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1.  Supporting Cancer Patients in Illness Management: Usability Evaluation of a Mobile App 
JMIR mHealth and uHealth  2014;2(3):e33.
Background
Mobile phones and tablets currently represent a significant presence in people’s everyday lives. They enable access to different information and services independent of current place and time. Such widespread connectivity offers significant potential in different app areas including health care.
Objective
Our goal was to evaluate the usability of the Connect Mobile app. The mobile app enables mobile access to the Connect system, an online system that supports cancer patients in managing health-related issues. Along with symptom management, the system promotes better patient-provider communication, collaboration, and shared decision making. The Connect Mobile app enables access to the Connect system over both mobile phones and tablets.
Methods
The study consisted of usability tests of a high fidelity prototype with 7 cancer patients where the objectives were to identify existing design and functionality issues and to provide patients with a real look-and-feel of the mobile system. In addition, we conducted semistructured interviews to obtain participants’ feedback about app usefulness, identify the need for new system features and design requirements, and measure the acceptance of the mobile app and its features within everyday health management.
Results
The study revealed a total of 27 design issues (13 for mobile apps and 14 for tablet apps), which were mapped to source events (ie, errors, requests for help, participants' concurrent feedback, and moderator observation). We also applied usability heuristics to identify violations of usability principles. The majority of violations were related to enabling ease of input, screen readability, and glanceability (15 issues), as well as supporting an appropriate match between systems and the real world (7 issues) and consistent mapping of system functions and interactions (4 issues). Feedback from participants also showed the cancer patients’ requirements for support systems and how these needs are influenced by different context-related factors, such as type of access terminal (eg, desktop computer, tablet, mobile phone) and phases of illness. Based on the observed results, we proposed design and functionality recommendations that can be used for the development of mobile apps for cancer patients to support their health management process.
Conclusions
Understanding and addressing users’ requirements is one of the main prerequisites for developing useful and effective technology-based health interventions. The results of this study outline different user requirements related to the design of the mobile patient support app for cancer patients. The results will be used in the iterative development of the Connect Mobile app and can also inform other developers and researchers in development, integration, and evaluation of mobile health apps and services that support cancer patients in managing their health-related issues.
doi:10.2196/mhealth.3359
PMCID: PMC4147703  PMID: 25119490
mobile applications; patients; cell phone; smartphone; symptom assessment; self-care; user-computer interface
2.  Plus disease in retinopathy of prematurity: qualitative analysis of diagnostic process by experts 
JAMA ophthalmology  2013;131(8):1026-1032.
Purpose
To examine the diagnostic reasoning process of experts for plus disease in retinopathy of prematurity (ROP) using qualitative research techniques.
Methods
Six experts were video-recorded while independently reviewing seven wide-angle retinal images from infants with ROP. Experts were asked to explain their diagnostic process in detail (think-aloud protocol), mark findings relevant to their reasoning, and diagnose each image (plus vs. pre-plus vs. neither). Subsequently, each expert viewed the images again while being asked to examine arteries and veins in isolation, and answer specific questions. Video-recordings were transcribed and reviewed. Diagnostic process of experts was analyzed using a published cognitive model.
Results
Based on the think-aloud protocol, 5/6 experts agreed on the same diagnosis in three study images, and 3/6 experts agreed in three images. When experts were asked to rank images in order of severity, the mean correlation coefficient between pairs of experts was 0.33 (range - 0.04–0.75). All experts considered arterial tortuosity and venous dilation while reviewing each image. Some considered venous tortuosity, arterial dilation, peripheral retinal features, and other factors. When experts were asked to re-review images to diagnose plus disease based strictly on definitions of sufficient arterial tortuosity and venous dilation, all but 1 expert changed their diagnosis compared to the think-aloud protocol.
Conclusions
Diagnostic consistency in plus disease is imperfect. Experts differ in their reasoning process, retinal features that they focus on, and interpretations of the same features. Understanding these factors may improve diagnosis and education. Future research defining more precise diagnostic criteria may be warranted.
doi:10.1001/jamaophthalmol.2013.135
PMCID: PMC3921179  PMID: 23702696
3.  Longitudinal Requirement for CD4+ T Cell Help for Adenovirus Vector–Elicited CD8+ T Cell Responses 
The Journal of Immunology Author Choice  2014;192(11):5214-5225.
