In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a single (...) institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies. (shrink)

What is the future of Philosophy of education? Or as many of scholars and thinkers in this final ‘future-focused’ collective piece from the philosophy of education in a new key Series put it, what are the futures—plural and multiple—of the intersections of ‘philosophy’ and ‘education?’ What is ‘Philosophy’; and what is ‘Education’, and what role may ‘enquiry’ play? Is the future of education and philosophy embracing—or at least taking seriously—and thinking with Indigenous ethicoontoepistemologies? And, perhaps most importantly, what is that (...) ‘Future’? These debates have been located in the work of diverse scholars: from the West, from Global South, from indigenous thinkers. In this collective piece, we purposefully juxtapose diverse takes on the future of these intersections. We have given up the urge to organise, place together, separate with subheadings or connect the paragraphs that follow. Instead, we let these philosophers of education and thinkers who use philosophical texts and ideas to sit together in one long read as potentially ‘strange and unusual bedfellows’. This text urges us to understand how these scholars and thinkers perceive our educational philosophical futures, and how the work and thinking they have done on thinking about what the future of that new key in philosophy of education may look like is embedded in a much deeper and richer literature, and personal experience. (shrink)

This essay illustrates what the Chinese family-based and harmony-oriented model of medical decision making is like as well as how it differs from the modern Western individual-based and autonomy-oriented model in health care practice. The essay discloses the roots of the Chinese model in the Confucian account of the family and the Confucian view of harmony. By responding to a series of questions posed to the Chinese model by modern Western scholars in terms of the basic individualist concerns and values (...) embedded in the modern Western model, we conclude that the Chinese people have justifiable reasons to continue to apply the Chinese model to their contemporary health care and medical practice. (shrink)

This paper is an experiment in Leibnizian analysis. The reader will recall that Leibniz considered all true sentences to be analytically so. The difference, on his account, between necessary and contingent truths is that sentences reporting the former are finitely analytic; those reporting the latter require infinite analysis of which God alone is capable. On such a view at least two competing conceptions of entailment emerge. According to one, a sentence entails another when the set of atomic requirements for the (...) first is included in the corresponding set for the other; according to the other conception, every atomic requirement of the entailed sentence is underwritten by an atomic constituent of the entailing one. The former conception is classical on the twentieth century understanding of the term; the latter is the one we explore here. Now if we restrict ourselves to the formal language of the propositional calculus, every sentence has a finite analysis into its conjunctive normal form. Semantically, then, every sentence of that language can be represented as a simple hypergraph, H, on the powerset of a universe of states. Entailment of the sort we wish to study can be represented as a known relation, subsumption between hypergraphs. Since the lattice of hypergraphs thus ordered is a DeMorgan lattice, the logic of entailment thus understood is the familiar system, FDE of first-degree entailment. We observe that, extensionalized, the relation of subsumption is itself a DeMorgan Lattice ordered by higher-order subsumption. Thus the semantic idiom that hypergraph-theory affords reveals a hierarchy of lattices capable of representing entailments of every finite degree. (shrink)

Many natural computational problems have input consisting of two or more parts, one of which may be considered a parameter. For example, there are many problems for which the input consists of a graph and a positive integer. A number of results are presented concerning parameterized problems that can be solved in complexity classes below P, given a single word of advice for each parameter value. Different ways in which the word of advice can be employed are considered, and it (...) is shown that the class FPT of tractable parameterized problems has interesting and natural internal structure. (shrink)

Biologists have long known that animal population dynamics are regulated by a combination of bottom-up and top-down forces. Yet, economists have argued that human population dynamics can also be influenced by intraspecific cooperation. Despite awareness of the role of interspecific cooperation in influencing resource availability and animal population dynamics, the role of intraspecific cooperation under different environmental conditions has rarely been considered. Here we examine the role of what we call “lateral forces” that act within populations and interact with external (...) top-down and bottom-up forces in influencing population dynamics using an individual-based model linking environmental quality, intraspecific cooperation, and population size. We find that the proportion of cooperators is higher when the environment is poor and population sizes are greatest under intermediate resources levels due to the contrasting effects of resource availability on behavior and population size. We also show that social populations are more resilient to environmental change than non-social ones because the benefits of intraspecific cooperation can outweigh the effects of constrained resource availability. Our study elucidates the complex relationship between environmental harshness, cooperation, and population dynamics, which is important for understanding the ecological consequences of cooperation. (shrink)

The structure of Au layers deposited by sputtering on oxidized p-type Si substrates is investigated by a combination of scanning electron microscopy and scanning probe microscopy. The effect of the temperature on the grain structure of the layers has been determined, revealing that an annealing temperature of 300° C results in a larger grain size and smoother surfaces but generates some cracks in the film surface. At an annealing temperature of 500° C, further grain growth is observed, but a high (...) density of cracks and voids also results while there is little enhancement regarding the smoothness of the grain surfaces. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

ABSTRACTDespite interest in exercise as a treatment for anxiety disorders the mechanism behind the anxiolytic effects of exercise is unclear. Two observations motivate the present work. First, engagement of attention control during increased working memory load can decrease anxiety. Second, exercise can improve attention control. Therefore, exercise could boost the anxiolytic effects of increased WM load via its strengthening of attention control. Anxiety was induced by threat of shock and was quantified with anxiety-potentiated startle. Thirty-five healthy volunteers participated in two (...) types of activity, exercise and control-activity. After each activity, participants completed a WM task at low- and high-load during safe and threat. Results were not consistent with the hypothesis: exercise vs. control-activity increased APS in high-load. However, this incre... (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Recently implemented Chinese health insurance schemes have failed to achieve a Chinese health care system that is family-oriented, family-based, family-friendly, or even financially sustainable. With this diagnosis in hand, the authors argue that a financially and morally sustainable Chinese health care system should have as its core family health savings accounts supplemented by appropriate health insurance plans. This essay’s arguments are set in the context of Confucian moral commitments that still shape the background culture of contemporary China.

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)

‘Neuroeconomics’ can be broadly defined as the research of how the brain interacts with the environment to make decisions that are functional given individual and contextual constraints. Deciphering such brain-environment transactions requires mechanistic understandings of the neurobiological processes that implement value-dependent decision making. To this end, a common empirical approach is to investigate neural mechanisms of reward-based decision making. Flexible updating of choices and associated expected outcomes in ways that are adaptive for a given task (or a given set of (...) tasks) at hand relies on dynamic neurochemical tuning of the brain’s functional circuitries involved in the representation of tasks, goals and reward prediction. Empirical evidence as well as computational theories indicate that various neurotransmitter systems (e.g., dopamine, norepinephrine, and serotonin) play important roles in reward-based decision making. In light of the apparent aging-related decline in various aspects of the dopaminergic system as well as the effects of neuromodulation on reward-related processes, this article focuses selectively on the literature that highlights the triadic relations between dopaminergic modulation, reward-based decision making, and aging. Directions for future research on aging and neuroeconomoics are discussed. (shrink)

Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)