Confirming multisite studies presents an ongoing challenge for researchers based in England. Those wishing to set up a multisite study must undergo local Research & Development review, in addition...

The Confidentiality Advisory Group is a specialised body that advises the Health Research Authority and the Secretary of State for Health on requests for access to confidential information, in the absence of informed consent from its owners. Its primary role is to oversee the safe use of such information and to counsel the governing bodies mentioned above as to whether such use is appropriate or inappropriate. Researchers who seek access to England or Wales-based confidential data, for medical purposes that are (...) in the interest of the public, are typically required to submit an application to this body. However, it is not always clear to researchers whether requests for access to patient data fit within the remit of the CAG or a Trust’s local information governance team. This commentary will, therefore, explore the role of the CAG and reflect on how best to support researchers with this question. (shrink)

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements (...) must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework—a dynamic knowledge repository—wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline. (shrink)

Heterogeneity within MDD has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP (...) biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A ([11C]WAY-100635), as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets. (shrink)

The authors show. by means of a finitary version $\square_{\lambda D}^{fin}$ of the combinatorial principle $\square_\lambda^{h*}$ of [7]. the consistency of the failure, relative to the consistency of supercompact cardinals, of the following: for all regular filters D on a cardinal A. if Mi and Ni are elementarily equivalent models of a language of size $\leq \lambda$ , then the second player has a winning strategy in the Ehrenfeucht- $Fra\uml{i}ss\acute{e}$ game of length $\lambda^{+}$ on $\pi_{i} M_{i}/D$ and $\pi_{i} N_{i}/D$ . (...) If in addition $2^{\lambda} = \labda^{+}$ and i < $\lambda$ implies | $M_{i}$ | +| $N_{i}$ | $\leq$ \lambda^{+} this means that the ultrapowers are isomorphic. This settles negatively conjecture 18 in [2]. (shrink)

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, (...) Georgetown University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

This Element takes a deep dive into Gödel's 1931 paper giving the first presentation of the Incompleteness Theorems, opening up completely passages in it that might possibly puzzle the student, such as the mysterious footnote 48a. It considers the main ingredients of Gödel's proof: arithmetization, strong representability, and the Fixed Point Theorem in a layered fashion, returning to their various aspects: semantic, syntactic, computational, philosophical and mathematical, as the topic arises. It samples some of the most important proofs of the (...) Incompleteness Theorems, e.g. due to Kuratowski, Smullyan and Robinson, as well as newer proofs, also of other independent statements, due to H. Friedman, Weiermann and Paris-Harrington. It examines the question whether the incompleteness of e.g. Peano Arithmetic gives immediately the undecidability of the Entscheidungsproblem, as Kripke has recently argued. It considers set-theoretical incompleteness, and finally considers some of the philosophical consequences considered in the literature. (shrink)

The Human Genome Project is expected to increase dramatically our ability to predict the likelihood of genetic disease in an individual. It is important to reject the myth of genetic determinism—i.e., the simple-minded belief that such complex outcomes as heart disease, cancer, or autoimmune diseases are caused exclusively by particular genes. But it is equally important to acknowledge that genes may play a role in making a person more or less susceptible to such diseases. The ever-increasing prospect of genetic prediction, (...) spurred by the Human Genome Project, has implications for social practices such as insurance, in which predicting the risk of disease or death plays a crucial role. Concerned that improved genetic prediction might have unfortunate social consequences unless the impact of such predictions were anticipated, the U.S. Human Genome Project's Working Group on Ethical, Legal, and Social Issues established a Task Force on Genetic Information and Insurance in May 1991. -/- The Task Force met seven times over its two-year life. By the end of the first year, it had reached several tentative conclusions. Most importantly, we became convinced that the problem posed by increased genetic prediction in insurance was a genuine and important one. When we began, the danger seemed plausible but far from certain. The information we gathered in the first year persuaded us that genetic prediction of disease was in one sense already with us and, in another sense, likely to grow massively in the foreseeable future. (shrink)

