A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R 2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.human disease | translational medicine | inflammation | immune response | injury M urine models have been extensively used in recent decades to identify and test drug candidates for subsequent human trials (1-3). However, few of these human trials have shown success (4-7). The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed (8-11). Despite commentaries that question the merit of an overreliance of animal systems to model human immunology (3,12,13), in the absence of systematic evidence, investigators and public regulators assume that results from animal research reflect human disease. To date, there have been no studies to systematically evaluate, on a molecular basis, how well the murine clinical models mimic human inflammatory diseases in patients.The Inflammation and Host Response to Injury, Large Scale Collaborative Research Program has completed multiple studies on the genomic responses to systemic inflammation in patients and human volunteers as well as murine models (14-18). These datasets include genome-wide expression analysis on white blood cells obtained from serial blood draws in 167 patients up to 28 d after severe blunt trauma (15), 244 patients up to 1 y after burn injury, and 4 healthy humans for 24 h after administration of low-dose bacterial endotoxin (14) and expression analysis on analogous samples from well-established mouse models of trauma, burns, and endotoxemia (16 treated and 16 controls per model) (16-18). In humans, severe inflammatory stress produces a genomic storm affecting all major cellular functions and pathways (15) and therefore, provided sufficient perturbations to allow comparisons between the genes in the human conditions and their orthologs in the murine models.In this article, we report on a systematic comparison of the genomic respo...

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes.

Although direct influences of media have been the primary focus of mass communication research, recent theoretical developments have suggested powerful and important indirect effects as well. Derived from the third-person effect hypothesis and related research, but describing a broader range of phenomena, the indirect effects model proposes that people (a) perceive some effect of a message on others and then (b) react to that perception. We call this model the influence of presumed influence. The general model was tested with evaluation data from a maternal health campaign in Nepal. A key aspect of the campaign was a serial radio drama directed at clinic health workers. Results showed, however, that many women in the general population also listened to the serial. The program had no direct positive influence on this population, but we found a significant indirect influence on their attitudes and reported behaviors when mediated by their perceptions of impact on the target population of clinic health workers.Interest in modern mass communication has focused primarily on the influences-direct influences-of mass media on individuals and on society. However, developments in theoretical research over the past 2 decades suggest that mass media may exert powerful and important indirect effects as well. The indirect effects model outlined in this article is based on the idea that people perceive some influence of a communication on others and, as a result, change their own attitudes or behaviors-what one might call the influence of presumed influence. 1 Arguably the most salient instances of such indirect effects take place in an unintended audience, a group that is not the target of a message but, in a Albert C. Gunther is a professor in the Department of Life Sciences Communication at the University of Wisconsin-Madison. J. Douglas Storey is senior research and evaluation officer in the Center for Communication Programs at Johns Hopkins University. The authors would like to gratefully acknowledge comments on an earlier draft from Dale Kunkel and Shelly Strom and assistance with analysis from Stella Chih-Yun Chia.

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BackgroundLocal public health agencies play a central role in response to an influenza pandemic, and understanding the willingness of their employees to report to work is therefore a critically relevant concern for pandemic influenza planning efforts. Witte's Extended Parallel Process Model (EPPM) has been found useful for understanding adaptive behavior in the face of unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among local public health workers. We thus aim to use the EPPM as a lens for examining the influences of perceived threat and efficacy on local public health workers' response willingness to pandemic influenza.Methodology/Principal FindingsWe administered an online, EPPM-based survey about attitudes/beliefs toward emergency response (Johns Hopkins∼Public Health Infrastructure Response Survey Tool), to local public health employees in three states between November 2006 – December 2007. A total of 1835 responses were collected for an overall response rate of 83%. With some regional variation, overall 16% of the workers in 2006-7 were not willing to “respond to a pandemic flu emergency regardless of its severity”. Local health department employees with a perception of high threat and high efficacy – i.e., those fitting a ‘concerned and confident’ profile in the EPPM analysis – had the highest declared rates of willingness to respond to an influenza pandemic if required by their agency, which was 31.7 times higher than those fitting a ‘low threat/low efficacy’ EPPM profile.Conclusions/SignificanceIn the context of pandemic influenza planning, the EPPM provides a useful framework to inform nuanced understanding of baseline levels of – and gaps in – local public health workers' response willingness. Within local health departments, ‘concerned and confident’ employees are most likely to be willing to respond. This finding may allow public health agencies to design, implement, and evaluate training programs focused on emergency response attitudes in health departments.