• N = 2 minimal models: A holographic needle in a symmetric orbifold haystack

      Belin, Alexandre; Benjamin, Nathan; Castro, Alejandra; Harrison, Sarah M.; Keller, Christoph A.; Univ Arizona, Dept Math (SCIPOST FOUNDATION, 2020-06)
      We explore large-N symmetric orbifolds of the N = 2 minimal models, and find evidence that their moduli spaces each contain a supergravity point. We identify single-trace exactly marginal operators that deform them away from the symmetric orbifold locus. We also show that their elliptic genera exhibit slow growth consistent with supergravity spectra in AdS(3). We thus propose an infinite family of new holographic CFTs.
    • n-3 Docosapentaenoic Acid Intake and Relationship with Plasma Long-Chain n-3 Fatty Acid Concentrations in the United States: NHANES 2003-2014

      Richter, Chesney K; Bisselou, Karl Stessy; Nordgren, Tara M; Smith, Lynette; Appiah, Adams Kusi; Hein, Nicholas; Anderson-Berry, Ann; Kris-Etherton, Penny; Hanson, Corrine; Skulas-Ray, Ann C; et al. (WILEY, 2019-04-01)
      The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (similar to 250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 +/- 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 +/- 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (beta = 138.5; p < 0.001) and DHA (beta = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (beta = 13.15; p = 0.001 and beta = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.
    • n-6 Linoleic Acid Induces Epigenetics Alterations Associated with Colonic Inflammation and Cancer

      Romagnolo, Donato F; Donovan, Micah G; Doetschman, Tom C; Selmin, Ornella I; Univ Arizona, Canc Ctr; Univ Arizona, Dept Nutr Sci; Univ Arizona, Interdisciplinary Canc Biol Grad Program; Univ Arizona, Dept Cellular & Mol Med (MDPI, 2019-01-15)
      The farnesoid-X-receptor (FXR) protects against inflammation and cancer of the colon through maintenance of intestinal bile acid (BA) homeostasis. Conversely, higher levels of BA and cyclooxygenase-2 (COX-2) are risk factors for inflammation and cancer of the colon. In the United States, n-6 linoleic acid (LA) is the most commonly used dietary vegetable fat. Metabolism of n-6 fatty acids has been linked to a higher risk of intestinal cancer. The objectives of this study were to investigate in colonic mucosa the effects of a high-fat diet rich in LA (n-6HFD) on CpG methylation of Fxr and prostaglandin-endoperoxide synthase-2 (Ptsg-2) genes, and the impact on the expression of tumor suppressor adenomatous polyposis Coli (Apc) and proliferative cyclin D1 (Ccnd1) genes. Weaned C57BL/6J male mice were fed for 6 weeks either an n-6HFD containing 44% energy (44%E) from 22% safflower oil (SO, 76% LA by weight) or a 13% energy (13%E) control diet (Control) from SO (5% by weight). Mice fed the n-6HFD had reduced (60%) Fxr promoter CpG methylation and increased (~50%) Fxr mRNA. The expression of FXR-target ileal bile acid-binding protein (Ibabp), small heterodimer protein (Shp), and anti-inflammatory peroxisome proliferator-activated-γ1 genes was increased. The n-6HFD reduced Ptgs-2 CpG methylation, increased the expression of Cox-2, and increased Apc CpG methylation in colonic mucosa. Accordingly, reduced expression of Apc was coupled to accumulation of c-JUN and Ccnd1, respectively cofactor and gene targets for the β-catenin/Wnt signaling pathway. Finally, the n-6HFD reduced the expression of histone deacetylase-1 while favoring the accumulation of acetylated histone 3. We conclude that an n-6HFD epigenetically modifies Fxr, leading to the activation of downstream factors that participate in BA homeostasis. However, epigenetic activation of Ptsg-2 coupled with silencing of Apc and accumulation of C-JUN and Ccnd1 may increase the risk of inflammation and cancer of the colon.
    • N-6-methyladenosine and RNA secondary structure affect transcript stability and protein abundance during systemic salt stress in Arabidopsis

      Kramer, Marianne C.; Janssen, Kevin A.; Palos, Kyle; Nelson, Andrew D. L.; Vandivier, Lee E.; Garcia, Benjamin A.; Lyons, Eric; Beilstein, Mark A.; Gregory, Brian D.; Univ Arizona, Sch Plant Sci; et al. (JOHN WILEY & SONS LTD, 2020-07)
      After transcription, a messenger RNA (mRNA) is further post-transcriptionally regulated by several features including RNA secondary structure and covalent RNA modifications (specifically N-6-methyladenosine, m(6)A). Both RNA secondary structure and m(6)A have been demonstrated to regulate mRNA stability and translation and have been independently linked to plant responses to soil salinity levels. However, the effect of m(6)A on regulating RNA secondary structure and the combinatorial interplay between these two RNA features during salt stress response has yet to be studied. Here, we globally identify RNA-protein interactions and RNA secondary structure during systemic salt stress. This analysis reveals that RNA secondary structure changes significantly during salt stress, and that it is independent of global changes in RNA-protein interactions. Conversely, we find that m(6)A is anti-correlated with RNA secondary structure in a condition-dependent manner, with salt-specific m(6)A correlated with a decrease in mRNA secondary structure during salt stress. Taken together, we suggest that salt-specific m(6)A deposition and the associated loss of RNA secondary structure results in increases in mRNA stability for transcripts encoding abiotic stress response proteins and ultimately increases in protein levels from these stabilized transcripts. In total, our comprehensive analyses reveal important post-transcriptional regulatory mechanisms involved in plant long-term salt stress response and adaptation.
    • N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes

      Li, Qike; Schissler, A. Grant; Gardeux, Vincent; Achour, Ikbel; Kenost, Colleen; Berghout, Joanne; Li, Haiquan; Zhang, Hao Helen; Lussier, Yves A.; Univ Arizona, Ctr Biomed Informat & Biostat; et al. (BIOMED CENTRAL LTD, 2017-05-24)
      Background: Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. Results: We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. Conclusion: The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.
    • The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.

      Ly, Thu; Moroz, Natalia; Pappas, Christopher T; Novak, Stefanie M; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M; Helms, Gregory; Gregorio, Carol C; Kostyukova, Alla S; et al. (AMER SOC CELL BIOLOGY, 2016-08-15)
      Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends.
    • An N-terminally truncated form of cyclic GMP–dependent protein kinase Iα (PKG Iα) is monomeric and autoinhibited and provides a model for activation

      Moon, Thomas M.; Sheehe, Jessica L.; Nukareddy, Praveena; Nausch, Lydia W.; Wohlfahrt, Jessica; Matthews, Dwight E.; Blumenthal, Donald K.; Dostmann, Wolfgang R.; Univ Arizona, Dept Chem & Biochem (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2018-05-25)
      The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG I activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (53). We found that the construct exists as a monomer as assessed by whole-protein MS, size-exclusion chromatography, and small-angle X-ray scattering (SAXS). Reconstruction of the SAXS 3D envelope indicates that 53 has a similar shape to the heterodimeric RI-C complex of PKA. Moreover, we found that the 53 construct is autoinhibited in its cGMP-free state and can bind to and be activated by cGMP in a manner similar to full-length PKG I as assessed by surface plasmon resonance (SPR) spectroscopy. However, we found that the 53 variant does not exhibit cooperative activation, and its cyclic nucleotide selectivity is diminished. These findings support a model in which, despite structural similarities, PKG I activation is distinct from that of PKA, and its cooperativity is driven by in trans interactions between protomers.
    • Naloxone availability and dispensing in Indiana pharmacies 2 years after the implementation of a statewide standing order

      Eldridge, Lori Ann; Agley, Jon; Meyerson, Beth E; Univ Arizona, Coll Med, Coll Social & Behav Sci Family & Community Med, Southwest Inst Res Women (ELSEVIER, 2020-06)
      Objectives: This study examined changes in rates of pharmacy naloxone stocking and dispensing in Indiana between 2016 and 2018 and explored supplemental variables and factors that may have affected observed differences. Methods: Researchers used data from 2 existing datasets that were collected from managing pharmacists who responded to statewide pharmacy censuses in 2016 and 2018. After identifying all cases in which a pharmacy's managing pharmacist responded in both 2016 and 2018 censuses, researchers conducted a nonparametric statistical comparison of naloxone stocking and dispensing rates in 107 Indiana pharmacies. Additional descriptive data regarding naloxone-related pharmacy policies and educational programs during those years were collected in 2019 from pharmacy corporations operating food stores or chain pharmacies in Indiana and from the Indiana Pharmacists Association. Results: Pharmacy stocking and dispensing in Indiana increased from 2016 to 2018. In 2016, 57% of pharmacies reported stocking naloxone compared with 92.5% in 2018 (P < 0.001). Similarly, 23.4% of pharmacies reported dispensing naloxone in 2016 compared with 76.6% of pharmacies in 2018 (P < 0.001). All responding pharmacy corporations and the state pharmacy association reported offering self-directed volunteer-training programs regarding naloxone since 2016. In addition, they reported that company policy and procedures regarding naloxone were put into place in response to the 2016 statewide standing order. Conclusion: Pharmacy naloxone stocking and dispensing increased in the 2 years after the statewide standing order was issued. The effect of the order itself was likely moderated or mediated by corporate responses to the law. Research examining the impact of naloxone-availability policies on pharmacy practice and patient incomes should longitudinally examine data after policy implementation and with covariates that include type of pharmacy (e.g., chain or independent), location, and opioid overdose-associated mortality rates. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
    • The Nancy Grace Roman Space Telescope Coronagraph Instrument (CGI) technology demonstration

      Kasdin, N. Jeremy; Bailey, Vanessa; Mennesson, Bertrand; Zellem, Robert; Ygouf, Marie; Rhodes, Jason; Luchik, Thomas; Zhao, Feng; Riggs, A J Eldorado; Seo, Byoung-Joon; et al. (SPIE, 2020-12-15)
      The Coronagraph Instrument (CGI) on the Nancy Grace Roman Space Telescope will demonstrate the highcontrast technology necessary for visible-light exoplanet imaging and spectroscopy from space via direct imaging of Jupiter-size planets and debris disks. This in-space experience is a critical step toward future, larger missions targeted at direct imaging of Earth-like planets in the habitable zones of nearby stars. This paper presents an overview of the current instrument design and requirements, highlighting the critical hardware, algorithms, and operations being demonstrated. We also describe several exoplanet and circumstellar disk science cases enabled by these capabilities. A competitively selected Community Participation Program team will be an integral part of the technology demonstration and could perform additional CGI observations beyond the initial tech demo if the instrument performance warrants it.
    • Nanofibre optic force transducers with sub-piconewton resolution via near-field plasmon–dielectric interactions

      Huang, Qian; Lee, Joon; Arce, Fernando Teran; Yoon, Ilsun; Angsantikul, Pavimol; Liu, Justin; Shi, Yuesong; Villanueva, Josh; Thamphiwatana, Soracha; Ma, Xuanyi; et al. (NATURE PUBLISHING GROUP, 2017-05-15)
      Ultrasensitive nanomechanical instruments, including the atomic force microscope (AFM)(1-4) and optical and magnetic tweezers(5-8), have helped shed new light on the complex mechanical environments of biological processes. However, it is difficult to scale down the size of these instruments due to their feedback mechanisms9, which, if overcome, would enable high-density nanomechanical probing inside materials. A variety of molecular force probes including mechanophores(10), quantum dots(11), fluorescent pairs(12,13) and molecular rotors(14-16) have been designed to measure intracellular stresses; however, fluorescence-based techniques can have short operating times due to photo-instability and it is still challenging to quantify the forces with high spatial and mechanical resolution. Here, we develop a compact nanofibre optic force transducer (NOFT) that utilizes strong near-field plasmon-dielectric interactions to measure local forces with a sensitivity of <200 fN. The NOFT system is tested by monitoring bacterial motion and heart-cell beating as well as detecting infrasound power in solution.
    • Nanoparticle doping for improved Er-doped fiber lasers

      Baker, Colin C.; Friebele, E. Joseph; Askins, Charles G.; Hunt, Michael P.; Marcheschi, Barbara A.; Fontana, Jake; Peele, John R.; Kim, Woohong; Sanghera, Jasbinder; Zhang, Jun; et al. (SPIE-INT SOC OPTICAL ENGINEERING, 2016-03-16)
      A nanoparticle (NP) doping technique was used for making erbium-doped fibers (EDFs) for high energy lasers. The nanoparticles were doped into the silica soot of preforms, which were drawn into fibers. The Er luminescence lifetimes of the NP-doped cores are longer than those of corresponding solution-doped silica, and substantially less Al is incorporated into the NP-doped cores. Optical-to-optical slope efficiencies of greater than 71% have been measured. Initial investigations of stimulated Brillouin scattering (SBS) have indicated that SBS suppression is achieved by NP doping, where we observed a low intrinsic Brillouin gain coefficient, of similar to 1x 10(-11) m/W and the Brillouin bandwidth was increased by 2.5x compared to fused silica.
    • Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

      Godfrey, Lisa; Iannitelli, Antonio; Garrett, Natalie L.; Moger, Julian; Imbert, Ian; King, Tamara; Porreca, Frank; Soundararajan, Ramesh; Lalatsa, Aikaterini; Schätzlein, Andreas G.; et al. (ELSEVIER SCIENCE BV, 2017-11-27)
      The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine(5)-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.
    • A narrow window of summer temperatures associated with shrub growth in Arctic Alaska

      Andreu-Hayles, Laia; Gaglioti, Benjamin V; Berner, Logan T; Levesque, Mathieu; Anchukaitis, Kevin J; Goetz, Scott J; D’Arrigo, Rosanne; Univ Arizona, Lab Tree Ring Res; Univ Arizona, Sch Geog & Dev (IOP PUBLISHING LTD, 2020-10-08)
      Warming in recent decades has triggered shrub expansion in Arctic and alpine tundra, which is transforming these temperature-limited ecosystems and altering carbon and nutrient cycles, fire regimes, permafrost stability, land-surface climate-feedbacks, and wildlife habitat. Where and when Arctic shrub expansion happens in the future will depend in part on how different shrub communities respond to warming air temperatures. Here, we analyze a shrub ring-width network of 18 sites consisting ofSalixspp. andAlnus viridisgrowing across the North Slope of Alaska (68-71 degrees N; 164-149 degrees W) to assess shrub temperature sensitivity and compare radial growth patterns with satellite NDVI (normalized difference vegetation index) data since 1982. Regardless of site conditions and taxa, all shrubs shared a common year-to-year growth variability and had a positive response to daily maximum air temperatures (Tmax) from ca. May 31 (i.e. Tmax similar to 6 degrees C) to early July (i.e. Tmax similar to 12 degrees C), two-thirds of which were significant correlations. Thus, the month of June had the highest shrub growth-temperature sensitivity. This period coincides with the seasonal increase in temperature and phenological green up on the North Slope indicated by both field observations and the seasonal cycle of NDVI (a proxy of photosynthetic activity). Nearly all of the sampled shrubs (98%) initiated their growth after 1960, with 74% initiated since 1980. This post-1980 shrub-recruitment pulse coincided with similar to 2 degrees C warmer June temperatures compared to prior periods, as well as with positive trends in shrub basal area increments and peak summer NDVI. Significant correlations between shrub growth and peak summer NDVI indicate these radial growth patterns in shrubs reflect tundra productivity at a broader scale and that tundra vegetation on the North Slope of Alaska underwent a greening trend between 1980 and 2012.
    • The NASA Roadmap to Ocean Worlds

      Hendrix, Amanda R; Hurford, Terry A; Barge, Laura M; Bland, Michael T; Bowman, Jeff S; Brinckerhoff, William; Buratti, Bonnie J; Cable, Morgan L; Castillo-Rogez, Julie; Collins, Geoffrey C; et al. (MARY ANN LIEBERT, INC, 2019-01-01)
      In this article, we summarize the work of the NASA Outer Planets Assessment Group (OPAG) Roadmaps to Ocean Worlds (ROW) group. The aim of this group is to assemble the scientific framework that will guide the exploration of ocean worlds, and to identify and prioritize science objectives for ocean worlds over the next several decades. The overarching goal of an Ocean Worlds exploration program as defined by ROW is to "identify ocean worlds, characterize their oceans, evaluate their habitability, search for life, and ultimately understand any life we find." The ROW team supports the creation of an exploration program that studies the full spectrum of ocean worlds, that is, not just the exploration of known ocean worlds such as Europa but candidate ocean worlds such as Triton as well. The ROW team finds that the confirmed ocean worlds Enceladus, Titan, and Europa are the highest priority bodies to target in the near term to address ROW goals. Triton is the highest priority candidate ocean world to target in the near term. A major finding of this study is that, to map out a coherent Ocean Worlds Program, significant input is required from studies here on Earth; rigorous Research and Analysis studies are called for to enable some future ocean worlds missions to be thoughtfully planned and undertaken. A second finding is that progress needs to be made in the area of collaborations between Earth ocean scientists and extraterrestrial ocean scientists.
    • Nasal delivery of a CRMP2-derived CBD3 adenovirus improves cognitive function and pathology in APP/PS1 transgenic mice

      Qi, Baochang; Yang, Yu; Cheng, Yingying; Sun, Di; Wang, Xu; Khanna, Rajesh; Ju, Weina; Univ Arizona, Ctr Innovat Brain Sci; Univ Arizona, Dept Pharmacol, Coll Med (BMC, 2020-04-09)
      Calcium dysregulation is a key pathological event in Alzheimer's disease (AD). In studying approaches to mitigate this calcium overload, we identified the collapsin response mediator protein 2 (CRMP2), an axonal guidance protein that participates in synapse dynamics by interacting with and regulating activity of N-methyl-D-aspartate receptors (NMDARs). We further identified a 15 amino acid peptide from CRMP2 (designated CBD3, for calcium-binding domain 3), that reduced NMDAR-mediated Ca2+ influx in cultured neurons and post-synaptic NMDAR-mediated currents in cortical slices. Whether targeting CRMP2 could be therapeutically beneficial in AD is unknown. Here, using CBD3, we tested the utility of this approach. Employing the APP/PS1 mouse model of AD which demonstrates robust pathophysiology including A beta 1-42 deposition, altered tau levels, and diminished cognitive functions, we asked if overexpression of CBD3 could rescue these events. CBD3 was engineered into an adeno-associated vector and nasally delivered into APP/PS1 mice and then biochemical (immunohistochemistry, immunoblotting), cellular (TUNEL apoptosis assays), and behavioral (Morris water maze test) assessments were performed. APP/PS1 mice administered adeno-associated virus (AAV, serotype 2) harboring CBD3 demonstrated: (i) reduced levels of A beta 1-42 and phosphorylated-tau (a marker of AD progression), (ii) reduced apoptosis in the hippocampus, and (iii) reduced cognitive decline compared with APP/PS1 mice or APP/PS1 administered a control virus. These results provide an instructive example of utilizing a peptide-based approach to unravel protein-protein interactions that are necessary for AD pathology and demonstrate the therapeutic potential of CRMP2 as a novel protein player in AD.
    • Nasal foreign bodies identified by rhinoscopy in dogs: 42 cases

      Dias, Maria Joana; Mouro, Sofia; Englar, Ryane E; Leal, Rodolfo O; Univ Arizona, Coll Vet Med (WILEY, 2020-09-28)
      Objective To evaluate signalment, clinical presentation, location and type of nasal foreign bodies identified by rhinoscopy in dogs. Materials and Methods We retrospectively reviewed medical records from dogs that presented for consultation between April 2012 and June 2019 and were diagnosed with nasal foreign body via rhinoscopy. Results Forty-two dogs met the study's inclusion criteria. Thirty (71.4%; 30/42) were purebreds. Males accounted for 59.5% (25/42) of cases. The median age was 4.0 years old and 76.2% (32/42) were dogs up to 7 years of age. Mean bodyweight was 21.8 kg and dogs weighing more than 10 kg were overrepresented (78.6%; 33/42). Sneezing occurred in 78.6% (33/42) of cases. Foreign body retrieval was achieved by rhinoscopy in all cases. The foreign body was extracted from the right nasal cavity in 52.4% (22/42) of cases and from the left one in 42.9% (18/42). Two dogs (4.8%; 2/42) presented with one foreign body in each nasal cavity. Most nasal cavity foreign bodies (90.5%; 38/42) were grass awns. Three (7.2%; 3/42) were mineral and one (1/42) was fabric. Follow-up was documented for 35 patients, of which 97.1% (34/35) experienced resolution of clinical signs. Seven cases (16.7%; 7/42) were lost to follow-up. Clinical Significance Nasal foreign bodies were more common in dogs up to 7 years of age and heavier than 10 kg. Sneezing was the primary clinical sign. The vast majority of foreign bodies were grass awns and rhinoscopy was an effective means of nasal cavity foreign body retrieval.
    • “Nash-in-Nash” Bargaining: A Microfoundation for Applied Work

      Collard-Wexler, Allan; Gowrisankaran, Gautam; Lee, Robin; Univ Arizona (UNIV CHICAGO PRESS, 2019-02-01)
      A "Nash equilibrium in Nash bargains" has become a workhorse bargaining model in applied analyses of bilateral oligopoly. This paper proposes a noncooperative foundation for "Nash-in-Nash" bargaining that extends Rubinstein's alternating offers model to multiple upstream and downstream firms. We provide conditions on firms' marginal contributions under which there exists, for sufficiently short time between offers, an equilibrium with agreement among all firms at prices arbitrarily close to Nash-in-Nash prices, that is, each pair's Nash bargaining solution given agreement by all other pairs. Conditioning on equilibria without delayed agreement, limiting prices are unique. Unconditionally, they are unique under stronger assumptions.
    • NASHA hyaluronic acid for the treatment of shoulder osteoarthritis: a prospective, single-arm clinical trial

      McKee, Michael D; Litchfield, Robert; Hall, Jeremy A; Wester, Tawana; Jones, John; Harrison, Andrew J; Univ Arizona, Coll Med (Dove Medical Press Ltd., 2019-06)
      Background: Osteoarthritis of the shoulder or glenohumeral joint is a painful condition that can be debilitating. Intra-articular injection with hyaluronic acid should be considered for patients not responding adequately to physical therapy or anti-inflammatory medication. Methods: This was a single-arm, open-label, prospective study of a single intra-articular injection of NASHA (non-animal hyaluronic acid) in patients with symptomatic glenohumeral osteoarthritis. Patients were followed up for 26 weeks post-treatment, during which time rescue medication with acetaminophen was permissible. The study objective was to demonstrate that a single injection of NASHA is well tolerated with an over-6-month 25% reduction in shoulder pain on movement, assessed using a 100-mm visual analog scale. Results: Forty-one patients were enrolled, all of whom received study treatment. The mean decrease in shoulder pain on movement score over the 6-month study period was -20.1 mm (95% CI: -25.2, -15.0 mm), corresponding to a mean reduction of 29.5% (22.0, 37.0%). Statistically significant improvements were also observed in shoulder pain at night and patient global assessment. There was no clear change over time in the percentage of patients using rescue medication and mean weekly doses were below 3500 mg. Seventeen patients (41.5%) experienced adverse events, all of which were mild or moderate. Two adverse events (both shoulder pain) were deemed related to study treatment. Conclusion: This study provides preliminary evidence that a single injection of NASHA may be efficacious over 6 months and well tolerated in patients with symptomatic glenohumeral osteoarthritis. Larger studies are needed for confirmation.
    • The National Clinical Assessment Tool for Medical Students in the Emergency Department (NCAT-EM)

