Will You Look Me in the Eye? The Embrace and Denial of Human Dignity on Marquette Campus

With a foundation in Levinas\u27 pseudo-ethical philosophy of the Phenomena of the Face, this project provided a definition of human dignity and considered whether or not the Marquette University community practices a common respect for human dignity in everyday interactions on the streets of Marquette campus -- focusing in on Wisconsin Avenue due to its constant traffic of both Marquette University students and faculty and Milwaukee community members. This project observed typical day to day interactions that occur while walking around Marquette University\u27s campus with a specific emphasis on how people affiliated with Marquette University react to other Marquette community members as well as members of the Milwaukee community on campus. Ultimately, the research sought to consider the level of awareness Marquette affiliates have upon the subject of human dignity and calls for we as a university to raise awareness about the necessity and nuances of human dignity in everyday interactions.https://epublications.marquette.edu/english_3210ur/1019/thumbnail.jp

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne bla KPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 bla KPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of bla KPC (predominantly bla KPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-bla KPC and bla KPC plasmids and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control

Extended-spectrum β-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing study

Background: Escherichia coli isolates producing extended-spectrum βlactamases (‘ESBL-E. coli’) cause >5000 bacteraemias annually in the UK. The contribution of the food chain to this challenge is debated. Methods: Selective media were used to seek ESBL-E. coli in routinely-submitted human faeces, sewage, farm slurry, and retail foodstuffs in London, East Anglia, Northwest England, Scotland and Wales. Recovered isolates were sequenced and compared with 293 bloodstream and 83 veterinary surveillance ESBL-E. coli isolates from the same regions. Findings: 10.7% (2157/20243) of human faeces contained ESBL-E. coli, rising to 17.0% (678/3995) in London. ESBL-E. coli also were frequent in sewage and present in 65.4% (104/159) of retail chicken, but rare in other meats and absent from plant-based foods. Sequence Type (ST) 131 dominated among ESBL-E. coli from human blood (188/293, 64.2%), faeces (128/360, 35.6%) and sewage (14/65, 21.5%) with STs 38 and 648 also widespread; CTX-M-15 was the predominant ESBL in these lineages. By contrast, STs 602, 23, 117 - mostly with CTX-M-1 ESBL - dominated among food and veterinary isolates, with only two ST131 organisms recovered. ST10 occurred in both animals and humans: being frequent in surveillance bovines and representing 4.2% (15/360) of human faecal isolates (but only 1% [3/293] from bacteraemias); however both human and animal ST10 isolates were diverse in serotype. Interpretation: Most human bacteraemias with ESBL-E. coli in the UK involve successful human-associated STs, particularly ST131; non-human reservoirs made little contribution to invasive human disease. Funding: NIHR Policy Research

Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

Background Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Methods We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. Results Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. Conclusions Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multicentre evaluation of a real-time PCR assay to detect genes encoding clinically relevant carbapenemases in cultured bacteria.

The performance and portability of a multiplex real-time PCR assay to detect KPC, NDM, OXA-48-like and VIM carbapenemase gene families from bacterial isolates was assessed using Rotor-Gene Q and ABI 7500 instruments. Gram-negative bacterial isolates (n=502) were comprised of 100 isolates each with KPC, NDM, VIM or OXA-48-like carbapenemases (including 17 with OXA-181) and 2 isolates with NDM+OXA-48-like enzymes (including 1 with OXA-181) as well as 100 assay-negative isolates comprised of 24 IMP-producers, 24 carbapenem-resistant isolates with no known carbapenemase gene and 52 extended-spectrum β-lactamase-producing carbapenem-susceptible isolates. A multicentre evaluation was carried out in five laboratories using a subset of 100 isolates comprised of 22 isolates each with KPC, NDM, OXA-48-like or VIM alleles and 12 isolates that were negative for the assay targets. Initial validation of the assay on both the Rotor-Gene Q and ABI 7500 instruments demonstrated 100% sensitivity amongst the 402 isolates that were positive for KPC, NDM, OXA-48-like (including OXA-181) and VIM carbapenemase genes, whilst the 100 assay-negative samples were correctly identified indicating 100% specificity. During the multicentre evaluation the same 100% level of sensitivity and specificity was observed in each of the five centres that participated. Neither invalid nor false-positive results were observed. In conclusion, the assay offers a portable and reliable option for the detection of bacteria carrying clinically significant carbapenemases encoded by KPC, NDM, VIM and OXA-48-like carbapenemase genes using either of the two most common real-time PCR instrument platforms