Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-19 (of 19 Records) |
Query Trace: Anton L [original query] |
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Changes in tobacco product use among students aged 13 to 15 years in 34 countries, Global Youth Tobacco Survey, 2012-2020
Njie GJ , Kirksey Jones C , Jacques N , Adetokun A , Ross J , Owens A , Anton L , Johns M , Pan L . Prev Chronic Dis 2023 20 E68 INTRODUCTION: Most adults who currently use tobacco start before age 21. Comprehensive, cost-effective strategies and interventions to prevent initiation and encourage tobacco use cessation among youth are critical aspects of protecting youth from the harms of commercial tobacco. We describe changes in current tobacco product use among youth in 34 sites using data from the Global Youth Tobacco Survey (GYTS). METHODS: GYTS is a nationally representative school-based survey of students aged 13 to 15 years. The analysis included 34 sites that completed 2 survey waves during 2012-2020. Prevalence of current tobacco use was assessed for each country. Marginal effects in multivariable logistic regression models were used to estimate adjusted prevalence difference (aPD) between waves. RESULTS: The adjusted prevalence of current tobacco product use remained unchanged in more than 60% of the included sites. For any tobacco use, significant decreases were reported for Bhutan (aPD = -8.1; 95% CI, -12.9 to -3.4), Micronesia (aPD = -7.2; 95% CI, -9.7 to -4.7), San Marino (aPD = -7.0; 95% CI, -11.2 to -2.7), Togo (aPD = -2.7; 95% CI, -4.6 to -0.7), and Panama (aPD = -2.2; 95% CI, -4.1 to -0.4); significant increases were reported for Moldova, Albania, and Paraguay. Current e-cigarette use increased significantly in 7 of 10 sites. CONCLUSION: Data show that progress toward reducing tobacco use among youth stalled during 2012-2020, while e-cigarette use increased in a few sites with available data. |
A Public Health Research Agenda for Managing Infodemics: Methods and Results of the First WHO Infodemiology Conference.
Calleja N , AbdAllah A , Abad N , Ahmed N , Albarracin D , Altieri E , Anoko JN , Arcos R , Azlan AA , Bayer J , Bechmann A , Bezbaruah S , Briand SC , Brooks I , Bucci LM , Burzo S , Czerniak C , De Domenico M , Dunn AG , Ecker UKH , Espinosa L , Francois C , Gradon K , Gruzd A , Gülgün BS , Haydarov R , Hurley C , Astuti SI , Ishizumi A , Johnson N , Johnson Restrepo D , Kajimoto M , Koyuncu A , Kulkarni S , Lamichhane J , Lewis R , Mahajan A , Mandil A , McAweeney E , Messer M , Moy W , Ndumbi Ngamala P , Nguyen T , Nunn M , Omer SB , Pagliari C , Patel P , Phuong L , Prybylski D , Rashidian A , Rempel E , Rubinelli S , Sacco P , Schneider A , Shu K , Smith M , Sufehmi H , Tangcharoensathien V , Terry R , Thacker N , Trewinnard T , Turner S , Tworek H , Uakkas S , Vraga E , Wardle C , Wasserman H , Wilhelm E , Würz A , Yau B , Zhou L , Purnat TD . JMIR Infodemiology 2021 1 (1) e30979 BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider. |
Antibodies to SARS-CoV-2 in All of Us Research Program Participants, January 2-March 18, 2020.
Althoff KN , Schlueter DJ , Anton-Culver H , Cherry J , Denny JC , Thomsen I , Karlson EW , Havers FP , Cicek MS , Thibodeau SN , Pinto LA , Lowy D , Malin BA , Ohno-Machado L , Williams C , Goldstein D , Kouame A , Ramirez A , Roman A , Sharpless NE , Gebo KA , Schully SD . Clin Infect Dis 2021 74 (4) 584-590 BACKGROUND: With limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January - March), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals. RESULTS: The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states. |
Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies.