      Jung, Julianna; Franzen, Douglas; Lawson, Luan; Manthey, David; Tews, Matthew; Dubosh, Nicole; Fisher, Jonathan; Haughey, Marianne; House, Joseph; Trainor, Arleigh; et al. (WESTJEM, 2018-01)
      Introduction: Clinical assessment of medical students in emergency medicine (EM) clerkships is a highly variable process that presents unique challenges and opportunities. Currently, clerkship directors use institution-specific tools with unproven validity and reliability that may or may not address competencies valued most highly in the EM setting. Standardization of assessment practices and development of a common, valid, specialty-specific tool would benefit EM educators and students. Methods: A two-day national consensus conference was held in March 2016 in the Clerkship Directors in Emergency Medicine (CDEM) track at the Council of Residency Directors in Emergency Medicine (CORD) Academic Assembly in Nashville, TN. The goal of this conference was to standardize assessment practices and to create a national clinical assessment tool for use in EM clerkships across the country. Conference leaders synthesized the literature, articulated major themes and questions pertinent to clinical assessment of students in EM, clarified the issues, and outlined the consensus-building process prior to consensus-building activities. Results: The first day of the conference was dedicated to developing consensus on these key themes in clinical assessment. The second day of the conference was dedicated to discussing and voting on proposed domains to be included in the national clinical assessment tool. A modified Delphi process was initiated after the conference to reconcile questions and items that did not reach an a priori level of consensus. Conclusion: The final tool, the National Clinical Assessment Tool for Medical Students in Emergency Medicine (NCAT-EM) is presented here.
    • The National Longitudinal Study of Young Life Scientists: Career differentiation among a diverse group of biomedical PhD students

      Wood, Christine V; Jones, Remi F; Remich, Robin G; Caliendo, Anne E; Langford, Nicole C; Keller, Jill L; Campbell, Patricia B; McGee, Richard; Univ Arizona, Coll Med (PUBLIC LIBRARY SCIENCE, 2020-06-09)
      Young biomedical PhD scientists are needed in a wide variety of careers. Many recent efforts have been focused on revising training approaches to help them choose and prepare for different careers. However, very little is known about how biomedical PhD students decide on and "differentiate" into careers, which limits the development of new training models. This knowledge gap also severely limits efforts to increase the representation of women and some racial/ethnic groups in academic research careers. Previous studies have used cross-sectional surveys of career interests and ratings, and have not been designed to identify career intentions. They also are limited by single-time data and response bias, having typically asked participants to recount decisions made years in the past. This report draws on annual, in-depth interviews with 147 biomedical PhD students from the start of the PhD to graduation. Qualitative content analysis methods were used to fully understand scientific development and career intentions over time. Longitudinal analysis reveals a striking level of fluidity and complexity in career intentions over time. Contrary to previous studies and the dominant narrative, data do not show generalized shifts away from academic careers. In addition to those who are consistent in this intention from the start, nearly as many students shift toward research academic careers as away from them, and only modest differences exist by gender and race/ethnicity. Thus, the dominant narrative misses the high fraction of individuals who acquire or sustain their intention to purse an academic research career during training. Efforts to increase diversity in academia must capitalize on and support those who are still considering and evolve toward an academic career. Efforts to revise research training should incorporate knowledge of the tremendous fluidity in when and how career differentiation occurs.