CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8+ T Cells to Generate Effector but Not Memory T cells

Background: The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8 + T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8 + T cell response have not been thoroughly evaluated. Methodology/Principal Findings: In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naïve CD8 + T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naïve CD8 + T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a Listeria monocytogenes infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8 + memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8 + memory T cells. Our results also suggest that inefficient generation of CD8 + memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8 + T cell response. Conclusions: Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cel

Learning and Educational Programs for Entrepreneurs

This chapter summarizes the latest studies in entrepreneurial learning in order to highlight their implications for the design of educational programs (Pittaway & Thorpe, 2012). It examines in detail the latest thinking on the subject, summarizes the key concepts and empirical contributions with a particular focus on expanding understanding of ‘situated’, social and contextual learning (Lave & Wenger, 1991). The chapter stems from Pittaway and Thorpe’s (2012: 850) summary of Cope’s framework. Here it highlights critical concepts, such as dynamic temporal phases, forms and characteristics of learning (Cope, 2010) and lays out the underlying principles of each concept. Following this initial framework recent contributions to the subject of entrepreneurial learning, both conceptual and empirical, are presented to provide an up-to-date picture of thinking in the field. The latter part of the chapter highlights implications of current thinking on the design of development programs for entrepreneurs. It focuses on how concepts in this field can be used to enhance efforts to consider, design and deliver educational programs for entrepreneurs. A number of forms of educational practice are recommended based on this analysis. The chapter closes by considering future developments and lines of inquiry in entrepreneurial learnin

Fostering deliberations about health innovation: what do we want to know from publics?

Contains fulltext : 80643.pdf (publisher's version ) (Closed access)As more complex and uncertain forms of health innovation keep emerging, scholars are increasingly voicing arguments in favour of public involvement in health innovation policy. The current conceptualization of this involvement is, however, somewhat problematic as it tends to assume that scientific facts form a "hard," indisputable core around which "soft," relative values can be attached. This paper, by giving precedence to epistemological issues, explores what there is to know from public involvement. We argue that knowledge and normative assumptions are co-constitutive of each other and pivotal to the ways in which both experts and non-experts reason about health innovations. Because knowledge and normative assumptions are different but interrelated ways of reasoning, public involvement initiatives need to emphasise deliberative processes that maximise mutual learning within and across various groups of both experts and non-experts (who, we argue, all belong to the "publics"). Hence, we believe that what researchers might wish to know from publics is how their reasoning is anchored in normative assumptions (what makes a given innovation desirable?) and in knowledge about the plausibility of their effects (are they likely to be realised?). Accordingly, one sensible goal of greater public involvement in health innovation policy would be to refine normative assumptions and make their articulation with scientific observations explicit and openly contestable. The paper concludes that we must differentiate between normative assumptions and knowledge, rather than set up a dichotomy between them or confound them

Implementation of a bundle to improve HIV testing during hospitalization for people who inject drugs

Background Increased HIV testing is essential to ending the HIV epidemic. People who inject drugs (PWID) are among the highest risk for HIV infection. Previous research at Tufts Medical Center identified low HIV testing rates in hospitalized PWID. Our research team aimed to identify and overcome barriers to inpatient HIV screening of PWID using implementation science methods. Methods Stakeholders were engaged to gather perspectives on barriers and facilitators of HIV testing. A PWID care bundle was developed and implemented, which included (1) HIV screening; (2) hepatitis A, B, and C testing and vaccination; (3) medications for opioid use disorder; and (4) naloxone prescription. Strategies from all nine Expert Recommendations for Implementing Change (ERIC) clusters guided the implementation plan. Stakeholder feedback was gathered throughout implementation, and implementation outcomes of acceptability and feasibility were assessed. Results PWID overall felt comfortable with HIV testing being offered while hospitalized. Clinicians cited that the main barriers to HIV testing were discomfort and confusion around consenting requirements. Many resident physicians surveyed reported that, at times, they forgot HIV testing for PWID. Overall, though, resident physicians felt that the PWID bundle was useful and did not distract from other patient care responsibilities. Conclusions Engagement of key stakeholders to increase HIV testing in an inpatient setting led to the implementation of a PWID bundle, which was feasible and acceptable. Bundling evidence-informed care elements for inpatient PWID should be investigated further

Prioritizing studies of COVID-19 and lessons learned

INTRODUCTION: COVID-19 altered research in Clinical and Translational Science Award (CTSA) hubs in an unprecedented manner, leading to adjustments for COVID-19 research. METHODS: CTSA members volunteered to conduct a review on the impact of CTSA network on COVID-19 pandemic with the assistance from NIH survey team in October 2020. The survey questions included the involvement of CTSAs in decision-making concerning the prioritization of COVID-19 studies. Descriptive and statistical analyses were conducted to analyze the survey data. RESULTS: 60 of the 64 CTSAs completed the survey. Most CTSAs lacked preparedness but promptly responded to the pandemic. Early disruption of research triggered, enhanced CTSA engagement, creation of dedicated research areas and triage for prioritization of COVID-19 studies. CTSAs involvement in decision-making were 16.75 times more likely to create dedicated diagnostic laboratories (95% confidence interval [CI] = 2.17–129.39; P < 0.01). Likewise, institutions with internal funding were 3.88 times more likely to establish COVID-19 dedicated research (95% CI = 1.12–13.40; P < 0.05). CTSAs were instrumental in securing funds and facilitating establishment of laboratory/clinical spaces for COVID-19 research. Workflow was modified to support contracting and IRB review at most institutions with CTSAs. To mitigate chaos generated by competing clinical trials, central feasibility committees were often formed for orderly review/prioritization. CONCLUSIONS: The lessons learned from the COVID-19 pandemic emphasize the pivotal role of CTSAs in prioritizing studies and establishing the necessary research infrastructure, and the importance of prompt and flexible research leadership with decision-making capacity to manage future pandemics