Dion is a human person, Lefty is his left foot, and Theon is Lefty-Complement, a proper part of Dion. Lefty is annihilated and Dion survives left-footless. After Lefty’s annihilation Theon, if he survives, occupies the same region as Dion. I suggest that this scenario be understood as a fusion case in which Dion and Theon, initially overlapping but distinct, are identical after Lefty’s annihilation and propose an account of proper names that allows us to say that Dion and Theon have (...) ‘become identical’ without commitment to occasional identity or other controversial metaphysical doctrines. The proposed solution employs the semantics developed by Wolfgang Schwarz to address the ‘paradox of occasional identity’, posed by puzzle cases of fission, to deal with the problem of Dion and Theon, a body-minus puzzle. (shrink)

This book identifies the physical, emotional, and psychological adjustments many boys have been forced to navigate alone during their most vulnerable, formative years and provides adjustments that adults must make to assist them in these transitions.

The doctrine of the Trinity developed in response to a range of theological interests, among them the project of reconciling claims about the divinity of Christ with monotheism and massaging Christian doctrine into the ambient (largely Platonic) philosophical framework of the period. More recently the Trinity doctrine has been deployed to promote normative claims concerning human nature, human relationships and social justice. During the past two decades analytic philosophers of religion have increasingly engaged with the doctrine. There are, however, a (...) number of foundational questions that have not been addressed in the philosophical literature. The Trinity: A Philosophical Investigation considers the competing accounts of the Trinity doctrine, whether orthodox or heterodox, and aims to respond to objections and explicate their motivations and entailments. (shrink)

_Rabghūzī’s_ _Stories of the Prophets_, written in Khwarezmian Turkish (14th century) contains an account of the life of the biblical prophets and of the Prophet Muḥammed.

According to many orthodox Christian theologies Jesus is not merely sinless but impeccable: he not only did not sin but could not. This is puzzling because one can only sin by doing something else and, prima face, Jesus can do actions that you or I could do by which we would sin. I suggest that appearances to the contrary, Jesus cannot do a variety of actions that a merely human duplicate could do. His doing sinful actions is compossible with a (...) range of empirical facts about his physical abilities and circumstances of the sort we ordinarily take into account in assessing what a person can do, but not with a wider range of theological facts concerning his divinity. Like Tim, Lewis’s time-traveler, who can kill Grandfather relative to facts about his immediate circumstances and abilities but not relative to a wider range of facts, Jesus ‘can’ in the ordinary sense sin, though he will not, but relative to a wider range of facts which obtain in virtue of his divinity, cannot. (shrink)

In 'Een handvol filosofen' staan de filosofen centraal die sinds de oprichting van de Vrije Universiteit in 1880 aan deze instelling verbonden zijn geweest. Het gaat hierbij niet alleen om de inhoud van hun werk, maar ook om de personen zelf. Er waren filosofiedocenten die zich met de universiteit identificeerden en zich volledig konden ontplooien. Er waren er echter ook voor wie dit niet gold, die geïsoleerd of in gewetensnood raakten. Veel filosofiestudenten waren actief betrokken bij wat er in hun (...) faculteit gebeurde. Zij namen initiatieven, protesteerden soms tegen de gang van zaken en kozen partij in conflictsituaties. Sinds het eind van de jaren zestig van de twintigste eeuw verloor de Vrije Universiteit geleidelijk haar christelijk karakter. Tegenwoordig werken alle stafleden vanuit hun eigen motivatie mee aan een hoofdzakelijk seculier geworden universiteit, die ruimte biedt voor religieuze en levensbeschouwelijke diversiteit. (shrink)

Background The consistency of codes governing disclosure of terminal illness to patients and families in Islamic countries has not been studied until now. Objectives To review available codes on disclosure of terminal illness in Islamic countries. Data source and extraction Data were extracted through searches on Google and PubMed. Codes related to disclosure of terminal illness to patients or families were abstracted, and then classified independently by the three authors. Data synthesis Codes for 14 Islamic countries were located. Five codes (...) were silent regarding informing the patient, seven allowed concealment, one mandated disclosure and one prohibited disclosure. Five codes were silent regarding informing the family, four allowed disclosure and five mandated/recommended disclosure. The Islamic Organization for Medical Sciences code was silent on both issues. Conclusion Codes regarding disclosure of terminal illness to patients and families differed markedly among Islamic countries. They were silent in one-third of the codes, and tended to favour a paternalistic/utilitarian, family-centred approach over an autonomous, patient-centred approach. (shrink)

