QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin

Background: There is no known effective therapy for patients with COVID-19. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP). Objective: to assess the change in QTc interval and arrhythmic events in patients with COVID-19 treated with HY/AZ METHODS: This is a retrospective study of 251 patients from two centers, diagnosed with COVID-19 and treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality. Results: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia (VT) suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting extreme QTc prolongation was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given

Different expectations: a comparative history of structure, experience, and strategic alliances in the U.S. and U.K. poultry sectors, 1920-1990

This comparative historical analysis demonstrates how memory and reflexive interpretations of the past can shape entrepreneurial willingness to collaborate with larger firms in an industry. Emphasizing the importance of spatial metaphors and periodization for developing historical knowledge, the paper focuses on how the historical space of experience explains how entrepreneurs make strategic choices regarding collaboration under conditions of complexity and uncertainty. Comparing the U.S. and U.K. emerging poultry sectors offers a methodologically novel analysis of an important but little‐studied agribusiness sector, offering a dual reading that compares two versions of historical reasoning both theoretically and empirically

Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation

According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding, whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

The social effects of entrepreneurship on society and some potential remedies: four provocations

A rapidly growing research stream examines the social effects of entrepreneurship on society. This research assesses the rise of entrepreneurship as a dominant theme in society and studies how entrepreneurship contributes to the production and acceptance of socio-economic inequality regimes, social problems, class and power struggles, and systemic inequities. In this article, scholars present new perspectives on an organizational sociology-inspired research agenda of entrepreneurial capitalism and detail the potential remedies to bound the unfettered expansion of a narrow conception of entrepreneurship. Taken together, the essays put forward four central provocations: 1) reform the study and pedagogy of entrepreneurship by bringing in the humanities; 2) examine entrepreneurship as a cultural phenomenon shaping society; 3) go beyond the dominant biases in entrepreneurship research and pedagogy; and 4) explore alternative models to entrepreneurial capitalism. More scholarly work scrutinizing the entrepreneurship–society nexus is urgently needed, and these essays provide generative arguments toward further developing this research agenda

Ideology and moral values in rhetorical framing:How wine was saved from the 19th Century Phylloxera Epidemic

Extant organizational research into crises has focused on the efforts of different actors to defend and legitimate their ideologies towards particular actions. Although insightful, such research has offered little knowledge about the moral reasoning underlying such action. In this paper, we explore how moral reasoning from different ideological viewpoints can lead to polarized debates and stalemate within the context of ecological crises. We apply our conceptual framework in an analysis of the 19th century French phylloxera epidemic. Drawing upon this analysis, we argue that, by adapting their moral reasoning, opposing stakeholder groups could maintain their underlying ideology, while at the same time pragmatically changing their actions towards the crisis. We discuss the theoretical implications of our analysis for historical research in organizational studies and research on organizations and the natural environment

New Economy, Old Central Banks?

Proponents of the so-called New Economy claim that it entails a structural change of the economy. Such a change, in turn, would require the central bank to rethink its monetary policy to the extent that traditional relationships between inf1ation and economic growth are no longer valid. But such a rethinking presupposes that prospective advances in information technology and other factors associated with the new economy do not threaten the capacity of central banks to stabilise the general level of prices. It is the aim of this paper to shed some light on the latter, by analysing the monetary transmission mechanism in a 'new economy' environment. We argue that, although the form of central bank instruments and current methods for implementing monetary policy may change, the goals that the policy makers try to achieve by employing these instruments remain valid, and achievable

Conceptualizing historical organization studies

© 2016 Academy of Management Review. The promise of a closer union between organizational and historical research has long been recognized. However, its potential remains unfulfilled: The authenticity of theory development expected by organization studies and the authenticity of historical veracity required by historical research place exceptional conceptual and empirical demands on researchers. We elaborate the idea of historical organization studies-organizational research that draws extensively on historical data, methods, and knowledge to promote historically informed theoretical narratives attentive to both disciplines. Building on prior research, we propose a typology of four differing conceptions of history in organizational research: History as evaluating, explicating, conceptualizing, and narrating. We identify five principles of historical organization studies-dual integrity, pluralistic understanding, representational truth, context sensitivity, and theoretical fluency-and illustrate our typology holistically from the perspective of institutional entrepreneurship. We explore practical avenues for a creative synthesis, drawing examples from social movement research and microhistory. Historically informed theoretical narratives whose validity derives from both historical veracity and conceptual rigor afford dual integrity that enhances scholarly legitimacy, enriching understanding of historical, contemporary, and future-directed social realities

The Materiality of Absence:Organizing and the case of the incomplete cathedral

This study explores the role of absences in making organizing possible. By engaging with Lefebvre’s spatial triad as the interconnections between conceived (planned), perceived (experienced through practice) and lived (felt and imagined) spaces, we challenge the so-called metaphysics of presence in organization studies. We draw on the insights offered by the project of construction of Siena Cathedral during the period 1259– 1357 and we examine how it provided a space for the actors involved to explore their different (civic, architectural and religious) intentions. We show that, as the contested conceived spaces of the cathedral were connected to architectural practices, religious powers and civic symbols, they revealed the impossibility for these intentions to be fully represented. It was this impossibility that provoked an ongoing search for solutions and guaranteed a combination of dynamism and persistence of both the material architecture of the cathedral and the project of construction. The case of Siena Cathedral therefore highlights the role of absence in producing organizing effects not because absence eventually takes form but because of the impossibility to fully represent it