Chapman AP , Tang X , Lee JR , Chida A , Mercer K , Wharton RE , Kainulainen M , Harcourt JL , Martines RB , Schroeder M , Zhao L , Bryksin A , Zhou B , Bergeron E , Bollweg BC , Tamin A , Thornburg N , Wentworth DE , Petway D , Bagarozzi DA Jr , Finn MG , Goldstein JM . Sci Rep 2021 11 (1) 9682 The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence. |
CATMoS: Collaborative Acute Toxicity Modeling Suite.
Mansouri K , Karmaus AL , Fitzpatrick J , Patlewicz G , Pradeep P , Alberga D , Alepee N , Allen TEH , Allen D , Alves VM , Andrade CH , Auernhammer TR , Ballabio D , Bell S , Benfenati E , Bhattacharya S , Bastos JV , Boyd S , Brown JB , Capuzzi SJ , Chushak Y , Ciallella H , Clark AM , Consonni V , Daga PR , Ekins S , Farag S , Fedorov M , Fourches D , Gadaleta D , Gao F , Gearhart JM , Goh G , Goodman JM , Grisoni F , Grulke CM , Hartung T , Hirn M , Karpov P , Korotcov A , Lavado GJ , Lawless M , Li X , Luechtefeld T , Lunghini F , Mangiatordi GF , Marcou G , Marsh D , Martin T , Mauri A , Muratov EN , Myatt GJ , Nguyen DT , Nicolotti O , Note R , Pande P , Parks AK , Peryea T , Polash AH , Rallo R , Roncaglioni A , Rowlands C , Ruiz P , Russo DP , Sayed A , Sayre R , Sheils T , Siegel C , Silva AC , Simeonov A , Sosnin S , Southall N , Strickland J , Tang Y , Teppen B , Tetko IV , Thomas D , Tkachenko V , Todeschini R , Toma C , Tripodi I , Trisciuzzi D , Tropsha A , Varnek A , Vukovic K , Wang Z , Wang L , Waters KM , Wedlake AJ , Wijeyesakere SJ , Wilson D , Xiao Z , Yang H , Zahoranszky-Kohalmi G , Zakharov AV , Zhang FF , Zhang Z , Zhao T , Zhu H , Zorn KM , Casey W , Kleinstreuer NC . Environ Health Perspect 2021 129 (4) 47013 BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495. |
Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir.
Patel MC , Chesnokov A , Jones J , Mishin VP , De La Cruz JA , Nguyen HT , Zanders N , Wentworth DE , Davis TC , Gubareva LV . Antiviral Res 2021 188 105035 Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting the cap-binding function of polymerase basic protein 2 (PB2). In this study, we used a combination of sequence analysis and phenotypic methods to evaluate pimodivir susceptibility of influenza A viruses collected from humans and other hosts. Screening PB2 sequences for substitutions previously associated with reduced pimodivir susceptibility revealed a very low frequency among seasonal viruses circulating in the U.S. during 2015-2020 (<0.01%; 3/11,934) and among non-seasonal viruses collected in various countries during the same period (0.2%; 18/8971). Pimodivir potently inhibited virus replication in two assays, a single-cycle HINT and a multi-cycle FRA, with IC(50) values in a nanomolar range. Median IC(50) values determined by HINT were similar for both subtypes of seasonal viruses, A (H1N1)pdm09 and A (H3N2), across three seasons. Human seasonal viruses with PB2 substitutions S324C, S324R, or N510K displayed a 27-317-fold reduced pimodivir susceptibility. In addition, pimodivir was effective at inhibiting replication of a diverse group of animal-origin viruses that have pandemic potential, including avian viruses of A (H5N6) and A (H7N9) subtypes. A rare PB2 substitution H357N was identified in an A (H4N2) subtype poultry virus that displayed >100-fold reduced pimodivir susceptibility. Our findings demonstrate a broad inhibitory activity of pimodivir and expand the existing knowledge of amino acid substitutions that can reduce susceptibility to this investigational antiviral. |
Detection of baloxavir resistant influenza A viruses using next generation sequencing and pyrosequencing methods.