Despite the widespread use of replication-incompetent recombinant adenovirus (Ad) vectors as candidate vaccine platforms, the mechanism by which these vectors elicit CD8+ T cell responses remains poorly understood. Our data demonstrate that induction and maintenance of CD8+ T cell responses by Ad vector immunization is longitudinally dependent on CD4+ T cell help for a prolonged period. Depletion of CD4+ T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8+ T cells, decreased T-bet and eomesodermin expression, impaired KLRG1+ effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L. Moreover, these CD8+ T cells failed to protect against a lethal recombinant Listeria monocytogenes challenge. Depletion of CD4+ T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8+ T cells. These data demonstrate a prolonged temporal requirement for CD4+ T cell help for vaccine-elicited CD8+ T cell responses in mice. These findings have important implications in the design of vaccines aimed at eliciting CD8+ T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4+ T cell immune deficiencies.
doi:10.4049/jimmunol.1302806
PMCID: PMC4025612  PMID: 24778441
4.  A Framework for Characterizing eHealth Literacy Demands and Barriers 
Background
Consumer eHealth interventions are of a growing importance in the individual management of health and health behaviors. However, a range of access, resources, and skills barriers prevent health care consumers from fully engaging in and benefiting from the spectrum of eHealth interventions. Consumers may engage in a range of eHealth tasks, such as participating in health discussion forums and entering information into a personal health record. eHealth literacy names a set of skills and knowledge that are essential for productive interactions with technology-based health tools, such as proficiency in information retrieval strategies, and communicating health concepts effectively.
Objective
We propose a theoretical and methodological framework for characterizing complexity of eHealth tasks, which can be used to diagnose and describe literacy barriers and inform the development of solution strategies.
Methods
We adapted and integrated two existing theoretical models relevant to the analysis of eHealth literacy into a single framework to systematically categorize and describe task demands and user performance on tasks needed by health care consumers in the information age. The method derived from the framework is applied to (1) code task demands using a cognitive task analysis, and (2) code user performance on tasks. The framework and method are applied to the analysis of a Web-based consumer eHealth task with information-seeking and decision-making demands. We present the results from the in-depth analysis of the task performance of a single user as well as of 20 users on the same task to illustrate both the detailed analysis and the aggregate measures obtained and potential analyses that can be performed using this method.
Results
The analysis shows that the framework can be used to classify task demands as well as the barriers encountered in user performance of the tasks. Our approach can be used to (1) characterize the challenges confronted by participants in performing the tasks, (2) determine the extent to which application of the framework to the cognitive task analysis can predict and explain the problems encountered by participants, and (3) inform revisions to the framework to increase accuracy of predictions.
Conclusions
The results of this illustrative application suggest that the framework is useful for characterizing task complexity and for diagnosing and explaining barriers encountered in task completion. The framework and analytic approach can be a potentially powerful generative research platform to inform development of rigorous eHealth examination and design instruments, such as to assess eHealth competence, to design and evaluate consumer eHealth tools, and to develop an eHealth curriculum.
doi:10.2196/jmir.1750
PMCID: PMC3222196  PMID: 22094891
eHealth; health literacy; cognition; Bloom’s taxonomy; cognitive task analysis; consumer health
5.  Focus and Breadth of Cellular Immune Responses Elicited by a Heterologous Insert Prime-Boost Vaccine Regimen in Rhesus Monkeys 
Vaccine  2011;30(3):506-509.
