Search

Background Access to timely, relevant research in health policy making has the potential to improve health outcomes by increasing the likelihood that decisions are informed by the best available evidence. Governments around the world are investing in strategies to increase the use of research in policies and programs, yet there is little evidence of their effectiveness. Objective The thesis addressed the following questions: 1. When do policymakers seek research through commissioned rapid reviews? 2. How do policymakers use commissioned rapid reviews and in what ways does use vary? 3. Can knowledge brokers play a useful role in aligning the focus of commissioned rapid reviews with the agency’s needs, and if so, what contributes to their effectiveness? Methods This thesis uses multiple methods to examine policymakers’ use of research within the Evidence Check rapid review program, with a view to developing a nuanced understanding of when, why and how policymakers seek and use research. Results Most health policymakers commissioned rapid reviews in response to questions arising in policy development and agenda setting and to identify alternative solutions to policy problems. Eighty-nine percent of commissioned rapid reviews were used by the policymakers who commissioned them, in multiple and diverse ways. Research was used in instrumental and conceptual ways with little symbolic use reported. There was some variation in use by different agencies. The clarity of the rapid reviews’ purpose, review questions, scope, method and report format improved significantly following knowledge. Knowledge brokers worked closely with policymakers to understand the policy context and how the review would be used in practice, characterised in this thesis as coproduction. Brokers used facilitative, diagnostic, interpretative and deliberative functions. Conclusion These findings demonstrate the value of commissioned rapid reviews to policy agencies and suggest that consideration be given to using knowledge brokers more widely to clarify how research can inform policy. Future research could examine the generalisability of these findings to other rapid review programs, and indeed other commissioned research programs. The thesis discusses the implications of these findings for increasing the use of research.

Yurchenko et al. discover that the Ig-like receptor molecule SLAMF1 enhances production of type I interferon induced by Gram-negative bacteria through modulation of MyD88-independent TLR4 signaling. This makes SLAMF1 a potential target for controlling inflammatory responses against Gram-negative bacteria., Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon β (IFNβ) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor–associated molecule (TRAM) from the endocytic recycling compartment (ERC) to Escherichia coli phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of E. coli, it is trafficked together with TRAM from ERC to E. coli phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1–TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4–TRAM–TRIF inflammatory signaling in human cells., Graphical Abstract

Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process. We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy. Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication. Freely available online through the PNAS open access option

Every summer, Lily Dale, New York, a community founded on spiritualist beliefs and steeped in an eccentric explosive past, hosts thousands of visitors seeking to communicate with dead friends and relatives, while the residents lead ordinary lives in the midst of the supernatural hype permeating their town. Their stories are considered by most to be secondary to the illustrious trappings of the community in which they occurred. My research employs oral histories prompted by personal photographs to showcase the residents' everyday experiences amidst the town's infamy, illuminating the undervalued individual experience of those living in communities of such extraordinary repute. The attitudes of the residents displayed when sharing their memories is contextualized in the material behavior exhibited historically in the Spiritualist religion, spirit photography, and the formative years of Lily Dale's growth from a summer camp in the late 1800s to a town of permanent yearlong residents practicing unorthodox beliefs. Through the residents' sharing of images and memories, they reveal that their "ordinary" lives include a deep-rooted understanding of the Spiritualist lifestyle by unconsciously weaving spirit encounters and metaphysical events in and out of their conversation without making distinctions that they are in any way unusual. Spirit is not only in the air in Lily Dale--to the residents it is the air.