“Beautiful Chaos”: Clinicians’ Learning Experience in Collaborative Theater Programming

This study provides insights into speech-language pathology graduate student learning experiences during a community-based clinical rotation that targets skill development within an interdisciplinary theater program. Theater-based programming has shown some utility toward promoting pragmatic language skill development for children and teens outside of traditional clinical practice. In addition, the interdisciplinary nature of the program provides opportunities for student clinicians to engage in interprofessional collaboration with arts professionals. The purpose of this study was to explore SLP graduate students’ experiences within a collaborative inclusion theater program. Semi-structured interviews collected from three graduate student clinicians were transcribed and analyzed according to Interpretive Phenomenological Analysis (IPA) methods to yield insights from student participant perspectives of this assigned clinical rotation. Analysis of interview data suggests participants found opportunities to problem-solve collaborative roles and balances while forming concrete ideas related to how to a therapeutic effect. The most salient concepts present across student accounts of experience included openness to the ongoing nature of the learning process, appreciation for the collaborative teaming involved in program activities, and the establishment of a set of ideas and tools to use for clinical utility. This study provides helpful information for clinical educators considering the benefit of embedding potential interprofessional collaborations with performing arts professionals in clinical education

Effect of Text Messaging and Cellphone Use on a Multi-sensory Tracking Task

This experiment studied subjects’ performance on a continuous multisensory tracking task. Different theories suggest that there is a decrease in performance due to attentional capacity; furthermore, talking or texting on a mobile phone will negatively affect task performance. Twenty-four college-age students were recruited to be tested on the Biodex Balance System SD with the texting condition, talking on a mobile phone condition, and control condition. Results showed that text messaging while performing a continuous multisensory tracking task negatively affected performance. There was no significant difference, however, between the control condition and talking on a mobile phone while completing the task. Results suggest that talking on a mobile phone has become second-nature to this sub-set of the population, thus not exceeding the resource capacity. However, the text messaging condition proved to be a more challenging secondary task, causing the amount of attention needed for this task to be increased. Attention was diverted from the primary task, causing a decrease in performance. It can be concluded that texting while performing a multi-sensory tracking task can have deleterious effects on attention. These findings have a direct application to texting while driving; it is not possible to safely communicate via text message while operating a motor vehicle

A qualitative investigation of the impact of coronavirus disease 2019 (COVID-19) on emergency physicians\u27 emotional experiences and coping strategies

Study objective Throughout the coronavirus disease 2019 (COVID-19) pandemic, emergency physicians in the United States have faced unprecedented challenges, risks, and uncertainty while caring for patients in an already vulnerable healthcare system. As such, the pandemic has exacerbated high levels of negative emotions and burnout among emergency physicians, but little systematic qualitative work has documented these phenomena. The purpose of this qualitative investigation was to study emergency physicians’ emotional experiences in response to COVID-19 and the coping strategies that they employed to navigate the pandemic. Methods From September 2020 to February 2021, we conducted semistructured interviews with 26 emergency physicians recruited from 2 early COVID-19 epicenters: New York City and the Metro Boston region. Interviews, coding, and analyses were conducted using a grounded theory approach. Results Emergency physicians reported heightened anxiety, empathy, sadness, frustration, and anger during the pandemic. Physicians frequently attributed feelings of anxiety to medical uncertainty around the COVID-19 virus, personal risk of contracting the virus and transmitting it to family members, the emergency environment, and resource availability. Emergency physicians also discussed the emotional effects of policies prohibiting patients’ family members from entering the emergency department (ED), both on themselves and patients. Sources of physician anger and frustration included changing policies and rules, hospital leadership and administration, and pay cuts. Some physicians described an evolving, ongoing coping process in response to the pandemic, and most identified collective discussion and processing within the emergency medicine community as an effective coping strategy. Conclusions Our findings underscore the need to investigate the effects of physicians’ pandemic-related emotional stress and burnout on patient care. Evidence-based interventions to support emergency physicians in coping with pandemic-related trauma are needed

Detection of Distant Relatedness in Biobanks To Identify Undiagnosed Cases of Mendelian Disease As Applied to Long Qt Syndrome

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this haplotype, which we confirm to carry p.Asp76Asn. Referral and non-referral carriers have prolonged QT interval corrected for heart rate (QTc) compared to controls, and, among carriers, the QTc polygenic score is independently associated with QTc prolongation. Thus, our innovative analysis of shared chromosomal segments identifies undiagnosed cases of genetic disease and refines the understanding of LQT5 penetrance and phenotype

