3,664 research outputs found
Elucidation of the Molecular Mechanisms That Contribute to Variation in Susceptibility Testing Show the Need for Alternative Detection Methods of KPC-producing Gram-negative Bacteria
No full textPathogens that produce the Klebsiella pneumoniae carbapenemase (KPC) have become a major threat to the global health care system. Patients infected with KPC-producing pathogens have a higher incidence of morbidity and mortality, as these infections have been associated with high levels of β- lactam resistance, in addition to other antibiotic drug classes. This, in addition to the lack of novel antimicrobials with activity against Gram-negative bacteria, forces physicians to treat infections caused by KPC-producing pathogens with potentially toxic antibiotics, such as the aminoglycosides and polymyxins. The rapid spread of blaKPC into multiple genera of Gram-negative bacteria, the lack of effective treatment regimens, and the difficulty of identifying these pathogens using current detection methods in the clinical laboratories are the biggest challenges the KPC-producing organisms pose.
Although in vitro testing indicates that the KPC β-lactamase can efficiently hydrolyze the carbapenems, multiple studies have reported variability in susceptibility testing of KPC-producing clinical isolates. The first hypothesis tested in this dissertation was that the variation observed during susceptibility testing was due to variations in gene expression and/or gene copy number. Variation in KPC enzyme production could contribute to the variability observed during susceptibility testing. However, the individual influence of the KPC β-lactamase cannot be determined in clinical isolates since all of the organisms evaluated to date produce multiple β-lactam resistance mechanisms. Little is known about the role gene expression plays in KPC-mediated resistance or its affect on KPC production during susceptibility testing. Therefore, I sought to elucidate the molecular mechanisms that contribute to the variation in susceptibility of Gram-negative bacteria harboring blaKPC.
To address this problem, we created a panel of four different genera of Gram-negative bacteria that expressed the blaKPC gene without the influence of other resistance mechanisms. Using this panel, we evaluated the relationship between blaKPC gene expression to β-lactam MICs, gene copy number, and protein production in comparison to KPC-producing clinical isolates. These studies identified variation in blaKPC gene copy number, expression and protein production in the clinical isolates compared to their
genus-specific control. These variations in expression and protein production did not always correlate with the β-lactam MICs observed during susceptibility testing. Evaluation of RNA expression identified two novel transcriptional start sites and promoter elements for blaKPC. Subsequent analysis of the
upstream promoter regions using constructed promoter deletion clones demonstrated that the proximal promoter elements were responsible for the β-lactam resistant phenotype.
As the expression and protein data do not elucidate the problems associated with susceptibility testing and the rapid spread of this gene among numerous genera, a second hypothesis was tested: Exposure to sub- inhibitory levels of antibiotics stimulates blaKPC expression and/or contributes to the mobilization of Tn4401 carrying blaKPC. I evaluated the effect of “collateral damage,” or the unintended effects of exposure to antibiotics on transmission and expression of KPC–mediated antimicrobial resistance. Five KPC-producing clinical isolates were exposed to antibiotics from five different drug classes to determine whether they would stimulate blaKPC expression or mobilization of the transposon Tn4401 carrying blaKPC. While no changes in Tn4401 mobility were observed, there were subtle increases in blaKPC gene
expression with gentamicin and tigecycline, both of which are used in the treatment of KPC-producing pathogens. Of note, non-β-lactam drugs influenced blaKPC gene expression more often than the β-lactam drugs, but strain to strain variation occurred.
The third hypothesis was that a high resolution melt assay would be able to detect and differentiate between blaKPC alleles. To circumvent the
difficulties that conventional phenotypic testing can pose an alternative testing algorithm was designed to decrease the turn around time required to identify the presence of the KPC carbapenemase in Gram-negative clinical isolates. To do so, a single tube, PCR-based assay was designed to detect and differentiate between blaKPC gene alleles. Validation of this study involved testing 166 Gram-negative clinical isolates, 66 of which were known to be KPC-positive. This assay demonstrated 100% diagnostic sensitivity and specificity for both blaKPC gene detection and differentiation into blaKPC-2-like and blaKPC-3like allele groups.
