• 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-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.
    • 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.
    • 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.
    • “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.
    • National patterns of physician management of sleep apnea and treatment among patients with hypertension

      Robbins, Rebecca; Seixas, Azizi; Jean-Louis, Girardin; Parthasarathy, Sairam; Rapoport, David M.; Ogedegbe, Gbenga; Ladapo, Joseph A.; Univ Arizona, Dept Med (PUBLIC LIBRARY SCIENCE, 2018-05-23)
      Study objectives Sleep apnea is associated with hypertension, and treatment may improve outcomes. We examine national burden of sleep apnea, rates of sleep apnea treatment, and whether racial/ethnic disparities exist among patients with hypertension. Methods Data from the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS), 2005-2012, were analyzed (N = 417,950). We identified hypertension patient visits where sleep apnea diagnosis or complaint was recorded. Primary outcome measures were sleep study, medication, or behavioral therapy (diet, weight loss, or exercise counseling). We used multivariate logistic regression to examine treatment by demographic/clinical factors. Results Among patients with hypertension, sleep apnea was identified in 11.2-per-1,000 visits. Overall, patients with hypertension and a sleep disorder were referred for sleep study in 14.4% of visits, prescribed sleep medication in 11.2% of visits, and offered behavioral therapy in 34.8% of visits. Adjusted analyses show behavioral therapy more likely to be provided to obese patients than normal/overweight (OR = 4.96, 95%CI[2.93-8.38]), but less likely to be provided to smokers than nonsmokers (OR = 0.54, 95%)/CI[0.32-0.93]). Non-Hispanic blacks were less likely to receive medications than non-Hispanic whites (OR = 0.19, 95% CI[0.06-0.65]). Conclusions In the U.S., sleep apnea were observed in a small proportion of hypertension visits, a population at high-risk for the disorder. One explanation for the low prevalence of sleep apnea observed in this patient population at high risk for the disorder is under-diagnosis of sleep related breathing disorders. Behavioral therapy was underutilized, and non-Hispanic Blacks were less likely to receive medications than non-Hispanic Whites.
    • A national study of sustained use of force complaints in law enforcement agencies

      Pryor, Cori; Boman, John H.; Mowen, Thomas J.; McCamman, Michael; Univ Arizona (ELSEVIER, 2019-07-27)
      Purpose: This article examines how community and departmental characteristics relate to the number of sustained use of force complaints in a law enforcement agency. Methods: Using national-level data from Law Enforcement Management and Administrative Statistics 2007, Uniform Crime Reports 2007, American Community Survey 2009 and bivariate and multivariate techniques, we investigate whether sustained uses of force vary across 1) community and regional characteristics in the U.S. and across departmental 2) policies, 3) training tendencies, and 4) hiring practices. Results: Controlling for region, crime rate, and area median income, results demonstrate that sustained complaints increase when departments serve large, nonwhite populations. Regarding departmental policies, results are alarming: Departments with independent civilian complaint review boards, agencies which engage in community policing, and departments that implement personality tests when hiring sustain significantly higher numbers of use of force complaints. However, departments that screen for volunteer and community service histories in officer candidates have over one third fewer sustained complaints than departments that do not use this hiring screen. Conclusions: In order to significantly reduce the amount of sustained complaints against a department, results suggest that agencies should assess community service and volunteer histories for potential officer candidates.
    • A National Survey of Orthopaedic Residents Identifies Deficiencies in the Understanding of Medical Statistics