Patel MC , Mishin VP , De La Cruz JA , Chesnokov A , Nguyen HT , Wilson MM , Barnes J , Kondor RJG , Wentworth DE , Gubareva LV . Antiviral Res 2020 182 104906 Baloxavir, a new antiviral drug targeting cap-dependent endonuclease activity of polymerase acidic (PA) protein of influenza viruses, is now approved in multiple countries. Several substitutions at isoleucine 38 in PA protein (e.g., PA-I38T) have been associated with decreased baloxavir susceptibility in vitro and in vivo. In recent years, next generation sequencing (NGS) analysis and pyrosequencing have been used by CDC and U.S. Public Health Laboratories to monitor drug susceptibility of influenza viruses. Here we described an improved pyrosequencing assay for detecting influenza A viruses carrying substitutions at PA-38. Cyclic and customized orders of nucleotide dispensation were evaluated, and pyrosequencing results were compared to those generated using NGS. Our data showed that the customized nucleotide dispensation has improved the pyrosequencing assay performance in identification of double mixtures (e.g., PA-38I/T); however, identification of PA-38 variants in triple mixtures remains a challenge. While NGS analysis indicated the presence of PA-I38K in one clinical specimen and isolate, our attempts to detect this mutation by pyrosequencing or recover the virus carrying PA-I38K in cell culture were unsuccessful, raising a possibility of a rarely occurring sequencing error. Overall, pyrosequencing provides a convenient means to detect baloxavir resistant influenza viruses when NGS is unavailable or a faster turnaround time is required. |
Receptive anal sex contributes substantially to heterosexually-acquired HIV infections among at-risk women in twenty US cities: results from a modelling analysis
Elmes J , Silhol R , Hess KL , Gedge LM , Nordsletten A , Staunton R , Anton P , Shacklett B , McGowan I , Dang Q , Adimora AA , Dimitrov DT , Aral S , Handanagic S , Paz-Bailey G , Boily MC . Am J Reprod Immunol 2020 84 (2) e13263 PROBLEM: Receptive anal intercourse (RAI) is more efficient than receptive vaginal intercourse (RVI) at transmitting HIV, but its contribution to heterosexually-acquired HIV infections among at-risk women in the US is unclear. METHOD OF STUDY: We analysed sexual behaviour data from surveys of 9,152 low-income heterosexual women living in 20 cities with high rates of HIV conducted in 2010 and 2013 as part of US National HIV Behavioral Surveillance. We estimated RAI prevalence (past-year RAI) and RAI fraction (fraction of all sex acts (RVI and RAI) at the last sexual episode that were RAI among those reporting past-year RAI) overall and by key demographic characteristics. These results and HIV incidence were used to calibrate a risk-equation model to estimate the population attributable fraction of new HIV infections due to RAI (PAFRAI ) accounting for uncertainty in parameter assumptions. RESULTS: RAI prevalence (overall: 32%, city range: 19-60%) and RAI fraction (overall: 27%, city-range: 18-34%) were high overall and across cities, and positively associated with exchange sex. RAI accounted for an estimated 41% (uncertainty range: 18-55%) of new infections overall (city range: 21-57%). Variability in PAFRAI estimates was most influenced by uncertainty in the estimate of the per-act increased risk of RAI relative to RVI and the number of sex acts. CONCLUSIONS: RAI may contribute disproportionately to new heterosexually-acquired HIV infections among at-risk low-income women in the US, meaning that tools to prevent HIV transmission during RAI are warranted. Number of RVI and RAI acts should also be collected to monitor heterosexually-acquired HIV infections. |
Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011-2018.
Jorquera PA , Mishin VP , Chesnokov A , Nguyen HT , Mann B , Garten R , Barnes J , Hodges E , De La Cruz J , Xu X , Katz J , Wentworth DE , Gubareva LV . Sci Rep 2019 9 (1) 2676 Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011-2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection. |
Chikungunya fever outbreak identified in North Bali, Indonesia.
