Reclaiming Virtue Ethics for Economics

Virtue ethics is an important strand of moral philosophy which normative economists have largely neglected. It underpins influential critiques of the market (as a domain in which instrumental motivation corrodes virtue) and of economics (as justifying such motivation). We explain and respond to this critique. Using the methods of virtue ethics and with reference to the writings of major economists, we propose an understanding of the ‘telos’ (purpose) of markets as cooperation for mutual benefit, and identify traits that thereby count as virtues for market participants. We conclude that the market need not be seen as a virtue-free zone

Regulation of the retinoblastoma proteins by the human herpesviruses

Viruses are obligate intracellular parasites that alter the environment of infected cells in order to replicate more efficiently. One way viruses achieve this is by modulating cell cycle progression. The main regulators of progression out of G0, through G1, and into S phase are the members of the retinoblastoma (Rb) family of tumor suppressors. Rb proteins repress the transcription of genes controlled by the E2F transcription factors. Because the expression of E2F-responsive genes is required for cell cycle progression into the S phase, Rb arrests the cell cycle in G0/G1. A number of viral proteins directly target Rb family members for inactivation, presumably to create an environment more hospitable for viral replication. Such viral proteins include the extensively studied oncoproteins E7 (from human papillomavirus), E1A (from adenovirus), and the large T (tumor) antigen (from simian virus 40). Elucidating how these three viral proteins target and inactivate Rb has proven to be an invaluable approach to augment our understanding of both normal cell cycle progression and carcinogenesis. In addition to these proteins, a number of other virally-encoded inactivators of the Rb family have subsequently been identified including a surprising number encoded by human herpesviruses. Here we review how the human herpesviruses modulate Rb function during infection, introduce the individual viral proteins that directly or indirectly target Rb, and speculate about what roles Rb modulation by these proteins may play in viral replication, pathogenesis, and oncogenesis

Pharmacotherapy Use in Older Patients with Heart Failure and Reduced Ejection Fraction Living in Skilled Nursing Facilities

Background: Little is known about the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and β-blockers among older adults with heart failure and reduced ejection fraction (HFrEF) in skilled nursing facilities (SNFs). Methods: Using national data Minimum Data Set 3.0 cross-linked with Medicare data (2011-2012), we studied 31,675 patients with HFrEF (ICD-9 codes: 428.2 or 428.4) aged ≥65 years admitted to 9,659 SNFs. We estimated the prevalence of a Part D claim for ACEIs/ARBs or β-blockers during 3 months before the SNF stay and used log-binomial models to evaluate correlates of use by estimating prevalence ratios (PR) and 95% confidence intervals (CI). Results: The median age of the study population was 83 years, 60% were women, and 10% and 4% were African Americans and Hispanics, respectively. Approximately 46% had ≥3 important risk factors for HFrEF. Fifty-seven percent received an ACEI/ARB and 47% a β-blocker; 25% received neither. Older age was inversely associated with receipt of these therapies: adjusted PRs were 0.94 (95% CI: 0.91-0.96) for ACEIs/ARBs and 0.86 (95% CI: 0.84-0.89) for β-blockers for patients aged ≥85 years compared with those aged 65-74 years. Compared with Whites, use of these therapies was higher among African Americans (adjusted PRs were 1.07 [95% CI: 1.04-1.10] for ACEIs/ARBs and 1.11 [95% CI: 1.08-1.15] for β-blockers) and Hispanics (adjusted PRs were 1.13 [95% CI: 1.09-1.18] for ACEIs/ARBs and 1.12 [95% CI: 1.07-1.18] for β-blockers). The prevalence of ACEI/ARB use was greater in patients with ≥3 important risk factors than in those with ≤1 factor: adjusted PR was 1.16 (95% CI 1.13-1.19). Conclusions: Use of guideline-directed medications may be suboptimal in older patients with HFrEF receiving SNF care. Whether this is a result of adverse drug events from prior use or insufficient evidence in vulnerable populations needs to be examined. Acknowledgements: Lin Li has received funding from a National Institutes of Health Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (5T32HL120823-02

At Our Own Peril: DoD Risk Assessment in a Post-Primacy World

The U.S. Department of Defense (DoD) faces persistent fundamental change in its strategic and operating environments. This report suggests this reality is the product of the United States entering or being in the midst of a new, more competitive, post-U.S. primacy environment. Post-primacy conditions promise far-reaching impacts on U.S. national security and defense strategy. Consequently, there is an urgent requirement for DoD to examine and adapt how it develops strategy and describes, identifies, assesses, and communicates corporate-level risk. This report takes on the latter risk challenge. It argues for a new post-primacy risk concept and its four governing principles of diversity, dynamism, persistent dialogue, and adaptation. The authors suggest that this approach is critical to maintaining U.S. military advantage into the future. Absent change in current risk convention, the report suggests DoD exposes current and future military performance to potential failure or gross under-performance.https://press.armywarcollege.edu/monographs/1410/thumbnail.jp

