Caring, Investing, Empowering: Undergraduate Research Mentoring Practices by English Faculty

Mentoring undergraduate research has received attention in scholarly publications, particularly in STEM areas (Pierszalowski & Buser, 2021; National Academies; Pathways to Science). More general advice on mentoring appears in Temple et al (2010) and Vandermaas-Peeler et al, 2018). Attention to mentoring undergraduate researchers in the humanities has been addressed by Behling (2009), Klos, et al (2011), Crawford et al (2014). Grobman and Kinkead (2010) include a section on mentoring in their Undergraduate Research in English Studies. What are the characteristics of faculty mentors in a department of English? This study seeks to determine a profile of effective mentoring in this discipline. Do these characteristics match those identified by Shanahan, et al (2015) in their comprehensive review of literature, “Ten Salient Practices of Undergraduate Mentors: A Review of the Literature”

Folded cavity SOI microring sensors for high sensitivity and real time measurement of biomolecular binding.

We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding

Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model

Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14+ monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells (hu-PBMC) suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor do they induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14+ monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity

An intraoperative telemedicine program to improve perioperative quality measures: The ACTFAST-3 randomized clinical trial

IMPORTANCE: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed. OBJECTIVE: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures. DESIGN, SETTING, AND PARTICIPANTS: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients were randomized to receive either usual intraoperative care (control group; n = 12 980) or usual care augmented by telemedicine decision support (intervention group; n = 13 274). Data were initially analyzed from April 22 to May 19, 2021, with updates in November 2022 and February 2023. INTERVENTION: Patients received either usual care (medical direction from the anesthesia care team) or intraoperative anesthesia care monitored and augmented by decision support from the Anesthesiology Control Tower (ACT), a real-time, live telemedicine intervention. The ACT incorporated remote monitoring of operating rooms by a team of anesthesia clinicians with customized analysis software. The ACT reviewed alerts and electronic health record data to inform recommendations to operating room clinicians. MAIN OUTCOMES AND MEASURES: The primary outcomes were avoidance of postoperative hypothermia (defined as the proportion of patients with a final recorded intraoperative core temperature \u3e36 °C) and hyperglycemia (defined as the proportion of patients with diabetes who had a blood glucose level ≤180 mg/dL on arrival to the postanesthesia recovery area). Secondary outcomes included intraoperative hypotension, temperature monitoring, timely antibiotic redosing, intraoperative glucose evaluation and management, neuromuscular blockade documentation, ventilator management, and volatile anesthetic overuse. RESULTS: Among 26 254 participants, 13 393 (51.0%) were female and 20 169 (76.8%) were White, with a median (IQR) age of 60 (47-69) years. There was no treatment effect on avoidance of hyperglycemia (7445 of 8676 patients [85.8%] in the intervention group vs 7559 of 8815 [85.8%] in the control group; rate ratio [RR], 1.00; 95% CI, 0.99-1.01) or hypothermia (7602 of 11 447 patients [66.4%] in the intervention group vs 7783 of 11 672 [66.7.%] in the control group; RR, 1.00; 95% CI, 0.97-1.02). Intraoperative glucose measurement was more common among patients with diabetes in the intervention group (RR, 1.07; 95% CI, 1.01-1.15), but other secondary outcomes were not significantly different. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, anesthesia care quality measures did not differ between groups, with high confidence in the findings. These results suggest that the intervention did not affect the targeted care practices. Further streamlining of clinical decision support and workflows may help the intraoperative telemedicine program achieve improvement in targeted clinical measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02830126

Neisseria gonorrhoeae Suppresses Dendritic Cell-Induced, Antigen-Dependent CD4 T Cell Proliferation

Neisseria gonorrhoeae is the second most common sexually transmitted bacterial pathogen worldwide. Diseases associated with N. gonorrhoeae cause localized inflammation of the urethra and cervix. Despite this inflammatory response, infected individuals do not develop protective adaptive immune responses to N. gonorrhoeae. N. gonorrhoeae is a highly adapted pathogen that has acquired multiple mechanisms to evade its host's immune system, including the ability to manipulate multiple immune signaling pathways. N. gonorrhoeae has previously been shown to engage immunosuppressive signaling pathways in B and T lymphocytes. We have now found that N. gonorrhoeae also suppresses adaptive immune responses through effects on antigen presenting cells. Using primary, murine bone marrow-derived dendritic cells and lymphocytes, we show that N. gonorrhoeae-exposed dendritic cells fail to elicit antigen-induced CD4+ T lymphocyte proliferation. N. gonorrhoeae exposure leads to upregulation of a number of secreted and dendritic cell surface proteins with immunosuppressive properties, particularly Interleukin 10 (IL-10) and Programmed Death Ligand 1 (PD-L1). We also show that N. gonorrhoeae is able to inhibit dendritic cell- induced proliferation of human T-cells and that human dendritic cells upregulate similar immunosuppressive molecules. Our data suggest that, in addition to being able to directly influence host lymphocytes, N. gonorrhoeae also suppresses development of adaptive immune responses through interactions with host antigen presenting cells. These findings suggest that gonococcal factors involved in host immune suppression may be useful targets in developing vaccines that induce protective adaptive immune responses to this pathogen

Business Cycle Spillovers in the European Union: What is the Message Transmitted to the Core?

We examine business cycle spillovers in the European Union over the period 1977–2014. The results of our analysis reveal that: (i) The total spillover indices are of high magnitude and very responsive to extreme economic events. (ii) The direction and magnitude of spillovers among group members (i.e. Eurozone core, Eurozone periphery, new Euro Area countries and non-European Monetary Union countries) is changing overtime. (iii) The widening of the European debt crisis can be explained by business cycle shocks in the whole Eurozone periphery. Thus, appropriate macroprudential stabilization policies aiming to steer peripheral economies towards growth should be formulated

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy