Additional file 1: of The impact of rheumatologist-performed ultrasound on diagnosis and management of inflammatory arthritis in routine clinical practice

This file is the US questionnaire completed by Rheumatologists after using an US assessment in clinic. (DOC 77 kb

Additional file 1: of The impact of rheumatologist-performed ultrasound on diagnosis and management of inflammatory arthritis in routine clinical practice

This file is the US questionnaire completed by Rheumatologists after using an US assessment in clinic. (DOC 77 kb

Global Landscapes: Teaching Globalization through Responsive Mobile Map Design

<p>This article reports on the design and evaluation of Global Madison, a mobile map designed to support teaching and learning about globalization using Madison, Wisconsin, as a situated classroom. Our experience of place increasingly is mediated by mobile devices, opening new opportunities and challenges for research, industry, and education. Despite this rising popularity, few guidelines exist for creating and using mobile maps. Following tenets of user-centered design studies, we conducted two mixed-method evaluations of Global Madison to improve the tool and generate design insights that are potentially transferable to similar mobile mapping contexts: 244 students participated in an online survey after completing the tour and eighteen students were observed in the field. The evaluations generated new design considerations for mobile maps supporting situated learning, include: focus on critical issues that might leave students stranded, append location-based services with traditional mapping, enforce cognitive association between map and landscape, supply a consistent feed of information for new learners, encourage collaborative learning in the landscape, and promote student safety above all else.</p

Image_3_IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction.jpeg

<p>NK cells have potent antitumor capacity. They are enriched in the human liver, with a large subset specialized for tissue-residence. The potential for liver-resident versus liver-infiltrating NK cells to populate, and exert antitumor functions in, human liver tumors has not been studied. We examined liver-resident and liver-infiltrating NK cells directly ex vivo from human hepatocellular carcinomas (HCCs) and liver colorectal (CRC) metastases, compared with matched uninvolved liver tissue. We found that NK cells were highly prevalent in both HCC and liver CRC metastases, although at lower frequencies than unaffected liver. Up to 79% of intratumoral NK cells had the CXCR6⁺CD69⁺ liver-resident phenotype. Direct ex vivo staining showed that liver-resident NK cells had increased NKG2D expression compared to their non-resident counterparts, but both subsets had NKG2D downregulation within liver tumors compared to uninvolved liver. Proliferation of intratumoral NK cells (identified by Ki67) was selectively impaired in those with the most marked NKG2D downregulation. Human liver tumor NK cells were functionally impaired, with reduced capacity for cytotoxicity and production of cytokines, even when compared to the hypo-functional tissue-resident NK cells in unaffected liver. Coculture of human liver NK cells with the human hepatoma cell line PLC/PRF/5, or with autologous HCC, recapitulated the defects observed in NK cells extracted from tumors, with downmodulation of NKG2D, cytokine production, and target cell cytotoxicity. Transwells and conditioned media confirmed a requirement for cell contact with PLC/PRF/5 to impose NK cell inhibition. IL-15 was able to recover antitumor functionality in NK cells inhibited by in vitro exposure to HCC cell lines or extracted directly from HCC. In summary, our data suggest that the impaired antitumor function of local NK cells reflects a combination of the tolerogenic features inherent to liver-resident NK cells together with additional contact-dependent inhibition imposed by HCC itself. The demonstration that IL-15 can recover hepatic NK cell function following tumor exposure supports its inclusion in immunotherapy strategies.</p