Sari K , Myint KSA , Andayani AR , Adi PD , Dhenni R , Perkasa A , Ma'roef CN , Witari NPD , Megawati D , Powers AM , Jaya UA . Trans R Soc Trop Med Hyg 2017 111 (7) 1-3 Background: Chikungunya virus (CHIKV) infections have been reported sporadically within the last 5 years in several areas of Indonesia including Bali. Most of the reports, however, have lacked laboratory confirmation. Method: A recent fever outbreak in a village in the North Bali area was investigated using extensive viral diagnostic testing including both molecular and serological approaches. Results and conclusions: Ten out of 15 acute febrile illness samples were confirmed to have CHIKV infection by real-time PCR or CHIKV-specific IgM enzyme-linked immunosorbent assay (ELISA). The outbreak strain belonged to the Asian genotype with highest homology to other CHIKV strains currently circulating in Indonesia. The results are of public health concern particularly because Bali is a popular tourist destination in Indonesia and thereby the potential to spread the virus to non-endemic areas is high. GenBank accession numbers: KY885022, KY885023, KY885024, KY885025, KY885026, KY885027. |
No one dies of old age anymore: A coordinated approach to comorbidities and the rheumatic diseases
Theis KA , Brady TJ , Helmick CG . Arthritis Care Res (Hoboken) 2017 69 (1) 1-4 Any idiot can face a crisis; it's the day-to-day living that wears you out, so said Anton Chekhov, himself a practicing physician, as well as a prolific author. For a growing number of people, day-to-day living means managing long-term conditions that co-exist and often exacerbate other ailments, resulting in multiple morbidities, multiple chronic conditions, or comorbidities. Whatever they are labeled, co-existing, co-occurring, etc., “the simultaneous presence of two (or more) chronic diseases or conditions in a person,” is a substantial medical and public health challenge. This special theme issue in Arthritis Care & Research spotlights this under-recognized and under-addressed problem, which has significant impact on people, medicine, and public health. | Comorbidities are a common problem in the US and internationally, and arthritis and other rheumatic diseases are among the most common comorbidities. Failure to recognize and address comorbidities leads to, at best, diminished quality-of-life, and, at worst, increased mortality. Our editorial addresses comorbidities first from the exceptional perspective of rheumatic diseases, and then from a more general perspective, which is influenced by the high prevalence and impact of rheumatic disease. We use the term “comorbidities” and its derivatives throughout, with the exception of some specific quotes, to mirror the language of the original call for submissions that Arthritis Care & Research published on the theme of Comorbidities and the Rheumatic Diseases. |
A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants.
Mishin VP , Baranovich T , Garten R , Chesnokov A , Abd Elal AI , Adamczyk M , LaPlante J , George KS , Fry AM , Barnes J , Chester SC , Xu X , Katz JM , Wentworth DE , Gubareva LV . J Clin Microbiol 2016 55 (1) 145-154 Rapid evolution of influenza A(H3N2) viruses necessitates close monitoring of their antigenic properties so emergence and spread of antigenic drift variants can be rapidly identified. Changes in hemagglutinin (HA) acquired by contemporary A(H3N2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. Sequence-based approaches have been used to infer virus antigenicity; however, they are time-consuming and mid-throughput. To facilitate virological surveillance and epidemiological studies, we have developed and validated a pyrosequencing approach that enables identification of six HA clades of contemporary A(H3N2) viruses. The identification scheme of H3 clade 3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a and 3C.3b viruses is based on the interrogation of five SNPs within three neighboring HA regions: 412-431; 465-481; and 559-571. Two bioinformatics tools, IdentiFire (Qiagen) and FireComb (developed in-house) were utilized to expedite pyrosequencing data analysis. The assay's analytical sensitivity was 10 focus forming units; and respiratory specimens with CT value < 34 typically produced good quality pyrograms. When applied to 120 A(H3N2) virus isolates and 27 respiratory specimens, the assay displayed 100% agreement with clades determined by HA sequencing coupled with phylogenetics. The multi-SNP analysis described here was readily adopted by another laboratory with pyrosequencing capabilities. Implementation of this approach enhanced virological surveillance and epidemiological studies from 2013-2016 when over 3000 A(H3N2) viruses were examined. |
Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014-2015.
Flannery B , Zimmerman RK , Gubareva LV , Garten RJ , Chung JR , Nowalk MP , Jackson ML , Jackson LA , Monto AS , Ohmit SE , Belongia EA , McLean HQ , Gaglani M , Piedra PA , Mishin VP , Chesnokov AP , Spencer S , Thaker SN , Barnes JR , Foust A , Sessions W , Xu X , Katz J , Fry AM . J Infect Dis 2016 214 (7) 1010-9 BACKGROUND: During the 2014-15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). METHODS: A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. RESULTS: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014-15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. CONCLUSION: Effectiveness of 2014-15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. |
The Next Generation of Risk Assessment Multiyear Study- Highlights of Findings, Applications to Risk Assessment and Future Directions.
Cote I , Andersen ME , Ankley GT , Barone S , Birnbaum LS , Boekelheide K , Bois FY , Burgoon LD , Chiu WA , Crawford-Brown D , Crofton KM , DeVito M , Devlin RB , Edwards SW , Guyton KZ , Hattis D , Judson RS , Knight D , Krewski D , Lambert J , Maull EA , Mendrick D , Paoli GM , Patel CJ , Perkins EJ , Poje G , Portier CJ , Rusyn I , Schulte PA , Simeonov A , Smith MT , Thayer KA , Thomas RS , Thomas R , Tice RR , Vandenberg JJ , Villeneuve DL , Wesselkamper S , Whelan M , Whittaker C , White R , Xia M , Yauk C , Zeise L , Zhao J , DeWoskin RS . Environ Health Perspect 2016 124 (11) 1671-1682 BACKGROUND: The Next Generation (NexGen) of Risk Assessment effort is a multiyear collaboration among several organizations evaluating new, potentially more efficient molecular, computational and systems biology approaches to risk assessment. This paper summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions. OBJECTIVE: Our specific objectives were to test whether advanced biological data and methods could better inform our understanding of public health risks posed by environmental exposures. METHODS: New data and methods were applied and evaluated for use in hazard identification and dose-response assessment. Biomarkers of exposure and effect, and risk characterization were also examined. Consideration was given to various decision contexts with increasing regulatory and public health impacts. Data types included transcriptomics, genomics, and proteomics; methods included molecular epidemiology and clinical studies, bioinformatic knowledge mining, pathway and network analyses, short-duration in vivo and in vitro bioassays, and quantitative structure activity relationship modeling. DISCUSSION: NexGen has advanced our ability to apply new science by more rapidly identifying chemicals and exposures of potential concern, helping characterize mechanisms of action that influence conclusions about causality, exposure-response relationships, susceptibility and cumulative risk, and by elucidating new biomarkers of exposure and effects. Additionally, NexGen has fostered extensive discussion among risk scientists and managers and improved confidence in interpreting and applying new data streams. CONCLUSIONS: While considerable uncertainties remain, thoughtful application of new knowledge to risk assessment appears reasonable for augmenting major scope assessments, forming the basis for or augmenting limited scope assessments, and for prioritization and screening of very data limited chemicals. |
The association between circulating total folate and folate vitamers with overall survival after postmenopausal breast cancer diagnosis
McEligot AJ , Ziogas A , Pfeiffer CM , Fazili Z , Anton-Culver H . Nutr Cancer 2015 67 (3) 442-8 We studied the relationship between plasma total folate and folate vitamer concentrations [5-methyltetrahydrofolic acid, pteroylglutamic acid (folic acid) and tetrahydrofolic acid] with overall survival after breast cancer diagnosis. A secondary aim was to assess the relationship between folic acid supplement use with circulating total folate and folate vitamer concentrations. Participants were postmenopausal women diagnosed with breast cancer (n = 498) with an average follow-up of 6.7 yr. Plasma total folate and folate vitamers were measured by isotope-dilution LC-MS/MS in samples collected at or postdiagnosis. Cox proportional multivariate hazards models (controlled for stage, age at diagnosis, body mass index, parity, hormone replacement therapy use, treatment, alcohol use, folic acid use, and energy intake), were used to assess overall survival after breast cancer diagnosis. We found that the relative risk of dying for women with plasma total folate concentrations in the highest quartile was 59% lower (hazard ratio: 0.41, 95% confidence interval: 0.19-0.90) compared with the lowest quartile. Data on supplement use showed that women taking folic acid supplements had significantly higher circulating total folate and folate vitamer concentrations (P < 0.0001), suggesting that increased folate consumption through diet and/or supplementation may improve prognosis after breast cancer diagnosis. |
A prospective study of musculoskeletal outcomes among manufacturing workers: I. effects of physical risk factors
