Translational Mini-Review Series on Vaccines for HIV: T lymphocyte trafficking and vaccine-elicited mucosal immunity.

Many pathogens use mucosal surfaces to enter and propagate within the host, making particularly desirable vaccines that target immune responses specifically to mucosal compartments. The majority of mucosal vaccine design strategies to date have been empirical in nature. However, an emerging body of basic immunological knowledge is providing new insights into the regulation of tissue-specific lymphocyte trafficking and differentiation. These insights afford the opportunity for the rational design of vaccines that focus immune responses at mucosal surfaces. Mucosal cellular immunity may prove critical for protection in the context of HIV infection, and thus there has been considerable interest in developing vaccines that target HIV-specific cellular immune responses to the gastrointestinal and vaginal mucosa. However, the optimal strategies for eliciting mucosal cellular immune responses through vaccination remain to be determined. Here, we review both recent vaccine studies and emerging paradigms from the basic immunological literature that are relevant to the elicitation of potent and protective mucosal cellular immune memory. Increasing the synergy between these avenues of research may afford new opportunities for mucosal vaccine design.

Comprehension of sexual situations and its relationship to risky decisions by young adults.

This research examines the nature of the relationship between comprehension of sexual situations and decisions about risky sexual behaviour by young adults. Participants were 56 heterosexual students from Brooklyn College, NY, located in a community with a relatively high prevalence of HIV/AIDS. They read a sexual encounter scenario and verbally responded to open-ended questions and made decisions about condom use. The responses were recorded, transcribed and analysed. Prior beliefs were evaluated based on participants' initial responses to the scenario. High and low risk individuals showed a specific set of beliefs about safer sex practices, and they processed information differently during comprehension of the sexual situation. Low-risk individuals focused on cues that show "risks of unprotected sex", with the goal of not taking any risks. High-risk individuals processed given information as emotionally related, with the goal of 'immediate pleasure' in the situation. These processing variables influenced the young adults' decisions to practice (or not) safer sex behaviour. Educational interventions need to be tailored for different patterns of behaviour. The goal of a customization approach is to intervene at appropriate weak links in the decision-making process, including any contradictory or unjustified beliefs, to promote safer sex behaviour.

Patterns of reasoning and decision making about condom use by urban college students.

HIV infection rates are rapidly increasing among young heterosexuals, making it increasingly important to understand how these individuals make decisions regarding risk in sexual encounters. Our objective in this study was to characterize young adults' safer sex behaviour and associate this behaviour with patterns of reasoning, using cognitive, information processing methods to understand the process of sexual risk taking. Sixty urban college students from NYC maintained diaries for two weeks and then were interviewed regarding lifetime condom use and sexual history. Using cognitive analysis, we characterized four patterns of condom use behaviour: consistent condom use (35.0%), inconsistent condom use (16.7%), shifting from consistent to inconsistent condom use (35.0%), and shifting from inconsistent to consistent condom use (13.3%). Directionality of reasoning (i.e. data-driven and hypothesis-driven reasoning) was analysed in the explanations provided for condom use decisions. The consistent and inconsistent patterns of condom use were associated with data-driven heuristic reasoning, where behaviour becomes automated and is associated with a high level of confidence in one's judgment. In the other two patterns, the shift in behaviour was due to a significant event that caused a change in type of reasoning to explanation-based reasoning, reflecting feelings of uncertainty and willingness to evaluate their decisions. We discuss these results within the framework of identifying potentially high-risk groups (e.g. heterosexual young adults) as well as intervention strategies for risk reduction. Further, our findings not only identify different patterns of condom use behaviour, but our investigation of the cognitive process of decision-making characterizes the conditions under which such behaviour and reasoning change.

A primer on aspects of cognition for medical informatics.

As a multidisciplinary field, medical informatics draws on a range of disciplines, such as computer science, information science, and the social and cognitive sciences. The cognitive sciences can provide important insights into the nature of the processes involved in human- computer interaction and help improve the design of medical information systems by providing insight into the roles that knowledge, memory, and strategies play in a variety of cognitive activities. In this paper, the authors survey literature on aspects of medical cognition and provide a set of claims that they consider to be important in medical informatics.

Toward a framework for computer-mediated collaborative design in medical informatics.

