Academic literature on the topic 'Nicola Dickson'

Dans cet article, Nicole Nolette explore le potentiel du concept de « différenciation solidaire » pour l’analyse intertextuelle entre les littératures francophones de l’Ontario et de l’Ouest canadien. Les grandes figures des « trois D » de l’Ontario français (Patrice Desbiens, Robert Dickson et Jean Marc Dalpé), rejetées par la génération de Louis Patrick Leroux, réapparaissent dans la dramaturgie de Marc Prescott au Manitoba et de Gilles Poulin-Denis, originaire de la Saskatchewan. Nicole Nolette identifie les traces des trois D dans la langue, la route, la ville minière et les animaux représentés par Prescott et Poulin-Denis pour montrer comment la solidarisation littéraire de l’Ouest et de l’Ontario francophones peut également signifier une différenciation régionale.

Abstract Background E. coli is the predominant uropathogen isolated in uncomplicated urinary tract infections (UTI). Surveillance data suggest increasing antimicrobial resistance (AMR), although recent data from the outpatient setting are limited. Treatment is typically empiric and should be guided by local resistance rates; however, this is challenging in the absence of routine culture and assessment of regional AMR. We characterized AMR trends for E. coli isolated from females with outpatient UTI in the US, from 2011 to 2019. Methods A retrospective multicenter cohort study of antimicrobial susceptibility using data from the BD Insights Research Database (Franklin Lakes, NJ) was conducted. The first E. coli urine culture isolates representing each distinct susceptibility pattern within 30 days of index urine from 2011–2019 were included from females ≥ 12 years old. E. coli isolates were identified as not-susceptible (NS) if intermediate or resistant to trimethoprim-sulfamethoxazole (TMP-SMX NS), fluoroquinolone (FQ NS), nitrofurantoin (NFT NS), ESBL+ (by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime), and multi-drug resistant (MDR), defined as NS to ≥ 2 or ≥ 3 of FQ, TMP-SMX, NFT or ESBL+. Descriptive analyses characterized AMR (%) over time and generalized estimating equations were used to statistically assess AMR trends over time. Results A total of 1,513,882 E. coli isolates were tested at 106 to 295 US centers between 2011 and 2019. Over the study period, AMR remained persistently high (> 20%) for FQ and TMP-SMX and increased for the MDR (≥ 3 drugs) phenotype (from 3.1% to 4.0%) (Table). Prevalence of the ESBL+ phenotype increased year-on-year (from 4.1% to 7.3%). Modeling confirmed a significant increasing trend for the ESBL+ (7.7%/year) and MDR (≥ 3 drugs) phenotypes (2.7%/year) (P< 0.001), with decreasing or no trend change for NFT NS and other AMR phenotypes (Table). Table. Descriptive Statistics and Model-estimated Annual Change of AMR (count and % not-susceptible out of isolates tested) in E. coli among US Females (≥12 years of age) with Outpatient UTI Conclusion Characterization of AMR trends for E. coli over the last decade, in outpatient E. coli isolates in US females, shows persistently high AMR to FQ and TMP-SMX, and increasing AMR trends for the ESBL+ and MDR (≥ 3 drugs) phenotypes. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Gang Ye, PhD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Abstract Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, and is associated with an aggressive soft-tissue sarcoma, malignant peripheral nerve sheath tumours (MPNSTs), the greatest cause of mortality in people with NF1. The only potentially curative therapy involves en bloc resection with negative margins, which is not always appropriate. Even therapy with curative intent is associated with poor overall survival for both sporadic and NF1-related MPNSTs. The development of novel therapies has been largely hindered by a poor understanding of the molecular events underpinning MPNST pathogenesis. We report a comprehensive multi-omic study of MPNST evolution based on whole genome sequencing, transcriptomic and methylation profiling data on 95 tumors (64 NF1-related; 31 sporadic). In all cases, the early events in MPNST evolution involve biallelic inactivation of NF1 followed by inactivation of CDKN2A, as well as mutations in TP53 or PRC2 complex genes in a subset of cases. Analysis of the genomic architecture revealed distinct pathways of tumor evolution that can be identified through H3K27 trimethylation (H3K27me3) status. Integration of these data allows us to propose several mechanistic tumor evolution models. Tumors with H3K27me3 loss evolve through extensive copy number aberrations (CNAs) including haploidization followed by whole genome doubling and chromosome 8 amplifications, whereas tumors with H3K27me3 retention evolve through extensive chromosome instability and chromothripsis. Taken together, these genome-wide CNA profiles act as a surrogate for the loss of H3K27me3 status and correlate with prognosis, suggesting that CNA profiling of cell-free DNA could be incorporated in clinical decision-making. Citation Format: Isidro Cortes Ciriano, Chris D. Steele, Katherine Piculell, Alyaa Al-Ibraheemi, Vanessa Eulo, Marilyn M. Bui, Aikaterini Chatzipli, Brendan C. Dickson, Dana C. Borcherding, Alon Galor, Jesse Hart, Andrew Feber, Kevin B. Jones, Justin T. Jordan, Raymond H. Kim, Daniel Lindsay, Colin Miller, Yoshihiro Nishida, Jonathan Serrano, Nicole J. Ullrich, David Viskochil, Xia Wang, Matija Snuderl, Paula Proszek, Peter J. Park, Adrienne M. Flanagan, Angela C. Hirbe, Nischalan Pillay, David T. Miller, The Genomics of MPNST (GeM) Consortium. Recurrent genomic patterns of MPNST evolution correlate with clinical outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6084.

Abstract Background The 2019 CDC Threats Report lists extended spectrum β-lactamase (ESBL) producing Enterobacterales as a serious health threat. While the clinical epidemiology of uncomplicated urinary tract infection (uUTI) has remained stable, there has been a notable increase in antimicrobial resistance (AMR) among community-acquired uUTIs. Urine cultures are seldom ordered for uUTI as treatment is often empiric; local surveillance data may therefore be lacking. The study objective was to determine the prevalence and geographic distribution of AMR in urine E. coli isolates from females in the US outpatient setting. Methods A retrospective cross-sectional study of E. coli ambulatory urine isolates identified from females (≥ 12 years of age) at 296 facilities, with ≥ 1 quarter of data in 2019 (BD Insights Research Database, Franklin Lakes, NJ). Initial isolates representing each distinct susceptibility pattern within 30 days of index urine were included. E. coli isolates were identified as not-susceptible (NS) if intermediate/resistant to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone (FQ), nitrofurantoin (NFT), ESBL+ (by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime), and multi-drug resistant, defined as NS to ≥ 2 or ≥ 3 of FQ, TMP-SMX, NFT or ESBL+. Logistic regression models were used to evaluate resistance prevalence and variation across US census regions. Results Of 267,524 non-duplicate E. coli isolates evaluated, 25.1% (67,189) were TMP-SMX NS, 20.3% (54,359) were FQ NS, 7.3% (19,576) were ESBL+, 3.5% (9,453) were NFT NS, 14.0% (37,328) were NS to ≥ 2 drugs and 4.0% (10,814) were NS to ≥ 3 drugs. For all phenotypes, there was significant variation in resistance across census regions (all P< 0.001) with the highest in the East South Central region and lowest in the New England region of the US (Table). The figure shows regional prevalence of ESBL+ E. coli in 2019. Table. Antimicrobial resistance data from 30-day non-duplicate urine E. coli isolates in females ≥12 years old in 2019, by US census region. Figure. Heat map of the overall US geographic distribution of ESBL+ E. coli (30-day non-duplicate urine isolates) from females across 296 acute care facilities in 2019. Conclusion The 2019 prevalence of AMR in non-duplicate ambulatory E. coli urine isolates was notable: TMP-SMX NS and FQ NS were > 20%. In addition, there were significant regional differences in resistance, with the highest in the East South Central region of the US, for all NS phenotypes. These analyses inform, and may optimize, empiric treatment of uUTI and patient outcomes. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Anthony Boyles, MSc, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Abstract Background An estimated 12% of women experience ≥ 1 episode of urinary tract infection (UTI) annually. Incidence is bimodal, with peaks occurring in young, sexually active women (18–24 years) and in post-menopausal women. Previous studies suggest the prevalence of antimicrobial resistance (AMR) in UTI is rising; however recent AMR data for community-acquired UTI are lacking. We estimated the prevalence of AMR among US females with outpatient UTI in 2011–2019, stratified by age. Methods A retrospective, multicenter, cohort study of AMR among non-duplicate urine isolates in US females (≥ 12 years of age) from 296 institutions from 2011–2019 (BD Insights Research Database, Franklin Lakes, NJ). Phenotypes examined for Enterobacterales (ENT) were: extended spectrum β-lactamase positive (ESBL+; determined by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime); nitrofurantoin (NFT) not-susceptible (NS); fluoroquinolone (FQ) NS; trimethoprim-sulfamethoxazole (TMP-SMX) NS; and NS to ≥ 2 or ≥ 3 drug classes (including ESBL+). Gram-positive phenotypes were, methicillin resistant S. aureus and S. saprophyticus and vancomycin-resistant Enterococcus. Isolates were stratified by patient age (≥ 12 to < 18, ≥ 18 to < 55, ≥ 55 to < 65, ≥ 65 to < 75, ≥ 75 years). Chi-square tests were used to evaluate AMR difference between groups. Results In total, urine isolates were collected from 106 to 296 (2011–2019) US sites. Overall, the prevalence of antimicrobial NS increased with age for all E. coli phenotypes (all P< 0.001; Table 1), and for non-E. coli ENT (all P< 0.001), except NFT NS, which decreased from 70.6% to 59.7% (P=0.002; Table 2). The greatest difference between age groups in prevalence of resistance was observed for FQ NS E.coli: 5.8% (≥ 12 to < 18 years) vs 34.5% (≥ 75 years). For the multi-drug resistant E. coli phenotypes, resistance increased with age, ranging from 4.8–22.4% and 0.9–6.5% for ≥ 2 and ≥ 3 drug NS, respectively. Overall, the prevalence of resistance for Gram-positive phenotypes increased with age (all P< 0.001; Table 3). Table 1. Prevalence of antimicrobial resistance among E. coli isolates in US females with outpatient UTI by age group. Table 2. Prevalence of antimicrobial resistance among non-E. coli ENT isolates in US females with outpatient UTI by age group. Table 3. Prevalence of antimicrobial resistance among Gram-positive isolates in US females with outpatient UTI by age group. Conclusion The prevalence of AMR in E. coli and non-E. coli ENT increased with age among US females presenting for care in the outpatient setting overall. A similar trend increase by age is also seen in Gram-positive isolates. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Gang Ye, PhD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Reeve, Alison J., Anthony H. Dickenson, and Nicola C. Kerr. Spinal effects of bicuculline: modulation of an allodynia-like state by an A1-receptor agonist, morphine, and an NMDA-receptor antagonist. J. Neurophysiol. 79: 1494–1507, 1998. Single-unit recordings were made in the intact anesthetized rat of the responses of dorsal horn neurons to C-, Aδ-, and Aβ-fiber stimulation. The postdischarge and windup responses of the same cells along with responses to innocuous stimuli, prod and brush, also were measured. The effects of (−)-bicuculline-methobromide (0.5, 5, 50, and 250 μg) were observed on these neuronal responses. The C- and Aδ-fiber–evoked responses were facilitated significantly in a dose-dependent manner. The input was facilitated, but as the final overall response was not increased by the same factor, windup appeared to be reduced. However, postdischarge, resulting from the increase in the excitability produced by windup, tended to be facilitated. After doses of ≥5 μg bicuculline, stimulation at suprathreshold Aβ-fiber–evoked activity caused enhanced firing, mainly at later latencies corresponding to Aδ-fiber–evoked activity in normal animals. Few cells responded consistently to brush and so no significant change was observed. Responses evoked by innocuous pressure (prod) always were observed in cells that concurrently responded to electrical stimulation with a C-fiber response. This tactile response was facilitated significantly by bicuculline. The effects of N6-cyclopentyladenosine (N6-CPA), an adenosine A1-receptor agonist, was observed after pretreatment with 50 μg bicuculline, as were the effects of morphine and 7-chlorokynurenate (7-CK). N6-CPA inhibited prod, C- and Aδ-fiber–evoked responses as well as the initial and overall final response to the train of C-fiber strength stimuli. Inhibitions were reversed with 8(p-sulphophenyl) theophylline. Morphine, the mu-receptor agonist, also inhibited the postbicuculline responses to prod, C-, and Aδ-fiber responses and initial and final responses to a train of stimuli. Inhibitory effects of morphine were reversed partly by naloxone. 7-CK, an antagonist at the glycine site on the N-methyl-d-aspartate-receptor complex, inhibited the responses to C- and Aδ-fiber–evoked activity as well as prod. The postdischarges were inhibited by this drug. Again both the initial and overall responses of the cell were inhibited. To conclude, bicuculline caused an increase in the responses of deep dorsal horn cells to prod, Aδ-fiber–evoked activity, increased C-fiber input onto these cells along with the appearance of responses at latencies normally associated with Aδ fibers, but evoked by suprathreshold Aβ-fiber stimulation. These alterations may be responsible for some aspects of the clinical phenomenon of allodynia and hyperalgesia. These altered and enhanced responses were modulated by the three separate classes of drugs, the order of effectiveness being 7-CK, N6-CPA, and then morphine.

