scholarly journals Screening and Genomic Characterization of Filamentous Hemagglutinin-DeficientBordetella pertussis

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Michael R. Weigand ◽  
Lucia C. Pawloski ◽  
Yanhui Peng ◽  
Hong Ju ◽  
Mark Burroughs ◽  
...  
Keyword(s):  
United States ◽  
Vaccine Coverage ◽  
The United States ◽  
Vaccine Immunogen ◽  
Genetic Changes ◽  
Content Type ◽  
Capture Assay ◽  
Filamentous Hemagglutinin ◽  
Acellular Vaccines ◽  
Acellular Vaccine

ABSTRACTDespite high vaccine coverage, pertussis cases in the United States have increased over the last decade. Growing evidence suggests that disease resurgence results, in part, from genetic divergence of circulating strain populations away from vaccine references. The United States employs acellular vaccines exclusively, and currentBordetella pertussisisolates are predominantly deficient in at least one immunogen, pertactin (Prn). First detected in the United States retrospectively in a 1994 isolate, the rapid spread of Prn deficiency is likely vaccine driven, raising concerns about whether other acellular vaccine immunogens experience similar pressures, as further antigenic changes could potentially threaten vaccine efficacy. We developed an electrochemiluminescent antibody capture assay to monitor the production of the acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 U.S. surveillance isolates collected from 2010 to 2016 identified two that were both Prn and Fha deficient. Three additional Fha-deficient laboratory strains were also identified from a historic collection of 65 isolates dating back to 1935. Whole-genome sequencing of deficient isolates revealed putative, underlying genetic changes. Only four isolates harbored mutations to known genes involved in Fha production, highlighting the complexity of its regulation. The chromosomes of two Fha-deficient isolates included unexpected structural variation that did not appear to influence Fha production. Furthermore, insertion sequence disruption offhaBwas also detected in a previously identified pertussis toxin-deficient isolate that still produced normal levels of Fha. These results demonstrate the genetic potential for additional vaccine immunogen deficiency and underscore the importance of continued surveillance of circulatingB. pertussisevolution in response to vaccine pressure.

scholarly journals Complete Genome Sequences of Bordetella pertussis Isolates with Novel Pertactin-Deficient Deletions

2017 ◽  
Vol 5 (37) ◽  
Author(s):  
Michael R. Weigand ◽  
Yanhui Peng ◽  
Pamela K. Cassiday ◽  
Vladimir N. Loparev ◽  
Taccara Johnson ◽  
...  
Keyword(s):  
United States ◽  
Bordetella Pertussis ◽  
Complete Genome ◽  
The United States ◽  
Clinical Isolates ◽  
Respiratory Pathogen ◽  
Genome Sequences ◽  
Vaccine Immunogen ◽  
Content Type ◽  
Acellular Vaccine

ABSTRACT Clinical isolates of the respiratory pathogen Bordetella pertussis in the United States have become predominantly deficient for the acellular vaccine immunogen pertactin through various independent mutations. Here, we report the complete genome sequences for four B. pertussis isolates that harbor novel deletions responsible for pertactin deficiency.

scholarly journals Meningococcal Antigen Typing System (MATS)-Based Neisseria meningitidis Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Gowrisankar Rajam ◽  
Maria Stella ◽  
Ellie Kim ◽  
Simon Paulos ◽  
Giuseppe Boccadifuoco ◽  
...  
Keyword(s):  
United States ◽  
Vaccine Coverage ◽  
Binding Protein ◽  
The United States ◽  
Factor H ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immune Reactivity ◽  
Content Type ◽  
Efficacy Trials ◽  
Typing System

ABSTRACT The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates (n = 442) predicts high MenB-4C vaccine coverage in the United States. Neisseria meningitidis is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against N. meningitidis serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States. MATS data correlate with killing in the human complement serum bactericidal assay (hSBA) and predict the susceptibility of NmB strains to killing in the hSBA, the accepted correlate of protection for MenB-4C vaccine. A panel of 442 NmB United States clinical isolates (collected in 2000 to 2008) whose data were down weighted with respect to the Oregon outbreak was selected from the Active Bacterial Core Surveillance (ABCs; CDC, Atlanta, GA) laboratory. MATS results examined to determine strain coverage were linked to multilocus sequence typing and antigen sequence data. MATS predicted that 91% (95% confidence interval [CI95], 72% to 96%) of the NmB strains causing disease in the United States would be covered by the MenB-4C vaccine, with the estimated coverage ranging from 88% to 97% by year with no detectable temporal trend. More than half of the covered strains could be targeted by two or more antigens. NHBA conferred coverage to 83% (CI95, 45% to 93%) of the strains, followed by factor H-binding protein (fHbp), which conferred coverage to 53% (CI95, 46% to 57%); PorA, which conferred coverage to 5.9%; and NadA, which conferred coverage to 2.5% (CI95, 1.1% to 5.2%). Two major clonal complexes (CC32 and CC41/44) had 99% strain coverage. The most frequent MATS phenotypes (39%) were fHbp and NHBA double positives. MATS predicts over 90% MenB-4C strain coverage in the United States, and the prediction is stable in time and consistent among bacterial genotypes. IMPORTANCE The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates (n = 442) predicts high MenB-4C vaccine coverage in the United States.