This collection of previously unpublished essays addresses a number of issues arising out of philosophical controversies over the possibility of genuine moral dilemmas. Issues addressed include the form of a moral dilemma; the paradoxes a moral dilemma is said to entail; the question of whether a moral dilemma must exhibit inconsistency; the role of intractable circumstances in occasioning moral dilemmas; and the plausibility of supposing that there might be rational ways of addressing moral dilemmas in practice. The contributors, writing from (...) a number of widely differing points of view, include Simon Blackburn, Ruth Barcan Marcus, Alan Donagan, Terrance McConnell, Walter Sinnott-Armstrong, Mary Mothersill, Norman Dahl, David Brink, Peter Railton, Thomas E. Hill, Jr., Christopher Gowans, and H.E. Mason. (shrink)

In dit boek neemt de Tsjechisch-Nederlandse geleerde Jan Amos Comenius (1592-1670) een centrale plaats in. Met zijn filosofie en onderwijsleer wilde hij de menselijkheid in de samenleving bevorderen. Hij kwam ervoor op dat mensen met verschillende levensbeschouwelijke visies konden samenwerken om dit doel te helpen realiseren. Ook komen rozenkruisers en vrijmetselaars aan de orde, die reeds in de zestiende en zeventiende eeuw van zich lieten horen. Anders dan de kerken deden, manifesteerden zij een onafhankelijkheid van denken en een streven naar (...) meer menselijkheid in de cultuur.0In hun denken en spreken spelen ook de ideeën van Comenius een rol, direct of indirect, kritisch ondervragend of opbouwend, maar altijd inspirerend. (shrink)

I argue, first, that the deprived individuals whose predicaments Nussbaum cites as examples of "adaptive preference" do not in fact prefer the conditions of their lives to what we should regard as more desirable alternatives, indeed that we believe they are badly off precisely because they are not living the lives they would prefer to live if they had other options and were aware of them. Secondly, I argue that even where individuals in deprived circumstances acquire tastes for conditions that (...) we regard as bad, they are typically better off having their acquired preferences satisfied. If they are badly off it is because they cannot get what we and they, would regard as more desirable alternatives. Preference utilitarianism explains why individuals in such circumstances are badly off whether they have adapted to their deprived circumstances or not. Even if they prefer the conditions of their lives to all other available alternatives, most would prefer alternatives that are not available to them which would, on the preferentist account, make them better off. And that, on the preferentist account, is the basis for a radical critique of unjust institutions that limit people's options and prevent them from getting what they want. (shrink)

Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

Kant's philosophy of arithmetic / by Charles Parsons -- Visual geometry / by James Hopkins -- The proof-structure of Kant's transcendental deduction / by Dieter Henrich -- Imagination and perception / by P.F. Strawson -- Kant's categories and their schematism / by Lauchlan Chipman -- Transcendental arguments / by Barry Stroud -- Strawson on transcendental idealism / by H.E. Matthews -- Self-knowledge / by W.H. Walsh -- The age and size of the world / by Jonathan Bennett.

Public health agencies regularly survey randomly selected anonymous students to track drug use, sexual activities, and other risk behaviors. Students are unidentifiable, but a recent project that i...

Presence as ordinarily understood requires spatio-temporal proximity. If however Christ’s presence in the Eucharist is understood in this way it would take a miracle to secure multiple location and an additional miracle to cover it up so that the presence of Christ where the Eucharist was celebrated made no empirical difference. And, while multiple location is logically possible, such metaphysical miracles—miracles of distinction without difference, which have no empirical import—are problematic. I propose an account of Eucharist according to which Christ (...) is indeed really and objectively present in the religiously required sense, without benefit of metaphysical miracles. According to the proposed account, which draws upon Searle’s discussion of “social ontology” in The Construction of Social Reality and The Making of the Social World, the presence of Christ in the Eucharist is an institutional fact. I argue that such an account satisfies the requirements for a real presence doctrine. (shrink)