Ethical Issues with Simulating the Bridge Problem in VR

We aim to generate a dilemma for virtual reality-based research that we motivate through an extended case study of Judith Thomson’s (1985) Bridge variant of the trolley problem. Though the problem we generate applies more broadly than the Bridge problem, we believe it makes a good exemplar of the kind of case we believe is problematic. First, we argue that simulations of these thought experiments run into a practicality horn that makes it practically impossible to produce them. These problems revolve around concepts that we call “perspectival fidelity”and “context realism.” Moral dilemmas that include features present in the Bridge variant will, as a result, be practically impossible to simulate. We also argue that, should we be wrong about the practical impossibility of creating a VR simulation of Bridge, such a simulation must face an ethical horn which renders these simulations ethically impermissible to develop or use. For these reasons, we argue that it is virtually impossible to simulate the bridge problem (and other thought experiments with similar features) both practically and ethically in VR

The legacy of the Meno Paradox: Plato and Aristotle on learning and error

This thesis will argue that Plato's influential philosophical puzzle known as the Meno Paradox and the related Problem of False Belief are a more serious threat to Plato's philosophical programme (and ours) than many interpreters recognize. Furthermore, Plato's most obvious candidate for a solution to these problems, the Theory of Recollection, is not sufficient to explain how the Paradox misunderstands the epistemic processes of learning which it treats. This failure of Plato's account motivates a close consideration of Aristotle's sophisticated attempt to resolve the difficulties Plato raises. I will argue that a proper understanding of Aristotle's philosophy of mind and the forms of cognition through which he thinks humans progress yields the key to a powerful and heretofore unrecognized Aristotelian solution to the Meno Paradox and the Problem of False Belief

Facial plating industry payments: An analysis of the open payments database

Abstract Objective To compare industry payments from facial plating companies to plastic surgery, oral and maxillofacial surgery (OMFS), and otolaryngology (OHNS). Methods The Open Payments Database was queried from 2016 to 2021 to identify all industry disbursements related to facial plating products from Stryker, Zimmer Biomet, Depuy Synthes Products, Acumed, and KLS Martin. Total dollars, number of payments, and specialists paid were compared between plastic surgery, OMFS, and OHNS. Funding was correlated to estimated case volume and number of licensed surgeons determined by literature review. Results From 2016 through 2021, OMFS received an average of $786,497 annually, followed by plastic surgery ($765,482), and OHNS ($184,484). On average, facial plating companies distributed 2256, 963, and 917 yearly payments to 699 oral and maxillofacial surgeons, 378 plastic surgeons, and 354 otolaryngologists, respectively. Total dollars, number of payments, and specialists paid were significantly different between specialties (p < .05). Facial trauma coverage is 39.6% by plastic surgery, 36.6% by OMFS, and 23.3% by OHNS. There are 7560 licensed oral and maxillofacial surgeons, 4948 plastic surgeons, and 11,778 otolaryngologists in the United States. Decreased payment to OHNS was more than could be accounted for by case volume alone. Conclusions The facial plating industry allocates more funding dollars to OMFS and plastic surgery compared to OHNS. OMFS receives the greatest number of payments to the most specialists compared to plastic surgery and OHNS. Engagement between OHNS and the facial plating industry is a potential area of growth in the future. Level of evidence: Level 4

Evaluation of peripheral nerve regeneration in Murphy Roths Large mouse strain following transection injury.

Aim: Murphy Roths Large (MRL/MpJ) mice have demonstrated the ability to heal with minimal or no scar formation in several tissue types. In order to identify a novel animal model, this study sought to evaluate whether this attribute applies to peripheral nerve regeneration. Materials & methods: This was a two-phase study. 6-week-old male mice were divided into two interventional groups: nerve repair and nerve graft. The MRL/MpJ was compared with the C57BL/6J strain for evaluation of both functional and histological outcomes. Results: MRL/MpJ strain demonstrated superior axon myelination and less scar formation, however functional outcomes did not show significant difference between strains. Conclusion: Superior histological outcomes did not translate into superior peripheral nerve regeneration in MRL/MpJ strain

CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression.

The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells

Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping

Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid tumors. Using as little as 6.5 mg of input tumor tissue, we show successful extraction of high-molecular-weight genomic DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system’s utility in identifying somatic SVs affecting functional and cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment