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Loren E. Rodgers John Paulson Brian Fowler Rosemary Duffy 《American journal of public health》2015,105(2):236-239
Rapid mortality surveillance is critical for state emergency preparedness. To enhance timeliness during the 2009–2010 influenza A H1N1 pandemic, the Ohio Department of Health activated a drop-down menu within Ohio’s Electronic Death Registration System for reporting of pneumonia- or influenza-related deaths approximately 5 days postmortem. We used International Classification of Diseases—Tenth Revision (ICD-10) codes, available 2–3 months postmortem as the standard, and assessed their agreement with drop-down-menu codes for pneumonia- or influenza-related deaths. Among 56 660 Ohio deaths during September 2009–March 2010, agreement was 97.9% for pneumonia (κ = 0.85) and 99.9% for influenza (κ = 0.79). Sensitivity was 80.2% for pneumonia and 73.9% for influenza. Drop-down menu coding enhanced timeliness while maintaining high agreement with ICD-10 codes. 相似文献
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E. Binotto C. R. Boughton U. Vollmer-Conna R. Hawkes P. Robertson R. Whybin Y. Duffy A. R. Lloyd 《Internal medicine journal》2000,30(6):668-674
Background: The epidemiology and natural history of recently discovered viruses, which may be responsible for cases of seronegative infectious hepatitis, are currently being investigated. Retrospective studies of stored sera can provide a historical perspective of these infections. Aims: To re‐evaluate the serological, demographic and clinical characteristics of patients hospitalised in the early 1970s with acute hepatitis. Methods: The stored sera of 57 patients hospitalised between 1971 and 1974 with acute hepatitis, designated at that time as non‐A non‐B (NANB) hepatitis, were re‐tested using commercially available enzyme‐linked immunosorbent assays (ELISAs) for the presence of anti‐hepatitis A virus (HAV) IgM, hepatitis B surface antigen (HBsAg), anti‐hepatitis C virus (HCV) IgG, and anti‐hepatitis E virus (HEV) IgG. Stored sera from a group of 57 patients concurrently hospitalised for other conditions were also tested. Detailed records of the original epidemiological interviews were examined to compare patient demographics, risk factors for infectious hepatitis and clinical data for the NANB hepatitis group and an original control group of 604 hospitalised patients. Results: Serum from 15 of the 57 (26%) previously designated NANB hepatitis cases had elevated anti‐HAV IgM and are likely to represent missed cases of hepatitis A. Thirteen (23%) of cases previously designated as NANB hepatitis had positive hepatitis C antibody tests. These patients were younger and significantly more likely to have used intravenous drugs than control patients. Three NANB hepatitis and two hospital control patients were anti‐HEV IgG antibody positive. All of these individuals were born in, or had travelled to, developing countries. Serum from 27 (47%) of the NANB hepatitis patients were negative on all tests. These hepatitis non‐A‐E cases included children and elderly adults, but as a group were significantly more likely to have used intravenous drugs than hospitalised control patients. 相似文献
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Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist 总被引:2,自引:0,他引:2
Erickson-Miller CL DeLorme E Tian SS Hopson CB Stark K Giampa L Valoret EI Duffy KJ Luengo JL Rosen J Miller SG Dillon SB Lamb P 《Experimental hematology》2005,33(1):85-93
OBJECTIVE: Peptide and other small molecule agonists have been described for several cytokines and growth factors. Hydrazone compounds described here as thrombopoietin receptor agonists were identified as activating STAT proteins in a Tpo responsive cell line. METHODS: STAT activation and analysis of signal transduction pathways in cell lines and normal human platelets was elucidated by Western blot and electrophoretic mobility shift assays. Proliferation assays in cell types responsive to other cytokines determined specificity for Tpo receptor. Flow cytometry quantified differentiation of CD34(+) cells into CD41(+) megakaryocytes and platelet production in vitro. RESULTS: Activation of STAT5, mitogen-activated protein kinase, p38, and early response genes by SB 394725 was similar to that induced by Tpo. SB 394725 induced a reporter gene response under a STAT activation promoter as well as the megakaryocyte-specific gpIIb promoter. The compound induced proliferation of Tpo responsive lines but demonstrated no activity in cell lines responding to other cytokines, i.e., erythropoietin, granulocyte-colony stimulating factor, interleukin-3, interferon-gamma. The response of normal human Tpo receptors was elucidated by measuring growth and differentiation of human bone marrow in vitro. Activation of endogenous Tpo receptors by SB 394725 was demonstrated in human and chimp platelets, but not in platelets of other species including mouse, dog, rabbit, or cynomolgus monkey. CONCLUSIONS: SB 394725, a small molecule with a molecular weight of 452 Da, is capable of activating Tpo-specific signal transduction, proliferation, and differentiation responses similar to the responses and functions of the protein growth factor, Tpo. 相似文献
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Brian Cox James Duffy Victor Zdorichenko Corentin Bellanger Jessica Hurcum Benoît Laleu Kevin I. Booker-Milburn Luke D. Elliott Michael Robertson-Ralph Christopher J. Swain Stephen J. Bishop Irene Hallyburton Mark Anderson 《ACS medicinal chemistry letters》2020,11(12):2497
We utilized synthetic photochemistry to generate novel sp3-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold. Preliminary antimalarial screening of the library provided promising compounds with activity in the 1–5 μM range with an enhanced hit rate. Further evaluation (solubility, drug metabolism and pharmacokinetics (DMPK), and toxicity) of a selected compound (9) suggested that this series represents an excellent opportunity for further optimization with the framework offering multiple opportunities for the addition of uniquely vectorally positioned extra functionality. 相似文献
80.
Daxing Gao Michael J. Ciancanelli Peng Zhang Oliver Harschnitz Vincent Bondet Mary Hasek Jie Chen Xin Mu Yuval Itan Aurlie Cobat Vanessa Sancho-Shimizu Benedetta Bigio Lazaro Lorenzo Gabriele Ciceri Jessica McAlpine Esperanza Anguiano Emmanuelle Jouanguy Damien Chaussabel Isabelle Meyts Michael S. Diamond Laurent Abel Sun Hur Gregory A. Smith Luigi Notarangelo Darragh Duffy Lorenz Studer Jean-Laurent Casanova Shen-Ying Zhang 《The Journal of clinical investigation》2021,131(1)
Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3–/– mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell–derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity. 相似文献