The development and implementation of enabling tools and methods that provide ready access to knowledge and information are among the central goals of medical informatics. The need for multi-institutional collaboration in the development of such tools and methods is increasingly being recognized. Collaboration involves communication, which typically involves individuals who work together at the same location. With the evolution of electronic modalities for communication, we seek to understand the role that such technologies can play in supporting collaboration, especially when the participants are geographically separated. Using the InterMed Collaboratory as a subject of study, we have analyzed their activities as an exercise in computer- and network-mediated collaborative design. We report on the cognitive, sociocultural, and logistical issues encountered when scientists from diverse organizations and backgrounds use communications technologies while designing and implementing shared products. Results demonstrate that it is important to match carefully the content with the mode of communication, identifying, for example, suitable uses of E-mail, conference calls, and face-to-face meetings. The special role of leaders in guiding and facilitating the group activities can also be seen, regardless of the communication setting in which the interactions occur. Most important is the proper use of technology to support the evolution of a shared vision of group goals and methods, an element that is clearly necessary before successful collaborative designs can proceed.

Conceptual knowledge and decision strategies in relation to hypercholesterolemia and coronary heart disease.

This paper reports on a study that examines physicians' understanding of concepts and decision making in problems pertaining to hypercholesterolemia and coronary heart disease (CHD). The study was carried out in two phases: (1) a simulated clinical interview in which two clinical problems were presented and (2) a session in which subjects responded to a series of questions. The questions were related to the analysis of risk factors, diagnostic criteria (DC) for determining elevated lipid values, and differential diagnosis for lipid disorders. The subjects included 12 family practitioners who were randomly selected from a continuing medical education program at McGill University. The results indicate that all subjects exhibited gaps in their understanding of domain concepts. In particular, most physicians demonstrated a lack of knowledge concerning the primary genetic disorders that contribute to CHD, as well as deficiencies in understanding the secondary causes of hypercholesterolemia. The majority of subjects tended to overestimate the lipid value intervals for determining patients at high risk. Physicians had no difficulty diagnosing the first patient problem of familial hypercholesterolemia, but failed to identify the problem of elevated lipids secondary to hypothyroidism. We observed a dissociation between subjects' conceptual understanding and their application of knowledge in solving patient problems. The implications of this work are discussed in terms of the cognitive dimensions of technologies for supporting learning and evidence-based decision making.

Science and practice: a case for medical informatics as a local science of design.

Because scientific research is guided by concerns for uncovering "fundamental truths," its time frame differs from that of design, development, and practice, which are driven by immediate needs for practical solutions. In medicine, however, as in other disciplines, basic scientists, developers, and practitioners are being called on increasingly to forge new alliances and work toward common goals. The authors propose that medical informatics be construed as a local science of design. A local science seeks to explain aspects of a domain rather than derive a set of unifying principles. Design is concerned with the creation, implementation, and adaptation of artifacts in a range of settings. The authors explore the implications of this point of view and endeavor to characterize the nature of informatics research, the relationship between theory and practice, and issues of scientific validity and generalizability. They argue for a more pluralistic approach to medical informatics in building a cumulative body of knowledge.

Medical informatics and the science of cognition.

Recent developments in medical informatics research have afforded possibilities for great advances in health care delivery. These exciting opportunities also present formidable challenges to the implementation and integration of technologies in the workplace. As in most domains, there is a gulf between technologic artifacts and end users. Since medical practice is a human endeavor, there is a need for bridging disciplines to enable clinicians to benefit from rapid technologic advances. This is turn necessitates a broadening of disciplinary boundaries to consider cognitive and social factors pertaining to the design and use of technology. The authors argue for a place of prominence for cognitive science. Cognitive science provides a framework for the analysis and modeling of complex human performance and has considerable applicability to a range of issues in informatics. Its methods have been employed to illuminate different facets of design and implementation. This approach has also yielded insights into the mechanisms and processes involved in collaborative design. Cognitive scientific methods and theories are illustrated in the context of two examples that examine human-computer interaction in medical contexts and computer-mediated collaborative processes. The framework outlined in this paper can be used to refine the process of iterative design, end-user training, and productive practice.

Stimulus-dependent synergism of the antiapoptotic tumor necrosis factor receptor-associated factor 2 (TRAF2) and nuclear factor kappaB pathways.

