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)

Another exceptionally fine text by Suppes. Designed for those who can follow a mathematical argument, but presupposes no special knowledge of mathematics or symbolic logic. The system developed is that of Zermelo-Fraenkel. Especially noteworthy is the discussion of the exact role played by the various axioms.--N. D. B., Jr.

This is a first attempt to formalize the language required for analysis of purposive organizations or systems into the subordinate systems of which they organically consist. The authors take a philosophic position midway between Atomism and the Absolute; like Aristotle, they take a finite, complex individual as the ultimate referent of explanation. The sole primitive is "s///tOx," interpreted as "upon analytic dissection, the system t organized by [the property] x." It is claimed without argument that the relationship is independent of (...) who, so to speak, is doing the dissecting. This paper is welcome as a first attack on a difficult problem, although it does not pay off in the production of non-trivial theorems or in clarification much beyond that afforded by technical English.--N. D. B. Jr. (shrink)

An application of probabilistic, stimulus-response learning theory to game-like small group situations. The theory is axiomatic, precise, and quantitative; and is deductively fruitful. There is a running comparison of the predictive success of the stimulus-response theory and game theory. The authors claim to have demonstrated "in empirical detail and with quantitative accuracy" that "the social situation, qua social, does not require the introduction of new concepts" beyond those of stimulus-response learning theory. --N. D. B. Jr.

Representation of quantum states by statistical ensembles on the quantum phase space in the Hamiltonian form of quantum mechanics is analyzed. Various mathematical properties and some physical interpretations of the equivalence classes of ensembles representing a mixed quantum state in the Hamiltonian formulation are examined. In particular, non-uniqueness of the quantum phase space probability density associated with the quantum mixed state, Liouville dynamics of the probability densities and the possibility to represent the reduced states of bipartite systems by marginal distributions (...) are discussed in detail. These considerations are used to study ensembles of hybrid quantum-classical systems. In particular, nonlinear evolution of a single hybrid system in a pure state and unequal evolutions of initially equivalent ensembles are discussed in the context of coupled hybrid systems. (shrink)

Electrical resistivity and ac-calorimetric measurements reveal a complex magnetic phase diagram for single crystals of the ferromagnetic Kondo-lattice compound CeAgSb2 at high pressures up to 80 kbar. The ferromagnetic order at TC = 9.6 K at ambient pressure is completely suppressed at a critical pressure PC = 35 kbar. Another magnetic transition, possibly antiferromagnetic, found above 27 kbar, attains a maximum value TN 6 K at 44 kbar and then appears to be completely suppressed by 50 kbar. Thermodynamic and transport (...) measurements in the ferromagnetic state indicate an energy gap Δ 30 K in the spin-wave excitation spectrum at ambient pressure which decreases to Δ 10 K at P = 30 kbar. No superconductivity is observed at ambient pressure above T 0.1 K, under applied pressure in the ferromagnetic state (P = 28.5 kbar), nor in the antiferromagnetic state (P = 33 − 46 kbar) above 0.3 K. © 2003 The American Physical Society. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Diacritics 31.4 (2001) 54-82 [Access article in PDF] Seeing With The Body The Digital Image In Postphotography Mark B. N. Hansen In a well-known scene from the 1982 Ridley Scott film Bladerunner, Rick Deckard scans a photograph into a 3-D rendering machine and directs the machine to explore the space condensed in the two-dimensional photograph as if it were three-dimensional [see fig. 1]. Following Deckard's commands to zoom in (...) and to pan right and left within the image space, the machine unpacks the "real" three-dimensional world represented by the two-dimensional photograph [see figs. 2-3]. After catching a glimpse of his target—a fugitive replicant—reflected from a mirror within the space, Deckard instructs the machine to move around behind the object obstructing the two-dimensional photographic view of the replicant and to frame what it sees [see figs. 4-5]. Responding to the print command issued by Deckard, the machine dispenses a photograph of the replicant which is, quite literally, a close-up of an invisible—indeed nonexistent—part of the two-dimensional original [see fig. 6]. And yet, following the fantasy of this scene, this impossible photograph is—or would be—simply the image of one particular data point within the data set comprising this three-dimensional data space. As fascinating as it is puzzling, this scene of an impossible rendering—a rendering of two-dimensional data as a three-dimensional space—can be related to the crisis brought to photography by digitization in two ways. On the one hand, in line with the film's thematic questioning of photography as a reliable index of memory, this scene foregrounds the technical capacity of digital processing to manipulate photographs. In this way, it thematizes the threat posed by digital technologies to traditional indexical notions of photographic realism. On the other hand, in what has turned out to be a far more prophetic vein, the scene presents a radically new understanding of the photographic image as a three-dimensional "virtual" space. Such an understanding presupposes a vastly different material existence of the photographic image: instead of a physical inscription of light on sensitive paper, the photograph has become a data set that can be rendered in various ways and thus viewed from various perspectives.The first position corresponds to the arguments made by William Mitchell in his now classic book, The Reconfigured Eye. In a comprehensive analysis of the techniques and possibilities of digital imaging, Mitchell concentrates on demarcating the traditional photographic image from its digital doppelgänger. While the specter of manipulation has always haunted the photographic image, it remains the exception rather than the rule: "There is no doubt that extensive reworking of photographic images to produce seamless transformations and combinations is technically difficult, time-consuming, and outside the mainstream of photographic practice. When we look at photographs we presume, unless we have some clear indications to the contrary, that they have not been reworked" [Mitchell 7]. To buttress this claim, Mitchell sketches three criteria for evaluating traditional photographic images: (1) does the image follow the conventions of photography and seem internally coherent? (2) does the visual evidence it presents [End Page 54]Stills from Blade Runner (Ridley Scott, 1982), courtesy of Warner Brothers Home Video. Rick Deckard navigates a two-dimensional image as a three-dimensional space." width="72" height="33" />Click for larger viewFigure 1Still from Blade Runner (Ridley Scott, 1982), courtesy of Warner Brothers Home Video. Rick Deckard navigates a two-dimensional image as a three-dimensional space.Stills from Blade Runner (Ridley Scott, 1982), courtesy of Warner Brothers Home Video. Rick Deckard navigates a two-dimensional image as a three-dimensional space." width="72" height="32" />Click for larger viewFigure 2Still from Blade Runner (Ridley Scott, 1982), courtesy of Warner Brothers Home Video. Rick Deckard navigates a two-dimensional image as a three-dimensional space.Stills from Blade Runner (Ridley Scott, 1982), courtesy of Warner Brothers Home Video. Rick Deckard navigates a two-dimensional image as a three-dimensional space." width="72" height="33" />Click... (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

This paper argues that professionals who make boundary-related decisions should be guided by relationship-based practice. In our roles as service users and professionals, drawing from our lived experiences of professional relationships, we argue we need to move away from distance-based practice. This includes understanding the boundary stories and narratives that exist for all of us – including the people we support, other professionals, as well as the organisations and systems within which we work. When we are dealing with professional boundary (...) issues, we should centre relationship-building skills that are central to many other aspects of our work. Skills that foster relationships at all levels – between professionals, service users, and services – need to be revalued. Our final recommendation is to create, develop, and foster safer spaces within and outside of organisations, as well as inter-professionally, for the discussion and exploration of boundary-related issues and practice. We are interested in hearing from those with experiences of being marginalised by boundaries so that they can inform a reshaping of our collective ideas around boundary related practices. To foster relationship-based practices in organisations, we have outlined several recommendations here; however, we recognize that these do not go far enough, and that collective action is needed to inform systemic change. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)