Self-management of exacerbations in COPD patients is important to reduce exacerbation impact. There is a need for more comprehensive and individualized interventions to improve exacerbation-related self-management behavior. The use of mobile health  could help to achieve a wide variety of behavioral goals. Understanding of patients and health care providers perspectives towards using mHealth in promoting self-management will greatly enhance the development of solutions with optimal usability and feasibility. Therefore, the aim of this study was to explore perceptions of COPD patients and their health care providers towards using mHealth for self-management of exacerbations.n = 13) and health care providers (HCPs) (n = 6) was performed to explore perceptions towards using mHealth to support exacerbation-related self-management. Data were analyzed by a thematic analysis.A qualitative study using focus group interviews with COPD patients  contains supplementary material, which is available to authorized users. Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent chronic disease worldwide and is associated with a significant burden on both patients and society , 2. The The absence of an adequate imminent exacerbation marker requires to focus on supporting COPD patients in developing self-management skills to be able to adequately detect exacerbations and to take prompt actions and thereby reduce the impact of exacerbations , 10. A rTo further reduce the impact of exacerbations, a more comprehensive, dynamic and individualized strategy is needed that improves the full spectrum of exacerbation-related self-management behavior , 14, 15.Explore both COPD patients and health care providers willingness to use mHealth for self-management of exacerbations.Identify potential benefits and barriers of using mHealth for self-management of exacerbations.Explore needs and preferences of both COPD patients and health care providers regarding content of an mHealth intervention for self-management of exacerbations.The main aim of the study was to explore perceptions of COPD patients and their health care providers towards using mHealth for self-management of exacerbations. More specific, the objectives were to:A qualitative study using focus group interviews with COPD patients and health care providers was performed to elicit ideas, thoughts and perceptions towards using mHealth to support exacerbation-related self-management . Focus gA purposive sample of Dutch patients with a clinical diagnosis of COPD, who had experienced at least one exacerbation in the last twelve months, was selected from two general practices, two physiotherapy practices and one hospital in the region of Utrecht. Patients had to meet the inclusion- and exclusion criteria as described in Table Patients were informed about the study by their HCP and received written study information. A patient willing to participate, was contacted by the researcher to provide further information and to verify willingness to participate in the study. Two patients were approached for this study during their participation in a previous study focusing on perceptions towards exacerbation-related self-management , and onen = 6–8) were performed using a topic list for formulating open questions [Focus group interviews .Data were analysed according to a thematic analysis as described by Braun&Clarke, to identify, analyse and report themes within the data . Data weFirstly, the two researchers read the transcripts in its entirety to get an overall picture and summarized information obtained with regard to the research objectives. Secondly, the interviews were reread in more detail, initial codes were connected to meaningful paragraphs by both researchers and discussed afterwards to reach consensus. Third, identified codes were brought under potential themes and, subsequently, reviewed for correspondence to the coded paragraphs. Finally, potential themes were further defined and clear definitions were generated . The proCredibility of the study was enhanced by emphasizing the aim to learn from participants and an open, non-judgmental attitude of the moderator during the focus group. Furthermore, discussions with two experts on the interpretation of data (JT&MS) contributed to the study’s credibility . Transcrn=13 COPD patients  and n=6 HCPs  participated in the study. Baseline characteristics of the participants are presented in Tables A total of The results of the focus group interviews are described in the following paragraphs and further illustrated by quotes of the participants in Tables Mobile technology use was introduced as either smartphone or tablet use. Some patients not using these mobile devices did use a computer or laptop and were encouraged to think about opportunities to support self-management through these devices. Most common purposes of mobile technology use by patients were: phoning, social media, seeking information on the internet, application use, messaging and gaming. Mobile technology was barely used for health purposes. Two patients had some experience with health applications by participating in previous eHealth research. According to patients, most common advantages of mobile technology use were the low threshold to use mobile technology and opportunities for social networking. Experienced disadvantages were: privacy sensitiveness and limited usability since mobile devices are too small to navigate properly. Although most patients were currently using mobile devices, some patients did not have a mobile device. Reasons not to use mobile devices were: no interest in mobile technology, poor digital skills and high costs. By asking HCP’s about their experience with mobile technology in health care, only one HCP mentioned to have experience with health applications in daily practice.Before focusing on patient and HCP perspectives towards using mobile technology for exacerbation-related self-management, they were both asked about patient needs toward self-management support. Based on both patient and HCP responses, patient needs varied largely per individual. Although some patients mentioned that they had adequate skills for exacerbation-related self-management, a substantial part mentioned having difficulties with exacerbation detection and taking prompt action. One of the most important needs, according to both patients and HCPs, was that patients are properly heard by their HCP and receive adequate support from their HCP (Q1&2). Having a good relationship with HCPs was considered to be important for the decision process to perform self-management actions. With regard to early exacerbation detection specifically, patients explained a need for tools to substantiate their current health status (Q3). Furthermore, adequate information regarding self-management actions and social support were considered to be important to reduce patients insecurity regarding self-management actions (Q4&5). Finally, patients indicated a need for elimination of barriers in the health care system to reduce the threshold to contact a HCP since they are not always allowed to communicate with their HCP immediately (Q6).By asking patients about their perspectives towards using mHealth for exacerbation related self-management, several potential benefits were mentioned. Most importantly, patients thought that mHealth could contribute to awareness of symptom deterioration and explaining possible causes (Q7). In their opinion, mHealth could contribute to demonstrating and underpinning of their current health status, which could increase patients’ self-empowerment towards communication with HCPs and achieve that they feel to be heard (Q8). Furthermore, some patients felt that using mHealth could support them in taking adequate actions by reminding them of these actions and thereby eliminating feelings of insecurity and reducing the threshold to contact an HCP (Q9&10). Some patients thought that recently diagnosed patients would benefit most from an mHealth intervention, since they had realized that they had a lack of information at the early stage of their disease. HCPs perspectives towards potential benefits are largely in line with the patients perspectives.Potential barriers to use mHealth, according to both patients and HCPs, were patients avoiding confrontation with the disease (Q11), preference for personal contact with an HCP (Q12), difficulties with displaying feelings in an application leading to invalid patient measures and lack of trust in advising characteristics of an mHealth intervention (Q13&14). Additionally, already having adequate self-management skills and lack of enthusiasm for mHealth by HCPs, were mentioned as barriers according to patients (Q15&16). Furthermore, an important potential barrier according to HCPs was a potential limited group of eligible patients (Q17). HCPs explained having doubts regarding eligibility based on disease severity, limited health skills and a lack of patient motivation and enthusiasm for self-management as well as for using mHealth.The HCPs had various perspectives regarding the influence of mHealth on health care contact. In line with the patients perspective, some HCPs were convinced that mHealth could stimulate prompt health care contact, whereas others thought that advising patients through mHealth could lead to postponing health care contact, as it could result in patients seeking information on self-management actions too long themselves (Q18).Based on the patient and HCP responses, the perceived benefits should outweigh the barriers of using mHealth to be willing to use an mHealth intervention. In general, patients who expressed the most needs towards self-management support and perceived mostly benefits of using mHealth, were most willing to use mHealth. In contrast, patients who expressed that they had enough skills to manage exacerbations themselves were less willing to use mHealth for self-management support, as well as patients who perceive many barriers towards using mHealth or have no interest in using mobile technology at all. Some patients who were not using mobile devices stated that they might be willing