B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric ...antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy. In this work, we analyzed the expression of CD19 isoforms in a cohort of 14 children with CD19 B-ALL and 6 nonleukemia donors. We showed that an alternatively spliced CD19 mRNA isoform lacking exon 2, and therefore the CART-19 epitope, but not isoforms lacking the transmembrane and cytosolic domains are expressed in leukemic blasts at diagnosis in children and in the bone marrow of nonleukemia donors. Furthermore, we clarified the sequence of a further isoform lacking the epitope recognized by CART-19 therapy and disclosed the presence of new isoforms. In comparison with the children, we showed that alternatively spliced CD19 mRNA isoforms affecting exon 2 are also expressed in 6 adult patients with CD19 B-ALL. On top of that, one of the adults expressed an isoform lacking the CD19 transmembrane and cytosolic domains. In conclusion, we proved that some of the CD19 isoforms contributing to CART-19 escape already preexist at diagnosis and could evolve as a dominant clone during CART-19 therapy suggesting the application of combined treatment approaches.
Abstract
A long-term goal for warning-message designers is to determine the most effective type of message that can instruct individuals to act quickly and prevent loss of life and/or injury when ...faced with an imminent threat. One likely way to increase an individual’s behavioral intent to act when they are faced with risk information is to provide protective action information or guidance. This study investigated participant perceptions (understanding, believing, personalizing, deciding, milling, self-efficacy, and response efficacy) in response to the National Weather Service’s experimental product Twitter messages for three hazard types (tornado, snow squall, and dust storm), with each message varying by inclusion and presentation of protective action information placed in the tweet text and the visual graphic. We also examine the role of prior hazard warning experience on message perception outcomes. To examine the effects, the experiment used a between-subjects design in which participants were randomly assigned to one hazard type and received one of four warning messages. Participants then took a post-test measuring message perceptions, efficacy levels, prior hazard warning experience, and demographics. The results showed that, for each hazard and prior hazard experience level, messages with protective action guidance in both the text and graphic increase their understanding, belief, ability to decide, self-efficacy, and response efficacy. These results reinforce the idea that well-designed messages that include protective action guidance work well regardless of hazard type or hazard warning experience.
Significance Statement
Preventing injury and/or loss of life during a hazardous event is a prime concern for disaster communicators. The study provides insights to practitioners on how to effectively communicate protective actions to audiences with varying familiarity with the hazard through Twitter posts. We experimented with tweet message design and content for three hazards: tornado, snow squall, and dust storm, to find that posts that include protective action guidance in both the text and image increase participant perceptions that they could perform the suggested protective actions, regardless of hazard type or hazard warning experience. Given our findings, practitioners should consider including protective action guidance in message text and graphic to warn members of the public with varied prior warning experience.
Earthquake early warning (EEW) systems have the potential to facilitate the delivery of lifesaving information to individuals in the path of damaging shaking before it reaches them. While much ...attention has been devoted to measuring the technological feasibility in terms of reach, accuracy, and latency of EEW message delivery, one additional aspect that merits considerable attention is the effectiveness of alerts themselves; do they deliver actionable information that can lead to protective actions taken by message receivers? In this project, we investigated individual responses to a simulated EEW message in a laboratory environment. We employed eye-tracking technology to evaluate visual attention to specific message features; measured behavioral responses to the EEW message (i.e., the participants' ability to perform the recommended actions correctly); and collected self-reported perceptions of the messages (including participants’ intent to act in response to future EEW messages). We manipulated two variables selected to be likely to affect visual attention, behavioral responses, and message perceptions: 1) prior exposure to the relevant protective actions, and 2) the presence of informational icons about the protective actions within the message. We found that prior exposure to protective actions is the strongest predictor of behavioral response and message perceptions; however, the inclusion of informational icons had little effect on our results, suggesting a need for further research testing. The results of this study should inform recommendations for message design and public education and training, all of which are critical to the success of EEW.
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