Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Auerbach J[original query] |
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Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial
Schmader KE , Liu CK , Flannery B , Rountree W , Auerbach H , Barnett ED , Schlaudecker EP , Todd CA , Poniewierski M , Staat MA , Harrington T , Li R , Broder KR , Walter EB . Immun Ageing 2023 20 (1) 30 BACKGROUND: Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. RESULTS: The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. CONCLUSIONS: Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908. |
In silico toxicology protocols.
Myatt GJ , Ahlberg E , Akahori Y , Allen D , Amberg A , Anger LT , Aptula A , Auerbach S , Beilke L , Bellion P , Benigni R , Bercu J , Booth ED , Bower D , Brigo A , Burden N , Cammerer Z , Cronin MTD , Cross KP , Custer L , Dettwiler M , Dobo K , Ford KA , Fortin MC , Gad-McDonald SE , Gellatly N , Gervais V , Glover KP , Glowienke S , Van Gompel J , Gutsell S , Hardy B , Harvey JS , Hillegass J , Honma M , Hsieh JH , Hsu CW , Hughes K , Johnson C , Jolly R , Jones D , Kemper R , Kenyon MO , Kim MT , Kruhlak NL , Kulkarni SA , Kümmerer K , Leavitt P , Majer B , Masten S , Miller S , Moser J , Mumtaz M , Muster W , Neilson L , Oprea TI , Patlewicz G , Paulino A , Lo Piparo E , Powley M , Quigley DP , Reddy MV , Richarz AN , Ruiz P , Schilter B , Serafimova R , Simpson W , Stavitskaya L , Stidl R , Suarez-Rodriguez D , Szabo DT , Teasdale A , Trejo-Martin A , Valentin JP , Vuorinen A , Wall BA , Watts P , White AT , Wichard J , Witt KL , Woolley A , Woolley D , Zwickl C , Hasselgren C . Regul Toxicol Pharmacol 2018 96 1-17 The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. |
In silico approaches in organ toxicity hazard assessment: current status and future needs in predicting liver toxicity.
Bassan A , Alves VM , Amberg A , Anger LT , Auerbach S , Beilke L , Bender A , Cronin MTD , Cross KP , Hsieh JH , Greene N , Kemper R , Kim MT , Mumtaz M , Noeske T , Pavan M , Pletz J , Russo DP , Sabnis Y , Schaefer M , Szabo DT , Valentin JP , Wichard J , Williams D , Woolley D , Zwickl C , Myatt GJ . Comput Toxicol 2021 20 Hepatotoxicity is one of the most frequently observed adverse effects resulting from exposure to a xenobiotic. For example, in pharmaceutical research and development it is one of the major reasons for drug withdrawals, clinical failures, and discontinuation of drug candidates. The development of faster and cheaper methods to assess hepatotoxicity that are both more sustainable and more informative is critically needed. The biological mechanisms and processes underpinning hepatotoxicity are summarized and experimental approaches to support the prediction of hepatotoxicity are described, including toxicokinetic considerations. The paper describes the increasingly important role of in silico approaches and highlights challenges to the adoption of these methods including the lack of a commonly agreed upon protocol for performing such an assessment and the need for in silico solutions that take dose into consideration. A proposed framework for the integration of in silico and experimental information is provided along with a case study describing how computational methods have been used to successfully respond to a regulatory question concerning non-genotoxic impurities in chemically synthesized pharmaceuticals. |
Social determinants of health-an approach taken at CDC
Hacker K , Auerbach J , Ikeda R , Philip C , Houry D . J Public Health Manag Pract 2022 28 (6) 589-594 In the last decade, there has been an increasing awareness of the importance of addressing the social determinants of health (SDOH), the nonmedical conditions that influence health outcomes,1 as a systemic strategy for improving health, particularly among groups that are disproportionally affected by SDOH.2 While health care is important, it is estimated that these conditions, ranging from structural racism to socioeconomic factors, drive as much as 50% of health outcomes.3 |
Dispensing of Oral Antiviral Drugs for Treatment of COVID-19 by Zip Code-Level Social Vulnerability - United States, December 23, 2021-May 21, 2022.
Gold JAW , Kelleher J , Magid J , Jackson BR , Pennini ME , Kushner D , Weston EJ , Rasulnia B , Kuwabara S , Bennett K , Mahon BE , Patel A , Auerbach J . MMWR Morb Mortal Wkly Rep 2022 71 (25) 825-829 The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021() and were made available at no cost to recipients through the U.S. Department of Health and Human Services (HHS) on December 23, 2021. Beginning March 7, 2022, a series of strategies was implemented to expand COVID-19 oral antiviral access, including the launch of the Test to Treat initiative.() Data from December 23, 2021-May 21, 2022, were analyzed to describe oral antiviral prescription dispensing overall and by week, stratified by zip code social vulnerability. Zip codes represented areas classified as low, medium, or high social vulnerability; approximately 20% of U.S. residents live in low-, 31% in medium-, and 49% in high-social vulnerability zip codes.() During December 23, 2021-May 21, 2022, a total of 1,076,762 oral antiviral prescriptions were dispensed (Lagevrio = 248,838; Paxlovid = 827,924). Most (70.3%) oral antivirals were dispensed during March 7-May 21, 2022. During March 6, 2022-May 21, 2022, the number of oral antivirals dispensed per 100,000 population increased from 3.3 to 77.4 in low-, from 4.5 to 70.0 in medium-, and from 7.8 to 35.7 in high-vulnerability zip codes. The number of oral antivirals dispensed rose substantially during the overall study period, coincident with the onset of initiatives to increase access. However, by the end of the study period, dispensing rates in high-vulnerability zip codes were approximately one half the rates in medium- and low-vulnerability zip codes. Additional public health, regulatory, and policy efforts might help decrease barriers to oral antiviral access, particularly in communities with high social vulnerability. |
Safety, reactogenicity, and health-related quality of life after trivalent adjuvanted vs trivalent high-dose inactivated influenza vaccines in older adults: A randomized clinical trial
Schmader KE , Liu CK , Harrington T , Rountree W , Auerbach H , Walter EB , Barnett ED , Schlaudecker EP , Todd CA , Poniewierski M , Staat MA , Wodi P , Broder KR . JAMA Netw Open 2021 4 (1) e2031266 IMPORTANCE: Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. OBJECTIVE: To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. DESIGN, SETTING, AND PARTICIPANTS: This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. INTERVENTIONS: Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. MAIN OUTCOMES AND MEASURES: Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. RESULTS: A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference -2.7%; 95% CI, -5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. CONCLUSIONS AND RELEVANCE: Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908. |
Left ventricular dysfunction in Duchenne muscular dystrophy
James KA , Gralla J , Ridall LA , Do TN , Czaja AS , Mourani PM , Ciafaloni E , Cunniff C , Donnelly J , Oleszek J , Pandya S , Price E , Yang ML , Auerbach SR . Cardiol Young 2020 30 (2) 1-6 BACKGROUND: Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction. METHODS AND RESULTS: Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with >/=2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with >/=1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had >/=2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 +/- 4.6 years, with an average first ejection fraction of 63.1 +/- 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 +/- 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate. CONCLUSIONS: In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function. |
Policy brief: Nurse fatigue, sleep, and health, and ensuring patient and public safety
Caruso CC , Baldwin CM , Berger A , Chasens ER , Edmonson JC , Gobel BH , Landis CA , Patrician PA , Redeker NS , Scott LD , Todero C , Trinkoff A , Tucker S . Nurs Outlook 2019 67 (5) 615-619 Society needs critical nursing services around the clock and, as a result, nurses often work shift work and long work hours (SWLWH). These hours can prevent nurses from getting the seven or more hours of quality sleep each day that experts recommend (Watson, et al., 2015). Nurses on SWLWH are at risk for cardiovascular disease, gastrointestinal and psychological disorders, cancer, type 2 diabetes, injuries, musculoskeletal disorders, all-cause mortality, adverse reproductive outcomes, and difficulty managing chronic diseases (Caruso, et al., 2017; Caruso & Waters, 2008; Gan, et al. 2015; Gu, et al., 2015; DHHS, 2018; IARC Monographs Vol 124 Group, 2019; NIOSH, et al., 2015; Ramin, et al., 2014; Torquati, et al., 2017). Furthermore, tired nurses are at risk for making patient care errors and drowsy driving crashes (Bae & Fabry, 2014; Ftouni, et al., 2013; Geiger-Brown, et al., 2012; Geiger-Brown & Trinkoff, 2010; Lee, et al., 2016; Trinkoff, et al., 2011). The presence of SWLWH is also related to retention issues, including nurses expressing intention-to-leave or quitting the job (Hayes, et al., 2012; Moloney, et al., 2018). These conditions also have contributed to nursing shortages in certain specialties and practice locations (Marć, et al., 2018 ). Shortages are a grave concern, as the population is aging and the need for nurses is projected to strongly increase (Auerbach, Buerhaus, & Staiger, 2017). Thus, interventions to reduce nursing fatigue are sorely needed. The American Academy of Nursing (the Academy) supports efforts to reduce fatigue in nurses through education, workplace policies and management systems, and fatigue countermeasures. The Academy recommends that healthcare services and standard-setting organizations establish policies to address this pervasive workplace hazard, thereby promoting nurses’ health and safety along with patient and public safety. |
Cognitive testing of an instrument to evaluate acceptability and use of pre-exposure prophylaxis products among women
Zissette S , Atujuna M , Tolley EE , Okumu E , Auerbach JD , Hodder SL , Aral SO , Adimora AA . Appl Cogn Psychol 2019 34 (1) 78-84 Given the range of pre-exposure prophylaxis (PrEP) products currently being tested to prevent HIV in women, a standardized Acceptability and Use of PrEP Products Among Women Tool may facilitate comparisons of product acceptability and use across different geographies, trials, and users. We conducted three rounds of cognitive interviewing over 2 months in 2016, with 28 South African women who had experience participating in a range of PrEP product trials. The final instrument contained 41 items, including five new items that improved construct validity and 22 items modified for clarity. Changes were made due to unclear wording, difficulty answering, participant embarrassment, low response variability, and administrative formatting. Cognitive interviewing provided a means to address issues that would have inhibited this tool's ability to accurately collect data otherwise. This rapid, low-cost study provided valuable insight into participants' understanding of questions and demonstrated the utility of cognitive interviewing in international clinical trials. |
Improving hypertension control population-wide in Minnesota
Foti K , Auerbach J , Magnan S . J Public Health Manag Pract 2017 24 (5) 432-439 CONTEXT: Hypertension is a common and costly risk factor for cardiovascular disease, but just over half of all adults with hypertension have their blood pressure controlled nationally. In Minneapolis-St Paul, Minnesota, the rate of hypertension control is approximately 70% despite a rate of hypertension control similar to the national average as recently as the first half of the 1990s. OBJECTIVE: The purposes of this study were to identify factors in Minneapolis-St Paul and state-level policies and programs in Minnesota that may have contributed to the more rapid increase in blood pressure control there than that in the rest of the nation and to identify factors that can potentially be replicated in other jurisdictions. DESIGN, SETTING, PARTICIPANTS: The study included analysis of trends in hypertension control since 1980 based on the Minnesota Heart Survey and the National Health and Nutrition Examination Survey, as well as interviews with health care and public health leaders in Minnesota. MAIN OUTCOME MEASURE: Prevalence of hypertension control. RESULTS: Probable contributing factors identified include a focus on collaborative and continuous quality improvement; a forum for setting statewide clinical guidelines and measures; the willing participation from the largest health systems, purchasers, and nonprofit health plans; and the use of widely accepted mechanisms for providing feedback to clinicians and reporting performance. The relatively high rate of insurance coverage and socioeconomic status may have contributed but do not fully explain the difference in hypertension control as compared with the rest of the United States. CONCLUSIONS: The experience in Minnesota demonstrates that it is possible to dramatically increase hypertension control at the population level, across health systems, and health plans in a relatively short period of time. Lessons learned may be helpful to informing local, state, and national efforts to improve hypertension control. |
CDC's Public Health Associate Program: Serving the field today while creating the workforce of tomorrow
Duncan H , Auerbach J . J Public Health Manag Pract 2017 23 (5) 430-433 For the past several years, there has been a growing concern about the status and future of the public health workforce in America. Among the major concerns are the aging workforce, the lack of diversity in the workforce, and the changing nature of the work itself. | The average age of a state health agency worker today is 48 years, and approximately 38% of workers are planning on, or considering, leaving governmental public health before 2020.1,2 The racial/ethnic demographics of the public health workforce do not reflect the diversity of the public it serves: approximately 70% of the current state health agency workforce identifies as non-Hispanic white,1 yet the US population is less than 62% white.3 Finally, the nature of the work is changing. With the passage of the Affordable Care Act, government public health agencies at the local, state, and national levels are now less likely than ever before to offer direct services such as immunization and infectious disease treatment. There also are new tasks emerging, and with them, new skills are needed. For example, public health officials are now more likely to interact with the health care and non–health-related sectors. And there is an elevated focus on complex, nontraditional data sources and communication opportunities that require an understanding of social media, Internet communication, and data aggregation. The need to address these workforce issues has been highlighted by government and private organizations alike, and experts have written reports and articles encouraging action.4–8 |
Public health 3.0: Time for an upgrade