The global sequence diversity of HIV-1 presents a daunting challenge for vaccine development. We investigated whether a heterologous insert prime-boost regimen could expand global coverage by selectively boosting cellular immune responses to conserved epitopes. Rhesus monkeys were primed and boosted with recombinant adenovirus vectors expressing homologous or heterologous HIV-1 Gag sequences that were optimized to focus responses on highly conserved epitopes. We observed comparable responses directed to specific regions of the Gag protein in all experimental groups without evidence of improved coverage or expanded breadth in the heterologous insert group. These data suggest that antigen-independent factors contribute to the immunodominance patterns of vaccine-elicited cellular immune responses.
doi:10.1016/j.vaccine.2011.11.079
PMCID: PMC3246049  PMID: 22133509
6.  Vitamin A Deficiency Impairs Vaccine-Elicited Gastrointestinal Immunity1 
Vitamin A deficiency is highly prevalent in much of the developing world, where vaccination programs are of paramount importance to public health. However, the impact of vitamin A deficiency on the immunogenicity and protective efficacy of vaccines has not previously been defined. Here we show that the vitamin A metabolite retinoic acid is critical for trafficking of vaccine-elicited T-lymphocytes to the gastrointestinal mucosa and for vaccine protective efficacy in mice. Moderate vitamin A deficiency abrogated antigen-specific T-lymphocyte trafficking to the gastrointestinal tract, gastrointestinal cellular immune responses, and protection against a mucosal challenge following immunization with a recombinant adenovirus (rAd) vaccine vector. Oral vitamin A supplementation as well as retinoic acid administration fully restored the mucosal immune responses and vaccine protective efficacy. These data suggest that oral vitamin A supplementation may be important for optimizing the success of vaccines against HIV-1 and other mucosal pathogens in the developing world, highlighting a critical relationship between host nutritional status and vaccine efficacy.
doi:10.4049/jimmunol.1101248
PMCID: PMC3150351  PMID: 21765014
HIV; vitamin A deficiency; vaccine; gastrointestinal tract
7.  A Nurse’s Eye-View on Health Literacy in Older Adults 
Older adults are being asked to play a more active role in the management of their health, however low health literacy is pervasive in this population and is a major impediment to participation in healthcare activities. We sought to identify literacy-related challenges that older adults experience while managing their health. We interviewed 8 nurses who provided direct care to older adult populations. Thematic analysis was conducted exploring barriers, strategies and resources as they relate to health literacy in older adults. Three main themes were identified: literacy barriers, aging process and social resources. Problems associated with health literacy in this population were pervasive. Numeracy, a component of health literacy, was a central factor for a range of medication management problems. However, nurses reported that they were able to fashion solutions that enabled patients to comprehend quantitative information and act on it accordingly, resulting in better health management.
PMCID: PMC3799118  PMID: 24199086
8.  Modeling Knowledge Resource Selection in Expert Librarian Search 
Providing knowledge at the point of care offers the possibility for reducing error and improving patient outcomes. However, the vast majority of physician’s information needs are not met in a timely fashion. The research presented in this paper models an expert librarian’s search strategies as it pertains to the selection and use of various electronic information resources. The 10 searches conducted by the librarian to address physician’s information needs, varied in terms of complexity and question type. The librarian employed a total of 10 resources and used as many as 7 in a single search. The longer term objective is to model the sequential process in sufficient detail as to be able to contribute to the development of intelligent automated search agents.
PMCID: PMC3225202  PMID: 19380912
Information seeking; search strategies; knowledge resources; cognition
9.  A new adaptive testing algorithm for shortening health literacy assessments 
Background
Low health literacy has a detrimental effect on health outcomes, as well as ability to use online health resources. Good health literacy assessment tools must be brief to be adopted in practice; test development from the perspective of item-response theory requires pretesting on large participant populations. Our objective was to develop a novel classification method for developing brief assessment instruments that does not require pretesting on large numbers of research participants, and that would be suitable for computerized adaptive testing.
Methods
We present a new algorithm that uses principles of measurement decision theory (MDT) and Shannon's information theory. As a demonstration, we applied it to a secondary analysis of data sets from two assessment tests: a study that measured patients' familiarity with health terms (52 participants, 60 items) and a study that assessed health numeracy (165 participants, 8 items).
Results
In the familiarity data set, the method correctly classified 88.5% of the subjects, and the average length of test was reduced by about 50%. In the numeracy data set, for a two-class classification scheme, 96.9% of the subjects were correctly classified with a more modest reduction in test length of 35.7%; a three-class scheme correctly classified 93.8% with a 17.7% reduction in test length.