Taken together, these data demonstrate the level of complexity by which blaKPC is regulated and the preliminary findings may represent a means of differential expression under various selective pressures. Although the fold differences in blaKPC gene expression are subtle, these differences cannot be ignored. This variation may represent differences in metabolic processes or other compensatory mechanisms that may have been selected for in the patients they infect, where they can be exposed to a variety of different physiological conditions and stressors. It is imperative that we continue to evaluate the complexity of this resistance mechanism in order to better understand how it spreads to susceptible patient populations. As it is apparent that there may be several, strain dependent mechanisms involved in the susceptibility testing variation, the development of molecular assays in the clinical microbiology laboratory may be a superior testing method for the identification of KPCs.ProQuest Traditional Publishing Optionxv, 78 page
Censorship and claims making regarding problem framing in 5 published RCT's on social anxiety (as identified by the author and Amanda Reiman, PhD).
No full text<p>Censorship and claims making regarding problem framing in 5 published
RCT's on social anxiety (as identified by the author and Amanda
Reiman, PhD).</p
Unveiling Melodies in Shadows: An Analysis of Swedish Female Composer Amanda Maier’s Sonata for Violin and Piano in B Minor
No full textAmanda Maier (1853−1894), a pioneering Swedish violinist and composer of the late nineteenth century, holds a unique place in music history as the first-ever female music director in Sweden. Despite her significant achievements, her compositions have remained relatively unknown. Therefore, the document aims to illuminate Amanda Maier's violin works, focusing on investigating her violin sonata in terms of violin performance and pedagogy. Specifically, the study offers insights into the performance techniques employed and provides other pertinent pedagogical suggestions for each movement. The document features an introductory chapter and a review of the historical context of Maier's life and the violin sonata. Subsequent chapters shift the focus to performance practice and pedagogical suggestions with theoretical analysis. One distinctive feature of the study is the inclusion of practice exercises composed originally by the author, tailored specifically to the techniques found in the sonata. These exercises aid practitioners in incorporating Maier's violin sonata into their program. The study assists violinists in diversifying their performance and teaching literature. It seeks to inspire renewed appreciation for Amanda Maier's artistic legacy because it is important to recognize the remarkable contributions of women in the classical music industry, and Amanda Maier, an underrepresented composer, exemplifies this. The document not only contributes to music research but also enhances pedagogical practices, fostering a more inclusive and equitable environment for female composers in the classical music world
Belonging: natural histories of place, identity and home
No full textCanongate's synopsis:
"Reflecting on family, identity and nature, Belonging is a personal memoir about what it is to have and make a home. It is a love letter to nature, especially the northern landscapes of Scotland and the Scots pinewoods of Abernethy – home to standing dead trees known as snags, which support the overall health of the forest.
Belonging is a book about how we are held in thrall to elements of our past. It speaks to the importance of attention and reflection, and will encourage us all to look and observe and ask questions of ourselves.
Beautifully written and featuring Amanda Thomson’s artwork and photography throughout, it explores how place, language and family shape us and make us who we are."
Longlisted for the Highland Book Prize, 2023
Some of the reviews...
Outstanding - ROBERT MACFARLANE
Amanda Thomson’s new book manages to carve out a distinctive niche for itself . . . This is a passionate book and infused with a sense of rootedness - STUART KELLY, The Scotsman
In recent years rural landscapes have turned into battlegrounds, and nature writing has become increasingly polemical. Belonging is a quiet book of questions in a genre full of answers, but it is all the more powerful and beautiful for this - PATRICK GALBRAITH, TLS
One of the best things I have read in ages . . . Quiet and beautiful and powerful - ALYS FOWLER
Thomson writes of the natural in a way I have yet to encounter before. There is no real hoo-haa, no flowery description of which to speak yet somehow, I came away with that ache inside me — that renewed obsession with the world that is only borne of a very particular kind of writing — poetic, loving, raw . . . Like no other - KERRI Ní DOCHARTAIGH, Caught by the River
In strikingly original takes on Scottish history, environmentalism, Black feminist theory, artmaking, list-making, memory, and memoir, Thomson crafts a cadence that is as wise as it is vitally alive. - MARGOT DOUAIHY, author of Scorched Grac
Interview with Amanda Huron, author, Carving Out the Commons: Tenant Organizing and Housing Cooperatives in Washington, D.C.