DeSalvo KB , O'Carroll PW , Koo D , Auerbach JM , Monroe JA . Am J Public Health 2016 106 (4) 621-2 It is time to boldly expand the scope and reach of public health to address all factors that promote health and well-being, including those related to economic development, education, transportation, food, environment, and housing. Despite nearly $3.0 trillion in annual health care spending, the United States ranks 27th in the world in life expectancy, and relatively low in many other measures of health and well-being. Worse yet, for the poor in this country, life expectancy is actually decreasing. Given these trends, and persistent gaps in health status, it’s time for a major upgrade to Public Health 3.0. |
The 3 buckets of prevention
Auerbach J . J Public Health Manag Pract 2015 22 (3) 215-8 The US health care system is in a time of unprecedented change. The expansion of insurance coverage, redesign of the reimbursement systems, and growing influence of patient-centered medical homes and accountable care organizations all bring opportunities for those interested in the prevention of disease, injury, and premature death for entire communities as well as individual patients.1,2 It is, in short, a time when public health can come to the fore. | Public health practitioners can assist clinical providers in assuring that newly insured people receive services that promote health and do not simply treat illness. They can help insurers identify the quality measures and incentives that yield better health outcomes and control costs. They can provide evidence of effective interventions that were previously funded by public health grants but can now be brought to scale if paid for by the health care sector. And they can even point to ways to complement traditional health care treatment with community-oriented population health measures. | It is obvious that none of this will come easily. Nonetheless, at this moment—unprecedented in the careers of most public health practitioners, and of uncertain duration—it is critically important to try. |
Creating incentives to move upstream: developing a diversified portfolio of population health measures within payment and health care reform
Auerbach J . Am J Public Health 2015 105 (3) 427-31 I examined the feasibility of developing a balanced portfolio of population health measures that would be useful within the current deliberations about health care and payment reform. My commentary acknowledges that an obstacle to the selection of population health metrics is the differing definitions of population health. Rather than choosing between these definitions, I identified five categories of indicators, ranging from traditional clinical care prevention interventions to those that measure investment in community-level nonclinical services, that in various combinations might yield the most promising results. I offer concrete examples of markers in each of the categories and show that there is a growing number of individuals eager to receive concrete recommendations and implement population health pilot programs. |
Preventing HIV infection in women
Adimora AA , Ramirez C , Auerbach JD , Aral SO , Hodder S , Wingood G , El-Sadr W , Bukusi EA . J Acquir Immune Defic Syndr 2013 63 S168-S173 Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral, and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be performed to implement scientific advancements and to resolve many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities. |
Biological networks for predicting chemical hepatocarcinogenicity using gene expression data from treated mice and relevance across human and rat species.
Thomas R , Thomas RS , Auerbach SS , Portier CJ . PLoS One 2013 8 (5) e63308 BACKGROUND: Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. OBJECTIVES: To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. METHODS: Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. RESULTS: Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. CONCLUSIONS: Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species. |
Improved anamnestic response among adolescents boosted with a higher dose of the hepatitis B vaccine
Chaves SS , Groeger J , Helgenberger L , Auerbach SB , Bialek S , Hu DJ , Drobeniuc J . Vaccine 2010 28 (16) 2860-4 Some hepatitis B vaccine booster studies have suggested waning of vaccine-induced immunity in adolescents vaccinated starting at birth. Those studies, however, used a pediatric formulation of the hepatitis B vaccine as a booster to detect anamnestic response. We compared adolescents boosted with an adult dose of hepatitis B vaccine with those boosted with a pediatric dose. Among adolescents who had lost protective antibody levels against hepatitis B, a higher proportion had an anamnestic response when boosted with the adult dose (60.0% vs. 43.8%). Thus, higher antigen concentrations may be required to elicit an adequate immune memory response. Despite improved anamnestic response, our study still raises concerns about whether children immunized in early infancy will remain protected from hepatitis B as they age into adulthood. |
Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer
Pearson T , Giffard P , Beckstrom-Sternberg S , Auerbach R , Hornstra H , Tuanyok A , Price EP , Glass MB , Leadem B , Beckstrom-Sternberg JS , Allan GJ , Foster JT , Wagner DM , Okinaka RT , Sim SH , Pearson O , Wu Z , Chang J , Kaul R , Hoffmaster AR , Brettin TS , Robison RA , Mayo M , Gee JE , Tan P , Currie BJ , Keim P . BMC Biol 2009 7 78 BACKGROUND: Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. RESULTS: Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. CONCLUSION: We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer. |
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