NCSS notable trade book lesson plan: the girl who buried her dreams in a can

2020 ◽  
Vol 15 (2) ◽  
pp. 121-126
Author(s):  
Takisha Durm
Keyword(s):  
United States ◽  
Research Design ◽  
Design Methodology ◽  
Lesson Plan ◽  
The United States ◽  
Elementary Grades ◽  
Effect Change ◽  
Content Type ◽  
Similarities And Differences ◽  
Future Date

PurposeThe Girl Who Buried Her Dreams in a Can, written by Dr Tererai, profiles a cultural, yet global experience of the power of believing in one's dream. Through this study of the similarities and differences of how children in the United States and abroad live and dream of a better life, this lesson seeks to enhance students' understandings of the power and authority they possess to effect change not only within their own lives but also in the lives of countless others in world. After reading the text, students will work to create vision boards illustrating their plans to effect change within their homes, schools, communities, states or countries. They will present their plans to their peers. To culminate the lesson, the students will bury their dreams in can and collectively decide on a future date to revisit the can to determine how far they have progressed in accomplishing their goals.Design/methodology/approachThis is an elementary grades 3–6 lesson plan. There was no research design/methodology/approach included.FindingsAs this is a lesson plan and no actual research was represented, there are no findings.Originality/valueThis is an original lesson plan completed by the first author Takisha Durm.

Washington will rethink its foreign chip strategy

2021 ◽  
Keyword(s):  
United States ◽  
Supply Chain ◽  
The United States ◽  
Export Controls ◽  
Political Pressure ◽  
Technical Standards ◽  
Content Type ◽  
The Us ◽  
Technology Competition ◽  
Business In China

Significance Follow-on action from Washington and responses from foreign actors will shape the US government’s adversarial policy towards China in semiconductors and other strategic technologies. Impacts The Biden administration will likely conclude that broad-based diversion of the semiconductor supply chain away from China is not feasible. The United States will rely on export controls and political pressure to prevent diffusion to China of cutting-edge chip technologies. The United States will focus on persuading foreign semiconductor leaders to help develop US capabilities, thereby staying ahead of China. Washington will focus on less direct approaches to strategic technology competition with China, notably technical standards-setting. Industry leaders in the semiconductor supply chain worldwide will continue expanding business in China in less politically sensitive areas.

The Physiology of Body Weight Regulation: Relevance to the Etiology of Obesity in Children

PEDIATRICS ◽  
1998 ◽  
Vol 101 (Supplement_2) ◽  
pp. 525-539 ◽  
Author(s):  
Michael Rosenbaum ◽  
Rudolph L. Leibel
Keyword(s):  
United States ◽  
Body Weight ◽  
Environmental Factors ◽  
Regulatory System ◽  
The United States ◽  
Genetic Changes ◽  
Adult Body ◽  
Genes Encoding ◽  
Prevalence Of Obesity ◽  
Obesity In Children

The prevalence of obesity in children and adults in the United States has increased by more than 30% over the past decade. Recent studies of the physiology and molecular genetics of obesity in humans have provided evidence that body weight (fat) is regulated. Some of the genes encoding the molecular components of this regulatory system have been isolated from rodents. The increasing prevalence of obesity in the United States apparently represents the interaction of these genes with an environment that encourages a sedentary lifestyle and consumption of calories. The rapid increase in the prevalence of obesity emphasizes the role of environmental factors, because genetic changes could not occur at this rate. Thus, understanding of the relevant genes and how their effects are mediated by environment and development should lead to more effective prophylaxis and therapy of obesity. Although no clear environmental factors have been identified as causative of obesity, the rapid increases in the prevalence of obesity and the seeming voluntary immutability of adult body fatness can be taken as tacit evidence that the pediatric environment can be altered in a way that affects adult body weight.

Canada-US ties will see fewer irritants under Biden

2021 ◽  
Keyword(s):  
United States ◽  
Prime Minister ◽  
Oil Industry ◽  
The United States ◽  
Donald Trump ◽  
Federal Election ◽  
Content Type ◽  
Un Peacekeeping ◽  
Keystone Xl ◽  
Keystone Xl Pipeline

Significance Canada’s Liberal Prime Minister Justin Trudeau is preparing to welcome a more predictable and stable partner in Biden than outgoing Republican President Donald Trump. However, Biden is also expected quickly to cancel the Keystone XL pipeline, cutting another lifeline to Canada’s oil industry and creating some strain in Canada-US ties. Impacts Improved Canada-US ties will persist even if Trudeau loses the next federal election to Conservative Erin O’Toole. Canada will re-engage militarily with UN peacekeeping and NATO deployments. Trudeau will encourage Biden to end US prosecution of Meng Wanzhou, allowing Canada to release her; Biden may agree. Canada’s border with the United States will open in stages as COVID-19 recedes. Ottawa will push Biden to end ‘Buy American’ procurement policies, with little success.

Washington will engage more with South-east Asia

2021 ◽  
Keyword(s):  
United States ◽  
East Asia ◽  
The United States ◽  
South East Asia ◽  
National Unity ◽  
Content Type ◽  
Key Issues ◽  
Set Up

Significance She addressed two key issues during her trip: tensions in post-coup Myanmar and China’s growing regional footprint. Shortly after she left the region, the United States announced that it would donate unused COVID-19 vaccines abroad, including to South-east Asia. Impacts Washington will tighten its sanctions on the Myanmar military while supporting ASEAN’s five-point plan to ease the country’s crisis. The National Unity Government, a parallel administration to Myanmar’s junta set up by its opponents, will try to attract greater US backing. Manila and Washington may extend negotiations over renewing their Visiting Forces Agreement to prevent the pact expiring in August.

Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKD

2021 ◽  
pp. ASN.2020091281
Author(s):  
John Danziger ◽  
Kenneth J. Mukamal ◽  
Eric Weinhandl
Keyword(s):  
United States ◽  
Drinking Water ◽  
Kidney Disease ◽  
The United States ◽  
Water Systems ◽  
Adverse Outcomes ◽  
Content Type ◽  
Community Water Systems ◽  
Community Water ◽  
Lead Levels

BackgroundAlthough patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known.MethodsTo investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90th percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System.ResultsAmong 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90th percentile water lead. Findings were similar for the 208,912 patients with data from the first month of ESKD therapy, with lower hemoglobin and higher ESA use per 0.01 mg/L higher lead concentration. These associations were observed at lead levels below the EPA threshold (0.015 mg/L) that mandates regulatory action. We also observed environmental inequities, finding significantly higher water lead levels and slower declines over time among Black versus White patients.ConclusionsThis first nationwide analysis linking EPA water supply records to patient data shows that even low levels of lead that are commonly encountered in community water systems throughout the United States are associated with lower hemoglobin levels and higher ESA use among patients with advanced kidney disease.

Neither side is ready to step back in Georgian crisis

2021 ◽  
Keyword(s):  
United States ◽  
Foreign Direct Investment ◽  
Direct Investment ◽  
Prime Minister ◽  
The United States ◽  
Content Type ◽  
Eu Membership ◽  
National Movement ◽  
Election Victory ◽  
Political Turmoil

Significance The authorities went ahead with the arrest of Nika Melia, leader of the opposition United National Movement (UNM), on February 23 even after the prime minister resigned in protest. Georgian Dream's actions have caused concern in Western capitals that approved its election victory when the opposition cried foul. Impacts The crisis is a setback for the government's stated plan to apply for EU membership in 2024. There is growing talk in the United States about individual sanctions targeting Ivanishvili and his associates. Political turmoil will harm hopes of foreign direct investment and the imminent Anaklia port tender.

Online disinformation is greater risk for older users

2021 ◽  
Keyword(s):  
United States ◽  
Voter Turnout ◽  
Senior Citizens ◽  
Rapid Evolution ◽  
The United States ◽  
Content Type ◽  
News Source ◽  
The Us ◽  
Older Users ◽  
Special Concern

Significance The growing numbers of senior citizens in the United States, their rapidly increasing adoption of social media and their high levels of voter turnout make their vulnerability to disinformation a matter of special concern. Other advanced democracies likely mirror the US experience. Impacts Older US adults' use of television as their primary news source may provide some bulwark against being targeted by disinformation online. The rapid evolution of news distribution technologies will challenge older adults used to a more slowly changing media landscape. Further research is necessary to determine the causes of age-based vulnerability and levels of resilience.

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