Identification of human CD4+ T cell populations with distinct antitumor activity

How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies

Green Sturgeon Physical Habitat Use in the Coastal Pacific Ocean

The green sturgeon (Acipenser medirostris) is a highly migratory, oceanic, anadromous species with a complex life history that makes it vulnerable to species-wide threats in both freshwater and at sea. Green sturgeon population declines have preceded legal protection and curtailment of activities in marine environments deemed to increase its extinction risk. Yet, its marine habitat is poorly understood. We built a statistical model to characterize green sturgeon marine habitat using data from a coastal tracking array located along the Siletz Reef near Newport, Oregon, USA that recorded the passage of 37 acoustically tagged green sturgeon. We classified seafloor physical habitat features with high-resolution bathymetric and backscatter data. We then described the distribution of habitat components and their relationship to green sturgeon presence using ordination and subsequently used generalized linear model selection to identify important habitat components. Finally, we summarized depth and temperature recordings from seven green sturgeon present off the Oregon coast that were fitted with pop-off archival geolocation tags. Our analyses indicated that green sturgeon, on average, spent a longer duration in areas with high seafloor complexity, especially where a greater proportion of the substrate consists of boulders. Green sturgeon in marine habitats are primarily found at depths of 20–60 meters and from 9.5–16.0°C. Many sturgeon in this study were likely migrating in a northward direction, moving deeper, and may have been using complex seafloor habitat because it coincides with the distribution of benthic prey taxa or provides refuge from predators. Identifying important green sturgeon marine habitat is an essential step towards accurately defining the conditions that are necessary for its survival and will eventually yield range-wide, spatially explicit predictions of green sturgeon distribution

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

From macromolecular crowding to transcriptional regulation: Exploring the complexities of cytochrome P450s, cannabinoids, and inflammation

Cytochrome P450s are an extremely versatile group on enzymes capable of metabolizing fatty acids, eicosanoids, sterols, vitamins, and xenobiotics. Those that metabolize fatty acids are of particular interest since some of the eicosanoid products are anti-inflammatory and have been shown to interact with the endogenous cannabinoid system. The determination that eicosanoids also function as endocannabinoids has opened the door to comparisons with phytocannabinoids and questions about how the presence This work is aimed at untangling the complex web of P450 interactions with the environment and cannabinoids, the regulation of inflammation, and the intersection of these two topics. Described in Chapter 2 is the investigation of lipid composition and macromolecular crowding and their effects on the stability and protein-protein interactions of the Cytochrome P450 2J2 (CYP2J2) and its redox partner Cytochrome P450 Reductase (CPR). CYP2J2 is a membrane-bound epoxygenase expressed in cardiac tissue that is known to metabolize fatty acids as well as several xenobiotics. Previous studies on the effects of macromolecular crowding had all been performed on soluble enzymes, thus, we set out to determine the effects of macromolecular crowding on a membrane protein system. It was determined that crowding effects in a lipid-solubilized system are size-dependent and that crowding effects in nanodiscs depend on both size and crowding agent identity. Additionally, we thought to determine the effects of membrane lipids on protein activity as CYP2J2 is an integral membrane protein. By varying the percentage of anionic lipids, sphingolipids, and cholesterol, we were able to determine an optimal percentage range for anionic lipid composition. We were also able to determine that the presence of sphingolipids results in increased secondary metabolite, likely due to processive metabolism. Described in Chapter 3 is an exploration of the interactions of Cytochrome P450 2D6 (CYP2D6) and several of its polymorphisms with an array of phytocannabinoids (pCBs). CYP2D6 is a highly polymorphic CYP which has been shown previously to be inhibited by cannabidiol (CBD). In our current study, we examined the binding of eight pCBs to four common polymorphisms of CYP2D6 that are representative of different ethnic groups. We found that CYP2D6*17 has much larger spin-shifts than the other mutants tested, and that THC binds all four mutants more tightly than other pCBs. It was also determined that the inhibition of CYP2D6 by pCBs is dependent on the substrate molecules, as DXM and AEA metabolism were not inhibited by the same group of pCBs. Lastly, we were able use MD simulations to show differences in binding affinity and distance from the heme that are polymorphism dependent. Described in Chapter 4 is an examination of the interactions between different branches of the Arachidonase super-pathway. Arachidonic acid is an ω-6 polyunsaturated fatty acid that can be metabolized by COX, LOX, and CYP enzymes to produce pro- and anti-inflammatory metabolites. Each pathway metabolizes arachidonic acid into different products, which can either feed into each other, or work at cross-purposes. Described in Chapter 5 is the deconvolution of the murine IL-6 enhancer. Interleukin-6 (IL-6) is a known proinflammatory cytokine and participant in the acute inflammatory response. Although it is well studied, there is still much to be learned about the intricacies of how its expression is regulated. Gene expression is directly controlled through regulatory elements known as enhancers, which are regions of DNA containing transcription factor (TF) binding sites. Every TF has a unique motif to which it binds, which can in turn vary in strength according to sequence. Described within is the development of an IL-6 enhancer library which test multiple aspects of transcriptional regulation including binding site strength, distance, number, and order. Using MPRA, we are able to analyze our entire library simultaneously, affording us a high-throughput and experimentally equal view on how different aspects of the IL-6 enhancer affect regulation.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste