208 research outputs found

    Daily Anesthesia Apparatus Checkout: Objective Structured Clinical Exam (OSCE) for First Year Nurse Anesthesia Program Students

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    The anesthesia apparatus checkout is a vital task an anesthesia provider should be able to perform upon entering the clinical setting. In the past, more than half of anesthesia-related deaths throughout the nation were being attributed to assessable and avoidable causes involving the anesthesia machine. Therefore, the U.S. Food and Drug Administration (FDA) formulated and recently revised a detailed anesthesia apparatus checkout procedure to ensure patient safety within the operating room setting. Entering the clinical arena for the first time can be quite intimidating for anesthesia students; therefore, the objective structured clinical exam (OSCE) was developed with the intention that first-year students incorporate this study tool into their study routine. The purpose of the OSCE is to provide students with the appropriate information to assess for machine malfunctions and adequately perform an anesthesia apparatus checkout that could ultimately lead to unanticipated patient injury if not performed. The anesthesia apparatus checkout procedure OSCE was constructed and presented to The University of Southern Mississippi second and third-year SRNAs and four anesthesia faculty members, along with an anonymous evaluation survey. Twenty-five individuals contributed to the anonymous survey with all but one agreeing that the OSCE was clear and concise in delivery. The same theme applied to readiness and confidence within oneself when entering the clinical setting. All survey participants indicated that after the completion of the anesthesia apparatus checkout OSCE, everyone could adequately perform and understood each factor of the anesthesia apparatus checkout. Survey participants did not provide any additional feedback or suggestions to better improve the OSCE. Overall, it was concluded that the anesthesia apparatus checkout OSCE prepares future anesthesia providers with the confidence and knowledge needed to adequately perform the required daily routine, making their transition into the clinical arena less stressful while ensuring patient safety and positive outcomes within the operating room setting

    The CD-loop of PAI-2 (SERPINB2) is redundant in the targeting, inhibition and clearance of cell surface uPA activity

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    <p>Abstract</p> <p>Background</p> <p>Plasminogen activator inhibitor type-2 (PAI-2, SERPINB2) is an irreversible, specific inhibitor of the urokinase plasminogen activator (uPA). Since overexpression of uPA at the surface of cancer cells is linked to malignancy, targeting of uPA by exogenous recombinant PAI-2 has been proposed as the basis of potential cancer therapies. To this end, reproducible yields of high purity protein that maintains this targeting ability is required. Herein we validate the use <it>in vitro </it>of recombinant 6 × His-tagged-PAI-2 lacking the intrahelical loop between C and D alpha-helices (PAI-2 ΔCD-loop) for these purposes.</p> <p>Results</p> <p>We show that PAI-2 ΔCD-loop expressed and purified from the pQE9 vector system presents an easier purification target than the previously used pET15b system. Additionally, PAI-2 ΔCD-loop gave both higher yield and purity than wild-type PAI-2 expressed and purified under identical conditions. Importantly, absence of the CD-loop had no impact on the inhibition of both solution phase and cell surface uPA or on the clearance of receptor bound uPA from the cell surface. Furthermore, uPA:PAI-2 ΔCD-loop complexes had similar binding kinetics (K<sub>D </sub>~5 nM) with the endocytosis receptor Very Low Density Lipoprotein Receptor (VLDLR) to that previously published for uPA:PAI-2 complexes.</p> <p>Conclusion</p> <p>We demonstrate that the CD-loop is redundant for the purposes of cellular uPA inhibition and cell surface clearance (endocytosis) and is thus suitable for the development of anti-uPA targeted cancer therapeutics.</p

    Circle of Ramsey Greenway System

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    Report and posters completed by students enrolled in ARCH 3250: Community Design and Public Interest Architecture, taught by James Wheeler and LA 3002: Informants of Creating Landscape Space, taught by Jessica Rossi-Mastracci and Joe Favour in spring 2018.This project was completed as part of the 2017-2018 Resilient Communities Project (rcp.umn.edu) partnership with the City of Ramsey. The goal of this project was to examine the City of Ramsey’s current greenway system and propose changes and extensions to the system that make it easier to navigate and more efficient to use. Ramsey project lead Mark Riverblood collaborated with a team of students enrolled in James Wheeler’s ARCH 3250 course, and Jessica Rossi-Mastracci and Joe Favour’s LA 3002 course, to create conceptual designs and recommend specific improvements to the City’s greenway system. A final student report and posters from the project are available.This project was supported by the Resilient Communities Project (RCP), a program at the University of Minnesota whose mission is to connect communities in Minnesota with U of MN faculty and students to advance community resilience through collaborative, course-based projects. RCP is a program of the Center for Urban and Regional Affairs (CURA). More information at http://www.rcp.umn.edu

    Precise Infrared Radial Velocities from Keck/NIRSPEC and the Search for Young Planets

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    We present a high-precision infrared radial velocity study of late-type stars using spectra obtained with NIRSPEC at the W. M. Keck Observatory. Radial velocity precisions of 50 m/s are achieved for old field mid-M dwarfs using telluric features for precise wavelength calibration. Using this technique, 20 young stars in the {\beta} Pic (age ~12 Myr) and TW Hya (age ~8 Myr) Associations were monitored over several years to search for low mass companions; we also included the chromospherically active field star GJ 873 (EV Lac) in this survey. Based on comparisons with previous optical observations of these young active stars, radial velocity measurements at infrared wavelengths mitigate the radial velocity noise caused by star spots by a factor of ~3. Nevertheless, star spot noise is still the dominant source of measurement error for young stars at 2.3 {\mu}m, and limits the precision to ~77 m/s for the slowest rotating stars (v sin i < 6 km/s), increasing to ~168 m/s for rapidly rotating stars (v sin i > 12 km/s). The observations reveal both GJ 3305 and TWA 23 to be single-lined spectroscopic binaries; in the case of GJ 3305, the motion is likely caused by its 0.09" companion, identified after this survey began. The large amplitude, short-timescale variations of TWA 13A are indicative of a hot Jupiter-like companion, but the available data are insufficient to confirm this. We label it as a candidate radial velocity variable. For the remainder of the sample, these observations exclude the presence of any 'hot' (P < 3 days) companions more massive than 8 MJup, and any 'warm' (P < 30 days) companions more massive than 17 MJup, on average. Assuming an edge-on orbit for the edge-on disk system AU Mic, these observations exclude the presence of any hot Jupiters more massive than 1.8 MJup or warm Jupiters more massive than 3.9 MJup.Comment: Accepted for publication in The Astrophysical Journal. 18 pages, 7 figure

    Profile of Immune Cells in Axillary Lymph Nodes Predicts Disease-Free Survival in Breast Cancer

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    BACKGROUND: While lymph node metastasis is among the strongest predictors of disease-free and overall survival for patients with breast cancer, the immunological nature of tumor-draining lymph nodes is often ignored, and may provide additional prognostic information on clinical outcome. METHODS AND FINDINGS: We performed immunohistochemical analysis of 47 sentinel and 104 axillary (nonsentinel) nodes from 77 breast cancer patients with 5 y of follow-up to determine if alterations in CD4, CD8, and CD1a cell populations predict nodal metastasis or disease-free survival. Sentinel and axillary node CD4 and CD8 T cells were decreased in breast cancer patients compared to control nodes. CD1a dendritic cells were also diminished in sentinel and tumor-involved axillary nodes, but increased in tumor-free axillary nodes. Axillary node, but not sentinel node, CD4 T cell and dendritic cell populations were highly correlated with disease-free survival, independent of axillary metastasis. Immune profiling of ALN from a test set of 48 patients, applying CD4 T cell and CD1a dendritic cell population thresholds of CD4 ≥ 7.0% and CD1a ≥ 0.6%, determined from analysis of a learning set of 29 patients, provided significant risk stratification into favorable and unfavorable prognostic groups superior to clinicopathologic characteristics including tumor size, extent or size of nodal metastasis (CD4, p < 0.001 and CD1a, p < 0.001). Moreover, axillary node CD4 T cell and CD1a dendritic cell populations allowed more significant stratification of disease-free survival of patients with T1 (primary tumor size 2 cm or less) and T2 (5 cm or larger) tumors than all other patient characteristics. Finally, sentinel node immune profiles correlated primarily with the presence of infiltrating tumor cells, while axillary node immune profiles appeared largely independent of nodal metastases, raising the possibility that, within axillary lymph nodes, immune profile changes and nodal metastases represent independent processes. CONCLUSION: These findings demonstrate that the immune profile of tumor-draining lymph nodes is of novel biologic and clinical importance for patients with early stage breast cancer

    Seismically invisible fault zones: Laboratory insights into imaging faults in anisotropic rocks

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    Phyllosilicate‐rich rocks which commonly occur within fault zones cause seismic velocity anisotropy. However, anisotropy is not always taken into account in seismic imaging and the extent of the anisotropy is often unknown. Laboratory measurements of the velocity anisotropy of fault zone rocks and gouge from the Carboneras fault zone in SE Spain indicate 10–15% velocity anisotropy in the gouge and 35–50% anisotropy in the mica‐schist protolith. Greater differences in velocity are observed between the fast and slow directions in the mica‐schist rock than between the gouge and the slow direction of the rock. This implies that the orientation of the anisotropy with respect to the fault is key in imaging the fault seismically. For example, for fault‐parallel anisotropy, a significantly greater velocity contrast between fault gouge and rock will occur along the fault than across it, highlighting the importance of considering the foliation orientation in design of seismic experiments

    Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions

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    Cholesterol is considered indispensable for cell motility, but how physiological cholesterol pools enable cells to move forward remains to be clarified. The majority of cells obtain cholesterol from the uptake of Low-Density lipoproteins (LDL) and here we demonstrate that LDL stimulates A431 squamous epithelial carcinoma and Chinese hamster ovary (CHO) cell migration and invasion. LDL also potentiated epidermal growth factor (EGF) -stimulated A431 cell migration as well as A431 invasion in 3-dimensional environments, using organotypic assays. Blocking cholesterol export from late endosomes (LE), using Niemann Pick Type C1 (NPC1) mutant cells, pharmacological NPC1 inhibition or overexpression of the annexin A6 (AnxA6) scaffold protein, compromised LDL-inducible migration and invasion. Nevertheless, NPC1 mutant cells established focal adhesions (FA) that contain activated focal adhesion kinase (pY397FAK, pY861FAK), vinculin and paxillin. Compared to controls, NPC1 mutants display increased FA numbers throughout the cell body, but lack LDL-inducible FA formation at cell edges. Strikingly, AnxA6 depletion in NPC1 mutant cells, which restores late endosomal cholesterol export in these cells, increases their cell motility and association of the cholesterol biosensor D4H with active FAK at cell edges, indicating that AnxA6-regulated transport routes contribute to cholesterol delivery to FA structures, thereby improving NPC1 mutant cell migratory behaviour

    Learning to Teach About Ideas and Evidence in Science : The Student Teacher as Change Agent

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    A collaborative curriculum development project was set up to address the lack of good examples of teaching about ideas and evidence and the nature of science encountered by student teachers training to teach in the age range 11-16 in schools in England. Student and teacher-mentor pairs devised, taught and evaluated novel lessons and approaches. The project design required increasing levels of critique through cycles of teaching, evaluation and revision of lessons. Data were gathered from interviews and students' reports to assess the impact of the project on student teachers and to what extent any influences survived when they gained their first teaching posts. A significant outcome was the perception of teaching shifting from the delivery of standard lessons in prescribed ways to endeavours demanding creativity and decision-making. Although school-based factors limited newly qualified teachers' chances to use new lessons and approaches and therefore act as change-agents in schools, the ability to critique curriculum materials and the recognition of the need to create space for professional dialogue were durable gains

    Targeting GLP-1 receptor trafficking to improve agonist efficacy

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    Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in β-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments
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