The Future of Charge Card Networks

The general-purpose charge card is now ubiquitous and largely taken for granted. Annual charge card volume exceeds $5 trillion worldwide. Within the United States, nearly one billion cards are in use (about eight per household), and more than two billion worldwide. But charge cards, or more specifically, the cooperative networks that serve the largest card systems, Visa and MasterCard, are under legal attack through multiple lawsuits and under regulatory challenge in other countries. We trace in this essay multiple possible future 'scenarios'. This focus on possible futures distinguishes our work from many earlier studies of this subject.

The Time Has Come… To Talk About Why Research Data Management Isn’t Easy

For the last decade, academic libraries have talked with each other and with potential partners about their roles in helping to manage research data and their plans to expand or initiate research data services (RDS). Libraries have the capacity to provide these services, but the range and maturity of research data services from libraries vary considerably. In summer 2019, our team surveyed a sample of academic libraries of all sizes who are members of the Association of College and Research Libraries (ACRL) to find out about their current RDS and plans for the future. This study is a follow-up to surveys of this same group in 2012 and 2015. Our findings include the types of RDS currently being offered in academic libraries, the barriers that hinder RDS implementation, and staff capacity for creating RDS

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

FGFR2-activating mutations disrupt cell polarity to potentiate migration and invasion in endometrial cancer cell models

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that control a diverse range of biological processes during development and in adult tissues. We recently reported that somatic FGFR2 mutations are associated with shorter survival in endometrial cancer. However, little is known about how these FGFR2 mutations contribute to endometrial cancer metastasis. Here, we report that expression of the activating mutations FGFR2N550K and FGFR2Y376C in an endometrial cancer cell model induce Golgi fragmentation, and loss of polarity and directional migration. In mutant FGFR2-expressing cells, this was associated with an inability to polarise intracellular pools of FGFR2 towards the front of migrating cells. Such polarization defects were exacerbated in three-dimensional culture, where FGFR2 mutant cells were unable to form well-organised acini, instead undergoing exogenous ligand-independent invasion. Our findings uncover collective cell polarity and invasion as common targets of disease-associated FGFR2 mutations that lead to poor outcome in endometrial cancer patients

Assessment of the Severity of Paravalvular Regurgitation and its Role on Survival After Transcatheter Aortic Valve Replacement

Background: To evaluate the impact of various measurements of paravalvular regurgitation (PVR) on survival after transcatheter aortic valve replacement (TAVR). PVR can be difficult to grade and both its incidence and impact on survival may be decreasing as TAVR evolves. Methods: This retrospective study included 911 patients undergoing TAVR in two institutions. PVR was graded according to the 3-grade scheme proposed by the guidelines (PVR grade), and subsequently grade 2 and 3, and grade 0 and 1 were lumped together. PVR was also graded as a composite score (PVR score), based on 6 commonly used metrics. PVR grade, PVR score and its six individual components were tested against the risk of both 1-year and longer term mortality after TAVR. Results: Patients with moderate/severe PVR had a higher Society of Thoracic Sugeons (STS) score, higher levels of serum creatinine and larger left atria compared to patients with none/mild PVR. Moderate/severe PVR was more frequent with self-expandable and larger valves. After adjusting for American College of Cardiology (ACC) TAVR risk score, neither PVR grade, PVR score nor its six components were associated with an increased risk of mortality at 1-year (severe PVR adjusted HR: 0.75, 95% Confidence Interval [CI]: 0.19, 3.01, p = 0.50). However, intervention for clinically severe PVR increased the risk of mortality by more than 7-fold (adjusted hazard ratio [HR]: 7.6, 95% CI: 2.4, 23.5, p < 0.0001). Conclusions: In the contemporary era, moderate-severe PVR is uncommon. However, re-intervention for PVR portends a poor prognosis. This highlights the crucial importance of clinical judgment over imaging alone

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature