Multiple Sclerosis immunotherapies and COVID-19 mortality: an analysis of the FDA Adverse Event Reporting System.

Background Evidence on mortality risks associated with MS-immunotherapies during the SARS-CoV2 pandemic derived thus far mainly from single country experiences. Objective In this analysis, we aim to determine the frequency of COVID-19 associated fatality reports of patients receiving an MS-immunotherapy as reported to the international Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from February 2020 to March 2021. Methods In all, 1071 cases for this cross-sectional analysis were retrieved from FAERS and a multivariable logistic regression was performed. We adjusted for sex, age, region, month of report to FDA, immunotherapy-class and additionally for healthcare-system and pandemic-related metrics. Result Anti-CD20 therapies (60%) followed by sphingosine-1 phosphate modulators (12%) and dimethylfumarat (10%) were reported most frequently. In 50% of the cases, MS-phenotype is not reported, relapsing MS in 35% and progressive MS in 15%. Besides older age (odds ratio [OR]: 1.1; 95% confidence interval [CI]: 1.07-1.13; p < 0.01), anti-CD20 therapies were significantly associated with a higher risk of death (OR: 4.1; 95% CI: 1.17-14.46; p = 0.03), whereas female sex was associated with a reduced mortality risk (OR: 0.4, 95% CI: 0.22-0.72; p < 0.01). Conclusion Using international open access data and a multidisciplinary approach for risk prediction, we identified an increased mortality risk associated with anti-CD20 therapies, which is in line with national and multi-national cohort studies

What is Socialism Today? Conceptions of a Cooperative Economy

Socialism is back on the political agenda in the United States. Politicians and some economists who identify as socialists, however, do not discuss property relations, a topic that was central in the intellectual history of socialism, but rather limit themselves to advocacy of economic reforms, funded through taxation, that would tilt the income distribution in favor of the disadvantaged in society. In the absence of a more precise discussion of property relations, the presumption must be that ownership of firms would remain private or corporate with privately owned shares. This formula is identified with the Nordic and other western European social democracies. In this article, I propose several variants of socialism, which are characterized by different kinds of property relation in the ownership of society’s firms. In addition to varying property relations, I include as part of socialism a conception of what it means for a socialist society to possess a cooperative ethos, in place of the individualistic ethos of capitalist society. Differences in ethea are modeled as differences in the manner in which economic agents optimize. With an individualistic ethos, economic agents optimize in the manner of John Nash, while under a cooperative ethos, many optimize in the manner of Immanuel Kant. It is shown that Kantian optimization can decentralize resource allocation in ways that neatly separate issues of income distribution from those of efficiency. In particular, remuneration of labor and capital contributions to production need no longer be linked to marginal-product pricing of these factors, as is the key to efficiency with capitalist property relations. I present simulations of socialist income distributions, and offer some tentative conclusions concerning how we should conceive of socialism today

AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways

Ascertaining the notion of board accountability in Chinese listed companies

Accountability is a concept that has been frequently referred to in Anglo-American systems and in the OECD’s corporate governance documents, as well as in the English translations of corporate governance documents from non-English speaking jurisdictions. It is in the Anglo-American literature, in particular, where the word finds prominence. It has been suggested in China that accountability is one of the basic principles of corporate governance that needs to be consistently enforced. But does this mean that board accountability, as it has been provided for in the Anglo-American system, is actually an element of Chinese corporate governance? If not, should it be adopted? Or should China develop a concept that is more appropriately included as a critical part of its own particular corporate governance needs? The paper aims to address these matters in order to ascertain where Chinese corporate governance stands on accountability as far as the boards of large listed companies are concerned, and what it should do. We opine that while there are elements of accountability in Chinese corporate governance, it does not have the form of accountability embraced in Anglo-American systems. But, it is argued, as China moves from having a system totally based on administrative governance to one that is based more on economic governance the kind of approach that applies in Anglo-American jurisdictions is likely to become more relevant. Within a hybrid corporate governance system combining elements of both administrative and economic governance, we develop a unique “wenze system” with forms and characters of accountability that is likely to develop to address the needs of corporate governance in China and the fostering of its listed companies

Legal determinants of external finance revisited : the inverse relationship between investor protection and societal well-being

This paper investigates relationships between corporate governance traditions and quality of life as measured by a number of widely reported indicators. It provides an empirical analysis of indicators of societal health in developed economies using a classification based on legal traditions. Arguably the most widely cited work in the corporate governance literature has been the collection of papers by La Porta et al. which has shown, inter alia, statistically significant relationships between legal traditions and various proxies for investor protection. We show statistically significant relationships between legal traditions and various proxies for societal health. Our comparative evidence suggests that the interests of investors may not be congruent with the interests of wider society, and that the criteria for judging the effectiveness of approaches to corporate governance should not be restricted to financial metrics

The Key Events Dose-Response Framework: Its Potential for Application to Foodborne Pathogenic Microorganisms

The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions. The present study considers how the KEDRF might be applied to pathogenic microorganisms, using fetal listeriosis resulting from maternal ingestion of food contaminated with L. monocytogenes as an initial example. Major biological events along the pathway between food ingestion and the endpoint of concern are systematically considered with regard to dose (i.e., number of organisms), pathogen factors (e.g., virulence), and protective host mechanisms (e.g., immune response or other homeostatic mechanisms). It is concluded that the KEDRF provides a useful structure for systematically evaluating the complex array of host and pathogen factors that influence the dose-response relationship. In particular, the KEDRF supports efforts to specify and quantify the sources of variability, a prerequisite to strengthening the scientific basis for food safety decision making

Chronic kidney disease in children: the global perspective

In contrast to the increasing availability of information pertaining to the care of children with chronic kidney disease (CKD) from large-scale observational and interventional studies, epidemiological information on the incidence and prevalence of pediatric CKD is currently limited, imprecise, and flawed by methodological differences between the various data sources. There are distinct geographic differences in the reported causes of CKD in children, in part due to environmental, racial, genetic, and cultural (consanguinity) differences. However, a substantial percentage of children develop CKD early in life, with congenital renal disorders such as obstructive uropathy and aplasia/hypoplasia/dysplasia being responsible for almost one half of all cases. The most favored end-stage renal disease (ESRD) treatment modality in children is renal transplantation, but a lack of health care resources and high patient mortality in the developing world limits the global provision of renal replacement therapy (RRT) and influences patient prevalence. Additional efforts to define the epidemiology of pediatric CKD worldwide are necessary if a better understanding of the full extent of the problem, areas for study, and the potential impact of intervention is desired