Background:EULAR/ACR 2019 SLE Classification Criteria were validated in an international cohort.Objectives:To evaluate performance characteristics of SLE classification systems in sex, race/ethnicity, and disease duration subsets.Methods:Sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated in the validation cohort.Results:The cohort consisted of female (n=1098), male (n=172), Asian (n=118), Black (n=68), Hispanic (n=124) and White (n=941) patients; and patients with an SLE duration of 1-3 years (n=196), 3-5 years (n=157), and ≥5 years (n=879). Among patients with 1-3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% (95%CI 92-99%) vs 81% (95%CI 72-88%). The new criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). The new criteria had better sensitivity than the ACR criteria in White (95% vs 83%), Hispanic (100% vs 86%) and Asian patients (97% vs 77%).Conclusion:The EULAR/ACR 2019 criteria perform well in patients with early disease, and across sexes and ethnicities.Disclosure of Interests:Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Ralph Brinks: None declared, Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca, David Daikh: None declared, Marta Mosca: None declared, Rosalind Ramsey-Goldman: None declared, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche – grant/research support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker, David Wofsy: None declared, Dimitrios Boumpas Grant/research support from: Unrestricted grant support from various pharmaceutical companies, Diane L Kamen Consultant of: Consulted on SLE survey development for Lilly and consulted on SLE trial protocol development for EMD Serono in 2019, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Ricard Cervera: None declared, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institution, Betty Diamond: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Bevra H. Hahn Grant/research support from: Janssen Research & Development, LLC, Falk Hiepe: None declared, Soren Jacobsen: None declared, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB, Kirsten Lerstrom: None declared, Elena Massarotti: None declared, William Joseph McCune: None declared, Guillermo Ruiz-Irastorza: None declared, Jorge Sanchez-Guerrero: None declared, Matthias Schneider: None declared, Murray B Urowitz: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Bimba F. Hoyer: None declared, Nicolai Leuchten: None declared, Chiara Tani: None declared, Sara Tedeschi: None declared, Zahi Touma: None declared, Gabriela Schmajuk Grant/research support from: Pfizer, Branimir Anic: None declared, Florence Assan: None declared, Tak Chan: None declared, Ann E Clarke: None declared, Mary K. Crow: None declared, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Winfried Graninger: None declared, Bernadett Halda-Kiss: None declared, Sarfaraz Hasni: None declared, Peter Izmirly: None declared, Michelle Jung: None declared, Gabor Kumanovics Consultant of: Boehringer, Teva, Speakers bureau: Roche, Lilly, Novartis, Xavier Mariette: None declared, Ivan Padjen: None declared, Jose M Pego-Reigosa: None declared, Juanita Romero-Diaz Consultant of: Biogen, Iñigo Rua-Figueroa: None declared, Raphaèle Seror Consultant of: BMS, Medimmune, Novartis, Pfizer, GSK, Lilly, Georg Stummvoll: None declared, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer, Carlos Vasconcelos: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Daniel J Wallace: None declared, Sule Yavuz: None declared, Pier Luigi Meroni: None declared, Marvin Fritzler: None declared, Raymond Naden: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche

Abstract Background Over the past decade, extended spectrum β-lactamase producing Enterobacterales (ESBL) and multidrug resistance has risen among community-acquired uncomplicated urinary tract infections (uUTIs). This study was conducted to determine co-resistance among Klebsiella pneumoniae (K. pneumoniae) isolates in urine from female outpatients in the United States (US). Methods This was a retrospective, cross-sectional study of 30-day non-duplicate K. pneumoniae urine isolates from female outpatients (≥ 12 years of age) at 304 US facilities, with ≥ 3 months of data from 2011–2019 (Becton, Dickinson and Company [BD] Insights Research Database). K. pneumoniae isolates were defined as those that were ESBL-positive (ESBL+) (by commercial panel or not susceptible [NS] to ceftriaxone, cefotaxime, ceftazidime or cefepime), or NS if intermediate/resistant to any of the following: fluoroquinolones (FQs), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NFT). Co-resistance phenotypes were characterized in isolates NS to ≥ 2 of the 4 resistance phenotypes assessed. Results Among 250,719 non-duplicate K. pneumoniae isolates evaluated, 11,065 were ESBL+ (Table). Co-resistance among ESBL+ isolates was observed as follows: 54.9% to FQ; 65.7% to SXT; 75.5% to NFT; and 38.2% to all 4 resistance phenotypes. Of 10,962 isolates NS to FQ, co-resistance was observed as follows: 55.4% were ESBL+; 65.7% to SXT; 79.6% to NFT; and 38.6% to all 4 resistance phenotypes. Of 141,545 isolates NS to NFT, co-resistance was observed as follows: 5.9% were ESBL+; 6.2% to FQ; 11.8% to SXT; and 3.0% to all 4 resistance phenotypes. Among 23,887 isolates NS to SXT, co-resistance was observed as follows: 30.4% were ESBL+; 30.1% to FQ; 69.7% to NFT; and 17.7.% to all 4 resistance phenotypes. Table.Co-resistance phenotype combinations observed among Klebsiella pneumoniae isolates in urine from 2011–2019In total, 250,719 non-duplicate (30-day) Klebsiella pneumoniae isolates were evaluated.Note: Some isolates had overlapping susceptibilities/antimicrobial resistance types, hence individual phenotype totals do not reflect total number of isolates evaluated.Abbreviations: ESBL+, extended spectrum β-lactamase-producing or not susceptible to ceftriaxone, cefotaxime, ceftazidime or cefepime; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion The high prevalence of co-resistance in 30-day non-duplicate outpatient K. pneumoniae urinary isolates, particularly towards NFT (70–80% of isolates), limits the effective oral treatment options for uUTI. These analyses may help inform and optimize appropriate empiric treatment of female outpatients with uUTI in the US. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Janet Watts, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

Abstract Background In the past 10 years, there has been a substantial increase in antimicrobial resistance among uropathogens in community-acquired uncomplicated urinary tract infections (uUTIs), including extended spectrum β-lactamase producing (ESBL+) Enterobacterales and multidrug resistance. This study examined urine isolates from female outpatients in the United States (US) for co-resistance among Escherichia coli (E. coli). Methods This was a retrospective, cross-sectional study of 30-day non-duplicate E. coli urine isolates (first isolates collected within a 30-day period) from female outpatients (≥ 12 years of age) at 304 US facilities. Included patients had ≥ 3 months of data from 2011 to 2019 (Becton, Dickinson and Company [BD] Insights Research Database). Urine-isolated E. coli were defined as ESBL+ by 1) commercial panel or 2) not susceptible (NS; intermediate/resistant) to ceftriaxone, cefotaxime, ceftazidime, or cefepime), or NS to any of: fluoroquinolones (FQs), trimethoprim/sulfamethoxazole (SXT), or nitrofurantoin (NFT). Microbiological co-resistance phenotypes were characterized in isolates NS to ≥ 2 of the 4 resistance phenotypes assessed. Results In total, 856,918 unique isolates were evaluated. Co-resistance data are shown in the Table. Of ESBL+ isolates (96,306), 72.4% were co-resistant to FQ, 56.7% to SXT, and 11.9% to NFT; 6.8% had all 4 phenotypes. For FQ NS isolates (319,354), 21.8% were also ESBL+, 51.6% were co-resistant to SXT, 8.0% were co-resistant to NFT, and 2.0% had all 4 phenotypes. Among SXT NS isolates (384,304), 14.2% were also ESBL+, 42.9% were co-resistant to FQ, 6.8% were co-resistant to NFT, and 1.7% had all 4 phenotypes. Finally, for NFT NS isolates (56,954), 20.1% were ESBL+, 44.7% were co-resistant to FQ, 46.0% were co-resistant to SXT, and 11.5% had all 4 phenotypes. Table.Co-resistance phenotype combinations among urine-isolated Escherichia coli (2011–2019)In total, 856,918 non-duplicate (30-day) Escherichia coli isolates were evaluated.Note: Some isolates had overlapping susceptibilities/antimicrobial resistance types, hence individual phenotype totals do not reflect total number of isolates evaluated.Abbreviations: ESBL+, extended spectrum β-lactamase-producing (by commercial panel or not susceptible to ceftriaxone, cefotaxime, ceftazidime or cefepime); FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion Among urine-isolated E. coli, there was a high prevalence of co-resistance, particularly for ESBL+ isolates where co-resistance to FQ was > 70%. The availability of effective oral treatments for uUTI is limited by uropathogen antibiotic resistance. These data may help inform appropriate empiric prescribing practices to optimize the treatment of uUTI, mitigate multiple drug exposure for a uUTI event, and potentially influence long-term resistance patterns among E. coli. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Janet Watts, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

Abstract Background Infections caused by extended spectrum β-lactamase producing Enterobacterales (ESBLs), as well as antimicrobial resistance (AMR) and multi-drug resistance among uncomplicated urinary tract infections (uUTIs) in outpatients have risen in the past decade. The study objective was to determine the prevalence and geographic distribution of AMR among Klebsiella pneumoniae (K. pneumoniae) isolates in urine from female outpatients in the United States (US). Methods A retrospective, cross-sectional study of non-duplicate urine isolates from female outpatients (≥ 12 years of age) at 304 facilities, with ≥ 3 months of data, including initial isolates with distinct susceptibility patterns within 30 days of index urine samples, were used to assess regional AMR in 2019, and AMR trends from 2011 to 2019 (BD Insights Research Database, Franklin Lakes, NJ). K. pneumoniae isolates were identified as ESBL-positive (ESBL+) (confirmed by commercial panel or not susceptible [NS] to ceftriaxone, cefotaxime, ceftazidime, or cefepime), or NS if intermediate/resistant to any of the following: nitrofurantoin (NFT), trimethoprim/sulfamethoxazole (SXT), or fluoroquinolones (FQs). AMR prevalence and variation across US census regions was evaluated using logistic regression (with covariate adjustment) and generalized estimating equations. Results 44,056 non-duplicate K. pneumoniae isolates were evaluated in 2019 (Figure). For all microbiological phenotypes, there was significant variation in resistance for K. pneumoniae across all US census regions (p< 0.0001). Among 250,719 isolates evaluated from 2011 to 2019, AMR prevalence increased for all studied antimicrobials except for NFT NS (all p< 0.0041; Table). There was an increase in adjusted AMR rates by age groups with higher AMR rates for females ≥ 55 versus < 55, except for NFT, which showed the highest resistance in those aged < 55. Figure.Prevalence of antimicrobial resistance in Klebsiella pneumoniae isolates in 2019Abbreviations: ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole.Table.Klebsiella pneumoniae: model-estimated trends of relative average annual percentage change of antimicrobial resistance over time (2011 to 2019), by patient age, and by census region (N=250,719 isolates)All p values were p< 0.0001 apart from NFT trend over years, which was p=0.0041.*Relative average annual percentage change in resistance rate.Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion AMR prevalence in 2019 among non-duplicate K. pneumoniae isolates from urine in outpatients was notable. There were significant regional differences in resistance rates, which were higher in those aged ≥ 55 years, except for NFT. These analyses inform, and may be used to optimize, empiric treatment of uUTI. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Gang Ye, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

This thesis is comprised of two parts: a Studio Research component with an accompanying Exegesis (66%), and a Dissertation (33%). The Dissertation presented here examines the historical and cultural context of the production of natural history illustration and ornamentation, and the formal qualities of these visual forms that enabled them to inform and disseminate exotic constructions and perceptions. These visual forms were a significant part of the intellectual and cultural framework of the eighteenth and nineteenth centuries and frequently represented the 'other' as desirable and different. The aesthetic responses generated by such exotic representations operated subliminally to develop and reinforce dualistic notions surrounding the difference of the distant 'other' in comparison to the European self. The Dissertation examines the specificity of the operation of these visual forms in relation to exotic perceptions of the Australian 'other' from the late eighteenth to the early twentieth centuries, and develops an argument about the rise of a unique mode of perceiving the Australian 'other'. The Dissertation elaborates the theoretical context for the studio research which is an evocation and examination of the aesthetic experience of the exotic, informed by natural history illustration and ornamentation. A process of quotation and transformation of historical imagery has been developed to investigate foundational representations and perceptions of the Australian exoticised 'other' and the manner that this imagery persists and reforms as it circulates in society. The imagery is reworked by a painting process that utilises the material and formal properties of paint to explore the nature of the aesthetic perception of the exotic while also providing a metaphoric model of the manner that the self is defined in relation to the 'other'. The process offers an alternative mode of conceiving the 'other' within the post-colonial concept of hybridity. The results of the studio research are elaborated in the Exegesis and will be presented as a site-specific installation of paintings in the ANU School of Art Gallery from 17 to 26 March 2010.

Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Dickinson v Dodds (1876) 2 Ch D 463. The document also includes supporting commentary from author Nicola Jackson.

The contributors to Assembly Codes examine how media and logistics set the conditions for the circulation of information and culture. They document how logistics—the techniques of organizing and coordinating the movement of materials, bodies, and information—has substantially impacted the production, distribution, and consumption of media. At the same time, physical media, such as paperwork, along with media technologies ranging from phone systems to software are central to the operations of logistics. The contributors interrogate topics ranging from the logistics of film production and the construction of internet infrastructure to the environmental impact of the creation, distribution, and sale of vinyl records. They also reveal how logistical technologies have generated new aesthetic and performative practices. In charting the specific points of contact, dependence, and friction between media and logistics, Assembly Codes demonstrates that media and logistics are co-constitutive and that one cannot be understood apart from the other. Contributors Ebony Coletu, Kay Dickinson, Stefano Harney, Matthew Hockenberry, Tung-Hui Hu, Shannon Mattern, Fred Moten, Michael Palm, Ned Rossiter, Nicole Starosielski, Liam Cole Young, Susan Zieger

Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Dickinson v Dodds (1876) 2 Ch D 463. The document also includes supporting commentary from author Nicola Jackson.

Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Dickinson v Dodds (1876) 2 Ch D 463. The document also includes supporting commentary from author Nicola Jackson.

Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Dickinson v Dodds (1876) 2 Ch D 463. The document also includes supporting commentary from author Nicola Jackson.

Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Dickinson v Dodds (1876) 2 Ch D 463. The document also includes supporting commentary from author Nicola Jackson.

This chapter describes seven miniatures created by Peter Child. These songs are written in an accessibly ‘neo-tonal’ idiom. Here, lean, nimble, relatively undemanding vocal lines are supported, and often driven, by highly characterful piano parts which convey much of the detail of the textual images. The piece forms a nicely balanced whole, its hypnotic slow movements contrasted by more animated rhythmical settings. The first four songs muse, fleetingly, on various features of the natural world (both animate and inanimate), but the last two plumb more deeply beneath the surface. The final setting is particularly affecting in its ambivalent soul-searching. The composer has a distinctive way of concluding each song with a pithy musical comment, sometimes leaving a question hovering in the air.

This chapter examines Newton's take on the substantial alchemical corpus ascribed to the high medieval Mallorcan philosopher Ramon Lull. It begins with a brief consideration of the Epistola ad Theodorum Mundanum and Newton's synopsis of it. It then examines the cycle of Opera in their several complementary drafts, which will reveal the heavy influence exercised by Dickinson, pseudo-Lull, Snyders, and other authors. The Opera may be dated conservatively to the period between the publication of Dickinson's Epistola in 1686 and a later stage in Newton's alchemy, namely, his intense collaboration with Nicolas Fatio de Duillier in the early 1690s. The work with Fatio also contributed to Newton's production of a text that has received notice from other Newtonian scholars as in some sense the culmination of his alchemical endeavor, Huntington Library, Babson MS 420, otherwise known as Praxis.