Practical Strategies for Integrating a Conversation Analyst in an Iterative Design Process

We present a case study of an iterative design process that includes a conversation analyst. We discuss potential benefits of conversation analysis for design, and we describe our strategies for integrating the conversation analyst in the design process. Since the analyst on our team had no previous exposure to design or engineering, and none of the other members of our team had any experience with conversation analysis, we needed to build a foundation for our interaction. One of our key strategies was to pair the conversation analyst with a designer in a highly interactive collaboration. Our tactics have been effective on our project, leading to valuable results that we believe we could not have obtained using another method. We hope that this paper can serve as a practical guide to those interested in establishing a productive and efficient working relationship between a conversation analyst and the other members of a design team.Comment: 11 page

Targeting the Intrinsic Pathway of Coagulation with RNA Aptamers

<p>Thrombosis is associated with the occlusion of a blood vessel and can be triggered by a number of types of injury, such as the rupture of an atherosclerotic plaque on the artery wall, changes in blood composition, or blood stasis. The resulting thrombosis can cause major diseases such as myocardial infarction, stroke, and venous thromboembolic disorders that, collectively, account for the most common cause of death in the developed world. Anticoagulants are used to treat and prevent these thrombotic diseases in a number of clinical and surgical settings. Although commonly prescribed, currently approved anticoagulants have a major limitation of severe drug-induced bleeding that contributes to the high levels of morbidity and mortality associated with use. The "holy grail" for antithrombotic therapy is to identify a drug that inhibits thrombus formation without promoting bleeding. Understanding the differences between thrombosis and hemostasis in the vascular system is critical to developing these safe and effective anticoagulants, as this depends on striking the correct balance between inhibiting thrombus formation (efficacy) and reducing the risk of severe bleeding (safety). While it is commonly thought that the same factors play a similar role in hemostasis and thrombosis, recent evidence points to differing functions for FXI and FXII in each of these settings. Importantly, these factors seem to contribute to pathological thrombus formation without being involved in normal hemostasis.</p><p> The overall goal of this project was to evaluate the inhibition of the intrinsic pathway of coagulation as a potential anticoagulant strategy utilizing the aptamer platform. Aptamers are short, highly structured nucleic acids that act as antagonists by binding to large surface areas on their target protein and thus tend to inhibit protein-protein interactions. High affinity binding aptamers have been isolated that specifically target a diverse range of proteins, including transcription factors, proteases, viral proteins, and growth factors, as well as other coagulation factors. As synthetic molecules, aptamers have a small molecular weight, are highly amenable to modifications that can control their bioavailability, and have not been found to elicit an immune response, thus making them ideal drug candidates. Importantly, aptamers can be rapidly and effectively reversed with either a sequence specific antidote that recognizes the primary sequence of the aptamer or a universal antidote that binds to their backbone and reverses all aptamer activity independent of sequence. This ability lends itself well to their therapeutic application in coagulation, as rapid reversal of a drug upon the onset of bleeding is a key property for increasing the safety of this class of drugs.</p><p> Aptamers targeting FXI/FXIa and FXII/FXIIa were isolated in two separate SELEX (systematic evolution of ligands by exponential enrichment) procedures: the FXII aptamer was isolated in a convergent SELEX approach and the FXIa aptamer was isolated from a purified protein selection. In both processes, 2'fluoropyrimindine modified RNA with a 40-nucleotide random region was incubated with either the plasma proteome (in initial rounds of the convergent SELEX) or the purified protein target (FXII or FXIa). The nucleic acids that did not bind to the target were separated from those that bound, and these molecules were then amplified to generate an enriched pool with increased binding affinity for the target. This process was repeated under increasingly stringent conditions to isolate the aptamer that bound with the highest affinity to the purified target protein. Utilizing biochemical and in vitro coagulation assays, specific, high-affinity binding and functional anticoagulant aptamers were identified for both protein targets, and the mechanism of anticoagulation was ascertained for each aptamer. </p><p> Overall, both aptamers bound to an exosite on their target protein that was able to inhibit downstream activation of the next protein in the coagulation cascade. In order to specifically examine aptamer effects on several parameters of thrombin generation, a new assay was developed and fully characterized using aptamer anticoagulants targeting other coagulation factors. Aptamer inhibition of both FXI and FXII was able to decrease thrombin generation in human plasma. However, limited cross-reactivity in other animal species by both aptamers hindered our ability to assess aptamer inhibition in an in vivo setting. Moving forward, screening aptamers against a larger selection of animal plasmas will hopefully allow us to identify an animal species in which we can analyze aptamer inhibition of the intrinsic pathway for effectiveness and safety in inhibiting thrombosis. The further characterization and use of these aptamers in plasma and blood based settings will allow us to study the diverging functions of the intrinsic pathway in thrombosis and hemostasis.</p><p> A critical need exists for safe and effective anticoagulants to treat and prevent numerous thrombotic procedures and diseases. An ideal anticoagulant is one that strikes the correct balance between inhibiting thrombus formation and reducing drug-induced bleeding. Inhibition or depletion of factors XI and XII of the intrinsic pathway of coagulation have shown reduced thrombus formation without interruption of normal hemostasis in several models of thrombosis. By developing novel RNA aptamer anticoagulants to these factors, we have set the stage for evaluating the net therapeutic benefit of intrinsic pathway inhibition to effectively control coagulation, manage thrombosis, and improve patient outcome. As well as developing a safe anticoagulation, these agents can lead to important biological discoveries concerning the fundamental difference between hemostasis and thrombosis.</p>Dissertatio