      Araoye, Ibukunoluwa; He, Jun Kit; Gilchrist, Scott; Stubbs, Trevor; McGwin, Gerald; Ponce, Brent A; Univ Arizona (LIPPINCOTT WILLIAMS & WILKINS, 2020-03-04)
      Background: Biomedical research is essential for optimizing patient care. Research has suggested inadequacies in nonorthopaedic trainees' understanding of study design and biostatistics. This study assesses orthopaedic residents' knowledge of common biostatistical and study design concepts, as well as their confidence in utilizing the medical literature. Methods: A validated survey assessing knowledge and the application of study design concepts was administered to residents at 10 U.S. institutions. The survey tested knowledge as well as confidence and attitudes regarding common biostatistics principles. The association of demographic characteristics, work activities, and confidence and attitude ratings with test performance were examined using t tests and analysis of variance. Results: The survey response rate was 64% (178 of 279). The largest group of participants were men (83%, 137 of 165), were between the ages of 26 and 30 years (59%, 105 of 177), and had graduated medical school within the past 4 to 10 years (43%, 76 of 175). Fifty-three percent (93 of 176) had prior biostatistics training, while 44% (77 of 176) had prior epidemiology training. Less than 5% of biostatistics or epidemiology training had taken place after medical school. Forty-seven percent (83 of 176) were unable to determine a study's design. Thirty-eight percent (67 of 178) could not apply the concept of specificity and sensitivity. Eighty-three percent (147 of 178) could not assess the strength of a relationship using odds ratios. Sixty-nine percent (123 of 178) understood the implications of p values. Previous biostatistics training, but not epidemiology or evidence-based medicine training; inclusion of reading research, attending conferences, and data analysis; as well as a self-reported finding of statistics as important for the analysis of one's own research data were significantly associated with better test performance (p < 0.05). Conclusions: Notable deficits exist in orthopaedic residents' biostatistical knowledge. Greater emphasis is needed to improve biostatistics and research design training. The impact of biostatistics knowledge and/or aptitude on clinical decision-making is an area of suggested research.
    • Nationally Determined Contributions: Material climate commitments and discursive positioning in the NDCs

      Mills‐Novoa, Megan; Liverman, Diana M.; Univ Arizona, Sch Geog & Dev (WILEY, 2019-05-29)
      In the lead-up to the 2015 Conference of Parties meeting in Paris, 186 countries, representing over 95% of global emissions, submitted Nationally Determined Contributions (NDCs). The NDCs outline national goals for greenhouse gas emission reductions and identify financial needs for unfolding mitigation and adaptation efforts. In this study, we review various analyses of the NDCs that cover the aggregate impact and strength of emissions reduction commitments and discuss recent literature on the adequacy and sectoral focus of the NDCs. We then argue that the NDCs are more than just goal setting reports; they are important discursive documents that are contested, negotiated, and ongoing. To supplement the existing literature, we examine the discursive narratives embedded in the NDCs from the 19 founding nations of the Climate Vulnerable Forum and the top 10 greenhouse gas emitters. Our literature review of quantitative and sectoral aspects of the NDCs highlights the inadequacy of the NDC commitments in the context of limiting warming to 2 degrees C, discusses the uncertainties in the promised mitigation strategies, and identifies the reliance of many countries on policies such as those on forests or renewable energy. Our own analysis of the discourses in the NDCs adds critical depth by highlighting the stark contrasts in NDC discourses between North and South, as well as between historical emitters and emerging economies. These contrasts reflect deeper debates regarding justice and equity between nations within the UNFCCC negotiations. This article is categorized under: Climate and Development > Decoupling Emissions from Development
    • Nationwide Analysis of Resuscitative Endovascular Balloon Occlusion of the Aorta in Civilian Trauma