Conclusions
MDT-based approaches are a promising alternative to approaches based on item-response theory, and are well-suited for computerized adaptive testing in the health domain.
doi:10.1186/1472-6947-11-52
PMCID: PMC3178473  PMID: 21819614
10.  Variability in User Interaction with Physician Order Entry System 
Physician order entry systems offer numerous benefits to users and institutions, including the reduction of medical errors, and increase in the speed and quality of written communication. Standardization of care is also often cited as an important outcome facilitated by POE. However, order entry systems are frequently very complex and sophisticated tools that produce consistent results only if used in an efficient and consistent manner. The numerous benefits that order entry offers can only be realized when this technology is used to its full potential. This study characterizes the variations in user strategies in completing a task and the ensuing inconsistencies of output. Seven physicians were asked to enter orders based on a clinical scenario requiring inpatient admission. Inefficient task completion strategies, redundancy, omissions and errors in the entered orders are outlined and discussed.
PMCID: PMC2244383
12.  A technology selection framework for supporting delivery of patient-oriented health interventions in developing countries 
Journal of biomedical informatics  2009;43(2):300-306.
Health information technologies (HIT) have great potential to advance health care globally. In particular, HIT can provide innovative approaches and methodologies to overcome the range of access and resource barriers specific to developing countries. However, there is a paucity of models and empirical evidence informing the technology selection process in these settings. We propose a framework for selecting patient-oriented technologies in developing countries. The selection guidance process is structured by a set of filters that impose particular constraints and serve to narrow the space of possible decisions. The framework consists of three levels of factors: 1) situational factors, 2) the technology and its relationship with health interventions and with target patients, and 3) empirical evidence. We demonstrate the utility of the framework in the context of mobile phones for behavioral health interventions to reduce risk factors for cardiovascular disease. This framework can be applied to health interventions across health domains to explore how and whether available technologies can support delivery of the associated types of interventions and with the target populations.
doi:10.1016/j.jbi.2009.09.006
PMCID: PMC2838941  PMID: 19796709
Medical informatics; Health behavior; Developing countries; Patient care; Cellular Phone; Cardiovascular Disease
13.  Efficient Generation of Mucosal and Systemic Antigen-Specific CD8+ T-Cell Responses following Pulmonary DNA Immunization▿  
Journal of Virology  2010;84(11):5764-5774.
Although mucosal CD8+ T-cell responses are important in combating mucosal infections, the generation of such immune responses by vaccination remains problematic. In the present study, we evaluated the ability of plasmid DNA to induce local and systemic antigen-specific CD8+ T-cell responses after pulmonary administration. We show that the pulmonary delivery of plasmid DNA formulated with polyethyleneimine (PEI-DNA) induced robust systemic CD8+ T-cell responses that were comparable in magnitude to those generated by intramuscular (i.m.) immunization. Most importantly, we observed that the pulmonary delivery of PEI-DNA elicited a 10-fold-greater antigen-specific CD8+ T-cell response in lungs and draining lymph nodes of mice than that of i.m. immunization. The functional evaluation of these pulmonary CD8+ T cells revealed that they produced type I cytokines, and pulmonary immunization with PEI-DNA induced lung-associated antigen-specific CD4+ T cells that produced higher levels of interleukin-2 than those induced by i.m. immunization. Pulmonary PEI-DNA immunization also induced CD8+ T-cell responses in the gut and vaginal mucosa. Finally, pulmonary, but not i.m., plasmid DNA vaccination protected mice from a lethal recombinant vaccinia virus challenge. These findings suggest that pulmonary PEI-DNA immunization might be a useful approach for immunizing against pulmonary pathogens and might also protect against infections initiated at other mucosal sites.
doi:10.1128/JVI.02202-09
PMCID: PMC2876582  PMID: 20335249
14.  Evaluation of a Remote Training Approach for Teaching Seniors to Use a Telehealth System 
Objective
There has been a growth of home health care technology in rural areas. However, a significant limitation has been the need for costly and repetitive training in order for patients to efficiently use their home telemedicine unit (HTU). This research describes the evaluation of an architecture for remote training of patients in a telemedicine environment. This work examines the viability of a remote training architecture called REmote Patient Education in a Telemedicine Environment (REPETE). REPETE was implemented and evaluated in the context of the IDEATel project, a large-scale telemedicine project, focusing on Medicare beneficiaries with diabetes in New York State.
Methods
A number of qualitative and quantitative evaluation tools were developed and used to study the effectiveness of the remote training sessions evaluating: a) task complexity, b) changes in patient performance and c) the communication between trainer and patient. Specifically, the effectiveness of the training was evaluated using a measure of web skills competency, a user satisfaction survey, a cognitive task analysis and an interaction analysis.
Results
Patients not only reported that the training was beneficial, but also showed significant improvements in their ability to effectively perform tasks. Our qualitative evaluations scrutinizing the interaction between the trainer and patient showed that while there was a learning curve for both the patient and trainer when negotiating the shared workspace, the mutually visible pointer used in REPETE enhanced the computer-mediated instruction.
Conclusions
REPETE is an effective remote training tool for older adults in the telemedicine environment. Patients demonstrated significant improvements in their ability to perform tasks on their home telemedicine unit.
doi:10.1016/j.ijmedinf.2009.06.005
PMCID: PMC2757535  PMID: 19620023
telemedicine; older adults; training
15.  Multiple Innate Immune Pathways Contribute to the Immunogenicity of Recombinant Adenovirus Vaccine Vectors▿ † 
Journal of Virology  2010;85(1):315-323.
The innate immune pathways that contribute to the potent immunogenicity of recombinant adenovirus (rAd) vaccine vectors remain largely undefined. Previous studies assessing innate immunity triggered by vaccine vectors have largely focused on in vitro studies involving antigen-presenting cells and on early in vivo inflammatory responses. Here, we systematically explore the Toll-like receptor (TLR) signaling requirements for the generation of cellular immune responses by intramuscular immunization with common and alternative serotype rAd vectors in mice. Antigen-specific CD8+ T-lymphocyte responses elicited by these rAd vectors were significantly diminished in MyD88−/− mice but not in TRIF−/− or TLR3−/− mice, suggesting the importance of MyD88-dependent TLR signaling. However, the absence of each individual TLR resulted in minimal to no effect on vaccine-elicited cellular immune responses. Moreover, responses were not diminished in IL-1R−/− or IL-18R−/− mice. These data suggest that rAd vectors engage multiple MyD88-dependent signaling pathways, none of which are individually critical; rather, they are integrated to contribute to the potent immunogenicity of rAd vectors. Stimulation of multiple innate immune mechanisms may prove a generalizable property of potent vaccines, and this strategy could be harnessed in the development of next-generation vaccine vectors and adjuvants.
doi:10.1128/JVI.01597-10
PMCID: PMC3014160  PMID: 20962088
16.  The Effects of Redesigning the IDEATel Architecture on Glucose Uploads 
Telemedicine Journal and e-Health  2009;15(3):248-254.
The Informatics for Diabetes Education and Telemedicine (IDEATel) project has demonstrated significant changes in clinical outcome measures over the past years. This report describes upgrades and innovations in the system that allow a much more rapid upload of data and thus significant system improvement.
Abstract
The objective of this evaluation was to determine the effect of redesigning the Informatics for Diabetes Education and Telemedicine (IDEATel) telemedicine architecture on the average upload delay and on the average number of glucose uploads to a central database. These two measures positively influence our ability to deliver timely and accurate patient care to the study population. The redesign was also undertaken to improve the patients' experience in using the system and thereby increase the frequency and timeliness of their self-monitoring behavior. Using the total number of glucose uploads, we compared the delay in glucose upload times according to the type of home telemedicine unit the study participants used and the region where the participants lived. The participants were Medicare beneficiaries with diabetes living in medically underserved neighborhoods in New York City and rural Upstate New York. The populations in these two regions differed considerably in terms of ethnicity, language spoken (Spanish, English), and education level. Participants who had Generation 2 (Gen 2) (mean = 10.75, SD ± 7.96) home telemedicine units had significantly shorter upload delay times (p < 0.001) as measured in days than those participants with Generation 1 (Gen 1) (mean = 22.44, SD ± 11.18) and those who were upgraded from Gen 1 (mean = 20.67, SD ± 8.85) to Gen 2 (mean = 14.93, SD ± 9.37). Additionally, the delay was significantly shorter for participants living upstate (mean = 24.14 days, SD ± 11.95 days) than downstate (mean = 15.30 days, SD ± 7.87 days), t (975) = 13.98, p < 0.01. The system redesign made a significant impact in reducing glucose upload delays of IDEATel participants. However, upload delays were significantly impacted by the region where the participants resided.
doi:10.1089/tmj.2008.0101
PMCID: PMC2956565  PMID: 19382862
telemedicine evaluation; technical architecture; diabetes telemedicine
17.  Route of Adenovirus-Based HIV-1 Vaccine Delivery Impacts the Phenotype and Trafficking of Vaccine-Elicited CD8+ T Lymphocytes▿ †  
Journal of Virology  2010;84(12):5986-5996.
Candidate HIV-1 vaccine regimens utilizing intramuscularly (i.m.) administered recombinant adenovirus (rAd)-based vectors can induce potent mucosal cellular immunity. However, the degree to which mucosal rAd vaccine routing might alter the quality and anatomic distribution of vaccine-elicited CD8+ T lymphocytes remains unclear. We show that the route of vaccination critically impacts not only the magnitude but also the phenotype and trafficking of antigen-specific CD8+ T lymphocytes in mice. I.m. rAd immunization induced robust local transgene expression and elicited high-frequency, polyfunctional CD8+ T lymphocytes that trafficked broadly to both systemic and mucosal compartments. In contrast, intranasal (i.n.) rAd immunization led to similarly robust local transgene expression but generated low-frequency, monofunctional CD8+ T lymphocytes with restricted anatomic trafficking patterns. Respiratory rAd immunization elicited systemic and mucosal CD8+ T lymphocytes with phenotypes and trafficking properties distinct from those elicited by i.m. or i.n. rAd immunization. Our findings indicate that the anatomic microenvironment of antigen expression critically impacts the phenotype and trafficking of antigen-specific CD8+ T lymphocytes.
doi:10.1128/JVI.02563-09
PMCID: PMC2876628  PMID: 20357087
18.  Voice Capture of Medical Residents' Clinical Information Needs During an Inpatient Rotation 
Objective
To identify some of the challenges that medical residents face in addressing their information needs in an inpatient setting, by examining how voice capture in natural language of clinical questions fits into workflow, and by characterizing the focus, format, and semantic content and complexity of their questions.
Design
Internal medicine residents captured information needs on a digital recorder while on a hospital inpatient service and then participated in semi-structured interviews.
Measurements
Interviews were analyzed to identify emergent themes. Recorded questions were analyzed for focus (diagnosis, treatment, or epidemiology) and format, either foreground (specific knowledge relating to an individual patient) or background (general knowledge about a condition). Semantic concepts and types were identified using MetaMap (UMLS - Unified Medical Language System) and manually.
Results
Voice recording of questions appeared to unmask residents' latent information needs. Although residents were able to record questions during workflow, there was a delay from the time questions materialized to when they were recorded. Question focus was distributed among diagnosis (32%), treatment (40%), and epidemiology (28%), and the majority of questions were background (69%). Questions were semantically complex; foreground and background questions averaged 12.6 (SD 6.0) and 9.1 (SD 6.0) UMLS concepts, respectively. MetaMap failed to recognize concepts when residents used acronyms or abbreviations or omitted key terms.