No full textIs modern capitalism too far advanced in the U.S. to create common property regimes? Are there models for what an Urban Commons might look like? Join us as we speak with Amanda Huron, author of Carving Out the Commons: Tenant Organizing and Housing Cooperatives in Washington, D.C. (University of Minnesota Press, 2018). She’ll help us understand the theory and practice of Limited Equity Housing Cooperatives and the affordability, control, stability, and community they can provide to low-income communities and the people who live in them
Kathleen Jamie, Chitra Ramaswamy & Amanda Thomson: Antlers of Water - Live Event
No full text‘When we read and write, when we love our fellow creatures, when we walk on the beach, when we just listen and notice, we are not little cogs in the machine, but part of the remedy.’ These luminous words by Kathleen Jamie form part of the introduction to Antlers of Water, an outstanding collection of contemporary Scottish writing about nature and landscape.
The generosity of Jamie’s approach as editor of the collection goes beyond the stellar selection of contributors such as Amy Liptrot, Karine Polwart and Malachy Tallack: she also invokes the agency of readers to make a difference. ‘If, by reading, you are encouraged or confirmed in your love of the natural world, if you’re inspired simply to… look outside, then our job is done.’
In a discussion led by the BBC's Clare English, Jamie is joined by award-winning journalist Chitra Ramaswamy as well as visual artist and writer Amanda Thomson – both contributors to the anthology – to discuss Scotland, landscape and the more-than-human world around us.
This is a live event, with an author Q&A.
Part of the Edinburgh International Book Festival Making Climate Change Personal festival theme
Amanda Galvan Huynh, 46th Annual ODU Literary Festival
No full textAmanda Galvan Huynh (she/her) is a Xicana writer and educator from Texas. She is the author of a chapbook, Songs of Brujería (Big Lucks September 2019) and Co-Editor of Of Color: Poets’ Ways of Making: An Anthology of Essays on Transformative Poetics (The Operating System 2019). Her debut poetry collection, Where My Umbilical is Buried, is forthcoming in March 2023 with Sundress Publications. Amanda has been nominated for the Pushcart Prize, Best New Poets, and Sundress Publications’ Best of the Net. She was a 2016 AWP Intro Journal Project Award Winner, 2018 Best of the Net Winner, a finalist for the 2015 Gloria Anzaldúa Poetry Prize, and a finalist for the 2017 Poetry Society of America Chapbook Fellowship. Her poetry can be read in print and online journals such as Hayden’s Ferry Review, Puerto del Sol, The Southampton Review, and others.
Amanda earned her MFA in Poetry at Old Dominion University, BA in English at the University of Texas at Arlington, and BA in Biology at the University of Texas at Dallas. Currently, she is a doctoral student in English at the University of Hawaiʻi at Mānoa
Multi-Document Information Consolidation (Dagstuhl Seminar 19182)
No full textThis report documents the program and the outcomes of Dagstuhl Seminar 19182 "Multi-Document Information Consolidation". At this 5-day Dagstuhl seminar, an interdisciplinary collection of leading researchers discussed and develop research ideas to address multi-documents in machine learning and NLP systems. In particular, the seminar addressed four major topics: 1) how to represent information in multi-document repositories; 2) how to support inference over multi-document repositories; 3) how to summarize and visualize multi-document repositories for decision support; and 4) how to do information validation on multi-document repositories. General talks as well as topic-specific talks were given to stimulate the discussion between the participants, which lead to various new research ideas
Amanda Galvan Huynh, 44th Annual ODU Literary Festival
No full textAmanda Galvan Huynh is a Mexican American writer and educator from Texas. She is the author of Lotería (Sundress Publications, 2022), Songs of Brujería (Big Lucks, 2019) and co-editor for Of Color: Poets’ Ways of Making: An Anthology of Essays on Transformative Poetics (Operating System, 2019). Her writing has been supported by fellowships and scholarships from MacDowell, Vermont Studio Center, Robert Rauschenberg Foundation, Virginia Center for the Creative Arts, and others. She received a Master of Fine Arts in creative writing from Old Dominion University, and she is a doctoral student in English at the University of Hawai’i at Mānoa
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