to use mHealth when it is helpful in managing their disease and when they would be able to learn how to use mobile devices.Both patients and HCPs brought in a diversity in preferences regarding the content of an mHealth intervention to support self-management behavior and regarding intensity of mHealth use. All patients and HCPs perceived that an mHealth intervention should be a multi-component and tailored tool that improves self-management of exacerbations by determining their health status to adequately detect exacerbations, provides decision support to overcome barriers to take prompt actions and stimulates prompt healthcare contact.Both HCPs and patients were positive towards providing information regarding COPD and exacerbation-related self-management, an action plan for decision support and reminders for various activities (Q19–21). Both HCPs and patients perceived potential benefits regarding self-monitoring of symptoms over time, to create awareness on symptom deterioration and subsequently support exacerbation recognition. However, some patients and HCPs explained doubts about patient willingness to enter information in an application for self-monitoring (Q22). Some patients explained that they tried to avoid confrontation with their disease and were therefore not willing to monitor symptoms over time, whereas others were convinced that they could feel best themselves how they are doing and therefore need no self-monitoring tool. Patients mentioned various preferences regarding potential frequency of entering information and corresponding duration.Some HCPs and patients perceived potential benefits regarding information exchange between patients and HCPs through mobile devices. However, they explained doubts at the same time (Q23). Both patients and HCPs were positive towards a quick link to HCP contact details to support healthcare contact at the moment of symptom deterioration. Most patients expressed that they prefer to make the decision to communicate with their HCP themselves, instead of automatic communication through a mobile device. When talking about information exchange with HCPs, a more in-depth discussion focusing on positioning of the patients and HCPs role regarding mHealth use was elicited, which is described below.Most importantly, patients and HCPs considered a mHealth intervention as support to improve self-management and emphasized that it should never replace patients’ own feelings nor undermine their own decisions. An mHealth intervention should be complementary to regular contact with HCPs, as personal contact with a HCP was considered to be very important for patients, and for HCPs as well to be able to make adequate medical decisions. Some HCPs expressed that providing medical advice through mobile devices can be unsafe due to the large heterogeneity in patients and symptoms. These HCPS were convinced that a real life judgement on the patient’s health status is necessary to provide adequate medical advice. Based on all focus groups, acceptance of the disease and engagement with mobile device use were considered to be important preconditions for successful outcomes.Both patients and HCPs agreed that targeting and tailoring an mHealth intervention is important to optimize engagement with mHealth, although HCPs had their doubts regarding the feasibility of targeting and tailoring (Q24). Some HCPs were equivocal towards the efforts of tailoring an intervention to the patient versus the potential benefits for the patient, as they explained doubts regarding their ability to manage tailored interventions. HCPs emphasized the importance of attractiveness of an mHealth intervention for engagement, meaning that an intervention should be straightforward, not too complex and should include mainly visual information (Q25). Furthermore, both HCPs and patients expressed that receiving positive confirmation or rewards from a mobile device is important. Patients emphasized that an intervention should evoke positive feelings and lead to positive patient outcomes (Q26). All patients emphasized the importance of making their own choices regarding the use of mHealth and that information or feedback should be presented in an advisory manner (Q27). Moreover, an essential precondition from their perspective is that all their HCPs should be familiar with the intervention. In addition, HCPs were convinced that patients should already have some self-management skills and a positive attitude towards using mHealth to optimize engagement with an mHealth intervention (Q28). Finally, safety of an application should be guaranteed at all times.HCPs were asked about their perspectives towards their role in supporting self-management using mHealth. They emphasized the importance of adequate positioning of HCPs and patients responsibilities regarding mHealth use (Q29). Most HCPs were critical towards their own role and stated that a pro-active role is needed to achieve positive patient outcomes. Furthermore, most HCPs believe they have a role in estimating patient capabilities to use mHealth for self-management based on patient’s motivation, technical- and self-management skills and cognitive level.HCPs were asked about potential benefits and barriers regarding patient responsibility toward symptom monitoring and taking action in comparison to monitoring and management by an HCP. One HCP mentioned that increasing patient responsibilities towards managing their disease is preferable and should be a starting point. An important benefit is that it may lead to perceived control on the disease (Q30). However, one HCP mentioned that HCPs have an essential role in judging which actions are appropriate at what time since patients have not enough skills to do that themselves. On the other side, most HCPs were predominantly reluctant regarding symptom monitoring by a HCP. HCPs expressed that monitoring by HCPs could provide a certain feeling of safety by patients which they cannot guarantee. HCPs explained that they will not be able to monitor their patients continuously and were therefore afraid to miss important signals, which might lead to patients who remain waiting until a HCP seeks contact (Q31). Furthermore, patient measures can be invalid, which might result in inadequate  advice and negatively affect patient safety as well. Another barrier for HCPs to monitor patient symptoms through mHealth is the time investment for HCPs (Q32). Finally, HCPs discussed whether it remains self-management support when a HCP is monitoring a patient at home (Q33). Nevertheless, early detection of an exacerbation might be an important potential benefit of symptom monitoring by a HCP.From the HCPs perspective, an mHealth intervention should be suitable for a wide range of patients and should support them in developing self-management skills over time. The HCPs role should then focus on monitoring how patient self-management skills are developing over time, by discussing patients self-management behavior during consults and providing feedback on self-management skills, leading to future goal setting.This study provided insight into perceptions of COPD patients and their HCPs towards using mHealth for self-management of exacerbations. This study shows that patients’ needs regarding self-management of exacerbations vary widely and that patients and HCPs perceive mostly similar benefits and barriers regarding using mHealth for exacerbation-related self-management. Patient willingness to use mHealth seems to be driven by these perceived benefits and barriers. Both patients and HCPs are generally positive towards a multi-component and tailored mHealth intervention that aims at developing patients’ self-management skills over time by providing adequate information, decision support regarding prompt actions and feedback on self-management behavior. Although mHealth could support patients in developing self-management skills at home, discussing self-management skills with HCPs in person was considered to be essential for further improvement of these skills.Several findings of this study were in line with other studies. The patient needs regarding exacerbation-related self-management found in this study correspond with barriers for exacerbation-related self-management that were identified in a previous qualitative study of our research group . FurtherRecently, the Behavior Change Wheel has become increasingly important in the development of behavior change interventions . The BCWOur findings expand upon prior work by identifying benefits and barriers of using mHealth for exacerbation-related self-management specifically. Our study shows that both patients and HCPs perceived that mHealth could contribute to awareness of symptom deterioration and could help patients in underpinning their current health status, which might increase their self-empowerment and subsequently stimulate prompt health care contact. These are important benefits since previous research has shown that many patients have difficulties with exacerbation detection and taking prompt actions , 33, 34.Although multiple benefits of mHealth were expressed by our participants, this study also shows that both patients and HCPs have doubts regarding the validity of patient measures and have limited trust in advising characteristics of an mHealth intervention. Furthermore, while previous research on action plans aiming at stimulating prompt health care contact, have shown positive outcomes , 12, somMoreover, our study provided insight into patient and HCP preferences regarding content of an mHealth intervention. Based on a previous systematic review, a positive attitude regarding symptom monitoring by a HCP could be expected . HoweverAn important strength of this study was our focus on both the patient and healthcare provider perspectives, since both are considered to be very important for intervention development and successful implementation . FurtherA limitation of this study was the transferability of the results. The panel of HCPs consisted of 6 HCPs with different professions yet lacking an experienced pulmonologist. Most HCP’s had no experience with mHealth