96 research outputs found

    Integrated Serologic Surveillance of Population Immunity and Disease Transmission.

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    Antibodies are unique among biomarkers in their ability to identify persons with protective immunity to vaccine-preventable diseases and to measure past exposure to diverse pathogens. Most infectious disease surveillance maintains a single-disease focus, but broader testing of existing serologic surveys with multiplex antibody assays would create new opportunities for integrated surveillance. In this perspective, we highlight multiple areas for potential synergy where integrated surveillance could add more value to public health efforts than the current trend of independent disease monitoring through vertical programs. We describe innovations in laboratory and data science that should accelerate integration and identify remaining challenges with respect to specimen collection, testing, and analysis. Throughout, we illustrate how information generated through integrated surveillance platforms can create new opportunities to more quickly and precisely identify global health program gaps that range from undervaccination to emerging pathogens to multilayered health disparities that span diverse communicable diseases

    Divalent Metal Ion Coordination by Residue T118 of Anthrax Toxin Receptor 2 Is Not Essential for Protective Antigen Binding

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    The protective antigen (PA) subunit of anthrax toxin interacts with the integrin-like I domains of either of two cellular receptors, ANTXR1 or ANTXR2. These I domains contain a metal ion-dependent adhesion site (MIDAS) made up of five non-consecutive amino acid residues that coordinate a divalent metal ion that is important for PA-binding. The MIDAS residues of integrin I domains shift depending upon whether the domain exists in a closed (ligand-unbound) or open (ligand-bound) conformation. Of relevance to this study, the MIDAS threonine residue coordinates the metal ion only in the open I domain conformation. Previously it was shown that the MIDAS threonine is essential for PA interaction with ANTXR1, a result consistent with the requirement that the I domain of that receptor adopts an open conformation for PA-binding [1]. Here we have tested the requirement for the MIDAS threonine of ANTXR2 for PA-binding. We show that the toxin can bind to a mutant receptor lacking the MIDAS threonine and that it can use that mutant receptor to intoxicate cultured cells. These findings suggest that an open-like configuration of the ANTXR2 MIDAS is not essential for the interaction with PA

    Parents and the Evolving Math Curriculum: Supporting One\u27s Student in Elementary Mathematics

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    The current-day mathematics curriculum is evidently different from the traditional means of teaching math. Due to this, there exist disparities between a childā€™s math education and their parent or guardianā€™s math education. This thesis will present firsthand evidence on how these disparities affect a parentā€™s perception of current-day curriculum, the extent to which parents can support their child in their learning of mathematics at home, and will strive to attend to the needs of both the parents or guardians as well as students in supporting the learning of these new concepts and strategies. With this, the research question asks: What are parentsā€™ or guardiansā€™ perceptions of current-day math curricula, and how can I best support families in their understanding of the mathematics being taught? This research lies in the survey study that was sent to parents or guardians of kindergarten through sixth-grade students from a specific school that I was associated with at the time. The results determined the need for educators to better support parents in their support of their childrenā€™s mathematical understandings. Therefore, this thesis will provide educators with an understanding of parental perceptions and inquiries on mathematics as well as a plethora of resources, strategies, and examples that can be used as a stepping stone to bridge the gap between the ā€œoldā€ mathematics and the ā€œnewā€ mathematics

    Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

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    The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH āˆ¼6.0 or below when it is bound to ANTXR1, but only at pH āˆ¼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

    Use of image based sports case studies for teaching mechanics

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    Mechanics is a fundamental topic required for both undergraduate and postgraduate students on engineering and technology courses. It can be difficult to motivate and engage students in the theoretical aspects of the topic, especially if they are without a strong mathematical background. There are many sporting examples that can be used to explain some of the basic concepts in mechanics. As many sport interactions are highspeed, visualizing the relation to mechanics can be challenging. From our own research, and that published in the field, we now have access to a range of high quality images that have been generated from high-speed video and photogrammetry work, computational simulations or flow visualizations. Two case studies in which images from ball sport research have been used to explain two key engineering subjects: solid and fluid mechanics. A strategy for future collaboration of academics to share and have access to a range of high quality experimental images was also proposed

    Anthrax Toxin Receptor 2ā€“Dependent Lethal Toxin Killing In Vivo

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    Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis

    Uptake of synthetic low density lipoprotein by leukemic stem cells ā€” a potential stem cell targeted drug delivery strategy

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    Chronic Myeloid Leukemia (CML) stem/progenitor cells, which over-express Bcr-Abl, respond to imatinib by a reversible block in proliferation without significant apoptosis. As a result, patients are unlikely to be cured owing to the persistence of leukemic quiescent stem cells (QSC) capable of initiating relapse. Previously, we have reported that intracellular levels of imatinib in primary primitive CML cells (CD34<sup>+</sup>38<sup>lo/āˆ’</sup>), are significantly lower than in CML progenitor cells (total CD34<sup>+</sup>) and leukemic cell lines. The aim of this study was to determine if potentially sub-therapeutic intracellular drug concentrations in persistent leukemic QSC may be overcome by targeted drug delivery using synthetic Low Density Lipoprotein (sLDL) particles. As a first step towards this goal, however, the extent of uptake of sLDL by leukemic cell lines and CML patient stem/progenitor cells was investigated. Results with non-drug loaded particles have shown an increased and preferential uptake of sLDL by Bcr-Abl positive cell lines in comparison to Bcr-Abl negative. Furthermore, CML CD34<sup>+</sup> and primitive CD34<sup>+</sup>38<sup>lo/āˆ’</sup> cells accumulated significantly higher levels of sLDL when compared with non-CML CD34<sup>+</sup> cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication

    A global comprehensive vaccine-preventable disease surveillance strategy for the immunization Agenda 2030

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    As part of the Immunization Agenda 2030, a global strategy for comprehensive vaccine-preventable disease (VPD) surveillance was developed. The strategy provides guidance on the establishment of high-quality surveillance systems that are 1) comprehensive, encompassing all VPD threats faced by a country, in all geographic areas and populations, using all laboratory and other methodologies required for timely and reliable disease detection; 2) integrated, wherever possible, taking advantage of shared infrastructure for specific components of surveillance such as data management and laboratory systems; 3) inclusive of all relevant data needed to guide immunization program management actions. Such surveillance systems should generate data useful to strengthen national immunization programs, inform vaccine introduction decision-making, and reinforce timely and effective detection and response. All stakeholders in countries and globally should work to achieve this vision

    Antecedent causes of a measles resurgence in the Democratic Republic of the Congo

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    Introduction: Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the CongoĀ (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods: We conducted a descriptive epidemiological analysis usingĀ measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for eliminationĀ efforts in DRC. Results: During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were notĀ met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementaryimmunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (ā‰¤95%). In 2010, SIAs in five of 11Ā provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During JulyĀ 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1Ā coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10Ā years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measlesvirus strains that were previously identified in the region. Conclusion: The resurgence was likely caused by an accumulation of unvaccinated,Ā measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles eliminationĀ by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routineĀ services and SIAs.Keywords: Measles, outbreak, elimination, immunization, vaccination, surveillance, DRC, RD
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