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic signaling pathways. Thus, although TNF can cause apoptosis and may prove useful in the treatment of malignancies, most cells are resistant to TNF-induced cell death unless de novo protein synthesis is inhibited. Previous studies suggested that TNF activation of the nuclear factor (NF)-kappaB transcription factor family antagonizes the proapoptotic signals initiated by TNF-alpha. TNF receptor-associated factor (TRAF)2 has also been shown to mediate crucial antiapoptotic signals during TNF stimulation, yet is not essential in activation of NF-kappaB under physiologic conditions, thus raising questions about the relationship between these antiapoptotic pathways. We report here that inhibition of TRAF2 and NF-kappaB function in primary cells, by coexpression of a constitutive repressor of multiple NF-kappaB/Rel proteins (IkappaBalpha.DN) and a dominant negative form of TRAF2 (TRAF2.DN), synergistically enhanced TNF-induced apoptosis. The effects were stimulus dependent, such that neither inhibitory molecule affected Fas- and daunorubicin-induced apoptosis to the same degree as TNF-induced death. These findings indicate that the NF-kappaB and TRAF2 pathways activate independent antiapoptotic mechanisms which act in concert to suppress the proapoptotic signals induced by TNF-alpha.

Assessment of a computerized patient record system: a cognitive approach to evaluating medical technology.

Numerous research and development projects have been aimed at implementing computerized patient record (CPR) systems. Yet little emphasis has been placed on physicians' ability to learn and use these systems or on their effects on physicians' reasoning. This article describes an innovative approach to assessing these aspects of a CPR system. The method involves observing physicians' use of a CPR under various clinical conditions and analyzing the CPR system with a technique called the cognitive walkthrough. We will show how learning to use a CPR system can change a physician's performance, with accompanying effects on information gathering and reasoning.

Steering through the murky waters of a scientific conflict: situated and symbolic models of clinical cognition.

The situated action perspective, which embraces a diversity of views, challenges several of the fundamental assumptions of the symbolic information-processing framework underlying cognitive science and artificial intelligence. In this paper, we consider the following issues; symbolic representations, plans and actions, distributed cognition, and the transfer of learning. We evaluate each of these issues in terms of research and theories in clinical cognition and examine the implications for education and training, and for the integration of intelligent systems in medical practice. We argue for a reconceptualization of the symbolic framework in terms of the way the role of internal representations and cognitive activities are perceived. However, symbolic representations are integral to medical cognition and should continue to be central in any theoretical framework. A re-examination of cognitive science in medicine in terms of the relationship among physicians, technology, and the workplace could prove to be constructive in bridging the gap between theory and practice.

Bridging theory and practice: cognitive science and medical informatics.

Medical informatics has experienced dramatic growth, both as an applied and as a research discipline in recent years. In this paper, we argue that there is a need to expand the research base to characterize the cognitive dimension of informatics. Theories and methods from cognitive science can provide an effective counterpart to traditional medical informatics in addressing issues of usability of the systems, the processing of information, and the training of physicians. In the first part of the paper, we address the problems inherent in applying basic theories to practice and suggest some potential solutions. The second section deals with epistemological issues that are fundamental to cognitive science research and medical informatics. We then discuss two areas of application of cognitive scientific theories and methods to medical informatics: cognitive evaluation of human computer interface and intelligent medical decision support systems. The paper addresses the progress that has been made thus far and discusses how future cognitive research can facilitate further growth in the development of these applications.

Reasoning strategies and the use of biomedical knowledge by medical students.

This paper reports one of a series of studies conducted to investigate the role of biomedical knowledge in clinical reasoning. It was motivated by findings from our earlier studies that demonstrate that when specific basic science information is provided to medical students prior to solving a clinical case, they are unable to use this information in explaining the patient problem. An experiment was designed to investigate the use of biomedical information in the explanation of a clinical problem without any basic science information (spontaneous explanation) and where basic science information was provided after the clinical case (biomedically primed explanation). The results are discussed in the context of a two-stage model of diagnostic reasoning. The first stage is referred to as data-driven reasoning, and is characterized by the triggering of inferences from observations in the data to hypotheses. The second stage is designated as predictive reasoning, and is characterized by the generation of inferences driven by hypotheses. The results show that, with the exception of final-year medical students, the use of biomedical information interfered with the data-driven reasoning process. However, it did facilitate the process of predictive reasoning by the students. It is proposed that a sound disease classification scheme is necessary before biomedical knowledge can facilitate both data-driven and predictive reasoning during clinical problem-solving.

Expertise in the clinical interview: a cognitive analysis.

The present study evaluates differences between subjects at three levels of expertise in acquiring and using information obtained from a patient during the clinical review. The results of the study suggest that the selective acquisition and the efficient utilization of information are hallmarks of expertise in the clinical review.