      Joseph, Bellal; Zeeshan, Muhammad; Sakran, Joseph V; Hamidi, Mohammad; Kulvatunyou, Narong; Khan, Muhammad; O'Keeffe, Terence; Rhee, Peter (AMER MEDICAL ASSOC, 2019-06)
      IMPORTANCE The need for improved methods of hemorrhage control and resuscitation has resulted in a reappraisal of resuscitative endovascular balloon occlusion of the aorta (REBOA). However, there is a paucity of data regarding the use of REBOA on a multi-institutional level in the United States. OBJECTIVE To evaluate the outcomes in trauma patients after REBOA placement. DESIGN, SETTING, AND PARTICIPANTS A case-control retrospective analysis was performed of the 2015-2016 American College of Surgeons Trauma Quality Improvement Program data set, a national multi-institutional database of trauma patients in the United States. A total of 593 818 adult trauma patients (aged >= 18 years) were analyzed and 420 patients were matched and included in the study; patients who were dead on arrival or were transferred from other facilities were excluded. Trauma patients who underwent REBOA placement in the ED were identified and matched with a similar cohort of patients (the no-REBOA group). Both groups were matched in a 1: 2 ratio using propensity score matching for demographics, vital signs, mechanism of injury, injury severity score, head abbreviated injury scale score, each body region abbreviated injury scale score, pelvic fractures, lower extremity vascular injuries and fractures, and number and grades of intra-abdominal solid organ injuries. MAIN OUTCOMES AND MEASURES Outcome measures were the rates of complications and mortality. RESULTS Of 593 818 trauma patients, 420 patients (the REBOA group, 140 patients; 36 women and 104 men; mean [SD] age, 44 [20] years; the no-REBOA group, 280 patients; 77 women and 203 men; mean [SD] age, 43 [19] years) were matched and included in the analysis. Among the REBOA group, median injury severity score was 29 (interquartile range [IQR], 18-38) and 129 patients (92.1%) had a blunt mechanism of injury. There was no significant difference between groups in median 4-hour blood transfusion (REBOA: packed red blood cells, 6 U [IQR, 3-8 U]; platelets, 4 U [IQR, 3-9 U], and plasma, 3 U [IQR, 2-5 U]; and no-REBOA: packed red blood cells, 7 U [IQR, 3-9 U]; platelets, 4 U [IQR, 3-8 U], and plasma, 3 U [IQR, 2-6 U]) or 24-hour blood transfusion (REBOA: packed red blood cells, 9 U [IQR, 5-20 U]; platelets, 7 U [IQR, 3-13 U], and plasma, 9 U [IQR, 6-20 U]; and no-REBOA: packed red blood cells, 10 U [IQR, 4-21 U]; platelets, 8 U [IQR, 3-12 U], and plasma, 10 U [IQR, 7-20 U]), median hospital length of stay (REBOA, 8 days [IQR, 1-20 days]; and no-REBOA, 10 days [IQR, 5-22 days]), or median intensive care unit length of stay (REBOA, 5 days [IQR, 2-14 days]; and no-REBOA, 6 days [IQR, 3-15 days]). The mortality rate was higher in the REBOA group as compared with the no-REBOA group (50 [35.7%] vs 53 [18.9%]; P = .01). Patients who underwent REBOA placement were also more likely to develop acute kidney injury (15 [10.7%] vs 9 [3.2%]; P = .02) and more likely to undergo lower extremity amputation (5 [3.6%] vs 2 [0.7%]; P = .04). CONCLUSIONS AND RELEVANCE Placement of REBOA in severely injured trauma patients was associated with a higher mortality rate compared with a similar cohort of patients with no placement of REBOA. Patients in the REBOA group also had higher rates of acute kidney injury and lower leg amputations. There is a need for a concerted effort to clearly define when and in which patient population REBOA has benefit.
    • Native American Perspectives on Health and Traditional Ecological Knowledge

      Isaac, Gwyneira; Finn, Symma; Joe, Jennie R; Hoover, Elizabeth; Gone, Joseph P; Lefthand-Begay, Clarita; Hill, Stewart; Univ Arizona, Coll Med, Dept Family & Community Med (US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE, 2018-12-01)
      BACKGROUND: Traditional ecological knowledge (TEK) is a conceptual framework that highlights Indigenous knowledge (IK) systems. Although scientific literature has noted the relevance of TEK for environmental research since the 1980s, little attention has been given to how Native American (NA) scholars engage with it to shape tribal-based research on health, nor how non-Native scholars can coordinate their approaches with TEK. This coordination is of particular importance for environmental health sciences (EHS) research exploring interdisciplinary approaches and the integration of environmental and human health. OBJECTIVE: Our perspective on TEK arose from a series of Health and Culture Research Group (HCRG) workshops that identified gaps in existing EHS methodologies that are based on a reliance on Euro-American concepts for assessing environmental exposures in tribal communities. These prior methods neither take into account cultural behavior nor community responses to these. Our objective is to consider NA perspectives on TEK when analyzing relationships between health and the environment and to look at how these may be applied to address this gap. DISCUSSION: The authors-the majority of whom are NA scholars-highlight two research areas that consider health from a TEK perspective: food systems and knowledge of medicinal plants. This research has yielded data, methods, and knowledge that have helped Indigenous communities better define and reduce health risks and protect local natural food resources, and this TEK approach may prove of value to EHS research. CONCLUSION: NA perspectives on TEK resulting from the HCRG workshops provide an opportunity for developing more accurate Indigenous health indicators (IHI) reflecting the conceptualizations of health maintained in these communities. This approach has the potential to bridge the scientific study of exposure with methods addressing a tribal perspective on the sociocultural determinants of health, identifying potential new areas of inquiry in EHS that afford nuanced evaluations of exposures and outcomes in tribal communities.