Numerical Simulation of Heat Transfer and Chemistry in the Wake Behind a Hypersonic Slender Body at Angle of Attack

The effect of thermal and chemical boundary conditions on the structure and chemical composition of the wake behind a 3D Mach 7 sphere-cone at an angle of attack of 5 degrees and an altitude of roughly 30,000 m is explored. A special emphasis is placed on determining the number density of chemical species which might lead to detection via the electromagnetic spectrum. The use of non-ablating cold-wall, adiabatic, and radiative equilibrium wall boundary conditions are used to simulate extremes in potential thermal protection system designs. Non-ablating, as well as an ablating boundary condition using the “steady-state ablation” assumption to compute a surface energy balance on the wall are used in order to determine the impacts of ablation on wake composition. On-body thermal boundary conditions downstream of an ablating nose are found to significantly affect wake temperature and composition, while the role of catalysis is found to change the composition only marginally except at very high temperatures on the cone’s surface for the flow regime considered. Ablation is found to drive the extensive production of detectable species otherwise unrelated to ablation, whereas if ablation is not present at all, air-species which would otherwise produce detectable spectra are minimal. Studies of afterbody cooling techniques, as well as shape, are recommended for further analysis

Exosome-mediated MIR211 modulates tumor microenvironment via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

The microRNA MIR211 is an important regulator of melanoma tumor cell behavior. Previous studies suggested that in certain tumors, MIR211 acted as a tumor suppressor while in others it behaved as an oncogenic regulator. When MIR211 is expressed in BRAFV600E-mutant A375 melanoma cells in mouse xenografts, it promotes aggressive tumor growth accompanied by increased cellular proliferation and angiogenesis. We demonstrate that MIR211 is transferred to adjacent cells in the tumor micro-environment via exosomes. Cross-species genome-wide transcriptomic analysis showed that human tumor-derived MIR211 interacts with the mouse transcriptome in the tumor microenvironment, and activates ERK5 signaling in human tumor cells via the modulation of a feedback loop. Human miR211 directly inhibits human DUSP6 protein phosphatase at the post-transcriptional level. We provide support for the hypothesis that DUSP6 inhibition conferred resistance of the human tumor cells to the BRAF inhibitor vemurafenib and to the MEK inhibitor cobimetinib, with associated increases in ERK5 phosphorylation. These findings are consistent with a model in which MIR211 regulates melanoma tumor proliferation and BRAF inhibitor resistance by inducing ERK5 signaling within the complex tumor microenvironment. We propose that the MIR211-ERK5 axis represents an important and sensitive regulatory arm in melanoma with potential theranostic applications

Exosome-mediated MIR211 modulates tumor microenvironment via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

The microRNA MIR211 is an important regulator of melanoma tumor cell behavior. Previous studies suggested that in certain tumors, MIR211 acted as a tumor suppressor while in others it behaved as an oncogenic regulator. When MIR211 is expressed in BRAFV600E-mutant A375 melanoma cells in mouse xenografts, it promotes aggressive tumor growth accompanied by increased cellular proliferation and angiogenesis. We demonstrate that MIR211 is transferred to adjacent cells in the tumor micro-environment via exosomes. Cross-species genome-wide transcriptomic analysis showed that human tumor-derived MIR211 interacts with the mouse transcriptome in the tumor microenvironment, and activates ERK5 signaling in human tumor cells via the modulation of a feedback loop. Human miR211 directly inhibits human DUSP6 protein phosphatase at the post-transcriptional level. We provide support for the hypothesis that DUSP6 inhibition conferred resistance of the human tumor cells to the BRAF inhibitor vemurafenib and to the MEK inhibitor cobimetinib, with associated increases in ERK5 phosphorylation. These findings are consistent with a model in which MIR211 regulates melanoma tumor proliferation and BRAF inhibitor resistance by inducing ERK5 signaling within the complex tumor microenvironment. We propose that the MIR211-ERK5 axis represents an important and sensitive regulatory arm in melanoma with potential theranostic applications

Patient Safety Event Reporting and Opportunities for Emergency Medicine Resident Education

Introduction: Healthcare systems often expose patients to significant, preventable harm causing an estimated 44,000 to 98,000 deaths or more annually. This has propelled patient safety to the forefront, with reporting systems allowing for the review of local events to determine their root causes. As residents engage in a substantial amount of patient care in academic emergency departments, it is critical to use these safety event reports for resident-focused interventions and educational initiatives. This study analyzes reports from the Virginia Commonwealth University Health System to understand how the reports are categorized and how it relates to opportunities for resident education.Methods: Identifying categories from the literature, three subject matter experts (attending physician, nursing director, registered nurse) categorized an initial 20 reports to resolve category gaps and then 100 reports to determine inter-rater reliability. Given sufficient agreement, the remaining 400 reports were coded individually for type of event and education among other categories.Results: After reviewing 513 events, we found that the most common event types were issues related to staff and resident training (25%) and communication (18%), with 31% requiring no education, 46% requiring directed educational feedback to an individual or group, 20% requiring education through monthly safety updates or meetings, 3% requiring urgent communication by email or in-person, and <1% requiring simulation.Conclusion: Twenty years after the publication of To Err is Human, gains have been made integrating quality assurance and patient safety within medical education and hospital systems, but there remains extensive work to be done. Through a review and analysis of our patient safety event reporting system, we were able to gain a better understanding of the events that are submitted, including the types of events and their severity, and how these relate to the types of educational interventions provided (eg, feedback, simulation). We also determined that these events can help inform resident education and learning using various types of education. Additionally, incorporating residents in the review process, such as through root cause analyses, can provide residents with high-quality, engaging learning opportunities and useful, lifelong skills, which is invaluable to our learners and future physicians