in daily practice. Including a larger sample of HCPs with more mHealth experience, could have resulted in a more diverse range of HCP perspectives. However, striving for maximum variation in both the HCP and patient panel contributed to the transferability of the results to other HCP’s and COPD patients. Furthermore, it should be noted that the average age of the study population of COPD patients might be at the lower limit of the Dutch COPD population . Since mThe findings of this study are important for both health care providers supporting patients in exacerbation-related self-management as well as researchers focusing on the development of mHealth interventions. The knowledge on barriers towards using mHealth for exacerbation-related self-management might help health care providers to anticipate on potential barriers when using mHealth and to understand related patient behaviors.This study strengthens the need for multi-component and tailored self-management interventions in COPD care. Although evidence on effectiveness of current mHealth interventions is limited, recent studies suggest that mHealth interventions aimed at supporting self-management might improve patient outcomes , 37. WhiSince usability of mobile devices might depend on the size of devices, it is important that future mHealth interventions can be delivered on a tablet when experiencing problems with navigating on a smartphone. In general, for future development of mHealth interventions it is important to take into account the identified barriers in this study and to meet patient and HCP preferences regarding the content of an intervention. Therefore, both patients and HCPs should be actively involved during the intervention development stage. As self-management requires behavior change, it is important that an mHealth intervention focuses on effective behavior change techniques selected by a thorough analysis of patient capabilities, opportunities and motivation to use mHealth for self-management. Adequate positioning of HCP and patients responsibilities regarding the use of an mHealth intervention to support self-management is essential before implementing an mHealth intervention into COPD care.This study provided insight into perceptions of COPD patients and their HCPs towards using mHealth for self-management of exacerbations. The patients willingness to use mHealth seems to be driven by the perceived benefits and barriers of using mHealth. This study points out that future mHealth interventions should focus on developing self-management skills over time by providing adequate information, decision support and feedback on self-management behavior. To optimize engagement with mHealth, it is important that patients have a positive attitude toward using mHealth and that mHealth interventions are attractive, rewarding, safe and tailored to the patient needs. Although mHealth could support patients in developing self-management skills at home, both patients and health care providers believe that the use of mHealth should be complementary to regular care. Future development of mHealth interventions should focus on selecting effective behavior change techniques and take into account the identified potential barriers toward mHealth use identified by this study. Adequate positioning of the HCP and patients role regarding mHealth use is essential before implementing mHealth interventions into COPD care.Additional file 1:Topic lists for focus group interviews. (DOCX 24 kb)


Purpose: In the United States, HIV disproportionally affects Black and Latina transgender women (BLTW). Pre-exposure prophylaxis (PrEP) is a proven biomedical method for preventing HIV acquisition. However, the social stigma attached to using PrEP may deter uptake and persistence of PrEP among BLTW, two highly vulnerable populations. The purpose of this study was to explore the experiences of PrEP stigma among BLTW who are using PrEP in Los Angeles County.Methods: In-depth, semistructured interviews were conducted with BLTW PrEP users (N=19) to explore experiences of anticipated, enacted, and internalized PrEP stigma within the context of their unique social and contextual factors. A thematic analysis approach was used in the analysis of qualitative data.Results: We noted an underlying theme of HIV stigma related to participants' identification as trans women that served as the social context for other experiences. In addition, our data revealed five themes related to the experience of using PrEP. Three themes were specifically related to PrEP stigma and included: (1) Perception that BLTW PrEP users are HIV-positive; (2) perception that BLTW PrEP users engage in elevated sexual risk behaviors; and (3) negative labels ascribed to BLTW PrEP users. A fourth theme identified was the positive experiences of social support after PrEP disclosure reported by BLTW. Our fifth theme identified involved the dissemination of PrEP information by BLTW to friends/peers and sex partners.Conclusion: BLTW experience PrEP stigma within the context of PrEP disclosure. This experience is underscored by existing experiences of HIV stigma connected to their identity as trans women. PrEP providers should prepare BLTW to use selective disclosure practices when revealing their PrEP use to help minimize experiences of PrEP stigma or potential physical harm. PrEP implementation programs should also support peer-to-peer PrEP education programs for transgender women to promote positive views of PrEP and help facilitate PrEP uptake in this population. Of the total number (N=1974) of TW who were diagnosed with HIV between 2009 and 2014, the Centers for Disease Control and Prevention (CDC) reports that 51% identified as Black, 29% identified as Latina, and 11% were white.8 The persistent HIV disparity experienced by BLTW underscores the need to increase uptake of new HIV prevention strategies with this highly impacted and vulnerable population.In the United States, transgender women (TW) remain a population disproportionately affected by HIV. The term “transgender woman” refers to a person whose gender identity is female/woman , but who was assigned male sex at birth.9–11 The Pre-Exposure Prophylaxis Initiative (iPrEx) study was the only efficacy trial to enroll trans participants.12 A subanalysis of the TW enrolled in iPrEx (N=339) revealed that there were no HIV infections among TW who had PrEP drug concentrations that were commensurate with the suggested minimum dosing of four pills per week.13 Despite limited efficacy data on TW, PrEP remains a highly effective option for preventing the acquisition of HIV in this population. Unfortunately, disparities persist in the uptake of PrEP among TW.One biomedical strategy for reducing HIV transmission among high-risk populations is with the use of pre-exposure prophylaxis (PrEP) (emtricitabine/tenofovir disoproxil fumarate). Data from efficacy trials indicate that when taken daily, PrEP is up to 99% effective at preventing the transmission of HIV in high-risk populations.15 Multiple studies have shown that in addition to the sexual risks they share with men who have sex with men (MSM) , social and contextual factors such as mental health issues, incidences of gender-based violence or transphobia, economic marginalization, incarceration, and higher rates of sex work contribute to the heightened HIV risk profile of TW.16–18 This suggests a need to tailor PrEP implementation efforts to address the barriers to PrEP uptake, adherence, and continuation experienced by TW, particularly BLTW.According to recent CDC estimates, >1.1 million adults in the United States could benefit from the use of PrEP, yet <1% of those prescriptions were filled by eligible TW who could benefit from the use of the medication.19; a lack of access to gender-affirming health care19; concerns about the routine medical monitoring of PrEP and the management of multiple medications16; a higher prioritization for hormone therapy20; potential side effects or contraindications with hormone therapy20; lack of trans inclusive PrEP marketing20; and instability because of homelessness and economic marginalization.5 In addition, the intersection of HIV stigma and transphobia, particularly in the context of sex work, may also act as a deterrent to PrEP adoption among BLTW.20Previous research has identified multiple barriers to PrEP uptake and continuation that are specific to the trans community. These include medical mistrust because of perceived or experienced transphobia21–23 Stigma can be enacted, anticipated, and/or internalized.22 Enacted stigma refers to overt acts of discrimination, such as unfair treatment, social rejection, and violence; anticipated stigma deals with the expectation or belief that acts of prejudice and discrimination will likely occur in the future; and internalized stigma refers to the degree to which an individual endorses negative perceptions or feelings about themselves.22 An exploration of stigma among BLTW requires consideration of their unique social context.The purpose of the study was to explore experiences of anticipated, enacted, and internalized PrEP stigma among BLTW PrEP users. Stigma is defined as a negatively valued and enduring attribute that marks an individual as socially deviant and functions to maintain differences in social equality between those experiencing stigma and those who do not.A purposive sample of BLTW PrEP users was recruited from October 2017 through November 2018 to complete an in-depth, semistructured qualitative interview about their experiences using PrEP. BLTW were eligible to participate if they were 18 years of age or older, identified as Black/African American or Latina/Hispanic, self-identified as a trans woman, had sex with a cisgender man in the last 6 months, were currently prescribed and taking Truvada for PrEP, had been using PrEP for at least 1 month, and resided in Los Angeles County. All eligible participants received $50 in gift cards (VISA or Target) for their participation.Recruitment strategies included disseminating study promotional materials at trans-specific community events and at LGBT community agencies, and