Conclusions
We found that it is feasible for residents to capture their clinical questions in natural language during workflow and that recording questions may prompt awareness of previously unrecognized information needs. However, the semantic complexity of typical questions and mapping failures due to residents' use of acronyms and abbreviations present challenges to machine-based extraction of semantic content.
doi:10.1197/jamia.M2940
PMCID: PMC2732238  PMID: 19261939
19.  Trafficking of Antigen-Specific CD8+ T-Lymphocytes to Mucosal Surfaces Following Intramuscular Vaccination1 
A critical goal of vaccine development for a wide variety of pathogens is the induction of potent and durable mucosal immunity. However, it has been assumed that this goal would be difficult to achieve by systemic vaccination due to the anatomic and functional distinctness of the systemic and mucosal immune systems and the resultant compartmentalization of immune responses. Here we show that antigen-specific CD8+ T-lymphocytes traffic efficiently to mucosal surfaces following systemic vaccination. Intramuscular immunization with recombinant adenovirus (rAd) vector-based vaccines expressing SIV Gag resulted in potent, durable and functional CD8+ T lymphocyte responses at multiple mucosal effector sites in both mice and rhesus monkeys. In adoptive transfer studies in mice, vaccine-elicited CD8+ T-lymphocytes exhibited phenotypic plasticity, upregulated mucosal homing integrins and chemokine receptors, and trafficked rapidly to mucosal surfaces. Moreover, the migration of systemic CD8+ T-lymphocytes to mucosal compartments accounted for the vast majority of antigen-specific mucosal CD8+ T-lymphocytes induced by systemic vaccination. Thus, intramuscular vaccination can overcome immune compartmentalization and generate robust mucosal CD8+ T-lymphocyte memory. These data demonstrate that the systemic and mucosal immune systems are highly coordinated following vaccination.
PMCID: PMC2580672  PMID: 18768876
AIDS; Vaccination; Mucosa
20.  Discerning Patterns of HIV Risk in Healthy Young Adults 
The American journal of medicine  2008;121(9):758-764.
Prior research has questioned the effectiveness of existing methods to identify individuals at high risk for contracting and transmitting the Human Immunodeficiency Virus (HIV) and other sexually transmitted diseases (STDs). Thus, new approaches are needed to provide these individuals with risk-reduction strategies. We review our research on young adults’ sexual decision making, using theories and methods from social and cognitive sciences. Four patterns of condom use and associated levels of risks and beliefs were identified. These patterns suggest value in targeting intervention strategies to individuals at different levels of risk. Findings also imply that the monogamous population may be at higher risk for infection than they realize. Primary-care physicians are the first line of contact for many individuals in the health care system, and may be in the best position to screen for at-risk individuals. Given time demands and other barriers, easy-to-use evidence-based guidelines for such screening are needed. We propose such guidelines for primary-care physicians to use in identifying an individual’s risk, from which custom-tailored intervention strategies can be developed.
doi:10.1016/j.amjmed.2008.04.022
PMCID: PMC2597652  PMID: 18724961
youth; HIV/AIDS; decision-making; patterns of reasoning; risky sexual behavior; screening; education
21.  A Multi-Level Model of Information Seeking in the Clinical Domain 
Journal of biomedical informatics  2007;41(2):357-370.
Objective:
Clinicians often have difficulty translating information needs into effective search strategies to find appropriate answers. Information retrieval systems employing an intelligent search agent that generates adaptive search strategies based on human search expertise could be helpful in meeting clinician information needs. A prerequisite for creating such systems is an information seeking model that facilitates the representation of human search expertise. The purpose of developing such a model is to provide guidance to information seeking system development and to shape an empirical research program.
Design:
The information seeking process was modeled as a complex problem-solving activity. After considering how similarly complex activities had been modeled in other domains, we determined that modeling context-initiated information seeking across multiple problem spaces allows the abstraction of search knowledge into functionally consistent layers. The knowledge layers were identified in the information science literature and validated through our observations of searches performed by health science librarians.
Results:
A hierarchical multi-level model of context-initiated information seeking is proposed. Each level represents (1) a problem space that is traversed during the online search process, and (2) a distinct layer of knowledge that is required to execute a successful search. Grand strategy determines what information resources will be searched, for what purpose, and in what order. The strategy level represents an overall approach for searching a single resource. Tactics are individual moves made to further a strategy. Operations are mappings of abstract intentions to information resource-specific concrete input. Assessment is the basis of interaction within the strategic hierarchy, influencing the direction of the search.
