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51.
Tong S Lingappa JR Chen Q Shu B LaMonte AC Cook BT Birge C Chern SW Liu X Galloway R Mai le Q Ng WF Yang JY Butany J Comer JA Monroe SS Beard SR Ksiazek TG Erdman D Rota PA Pallansch MA Anderson LJ 《The Journal of infectious diseases》2004,190(6):1127-1131
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients--1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host. 相似文献
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AJ Geall A Verma GR Otten CA Shaw A Hekele K Banerjee Y Cu CW Beard LA Brito T Krucker DT O'Hagan M Singh PW Mason NM Valiante PR Dormitzer SW Barnett R Rappuoli JB Ulmer CW Mandl 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14604-14609
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted. 相似文献
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Georgina Limon Gerelmaa Ulziibat Batkhuyag Sandag Serjmyadag Dorj Dulam Purevtseren Bodisaikhan Khishgee Ganzorig Basan Tsolmon Bandi Sodnomdarjaa Ruuragch Mieghan Bruce Jonathan Rushton Philippa M. Beard Nicholas A. Lyons 《Transboundary and Emerging Diseases》2020,67(5):2034-2049
Mongolia is a large landlocked country in Central Asia and has one of the highest per capita livestock ratios in the world. During 2017, reported foot‐and‐mouth disease (FMD) outbreaks in Mongolia increased considerably, prompting widespread disease control measures. This study estimates the socio‐economic impact of FMD and subsequent control measures on Mongolian herders. The analysis encompassed quantification of the impact on subsistence farmers’ livelihoods and food security and estimation of the national‐level gross losses due to reaction and expenditure during 2017. Data were collected from 112 herders across eight provinces that reported disease. Seventy of these herders had cases of FMD, while 42 did not have FMD in their animals but were within quarantine zones. Overall, 86/112 herders reported not drinking milk for a period of time and 38/112 reduced their meat consumption. Furthermore, 55 herders (49.1%) had to borrow money to buy food, medicines and/or pay bills or bank loans. Among herders with FMD cases, the median attack rate was 31.7%, 3.8% and 0.59% in cattle, sheep and goats, respectively, with important differences across provinces. Herders with clinical cases before the winter had higher odds of reporting a reduction in their meat consumption. National‐level gross losses due to FMD in 2017 were estimated using government data. The estimate of gross economic loss was 18.4 billion Mongolian‐tugriks (US$7.35 million) which equates to approximately 0.65% of the Mongolian GDP. The FMD outbreaks combined with current control measures have negatively impacted herders’ livelihoods (including herders with and without cases of FMD) which are likely to reduce stakeholder advocacy. Possible strategies that could be employed to ameliorate the negative effects of the current control policy were identified. The findings and approach are relevant to other FMD endemic regions aiming to control the disease. 相似文献
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Brandon A. Mahal David R. Ziehr Ayal A. Aizer Andrew S. Hyatt Jesse D. Sammon Marianne Schmid Toni K. Choueiri Jim C. Hu Christopher J. Sweeney Clair J. Beard Anthony V. D׳Amico Neil E. Martin Christopher Lathan Simon P. Kim Quoc-Dien Trinh Paul L. Nguyen 《Urologic oncology》2014,32(8):1285-1291
ObjectivesTreating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP.Materials and methodsThe Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy.ResultsCompared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P<0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (Pinteraction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P<0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P<0.001) among insured men.ConclusionsAA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers. 相似文献
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Anderson AD Heryford AG Sarisky JP Higgins C Monroe SS Beard RS Newport CM Cashdollar JL Fout GS Robbins DE Seys SA Musgrave KJ Medus C Vinjé J Bresee JS Mainzer HM Glass RI 《The Journal of infectious diseases》2003,187(2):303-306
In February 2001, episodes of acute gastroenteritis were reported to the Wyoming Department of Health from persons who had recently vacationed at a snowmobile lodge in Wyoming. A retrospective cohort study found a significant association between water consumption and illness, and testing identified Norwalk-like virus (NLV) in 8 of 13 stool samples and 1 well. Nucleotide sequences from the positive well-water specimen and 6 of the positive stool samples were identical. This multistrain NLV outbreak investigation illustrates the importance of NLV as a cause of waterborne illness and should encourage monitoring for NLVs in drinking water. 相似文献
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Yingxia Wen James MonroeChristine Linton Jacob ArcherClayton W. Beard Susan W. BarnettGiuseppe Palladino Peter W. Mason Andrea Carfi Anders E. Lilja 《Vaccine》2014
Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that causes significant disease worldwide. Although evidence exists that neutralizing antibodies and cytotoxic T cell responses to HCMV antigens can prevent HCMV disease and/or infection, there are no approved vaccines to prevent HCMV disease. Over the past 10 years, multiple HCMV vaccines have been tested in man but only partial protection has been achieved in these studies. HCMV contains multiple surface-expressed glycoproteins that are critical to viral entry, including gB, the gM/gN complex, the gH/gL complex, and a pentameric gH/gL/UL128/UL130/UL131A complex. Recently we showed that viral replicon particles (VRPs) expressing the gH/gL complex elicited more potently neutralizing antibodies than VRPs expressing gB in mice. Here we compare the immunogenicity of VRPs encoding the HCMV gH/gL and pentameric complexes, as well as purified gH/gL and pentameric complexes administered in the presence or absence of the MF59 adjuvant. The results of these studies indicate that the pentameric complex elicits significantly higher levels of neutralizing antibodies than the gH/gL complex, and that MF59 significantly increases the potency of each complex. In addition, we show that animals immunized with pentamer encoding VRPs or the pentameric subunit produce antibodies that recognize a broad range of antigenic sites on the complex. Taken together, these studies support the utility of the pentameric complex in HCMV vaccine candidates. 相似文献