Novel plant–frugivore network on Mauritius is unlikely to compensate for the extinction of seed dispersers

Insular communities are particularly vulnerable to anthropogenic extinctions and introductions. Changes in composition of island frugivore communities may affect seed dispersal within the native plant community, risking ecological shifts and ultimately co-extinction cascades. Introduced species could potentially mitigate these risks by replacing ecological functions of extinct species, but conclusive evidence is lacking. Here, we investigate changes in plant–frugivore interactions involving frugivorous birds, mammals and reptiles in Mauritius, an oceanic island with an exceptionally well-specified frugivore community and well-described species introduction history. We demonstrate substantial losses of binary interaction partnerships (at the species level) resulting from native species extinctions, but also gains of equal numbers of novel interactions with introduced species, potentially supporting the idea that non-native species might compensate for lost seed dispersal. However, closer investigation of animal seed handling behaviour reveals that most interactions with seed dispersers are replaced by ecologically different interactions with seed predators. Therefore, restoration of seed dispersal functionality in this novel plant–frugivore community is unlikely

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

An Engineered Human Adipose/Collagen Model for In Vitro Breast Cancer Cell Migration Studies.

Adipocytes are one of the major stromal cell components of the human breast. These cells play a key role in the development of the gland and are implicated in breast tumorigenesis. Frequently, directional stromal collagen I fibers are found surrounding aggressive breast tumors. These fibers enhance breast cancer cell migration and are associated with poor patient prognosis. We sought to recapitulate these stromal components in vitro to provide a three-dimensional (3D) model comprising human adipose tissue and anisotropic collagen fibers. We developed a human mesenchymal stem cell (hMSC) cell line capable of undergoing differentiation into mature adipocytes by immortalizing hMSCs, isolated from breast reduction mammoplasties, through retroviral transduction. These immortalized hMSCs were seeded in engineered collagen I scaffolds with directional internal architecture, and adipogenesis was chemically induced, resulting in human adipose tissue being synthesized in vitro in an architectural structure associated with breast tumorigenesis. Subsequently, fluorescently labeled cells from an established breast cancer cell line were seeded into this model, cocultured for 7 days and imaged using multiphoton microscopy. Enhanced breast cancer cell migration was observed in the adipose-containing model over empty scaffold controls, demonstrating an adipocyte-mediated influence on breast cancer cell migration. Thus, this 3D in vitro model recapitulates the migratory effects of adipocytes observed on breast cancer cells and suggests that it could have utility with fresh breast tumor biopsies as an assay for cancer therapeutic efficacy in personalized medicine strategies

Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1−/−) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3–6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct

Space-based research in fundamental physics and quantum technologies

Space-based experiments today can uniquely address important questions related to the fundamental laws of Nature. In particular, high-accuracy physics experiments in space can test relativistic gravity and probe the physics beyond the Standard Model; they can perform direct detection of gravitational waves and are naturally suited for precision investigations in cosmology and astroparticle physics. In addition, atomic physics has recently shown substantial progress in the development of optical clocks and atom interferometers. If placed in space, these instruments could turn into powerful high-resolution quantum sensors greatly benefiting fundamental physics. We discuss the current status of space-based research in fundamental physics, its discovery potential, and its importance for modern science. We offer a set of recommendations to be considered by the upcoming National Academy of Sciences' Decadal Survey in Astronomy and Astrophysics. In our opinion, the Decadal Survey should include space-based research in fundamental physics as one of its focus areas. We recommend establishing an Astronomy and Astrophysics Advisory Committee's interagency ``Fundamental Physics Task Force'' to assess the status of both ground- and space-based efforts in the field, to identify the most important objectives, and to suggest the best ways to organize the work of several federal agencies involved. We also recommend establishing a new NASA-led interagency program in fundamental physics that will consolidate new technologies, prepare key instruments for future space missions, and build a strong scientific and engineering community. Our goal is to expand NASA's science objectives in space by including ``laboratory research in fundamental physics'' as an element in agency's ongoing space research efforts.Comment: a white paper, revtex, 27 pages, updated bibliograph