Findings from a National home food Environment Survey: How does Georgia Compare?

Background: Aspects of the home food environment, both social and physical, influence healthy eating and weight management practices. Healthy eating, according to the Dietary Guidelines for Americans, 2015, centers on balancing calories consumed and calories expended for weight management combined with consumption of nutrient-dense foods and drinks. Obesity and excess weight increase the risk of numerous chronic diseases including cancer, diabetes, and heart disease. With this presentation, we will explore how Georgia home food environments and eating behaviors are similar or different from the rest of the nation. Methods: Survey participants (n=4,942) were recruited from a reputable online survey panel service. Eligible participants were English-speaking U.S. adults ages 18-75; the final sample was representative of the U.S. population in terms of age, race/ethnicity, geographic region, and income level. Georgia participants represented 3% of the overall sample (n=158). Incentives for completing the 30-minute online survey were provided by the panel service. Survey measures included sociodemographics, healthy eating behaviors (e.g., fruit, vegetable, and fat intake), social home food environment (e.g., food shopping/preparation, household member support) physical home food environment (e.g., food/drink inventories/placement), household food security and coping strategies, and broader contextual factors (e.g., the community food environment, and community capacity and assets). Results: Descriptive data to be presented will include characteristics of participant households, including levels of social and environmental support for healthy eating. Prevalence estimates for key environmental (food/drink inventories/placement, social support among household members) and behavioral (dietary behavior) variables across the sample and among Georgia participants will also be shared. Statistically significant differences between Georgia and the nation will be highlighted. Conclusions: This study presents a unique opportunity to explore socio-environmental influences on healthy eating behaviors nationwide and specifically among Georgians. Findings may be useful in informing tailored messages, healthy eating interventions, and related public health priorities for the state of Georgia

Potent Anticoagulant Aptamer Directed against Factor IXa Blocks Macromolecular Substrate Interaction

An aptamer targeting factor IXa has been evaluated in animal models and several clinical studies as a potential antithombotic therapy. We elucidate the molecular mechanism by which this aptamer acts as an anticoagulant. The aptamer binds tightly to factor IXa and prolongs the clotting time of human plasma. The aptamer completely blocks factor IXa activation of factor X regardless of the presence of factor VIIIa. However, the aptamer does not completely block small synthetic substrate cleavage, although it does slow the rate of cleavage. These data are consistent with the aptamer binding to the catalytic domain of factor IXa in such a way as to block an extended substrate-binding site. Therefore, unlike small molecule inhibitors, aptamers appear to be able to bind surfaces surrounding an active site and thereby sterically interfere with enzyme activity. Thus, aptamers may be useful agents to probe and block substrate-binding sites outside of the active site of an enzyme

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research.

BackgroundThe National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns.ObjectivesOur aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research.MethodsWe searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring.ResultsFor the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring.DiscussionThe 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133

Evaluation Results of an Innovative Pilot Program to Increase Access to Fresh Fruits and Vegetables in Cobb County, GA

Background: This abstract describes a public health practice initiative called the Farm Fresh Market (FFM) and presented pilot evaluation results. Methods: The FFM, developed by Cobb and Douglas Public Health, the McCleskey-East Cobb Family YMCA, and Cobb2020, sold low-cost fruits and vegetables to families living in the 30168 zip code of Austell, Georgia. The evaluation focused on documenting to what extent the FFM reached its intended population and increased perceived access to fresh fruits and vegetables among customers. A convenience sample of 100 returning FFM customers completed self-administered, written intercept surveys at the end of the 2014 market season. Results: The market served customers from a range of socioeconomic backgrounds. Most customers strongly agreed that the FFM made it easier (69%) and less expensive (79%) for them to buy fresh fruits and vegetables and easier for them (63%) and their families (64%) to eat a healthy diet. Most customers reported that they ate more vegetables (65%) and fruit (55%) as a result of shopping at the FFM and reported high levels of satisfaction with all aspects of the FFM. Conclusions: The results suggest that the FFM served customers from the local area and that the FFM may have increased perceived access to healthy food options among customers. Community-level interventions to increase access to healthy foods may play an important role in chronic disease prevention

RT Slowing to Valid Cues on a Reflexive Attention Task in Children and Young Adults

Peripheral cueing tasks can be used to measure reflexive (automatic) attention. In these tasks, increases in response time or RT (costs) typically follow contralateral (invalid) cues as attention must move from the location of the cue to the target. Reductions in RT (benefits) to a target typically follow ipsilateral (valid) cues because the cue draws attention to where the target will appear. Two exceptions to RT benefits are inhibition of return (IOR) and masking. IOR is the tendency to respond slower to targets that appear in locations attended within the last 200–2000 ms. Masking occurs when the visibility of a target is blocked by another stimulus (e.g., the cue). Herein, we describe two experiments, both using a modified Posner task with “earth rockets” as cues and “alien spaceships” as targets. Cues were equally likely to appear on the left or right side of a display following targets. Participants were instructed to press a left or right key corresponding to a left or right target. In Experiment 1, we obtained data from 203 children (10.58–16.55 years old). We discovered unexpected costs following cues that typically provide RT benefits. In Experiment 2, we explored IOR, masking, and age differences in the occurrence of these costs. We manipulated the cue-target temporal distance (“stimulus onset asynchrony” or SOA) to explore IOR and the cue-target spatial distance to explore masking. We also considered a wider age range. Sixty-three children and 41 young adults participated. Experiment 2 revealed a three-way interaction between SOA, spatial distance, and age. At the shorter SOA (100 ms) and moderate spatial distance, unexpected costs followed valid cues for younger children (7.07–10.15 years old). These costs also occurred in young adults (18.00–23.02 years old) following far distance cues at this SOA. At the longer SOA (200 ms), these costs followed moderate and far cues for younger children and near cues for young adults. Older children (10.31–14.92 years) did not have unexpected costs. We explain the findings in terms of masking, IOR, and possible developmental mechanisms

Sotto Voce: Exploring the Interplay of Conversation and Mobile Audio Spaces

In addition to providing information to individual visitors, electronic guidebooks have the potential to facilitate social interaction between visitors and their companions. However, many systems impede visitor interaction. By contrast, our electronic guidebook, Sotto Voce, has social interaction as a primary design goal. The system enables visitors to share audio information - specifically, they can hear each other's guidebook activity using a technologically mediated audio eavesdropping mechanism. We conducted a study of visitors using Sotto Voce while touring a historic house. The results indicate that visitors are able to use the system effectively, both as a conversational resource and as an information appliance. More surprisingly, our results suggest that the technologically mediated audio often cohered the visitors' conversation and activity to a far greater degree than audio delivered through the open air.Comment: 8 page