a concave maximization and solved using conventional methods. Finally, we demonstrate the practical utility of our methods using data from the Women’s Health Initiative. (shrink)

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as (...) economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. -/- To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. -/- We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations. (shrink)

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and (...) mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability. (shrink)

Copyright © 2015 by the Society of Criti. Objective: Global lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress. We aimed to determine whether the volume delivered during a recruitment maneuver is inversely associated with lung stress and mortality in acute respiratory distress syndrome. Design: Substudy of an acute respiratory distress (...) syndrome clinical trial on esophageal pressure-guided positive end-expiratory pressure titration. Setting: U.S. academic medical center. Patients: Forty-two patients with acute respiratory distress syndrome in whom airflow, airway pressure, and esophageal pressure were recorded during the recruitment maneuver. Interventions: A single recruitment maneuver was performed before initiating protocol-directed ventilator management. Recruitment maneuvers consisted of a 30-second breath hold at 40 cm H2O airway pressure under heavy sedation or paralysis. VRM was calculated by integrating the flow-time waveform during the maneuver. End-inspiratory stress was defined as the transpulmonary pressure during end-inspiratory pause of a tidal breath and tidal stress as the transpulmonary pressure difference between end-inspiratory and end-expiratory pauses. Measurements and Main Results: VRM ranged between 7.4 and 34.7 mL/kg predicted body weight. Lower VRM predicted high end-inspiratory and tidal lung stress. After adjusting for Pao2/Fio2 and either driving pressure, tidal volume, or plateau pressure and positive end-expiratory pressure, VRM remained independently associated with both end-inspiratory and tidal stress. In unadjusted analysis, low VRM predicted increased risk of death. VRM remained significantly associated with mortality after adjusting for study arm. Conclusions: Low VRM independently predicts high lung stress and may predict risk of death in patients with acute respiratory distress syndrome. (shrink)

We take up the challenge of developing an international network with capacity to survey the world’s scientists on an ongoing basis, providing rich datasets regarding the opinions of scientists and scientific sub-communities, both at a time and also over time. The novel methodology employed sees local coordinators, at each institution in the network, sending survey invitation emails internally to scientists at their home institution. The emails link to a ‘10 second survey’, where the participant is presented with a single statement (...) to consider, and a standard five-point Likert scale. In June 2023, a group of 30 philosophers and social scientists invited 20,085 scientists across 30 institutions in 12 countries to participate, gathering 6,807 responses to the statement Science has put it beyond reasonable doubt that COVID-19 is caused by a virus. The study demonstrates that it is possible to establish a global network to quickly ascertain scientific opinion on a large international scale, with high response rate, low opt-out rate, and in a way that allows for significant (perhaps indefinite) repeatability. Measuring scientific opinion in this new way would be a valuable complement to currently available approaches, potentially informing policy decisions and public understanding across diverse fields. (shrink)

Environmental ethicists have frequently criticized ancient Greek philosophy as anti-environmental for a view of philosophy that is counterproductive to environmental ethics and a view of the world that puts nature at the disposal of people. This provocative collection of original essays reexamines the views of nature and ecology found in the thought of Plato, Aristotle, the Stoics, and Plotinus. Recognizing that these thinkers were not confronted with the environmental degradation that threatens contemporary philosophers, the contributors to this book find that (...) the Greeks nevertheless provide an excellent foundation for a sound theory of environmentalism. (shrink)

"In the great English tradition of the lay specialist, Barfield, a lawyer, modernizes the Platonic dialogue format to focus on the philosophic problems of reality and ways of knowing.. This is the solvent mind at its best-distinguished exchanges giving provocative, open-ended results at every point. Highly recommended. of permanent value." -Choice: Books for College Libraries Owen Barfield, who died in 1997 shortly after entering his hundredth year, was one of the seminal minds of the twentieth century, of whom C. (...) S. Lewis wrote "he towers above us all." His books have won respect from many writers other than Lewis, among them T. S. Eliot, J. R. R. Tolkein, and Saul Bellows, and John Lukacs. He was born in North London in 1898 and received his B.A. with first-class honors from Wadham College, Oxford, in 1921. He also earned B.C.L., M.A., and B.Litt. degrees from Oxford and was a fellow of the Royal Society of Literature. He served as a solicitor for twenty-eight years until his retirement from legal practice in 1959. Barfield was a visiting professor at Brandeis and Drew Universities, Hamilton College, the University of Missouri at Columbia, UCLA, SUNY-Stony Brook, and the University of British Columbia, Vancouver. His books include seven others published by The Barfield Press: Romanticism Comes of Age, Worlds Apart: A Dialogue of the 1960s, Unancestral Voice, Speaker's Meaning, What Coleridge Thought, The Rediscovery of Meaning, and History, Guilt and Habit. (shrink)

There is a debate about the nature of addiction, whether it is a result of brain damage, brain dysfunction, or normal brain changes that result from habit acquisition, and about whether it is a disease. I argue that the debate about whether addiction is a disease is much ado about nothing, since all parties agree it is “unquestionably destructive.” Furthermore, the term ‘addiction’ has disappeared from recent DSM’s in favor of a spectrum of ‘abuse’ disorders. This may be a good (...) thing indicating more nuance in typing the heterogeneous phenomena we used to call ‘addiction’. (shrink)

We take up the challenge of developing an international network with capacity to survey the world’s scientists on an ongoing basis, providing rich datasets regarding the opinions of scientists and scientific sub-communities, both at a time and also over time. The novel methodology employed sees local coordinators, at each institution in the network, sending survey invitation emails internally to scientists at their home institution. The emails link to a ‘10 second survey’, where the participant is presented with a single statement (...) to consider, and a standard five-point Likert scale. In June 2023, a group of 30 philosophers and social scientists invited 20,085 scientists across 30 institutions in 12 countries to participate, gathering 6,807 responses to the statement Science has put it beyond reasonable doubt that COVID-19 is caused by a virus. The study demonstrates that it is possible to establish a global network to quickly ascertain scientific opinion on a large international scale, with high response rate, low opt-out rate, and in a way that allows for significant (perhaps indefinite) repeatability. Measuring scientific opinion in this new way would be a valuable complement to currently available approaches, potentially informing policy decisions and public understanding across diverse fields. (shrink)

Human beings have the unique ability to consciously reflect on the nature of the self. But reflection has its costs. We can ask what the self is, but as David Hume pointed out, the self, once reflected upon, may be nowhere to be found. The favored view is that we are material beings living in the material world. But if so, a host of destabilizing questions surface. If persons are just a sophisticated sort of animal, then what sense is there (...) to the idea that we are free agents who control our own destinies? What makes the life of any animal, even one as sophisticated as Homo sapiens, worth anything? What place is there in a material world for God? And if there is no place for a God, then what hold can morality possibly have on us--why isn't everything allowed? Flanagan's collection of essays takes on these questions and more. He continues the old philosophical project of reconciling a scientific view of ourselves with a view of ourselves as agents of free will and meaning-makers. But to this project he brings the latest insights of neuroscience, cognitive science, and psychiatry, exploring topics such as whether the conscious mind can be explained scientifically, whether dreams are self-expressive or just noise, the moral socialization of children, and the nature of psychological phenomena such as multiple personality disorder and false memory syndrome. What emerges from these explorations is a liberating vision which can make sense of the self, agency, character transformation, and the value and worth of human life. Flanagan concludes that nothing about a scientific view of persons must lead to nihilism. (shrink)

The internet is widely used for health information and support, often by vulnerable people. Internet-based research raises both familiar and new ethical problems for researchers and ethics committees. While guidelines for internet-based research are available, it is unclear to what extent ethics committees use these. Experience of gaining research ethics approval for a UK study (SharpTalk), involving internet-based discussion groups with young people who self-harm and health professionals is described. During ethical review, unsurprisingly, concerns were raised about the vulnerability of (...) potential participants. These were dominated by the issue of anonymity, which also affected participant safety and consent. These ethical problems are discussed, and our solutions, which included: participant usernames specific to the study, a closed website, private messaging facilities, a direct contact email to researchers, information about forum rules displayed on the website, a ‘report’ button for participants, links to online support, and a discussion room for forum moderators. This experience with SharpTalk suggests that an approach to ethics, which recognises the relational aspects of research with vulnerable people, is particularly useful for internet-based health research. The solutions presented here can act as guidance for researchers developing proposals and for ethics committees reviewing them. (shrink)

Students often invoke quantum mechanics in class or papers to make philosophical points. This tendency has been encouraged by pop culture influences like the film What the Bleep do We Know? There is little merit to most of these putative implications. However, it is difficult for philosophy teachers unfamiliar with quantum mechanics to handle these supposed implications in a clear and careful way. This paper is a philosophy of science version of MythBusters. We offer a brief primer on the nature (...) of quantum mechanics, enumerate nine of the most common implications associated with quantum mechanics, and finally clarify each implication with the facts. Our goal is to explain what quantum mechanics doesn’t show. (shrink)

David Brink presents a study of T. H. Green's Prolegomena to Ethics (1883), a classic of British idealism. Green develops a perfectionist ethical theory that brings together the best elements in the ancient and modern traditions and that provides the moral foundations for Green's own influential brand of liberalism. Brink's book situates the Prolegomena in its intellectual context, examines its main themes, and explains Green's enduring significance for the history of ethics and contemporary ethical theory.

Todd Moody’s Zombie Earth thought experiment is an attempt to show that ‘conscious inessentialism’ is false or in need of qualification. We defend conscious inessentialism against his criticisms, and argue that zombie thought experiments highlight the need to explain why consciousness evolved and what function(s) it serves. This is the hardest problem in consciousness studies.

"In the great English tradition of the lay specialist, Barfield, a lawyer, modernizes the Platonic dialogue format to focus on the philosophic problems of reality and ways of knowing.. This is the solvent mind at its best-distinguished exchanges giving provocative, open-ended results at every point. Highly recommended. of permanent value." Owen Barfield, who died in 1997 shortly after entering his hundredth year, was one of the seminal minds of the twentieth century, of whom C. S. Lewis wrote "he towers (...) above us all." His books have won respect from many writers other than Lewis, among them T. S. Eliot, J. R. R. Tolkein, and Saul Bellows, and John Lukacs. He was born in North London in 1898 and received his B.A. with first-class honors from Wadham College, Oxford, in 1921. He also earned B.C.L., M.A., and B.Litt. degrees from Oxford and was a fellow of the Royal Society of Literature. He served as a solicitor for twenty-eight years until his retirement from legal practice in 1959. Barfield was a visiting professor at Brandeis and Drew Universities, Hamilton College, the University of Missouri at Columbia, UCLA, SUNY-Stony Brook, and the University of British Columbia, Vancouver. His books include seven others published by The Barfield Press: Romanticism Comes of Age, Worlds Apart: A Dialogue of the 1960s, Unancestral Voice, Speaker's Meaning, What Coleridge Thought, The Rediscovery of Meaning, and History, Guilt and Habit. (shrink)

The paper aims to provide an account of the phenomenological differences between perception, recognition and recall. In the first section, recall is distinguished from non-experiential forms of memory. In the second section, it is argued that we can't distinguish perceptual experience from the experience of recall by means of perception's present tense content because it is possible to perceive as well as to recall the past. The Lockean theory of recall as a revival of previous perceptual experience is then introduced, (...) applied and defended against objections. Next, recall is distinguish from memory recognition. Finally, some relevant psychological data is described. (shrink)

In our thinking about what to do, we consider reasons which count for or against various courses of action. That having a glass of wine with dinner would be pleasant and make me sociable recommends the wine. That it will disturb my sleep and inhibit this evening’s work counts against it. I determine what I ought to do by weighing these considerations and deciding what would be best all things considered. A practical reason makes sense of a course of action (...) by recommending it, by highlighting some good or desirable feature of it which could move a reasonable agent to perform it. When thinking about what to do, we also attend to our obligations. Perhaps I have promised to remain clearheaded this evening. Given this I am obliged not to drink. How should this consideration affect my deliberations? According to Davidson, the fact that an action would be a breach of a promise ‘is a count against the action, to be weighed along with other reasons for the action’ (Davidson 2004: 177). This suggests that obligations are a sub-set of our reasons, they are one input into the process of determining what action would be reasonable or justified all things considered. One can see why Davidson might say this. After all, having carefully considered the matter, I may decide not to keep my promise. Furthermore this may be the right thing to do, the most reasonable course of action available to me in the light of all the relevant factors. Nevertheless this description seems to miss something important about a promise. The fact that I promised not to drink does not merely recommend not drinking as does the prospect of a restless night; it places a demand on me. Drinking would not be just inadvisable; it would now be a wrong. And even if such a wrong might on the whole be justified, even if committing this wrong is the right thing to do, in drinking I refuse a demand, I don’t just reject a recommendation. It is widely held that a promise provides you with a moral reason to fulfill it, whereas the fact that drinking would make you lose sleep does not, typically, constitute such a reason.. (shrink)

Unlike many other animals, human beings enjoy freedom of action. They are capable of acting freely because they have certain psychological capacities which other animals lack. In this paper, I argue that the crucial capacity here is our ability to make practical judgements; to make judgements about what we ought to do. A number of other writers share this view but they treat practical judgement as a form of belief. Since, as I argue, we don't control our beliefs, that undermines (...) this model of human freedom. I suggest a different account of practical judgement, according to which they are cognitive states but not beliefs and I show how this provides us with a better model of practical freedom. (shrink)

Moral enhancement is an ostensibly laudable project. Who wouldn’t want people to become more moral? Still, the project’s approach is crucial. We can distinguish between two approaches for moral enhancement: direct and indirect. Direct moral enhancements aim at bringing about particular ideas, motives or behaviors. Indirect moral enhancements, by contrast, aim at making people more reliably produce the morally correct ideas, motives or behaviors without committing to the content of those ideas, motives and/or actions. I will argue, on Millian grounds, (...) that the value of disagreement puts serious pressure on proposals for relatively widespread direct moral enhancement. A more acceptable path would be to focus instead on indirect moral enhancements while staying neutral, for the most part, on a wide range of substantive moral claims. I will outline what such indirect moral enhancement might look like, and why we should expect it to lead to general moral improvement. (shrink)