through participant referrals. Several barriers to recruitment of trans women observed in the study included loss of contact with potential participants because of a lost or stolen phone, incarceration, or housing instability. An additional barrier was PrEP discontinuation among BLTW PrEP users, which occurred between the initial contact about the study and the point of enrollment. Recruitment of participants was terminated when data saturation was reached with completed interviews .A semistructured interview guide was developed to explore experiences of stigma related to the use of PrEP among BLTW. As part of the interview, participants were asked to describe the following: (1) experiences disclosing their PrEP use to friends/peers, family, sex partners, and medical providers; (2) experiences where they did not disclose their PrEP use because they thought they would be judged or treated differently; and (3) personal feelings related to their PrEP use. Interviews were audio recorded and lasted 60–90 min. All interviews were transcribed verbatim and checked for accuracy by two research staff members. A self-administered ACASI was used to gather quantitative data on participants' sociodemographic information, PrEP adherence and disclosure practices, and sexual behaviors. Each participant was assigned a unique participant identification number to maintain confidentiality. The Institution Review Board  approved all study materials and all participants provided informed consent before the initiation of any study procedures.24 In short, initial codes were developed from the interview guide, field notes, and multiple readings of the transcripts. Once consensus was reached on the codebook, a subset of codes was used to test for intercoder reliability. Two research team members independently coded two randomly selected transcripts and an intercoder reliability score was computed . The final codes were entered into ATLAS.ti (version 8.3.20.0) and attached to their associated quotations for all transcripts. A thematic analysis approach was then used for analyzing all qualitative data.25 Coded data extracts were sorted into potential themes and reviewed by the study team to refine each theme. Major themes were selected based on their frequency across the dataset or the depth of the discussions.25The coding process is detailed in a previous article.Demographic, PrEP use characteristics, and sexual behaviors are provided in In describing their experiences using PrEP, participants reported an underlying experience of HIV stigma related to their identity as a transgender woman. Participants shared that family members and those within the cisgender community, particularly cis women, hold the beliefs that all TW will contract HIV in their lifetime, are already HIV-positive, and are to blame for the continuing spread of HIV  perception that BLTW PrEP users are HIV-positive; (2) perception that BLTW PrEP users engage in elevated sexual risk behaviors; and (3) negative labels ascribed to BLTW PrEP users. The prevailing sources of anticipated and enacted stigma included family, peers/friends, sex partners, and those within the cisgender community. In addition, we identified a robust theme related to social support of PrEP use among BLTW. Sources of social support included peers/friends, family, and sex partners. A related theme involved the dissemination of PrEP information to trans peers and sex partners.A prominent theme related to PrEP stigma was the assumption that BLTW PrEP users are HIV-positive because they are taking an HIV medication. This resulted in other trans peers discrediting the individual because of their presumed HIV-positive status , Quote 1Another theme that emerged was the perception that BLTW PrEP users are more likely or willing to engage in risky sexual behaviors. This perception led some to express internalized feelings of guilt for continuing to engage in behaviors that put them at increased risk for contracting HIV  , Quote 1A related theme was the experience of being assigned a negative label or identity because of their PrEP use. This included the attachment of negative labels such as “whore” or “slut” . Nonetheless, participants reported high levels of medication adherence. When disclosing their PrEP use, BLTW were met with both negative and positive responses from friends/peers, family members, and sex partners. Negative responses commonly included the assumption that BLTW are HIV-positive and/or engage in risky sexual behaviors, and resulted in others labeling them as hypersexual . These findings are similar to what have been reported among MSM PrEP using populations.32 With regard to their PrEP use, BLTW were also confronted with the assumption that they are HIV-positive and trying to conceal their status. In certain situations, this assumption may carry with it the potential for physical harm or intimate partner violence (IPV). For example, HIV stigma is often magnified within the context of sex work, which manifests in the individual's presumed HIV-positive status being leveraged against them by other trans peers to limit their ability to secure work and in the potential for retaliatory violence from clients.32 The social stigmas attached to PrEP may therefore act as a barrier to PrEP uptake among vulnerable BLTW, who may wish to avoid further marginalization or harm should their PrEP use be discovered.33 PrEP implementation programs will need to address multiple stigmas  to successfully support the adoption and continuation of PrEP among BLTW.This study revealed an underlying experience of HIV stigma directly related to the identity of TW, such as the belief that all TW are vectors of HIV infection. This finding is supported by previous research.While an outlier supported by the experience of one participant, medical providers emerged as an important source of information for TW regarding the potential harm that may result if their PrEP use is discovered and others assume she is HIV-positive. We believe that health care providers who deliver PrEP should be prepared to assist BLTW with developing adaptive strategies to mitigate experiences of stigma and IPV associated with their PrEP use . These types of supportive services should be embedded within the delivery of PrEP to BLTW.35 Conversely, Seibel et al.36 posit that TW who report increased familial support experience higher self-esteem and advancement of their gender confirmation. Although not fully explored in this study, or with the authors cited previously, these findings suggest that family support may play an instrumental role in helping to facilitate PrEP adoption among at-risk BLTW and in improving their overall mental and emotional well-being. In addition, in this study we found trans peers were particularly supportive of participants' PrEP use, especially in relation to their shared experiences of sex work. Social support within the trans community may help lessen the effects of PrEP stigma much in the same way that it has done with other forms of stigma.38 Social support in the context of PrEP use may also help facilitate PrEP uptake and persistence among highly marginalized BLTW.37Another important finding in this study was the social support BLTW PrEP users received regarding their use of PrEP. Sources of encouragement and praise included family members, friends, and trans peers. In particular, the support participants received from family in their initiation of PrEP was a unique finding given that TW have typically reported hostility , rejection, and a lack of social support from their family of origin.16 We believe that peer educators can support the adoption of PrEP among BLTW by promoting a more positive social view of PrEP and highlighting the benefits for individuals and the community. This would include dispelling common myths about PrEP found among TW , which is a recognized barrier to PrEP uptake in this population.20Sharing information about PrEP with peers is another way to help foster PrEP uptake in marginalized populations. In this study, BLTW described experiences of disseminating PrEP information to their peers who are at a high risk for HIV infection. This finding aligns with other literature suggesting that peer education may be an appropriate model for disseminating information about PrEP to high-risk populations, including trans populations.Interpretation of these findings should take into account our study limitations. We recruited a convenience sample of BLTW PrEP users in Los Angeles, and results may not reflect the experiences of BLTW PrEP users in other geographic locations. In addition, the sample consists exclusively of English-speaking Latina TW and may not reflect the experiences of Spanish-speaking Latina TW. Research with monolingual Spanish-speaking Latina TW is needed to assess if experiences of PrEP stigma differ for Spanish speakers, particularly for undocumented TW. A potential bias in our sample is that the study population included BLTW who had been on PrEP, on average, for only 6 months, and who may still be adapting to the experiences of PrEP stigma. Future research should include BLTW PrEP users who are long-term users  to assess if long-term use of PrEP heightens or lessens experiences of PrEP stigma and its personal and social consequences.Despite these limitations, the study has important implications for mitigating PrEP stigma in the context of disclosure and supporting uptake and continuation of PrEP among BLTW. Given the vulnerability and victimization experienced by some BLTW, there is a need for BLTW PrEP users to possess the skills needed to assess the potential consequences of each disclosure event. We believe that medical staff working with this population need to understand the unique social and contextual factors of BLTW to provide appropriate support to them in their use of PrEP. Our findings also highlighted the importance of peers in supporting adoption and disseminating PrEP information. This suggests to us that peer educators could help in deconstructing the existing PrEP stigma and promoting a positive view of PrEP users within the trans community.


Decades of research have emphasized the importance of the medial temporal lobes for spatial navigation and long-term memory. Recent evidence suggests that structures outside of the medial temporal lobes contribute to spatial navigation by providing additional spatial coding and computations relevant for long-term memory, decision-making, and executive function. Together, multiple neural systems may dynamically interact to provide neural architecture that (1) supports dynamic encoding, maintenance, and updating of spatial information and (2) translates convergent spatial and non-spatial information into navigational memories and goal-directed behavior. It is essential that the field pursue mechanistic accounts of how such spatial codes emerge and interact across the brain, bridging theories of spatial navigation, episodic memory, and executive functions.Arnold et al. demonstrated that not only does the hippocampus serve as a network hub, but this functional position changes across encoding and retrieval. Hippocampal network centrality decreased as encoding demands lessened, both as a connector between modules and within the hippocampal neighborhood. Notably, they observed increased hippocampal network connections during mental simulations based on retrieval. Their results indicate a shift in the network dynamics surrounding the hippocampus as encoding demands change, reconfiguring from global integration to localized processing based on the degree of integration of environmental information. These findings connect with recent explorations of the interaction between “semanticized” spatial knowledge (schemas) and episodic navigational memories . This line of investigation demonstrates that the role of the hippocampus in spatial memory is quite dynamic, such that modulation after one-shot learning depends on the fidelity of prior spatial knowledge of the environment. Such data suggest that spatial schemas can accelerate new learning, while also reducing the computational demands on the hippocampus for subsequent simulations about the environment.Recent empirical and theoretical work on these fronts has begun to tackle that very challenge. For example, one way to advance our understanding of the established role of the hippocampus in spatial memory is to explicitly interrogate its position as a node within broader network dynamics. Sulpizio et al. combined fMRI with stimuli assessing larger-scale vista space knowledge in a real-world environment. They found that hippocampal activity showed neural adaptation for repeated facing directions, suggesting a spatial heading signal. Conversely, scene-responsive cortical areas showed adaptation to distances, but the hippocampus did not. Critically, the strength of spatial position coding in retrosplenial cortex tracked individuals' ratings of their spatial abilities—suggesting that the locus of individual navigation abilities may extend beyond the hippocampus. This observation complements evidence from Burte et al. that directional sense is tied to an extended hippocampal-cortical network. Here, they observed that gray matter volumes in the hippocampus predicted individual sense of direction, whereas functional brain activity spanning frontoparietal regions—including retrosplenial cortex—were involved in comparing heading directions. Izen et al. examined individual abilities in a path integration task using resting state functional connectivity. They found that functional connections between medial temporal areas and both the right frontoparietal executive network and the default mode network were increased in better navigators. Together, these findings highlight the importance of interactions between the hippocampus and extra-hippocampal regions in defining individual navigational abilities.In light of these insights into the dynamics of navigational memory, an important question to ask is how such hippocampal-extrahippocampal interactions relate to memory performance. Burles et al. demonstrate that functional heterogeneity in medial parietal cortex, spanning classically-defined retrosplenial cortex and posterior cingulate, is non-trivial for navigation research. Indeed, there appears to be a dorsal-ventral functional gradient surrounding the posterior cingulate. Regions which are commonly labeled as “retrosplenial cortex” in fMRI studies may therefore be more appropriately referred to as distinct subregions that differentially subserve spatial recall  and encoding .The role of retrosplenial cortex in human navigation is a fascinating target for continued research, as evidenced by the studies on individual abilities in this special topic. Not only does this region provide clear direction-related signals in navigating rodents that are distinct from hippocampal spatial codes, but there is considerable variability in the anatomical loci and functional associations of retrosplenial activity across human studies. Burte et al. observed relationships between orbitofrontal cortex volume and task accuracy in their study; Izen et al. demonstrated that resting state functional connectivity between the medial temporal areas and networks with prominent prefrontal components predict better path integration ability. This work underlines the importance of future research generating a greater understanding of prefrontal-related executive function in spatial cognition.This special topic also drew important attention to prefrontal circuitry and its relationship to navigational performance. For example, Sneider et al. examined hippocampal and prefrontal brain activity in adolescents during a virtual Morris water maze task. They observed that during adolescence, worse performance during spatial retrieval was associated with greater BOLD activation of angular gyrus and supramarginal gyrus, whereas worse performance during visible platform navigation was associated with less activation of anterior prefrontal cortex. They suggest that in adolescents, less BOLD activation of the frontal pole in worse navigators could be a sign of less effective navigational path planning. Such questions can also be asked in aging populations, where spatial abilities and strategies may regress in the other direction. In particular, Zhong and Moffat's careful survey of the literature indicates that changes in prefrontal function may play a major role in both strategy switching and spatial association learning as we age.What are the ramifications of such observations? One answer is they can provide insight into cognitive development across the lifespan. For example, Goodroe et al., the classic dichotomy of attributing allocentric spatial memory to the hippocampus and egocentric route-based memories to the striatum is not comprehensive enough to include all of the mechanisms needed for many navigation scenarios. For example, some route-based memories may draw on episodic-memory mechanisms and prefrontal control processes, even after much practice. One alternative to describing navigational scenarios based on modularized brain function or spatial reference frame is to adopt a model-based vs. model-free reinforcement learning perspective of task demands. Starrett and Ekstrom offer a complementary examination of such issues, focusing specifically on challenges for distinguishing egocentric and allocentric spatial representations, while introducing a new task—the relative vector discrimination task. This new paradigm may better target the allocentric dimension of spatial representations than established virtual navigation tasks. Such advances in paradigm structure may help researchers resolve how we flexibly acquire, integrate, and draw on different reference frames of our environments. Understanding reference frames and how they relate to other theoretical perspectives such as reinforcement learning is critical for the field. As He and McNamara show, initial headings when experiencing an environment define a reference frame for the space that can influence subsequent learning and spatial updating. Together, these articles are pushing the boundaries of how we understand reference frames.The mechanistic basis for spatial strategy shifts and