Conclusion:
The described multi-level model provides a framework for future research and the foundation for development of an automated information retrieval system that uses an intelligent search agent to bridge clinician information needs and human search expertise.
doi:10.1016/j.jbi.2007.09.005
PMCID: PMC2384229  PMID: 18006383
information retrieval; information seeking; online searching; search strategies; problem solving; user expertise; cognitive model; clinician information needs; intelligent agent
22.  Evaluation of a Prototype Search and Visualization System for Exploring Scientific Communities 
Searches of bibliographic databases generate lists of articles but do little to reveal connections between authors, institutions, and grants. As a result, search results cannot be fully leveraged. To address this problem we developed Sciologer, a prototype search and visualization system. Sciologer presents the results of any PubMed query as an interactive network diagram of the above elements. We conducted a cognitive evaluation with six neuroscience and six obesity researchers. Researchers used the system effectively. They used geographic, color, and shape metaphors to describe community structure and made accurate inferences pertaining to a) collaboration among research groups; b) prominence of individual researchers; and c) differentiation of expertise. The tool confirmed certain beliefs, disconfirmed others, and extended their understanding of their own discipline. The majority indicated the system offered information of value beyond a traditional PubMed search and that they would use the tool if available.
PMCID: PMC2815483  PMID: 20351816
PubMed; Medline; search; visualization; social networks; translational research
23.  A Taxonomy Characterizing Complexity of Consumer eHealth Literacy 
There are a range of barriers precluding patients from fully engaging in and benefiting from the spectrum of eHealth interventions developed to support patient access to health information, disease self-management efforts, and patient-provider communication. Consumers with low eHealth literacy skills often stand to gain the greatest benefit from the use of eHealth tools. eHealth skills are comprised of reading/writing/numeracy skills, health literacy, computer literacy, information literacy, media literacy, and scientific literacy [1]. We aim to develop an approach to characterize dimensions of complexity and to reveal knowledge and skill-related barriers to eHealth engagement. We use Bloom’s Taxonomy to guide development of an eHealth literacy taxonomy that categorizes and describes each type of literacy by complexity level. Illustrative examples demonstrate the utility of the taxonomy in characterizing dimensions of complexity of eHealth skills used and associated with each step in completing an eHealth task.
PMCID: PMC2815448  PMID: 20351828
24.  Consumer Health Information Seeking as Hypothesis Testing 
Objective
Despite the proliferation of consumer health sites, lay individuals often experience difficulty finding health information online. The present study attempts to understand users' information seeking difficulties by drawing on a hypothesis testing explanatory framework. It also addresses the role of user competencies and their interaction with internet resources.
Design
Twenty participants were interviewed about their understanding of a hypothetical scenario about a family member suffering from stable angina and then searched MedlinePlus® consumer health information portal for information on the problem presented in the scenario. Participants' understanding of heart disease was analyzed via semantic analysis. Thematic coding was used to describe information seeking trajectories in terms of three key strategies: verification of the primary hypothesis, narrowing search within the general hypothesis area and bottom-up search.
Results
Compared to an expert model, participants' understanding of heart disease involved different key concepts, which were also differently grouped and defined. This understanding provided the framework for search-guiding hypotheses and results interpretation. Incorrect or imprecise domain knowledge led individuals to search for information on irrelevant sites, often seeking out data to confirm their incorrect initial hypotheses. Online search skills enhanced search efficiency, but did not eliminate these difficulties.
Conclusions
Regardless of their web experience and general search skills, lay individuals may experience difficulty with health information searches. These difficulties may be related to formulating and evaluating hypotheses that are rooted in their domain knowledge. Informatics can provide support at the levels of health information portals, individual websites, and consumer education tools.
doi:10.1197/jamia.M2449
PMCID: PMC2442260  PMID: 18436912
25.  Differential Antigen Requirements for Protection against Systemic and Intranasal Vaccinia Virus Challenges in Mice ▿  
Journal of Virology  2008;82(14):6829-6837.
The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines.
doi:10.1128/JVI.00353-08
PMCID: PMC2446990  PMID: 18448519

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