Gerr F , Fethke N , Merlino L , Anton D , Rosecrance J , Jones MP , Marcus M , Meyers A . Hum Factors 2013 56 (1) 112-30 OBJECTIVE: To better characterize associations between physical risk factors and upper-extremity musculoskeletal symptoms and disorders, a prospective epidemiologic study of 386 manufacturing workers was performed. BACKGROUND: Methodological limitations of previous studies have resulted in inconsistent associations. METHOD: An individual, task-based exposure assessment strategy was used to assess upper-extremity exertion intensity, repetition, and time-in-posture categories. Participants recorded time spent performing daily work tasks on a preprinted log, which was then used to calculate time-weighted-average exposures across each week of follow-up. In addition, a weekly Strain Index (SI) risk category was assigned to each participant. Incident musculoskeletal symptoms and disorders were assessed weekly. Proportional hazards analyses were used to examine associations between exposure measures and incident hand/arm and neck/shoulder symptoms and disorders. RESULTS: Incident symptoms and disorders were common (incident hand/arm symptoms = 58/100 person-years (PY), incident hand/arm disorders = 19/100 PY, incident neck/shoulder symptoms = 54/100 PY, incident neck/shoulder disorders = 14/100 PY). Few associations between separate estimates of physical exposure and hand/arm and neck/shoulder outcomes were observed. However, associations were observed between dichotomized SI risk category and incident hand/arm symptoms (hazard ratio [HR] = 1.73, 95% confidence interval [CI] = [0.99, 3.04]) and disorders (HR = 1.93, 95% CI = [0.85, 4.40]). CONCLUSION: Evidence of associations between physical risk factors and musculoskeletal outcome was strongest when exposure was estimated with the SI, in comparison to other metrics of exposure. APPLICATION: The results of this study provide evidence that physical exposures in the workplace contribute to musculoskeletal disorder incidence. Musculoskeletal disorder prevention efforts should include mitigation of these occupational risk factors. |
Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York, USA, 2003
Ostrowsky B , Huang A , Terry W , Anton D , Brunagel B , Traynor L , Abid S , Johnson G , Kacica M , Katz J , Edwards L , Lindstrom S , Klimov A , Uyeki TM . Emerg Infect Dis 2012 18 (7) 1128-31 In 2003, infection with low pathogenic avian influenza A (H7N2) virus was identified in an immunocompromised man with fever and community-acquired pneumonia in New York, USA. The patient recovered. Although the source of the virus was not identified, this case indicates the usefulness of virus culture for detecting novel influenza A viruses. |
Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells
Milush JM , Mir KD , Sundaravaradan V , Gordon SN , Engram J , Cano CA , Reeves JD , Anton E , O'Neill E , Butler E , Hancock K , Cole KS , Brenchley JM , Else JG , Silvestri G , Sodora DL . J Clin Invest 2011 121 (3) 1102-10 SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4-CD8- T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell-like helper functions upon SIV-induced CD4+ T cell depletion in this species. |
Multi-site comparison of anti-HIV microbicide activity in explant assays using a novel endpoint analysis
Richardson-Harman N , Lackman-Smith C , Fletcher PS , Anton PA , Bremer JW , Dezzutti CS , Elliott J , Grivel JC , Guenthner P , Gupta P , Jones M , Lurain NS , Margolis LB , Mohan S , Ratner D , Reichelderfer P , Roberts P , Shattock RJ , Cummins JE Jr . J Clin Microbiol 2009 47 (11) 3530-9 Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of HIV-1, such as tonsil, cervical or rectal tissue. To compare virus growth or the anti-HIV-1 efficacy of candidate microbicides in tissue explants, a novel 'soft endpoint' method, was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft endpoint was compared to several other endpoint methods including: 1) the growth of virus on specific days after infection; 2) the area under the virus growth curve; and 3) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods and experimental conditions using non-parametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when: (i) the soft endpoint or other standardized endpoint is used; (ii) drugs and/or virus reagents are centrally sourced and; (iii) the same explant tissue type and method are used. Application of the soft endpoint reduces the inherent variability in comparisons of pre-clinical assays used for microbicide development. |
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