associative memory are ripe for continued research, even in the canonical sample of healthy college age adults. As reviewed by Pazzaglia et al. show, latent spatial abilities better predicted route-tracing performance, whereas measures of anxiety, efficacy, and pleasure in exploring  were more likely to predict shortcut-finding performance. It is intriguing to think about how such relationships interact with the dynamic nature of real world environments. For example, in this special topic, Piccardi et al. examined spatial memory in L'Aquila earthquake-exposed survivors, and suggest that continuous and extreme environmental changes could mean that people need to attend more to navigational space, leading to improvements in topographical learning. The ability to adjust learning and attentional strategies in a dynamic world may be a critical trait related to whether and how effectively people balance exploration and exploitation to maximize learning and navigational efficiency.How “non-spatial” cognitive differences are associated with different behavioral strategies is also a particularly important direction for continued research. For example, although spatial ability is a clear driving factor, predispositions to anxiety, risk aversion, and enjoyment from the act of exploration, can manifest in profound differences in how we choose to traverse our environment. In fact, as Herweg and Kahana, behavioral work in humans does not unequivocally support the use of a metric Euclidean map for navigation. Formal models of navigational behavior, which account for environmental scale and complementary learning mechanisms, may help to better understand different navigational strategies. One approach to refining such models could be to study how place- (and concept-) responsive single-cell activity relates to ongoing theta oscillations during both the encoding and retrieval of spatial and non-spatial associations. These temporally-extended and recurring oscillatory signals could complement fMRI work in the grand objective of unifying theories of medial temporal lobe function under the umbrella of mechanisms that relate or discriminate experiences across multiple temporal and spatial scales.One exciting aspect of bringing such a diverse range of scholars together for a special topic such as this is its power to generate new ideas. Convergent and divergent findings in the empirical work, as well as in the literature reviews, compile and underscore key future directions for the field. For example, as highlighted in the extensive review by Brunyé), recent advances in functional connectivity analyses have revealed stable functional networks that include both deep subcortical structures and regions on the cortical surface. This finding suggests that the modulation of superficial brain regions such as the inferior parietal lobule and lateral prefrontal cortex may carry powerful downstream consequences for deeper brain systems involved in spatial processing and real-world navigation. Transcranial electrical stimulation has gained popularity as a tool for modulating several aspects of perception and cognition. As we come to understand the parameters underlying effective excitation and disruption protocols with this tool, we may be able to gain causal understanding of the relationships between, for example, neocortical oscillations and spatial computations. Moreover, our growing understanding of functional network profiles within the navigation system may enable the use of such tools to indirectly target subcortical brain regions by altering neuronal activity in distant—yet functionally connected—cortical areas.Other opportunities for continued research into extra-hippocampal mechanisms exist in causal/interventionist approaches. As highlighted in Brunye's review (Collectively, the articles in this special topic highlight new and exciting directions for the field of spatial navigation. The studies all look beyond the traditional boundaries of spatial navigation research, either by examining functional brain networks, new techniques, individual differences, or establishing connections with personality traits and executive functions. The innovative ideas generated in this special topic provide a wealth of avenues for future research.TB and EC co-wrote all aspects of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Immobility during hospitalization is widely recognized as a contributor to deconditioning, functional loss, and increased need for institutional post-acute care. Several studies have demonstrated that inpatient walking programs can mitigate some of these negative outcomes, yet hospital mobility programs are not widely available in U.S. hospitals. STRIDE  is a supervised walking program for hospitalized older adults that fills this important gap in clinical care. This paper describes how STRIDE works and how it is being disseminated to other hospitals using the Replicating Effective Programs (REP) framework. Guided by REP, we define core components of the program and areas where the program can be tailored to better fit the needs and local conditions of its new context . We describe key adaptations made by four hospitals who have implemented the STRIDE program and discuss lessons learned for successful implementation of hospital mobility programs. Hospitalized adult patients spend 95% of their time in beds or chairs ,2,3. PatMany factors may contribute to the negative outcomes related to low patient mobility, including patient-related and treatment factors . The mosInterventions to systematically promote early, safe mobility in older hospitalized patients—designed to address clinical and logistical challenges of promoting mobility—are needed to avert the negative and costly consequences of immobility during inpatient stays. Previous studies have demonstrated the potential of inpatient walking to prevent declines in mobility during hospital stays and to reduce hospital lengths of stay ,17,18,19p = 0.007) [STRIDE  is a supervised walking program for hospitalized older adults focused on maintaining musculoskeletal strength and mobility during hospitalization, a highly vulnerable time for development of disability. It was adapted from a mobility program, studied in a randomized controlled trial in three non-Veterans Health Administration (non-VA) hospitals, that led to reduced hospital lengths of stay . Origina= 0.007) . Based o= 0.007) .Initial positive results suggested that STRIDE had the potential to become a system-wide approach to address hospital-associated disability in the VA; however, differences in resources, staffing, and priorities among other conditions in VA facilities presented barriers to successful implementation at other sites. Therefore in 2016 we launched an ongoing project, Optimizing Function and Independence Quality Enhancement Research Initiative (known as “Function QUERI”) to implement STRIDE in eight additional VA hospitals  in 2017–n = 35 interviews) and summarized into case summaries for each of the four sites. Data from all sources  were combined in a matrix to view emergent patterns that served as the basis for program characteristics and REP adaptations described in We used VA administrative data sources ,26 to deOne of the goals of Function QUERI is to study the process of starting a STRIDE program so that these lessons can be applied in broader efforts to promote hospital mobility programs. Eight VA hospitals volunteered to begin STRIDE programs at their sites and were randomized to begin at a specific time . To dateA one-size-fits-all approach is rarely effective for addressing the barriers of implementing a program in multiple new settings ; therefoAll expansion sites identified a need to improve mobility of their hospitalized patients and selected the STRIDE program as a means to address this clinical problem. The Pre-Conditions phase of REP focuses on leveraging the pre-existing resources in the health care system essential to implementing a new clinical program. Key tasks include identification of local champions or advocates who are essential in establishing widespread buy-in and ensuring the program fits pre-existing culture, local programmatic goals, and resources . Each exThe Pre-Implementation phase focuses on preparation for program implementation and obtaining broad buy-in for the new clinical program. The key tasks include identifying key stakeholders and tailoring the program materials to fit the local context. Each expansion site identified key stakeholders to serve on the local STRIDE implementation team, including VA Medical Center leadership, service-line chiefs, and front-line staff. They identified champions from the services lines with key roles in program implementation. Topics covered during pre-implementation phase calls including describing the intervention protocol  and providing technical assistance to guide sites on options for customization and prepare for program launch. During this phase, the expansion site teams discussed their site’s staffing model, patient eligibility criteria, and target distance and time for daily patient walks. The Function QUERI team conducted a site visit prior to program launch to provide on-site technical assistance  and market the program to local leadership and front-line staff.The Implementation phase begins with program launch and includes ongoing training and technical assistance, program promotion to increase buy-in among front-line staff and leadership, and process monitoring to ensure program feasibility and fidelity to the core components of the STRIDE program. The local STRIDE implementation team at expansion sites received weekly reports of program activity to facilitate ongoing improvements. For example, reports included counts of STRIDE consults and percentage of hospital days that STRIDE patients had at least one documented walk. Data review helped to identify barriers to successful implementation and promote discussion of strategies to overcome these. For example, if the number of consults at an expansion site was low, the Function QUERI and expansion site teams discussed strategies for improvement, such as increased marketing of the program to residents and other medical staff.The final Maintenance and Evolution phase involves compiling program results and reporting to leadership and other relevant stakeholders, as well as using process and outcome results to further refine program implementation for other sites. For example, some sites are reporting data to leadership on veteran satisfaction with the program and relevant performance metrics  on wards which implemented STRIDE. The final phase includes continued technical assistance, continued reports of program activity, and ongoing consultation about program implementation and evolution to ensure sustainability. The Function QUERI team is refining a STRIDE implementation package, with the sites’ input, in preparation for wider-scale dissemination.(1)Proactive, no baseline functional deficits required(2)Early enrollment, ideally within 24 h of admission(3)Supervised walking, up to 20 min daily until dischargeThe Function QUERI team viewed the REP Framework as ideal for the rollout of STRIDE because the framework provides a standard structure for specifying core elements of the program while allowing sites flexibility to determine which components can be adapted to local settings. Essential core elements of STRIDE were defined as:The STRIDE team encouraged program adaptations in the areas of how to identify patients for the program  and the role of the staff who would conduct the assessment and supervise the walks (staffing model). Function QUERI’s experience with STRIDE implementation at four expansion sites has resulted in several lessons learned that are relevant for future dissemination efforts and also for individual hospitals interested in starting a mobility program.Due to competing demands on staff time, flexibility around the STRIDE staffing model is important. Decisions about which staff roles are best suited to supervise walks and how these are structured , should be made collaboratively with representation from all key stakeholders. Leadership buy-in and front-line clinical champions have been critical to initiate the program and sustain the weekly consults, gait assessments, and walking sessions. Because most models have incorporated physical therapists to conduct the gait assessment and nurses or CNAs to supervise the walks, effective interdisciplinary communication between those two professional groups is particularly vital. Coordination with other groups charged with improving quality and safety in the hospital, such as fall prevention committees and safe patient handling and mobility coordinators is also key to ensure programmatic alignment. From a training and documentation perspective, providing competency checklists to the facility to adapt for staff training and modifiable electronic health record templates to document gait assessments and walks in a standardized, reportable manner have helped save time and effort for facilities and enhanced the ability of sites to track their progress. The electronic health record templates have included standardized data that can be extracted as structured text fields such as patient enrollment in the program, walk distance and time, and how the patient felt after the walk. The ability to compile these data periodically has helped sites to monitor their progress, troubleshoot issues that arise, and begin to build a case with leadership for program growth and sustainability. For Function QUERI, it is essential that all hospitals use standardized data collection templates to facilitate combining data across sites. For implementation support provided outside of a study context we anticipate that fewer calls would be required to meet the data needs of individual sites.Through interviews with the expansion sites’ staff and leadership, we discovered that service line leadership and other key stakeholders often viewed the STRIDE program as a platform for broader culture change around patient mobility. We found that site personnel usually recognized the value of patient mobility but needed the presence of an evidence-based, implementable program to “jumpstart” change in that area and address the biases of some staff or facility procedures that were hindering mobility. For example, two sites changed activity orders to reduce bedrest orders and encourage ambulation. One site developed a ‘huddle board’ at the nursing station to communicate about patient mobility and STRIDE consults. STRIDE was based on a hospital mobility intervention proven effective in a randomized controlled trial , howeverCombining data from all eight expansion sites that ultimately implement STRIDE as part of Function QUERI will expand our understanding of the impact of hospital mobility programs on patient and system-level outcomes. Our implementation evaluation will focus on the roles of teams in successfully initiating and sustaining STRIDE, and whether a teamwork training intervention can enhance implementation of new clinical programs. Future research should address whether there are differential effects of hospital mobility programs according to patient characteristics  as well as whether extending interventions into the home setting after discharge may be beneficial. Direct patient feedback from pedometers or other activity trackers and/or motivational incentives may offer a means of enhancing activity during hospitalization between STRIDE walks.Although the hazards of immobility during hospitalization have been long-known, sustained solutions to this problem have been elusive. STRIDE offers a promising approach for hospitals to support increased mobility in their patients, thus supporting better patient outcomes and reduced need for post-acute institutional care. As part of the final REP phase (Maintenance and Evolution), we plan to package a clinical program guide to assist with wider dissemination of the STRIDE program to sites outside of the Function QUERI study. Using the REP framework processes may help individual sites considering hospital mobility programs to tailor their program to best meet their needs, while ensuring that key components shown previously to be effective are retained.


We examine when and how police officers may avoid costly errors under stress by leveraging theoretical and empirical work on the biopsychosocial (BPS) model of challenge and threat. According to the BPS model, in motivated performance contexts , the evaluation of situational and task demands in relation to one’s perceived resources available to cope with those demands engenders distinct patterns of peripheral physiological responding. Individuals experience more challenge-like states in which blood circulates more efficiently in the periphery when they evaluate their coping resources as meeting or exceeding the task demands. Conversely, individuals experience more threat-like states in which blood circulates less efficiently in the periphery when they view the situation or task demands as exceeding their coping resources. Patterns of response consistent with challenge and threat states have been shown to predict important performance and decision-making outcomes in stressful contexts, and repeated experiences of threat-like patterns of physiological activity are thought to have detrimental effects on long-term cardiovascular health. To date, however, research has not used the biopsychosocial model to understand police decision-making under stress. Here, we review relevant empirical work from the perspective of the BPS model concerning how minority status and power can shape challenge and threat responding and contribute to decision-making under stress. We then detail a research agenda aimed at improving the translational value of research being conducted within the BPS model for understanding complex performance and decision-making in the real world, including among law enforcement personnel. Police work is often stressful and requires execution of difficult tasks where outcomes are of high consequence. In this paper, we propose that many situations involving police decision-making or performance can be understood as motivated performance contexts: the situations are goal-relevant, involve instrumental cognitive processing, have uncertain outcomes, and require active rather than passive responding . MotivatThis article briefly introduces the BPS model of challenge and threat and reviews recent empirical work that may shed light on the different ways that stress can influence police performance  and decAccording to the BPS model, challenge and threat represent motivational orientations involving the interplay of affective and cognitive processes that result from the evaluation of situational and task demands relative to one’s available resources to cope with them , 2010. Monly occur in self-relevant contexts and are associated with evaluations of the relative balance of demands and coping resources , was a marker of “physiological toughness” because it was associated with favorable outcomes like increased performance, more emotional stability, and lower anxiety, leaving individuals more likely to appraise situations positively  has been associated with better performance in situations that unfold over longer durations of time such as surgery , cricketAlthough a complete review of the BPS literature examining performance under stress is outside the scope of this article, we briefly highlight empirical findings in content areas that are particularly relevant to police decision-making and performance given the current sociopolitical context in the United States.Empirical studies with lay people have consistently demonstrated that, relative to White targets, participants are significantly quicker to shoot armed Black targets, significantly slower to “not shoot” unarmed Black targets, and have a lower shooting threshold for Black targets  in computer-based shooting simulations . LaboratThese findings on shooting simulation tasks are consistent with empirical work from the BPS model on challenge and threat responding during interactions with individuals from stigmatized groups. For example, However, researchers have found that increased interaction with stigmatized groups is positively related to challenge-like physiological responses during intergroup interactions . These fResearch on the BPS model has examined the nuanced ways in which social status and power influence patterns of biopsychological activity. Specifically, individuals high in social status or power tend to experience more challenge-like states during social interactions with people of lower status e.g., . For exaCritically, research suggests that the relationship between power and biopsychological responding relies on the stability of the power hierarchy; those high in status show more threat-like responses when their status is perceived as unstable or illegitimate . These fAlthough the BPS model has proven useful in examining performance under stress across a variety of motivated performance contexts see , there rData from this field study highlight several critical theoretical and methodological considerations for researchers interested in pursuing translational research examining the relevance of the BPS model in realistic decision-making and performance scenarios. First, the vast majority of research using the BPS model has focused on group comparisons between samples of individuals exhibiting more threatened versus more challenged appraisals, failing to examine challenge and threat responses at the level of the individual . Comparing diverse scenarios may offer insights on the psychological and physiological mechanisms by which challenge and threat orientations influence performance or decision-making across contexts.directly linked to health outcomes, prolonged physiological activation (particularly in the HPA) can result in profound negative health consequences (e.g., The BPS model appears well-suited for studying the psychophysiology of police performance and decision-making because challenge- and threat-like states are relevant across a wide range of social evaluative and motivated performance domains e.g., , are asses e.g., . Thus, res e.g., .DK and JW drafted the manuscript. ES provided substantial edits and feedback on the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The ability of certain tumor cells of mammals and molluscs to spread from the original host to others reopens the question of distinguishing self from non-self. It is part of a wider phenomenon of cellular parasitism and cell chimerism including germ cells. Dictyostelium mucoroides, Leo Buss coined the term somatic cell parasitism [Let us consider a multicellular animal—a human, for example. Each of us is a mobile ecosystem carrying a commensal microbiome including 1000s of species of bacteria outnumbering human cells by about 100:1 and a virome by about 10,000:1. But we assume that all our human cells are derived by cell division from a single fertilized egg. I shall discuss some exceptions, chimeric animals and the emergence of selfish cells that colonize new individuals, for which, from his studies of chimerism in the fruiting bodies of the cellular slime mold The individual in the animal kingdom and in 1958, Peter Medawar published The uniqueness of the individual (recently reissued by Scholar Select). Huxley and Medawar addressed the self/non-self paradigm of recognition and rejection of cells of a ‘foreign’ provenance. Huxley noted that when cells taken from sponges of two species are mixed together, they initially form one reaggregated organism but later separate to form two, one of each genotype. Clearly, some form of self-recognition operates even among the most primitive multicellular animals. Medawar investigated graft rejection in mice mediated by transplantation (histocompatibility) antigens that vary between individuals within a species. Although the nature of these molecules and the role of the dominant component, the major histocompatibility complex (MHC), in antigen presentation had yet to be elucidated, he and his colleagues deduced the basis of genetic individuality and demonstrated acquired immunological tolerance when mismatched cells were mixed early in development.My interest in what constitutes an individual was first aroused by two books I read when I was a zoology undergraduate. In 1911, Julian Huxley wrote a slim volume called In 1983, my curiosity was further piqued by a paper from epidemiologists at the US National Cancer Institute suggesting that canine transmissible venereal tumor (CTVT) might serve as a model for Kaposi’s sarcoma in AIDS. CTVT was thought by some veterinarians to be a naturally transplantable tumor among outbred dogs and certain chromosome and genetic markers supported this hypothesis. However, oncologists well versed in transplant immunology regarded it with deep suspicion. When Yuan Chang and Pat Moore showed in 1994 that Kaposi’s sarcoma is actually caused by a novel herpesvirus, KSHV, I began to study KSHV, but the notion of transmissible tumors remained lodged in my mind. So, I later persuaded a young veterinarian, Claudio Murgia, to address the question using ‘forensic DNA’ markers of dogs. We were able to confirm that the transmissible agent of CTVT is indeed the tumor cell itself and that it has spread globally amongst dogs as a single somatic cell clone.Sarcophilus harrisii), and in several species of marine bivalve molluscs. Extensive phylogenetic studies on the canine and devil tumors led by Liz Murchison in Cambridge have provided much insight into naturally transplantable tumors. The canine transmissible venereal tumor has diversified genetically since it emerged in an ancient dog breed [To date, transmissible tumor cells have been identified in dogs, in the Tasmanian devil , the sessile corals and the floating Portuguese man-o-war?The ultimate sneaky way to propagate one’s own genes with minimal investment into body-building occurs when germ cells migrate into the soma of a neighboring zooid . I wondeTetrahymena represent analogous recognition systems of self from non-self, in this case to block self-fertilization. But the most sophisticated recognition system is that of within-species MHC polymorphism that evolved concomitantly with adaptive immunity in the vertebrate lineage.Most multicellular animals have rudimentary identification systems for recognizing cells of different genetic origin, as mentioned already for sponges, cellular slime molds and ascidians. Indeed, multiple mating types in sexual eukaryotes such as fungi and In the Division of Infection & Immunity, which is my emeritus home, we teach students that adaptive immunity and the MHC system serve to protect the host from pathogenic infections. Quite so, they do, since more frequent infections and increased virulence are evident in immunodeficient individuals, and past epidemics have influenced MHC allele frequencies in populations. However, like Buss , I wouldIn mammals, adaptive cellular immunity develops late in gestation or after birth. If exchange of blood cells or stem cells occurs between fetuses in utero, the resulting individuals do not reject each other’s cells or tissues and form chimeras with long-lasting cells derived from both individuals. This was first recognized by Ray Owen in 1945 in ‘freemartin’ twin cattle and led Medawar and colleagues towards the discovery of acquired immunological tolerance. We now know that some New World primates such as marmoset twins naturally exchange fetal cells in fused placentas, leading to sibling chimerism of many tissues, including germ cells [Returning to the theme of tumor cells, humans can be prenatally seeded with allogeneic leukemic cell precursors from a twin via placental anastomoses or exposure to the maternal circulation . Of courOverall, the concept of individuality and the phenomenon of cellular transmission still present us with open questions.