Maintaining the Strength of American Capitalism

The American economic system has always been the foundation of our national strength. But this foundation is showing cracks—from high levels of income inequality, declining economic mobility, and persistent economic insecurity among low- and middle-income Americans.Many now conclude that our economic system is broken. Recent polling data show that trust in capitalism is declining, especially among younger people. A 2018 Gallup poll found that less than half of respondents (45%) ages 18-29 held positive views of capitalism. This shift represents a 20-point decline since 2010 in the share of young adults' who held positive views of capitalism.The upshot is clear: American capitalism is in trouble. We need to strengthen our system to ensure that more people participate in our economic success. This means updating and adjusting our policies to ensure the outcomes of our market-based economy are consistent with fundamental American values of freedom, opportunity, and equality.Doing so isn't just an imperative for economic reasons. We believe that strengthening capitalism is as important for the health of the American economy as it is for the strength of our democracy. High levels of economic inequality will only contribute to increasing political dysfunction.The essays contained in this volume seek to clarify the lines of debate on some of the greatest economic policy challenges of our time and present evidence- based analysis on how to address them. It examines the hypothesis that growing market concentration is inhibiting a dynamic and competitive economy. Next, it examines the health of America's fiscal situation and what it implies about the continued strength of our market-based economy. Finally, it takes a hard look at recent policy proposals that would dramatically raise taxes on the rich and expand access to public benefit programs in response to high levels of income inequality and declining economic mobility.The perspectives presented in this volume are not intended to represent the consensus view of Aspen Economic Strategy Group members. Our goal is to equip policymakers with the best analysis available to better inform decision making and to help Americans better understand the difficult trade-offs our leaders face in making such decisions.There is no single solution to the challenges facing the American economy. The important role of evidence-based policies with bipartisan appeal, however, is difficult to overstate. This volume cannot claim to represent the end of thinking on ways to strengthen American capitalism, but we believe it provides a useful start

Cytotoxic and Pathogenic Properties of Klebsiella oxytoca Isolated from Laboratory Animals

Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Cytotoxic and Pathogenic Properties of <i>Klebsiella oxytoca</i> Isolated from Laboratory Animals

Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease.</p

Animal isolates of <i>K. oxytoca</i> produce cytotoxin.

<p>HEp-2 cell culture inoculated with <i>K. oxytoca</i> supernatant and media control at 4, 10, and 30× magnifications. <b>A)</b> Media control showing normal morphology of cells stained with Diff-quick after 48 hours of incubation. <b>B)</b><i>K. oxytoca</i>, ATCC 13182, isolate negative for cytotoxin production showing normal cell morphology. <b>C)</b><i>K. oxytoca</i> isolate, 09-7231-1, positive for cytotoxin production showing abnormal cell morphology, decreased concentration of attached cells, small round cells, and multinucleated cells.</p

Antimicrobial resistance of <i>K. oxytoca.</i>

<p>Antibiotic discs: ampicillin10µg; cephalothin 30µg; amoxicillin/clavulanic acid 20/10µg; trimethoprim/sulfamethoxazole 1.25/23.75µg; enrofloxacin 5µg; and gentamicin 10µg.</p

The reference proteins encoded by CTA, CFX B, and PAX B are displayed as colored bars.

<p>The arrow beneath the bar shows the region in the reference protein to which the corresponding <i>K. Oxytoca</i> protein aligns from the BLAST analysis.</p

Tilivalline induced HEp-2 cell detachment and death.

<p><b>A)</b> HEp-2 cells incubated with the control DMSO, which was used to dissolve tilivalline. The majority of cells adhered to the bottom of the cell culture well after 48 hours of culture; <b>B)</b> HEp-2 cells treated with purified tilivalline (1 µg/ml) were detached from the cell culture well after 48 hours of incubation.</p

Sources and origin of <i>Klebsiella oxytoca</i> used in this study.

<p>Sources and origin of <i>Klebsiella oxytoca</i> used in this study.</p