BackgroundThe recent proliferation of self-tracking technologies has allowed individuals to generate significant quantities of data about their lifestyle. These data can be used to support health interventions and monitor outcomes. However, these data are often stored and processed by vendors who have commercial motivations, and thus, they may not be treated with the sensitivity with which other medical data are treated. As sensors and apps that enable self-tracking continue to become more sophisticated, the privacy implications become more severe in turn. However, methods for systematically identifying privacy issues in such apps are currently lacking.ObjectiveThe objective of our study was to understand how current mass-market apps perform with respect to privacy. We did this by introducing a set of heuristics for evaluating privacy characteristics of self-tracking services.MethodsUsing our heuristics, we conducted an analysis of 64 popular self-tracking services to determine the extent to which the services satisfy various dimensions of privacy. We then used descriptive statistics and statistical models to explore whether any particular categories of an app perform better than others in terms of privacy.ResultsWe found that the majority of services examined failed to provide users with full access to their own data, did not acquire sufficient consent for the use of the data, or inadequately extended controls over disclosures to third parties. Furthermore, the type of app, in terms of the category of data collected, was not a useful predictor of its privacy. However, we found that apps that collected health-related data (eg, exercise and weight) performed worse for privacy than those designed for other types of self-tracking.ConclusionsOur study draws attention to the poor performance of current self-tracking technologies in terms of privacy, motivating the need for standards that can ensure that future self-tracking apps are stronger with respect to upholding users’ privacy. Our heuristic evaluation method supports the retrospective evaluation of privacy in self-tracking apps and can be used as a prescriptive framework to achieve privacy-by-design in future apps.

The encapsulated pathogenic yeast Cryptococcus neoformans is poorly recognized by phagocytic cells in the absence of opsonins. Macrophages will bind and internalize complement-or antibody-opsonized C. neoformans; however, less is known about the role of opsonins in dendritic cell (DC)-mediated recognition of the organism. Thus, we studied the opsonic requirements for binding to C. neoformans by cultured human monocyte-derived and murine bone marrow-derived DCs and whether binding leads to antifungal activity and cytokine release. Binding of unopsonized C. neoformans to human and murine DCs was negligible. Opsonization with pooled human serum (PHS) increased binding, while heat treatment of PHS virtually abolished this binding, thus suggesting a role for heat-labile complement components. PHS plus a monoclonal anticapsular antibody, 3C2, had an additive effect on binding for most cryptococcal strains. Human and murine DCs exhibited pronounced anticryptococcal activity in the presence of the antibody at early (2-h) and late (24-h) time points; however, PHS opsonization did not supplement this anticryptococcal activity. Antifungal activity against C. neoformans opsonized in PHS and/or antibody was partially reduced in the presence of inhibitors of the respiratory burst response. Human, but not murine, DCs released modest amounts of tumor necrosis factor alpha when stimulated with C. neoformans opsonized in PHS and/or antibody. However, opsonized C. neoformans failed to stimulate detectable release of interleukin 10 (IL-10) or IL-12p70 from either DC population. Thus, human and murine DCs show maximal binding to and antifungal activity against C. neoformans via a process highly dependent on opsonization.

A growing body of research is examining the way that virtual reality (VR) technology might enrich the lives of older adults. However, no studies have yet examined how this technology-combining head mounted displays, motion tracking, avatars, and virtual environments-might contribute to older adult wellbeing by facilitating greater social participation (social VR). To address this gap, we conducted three workshops in which 25 older adults aged 70 to 81 explored the utility of social VR as a medium for communicating with other older adults. Participants first created embodied avatars that were controlled through natural gestures, and subsequently used these avatars in two high-fidelity social VR prototypes. Findings from the workshops provide insight into older adults' design motivations when creating embodied avatars for social VR; their acceptance of social VR as a communication tool; and their views on how social VR might play a beneficial role in their lives. Outcomes from the workshops also illustrate the critical importance our participants placed on behavioural anthropomorphism-the embodied avatars' ability to speak, move, and act in a human-like manner-alongside translational factors, which encapsulate issues relating to the way physical movements are mapped to the embodied avatar and the way in which errors in these mappings may invoke ageing stereotypes. Findings demonstrate the critical role that these characteristics might play in the success of future social VR applications targeting older users. We translate our findings into a set of design considerations for developing social VR systems for older adults, and we reflect on how our participants' experiences can inform future research on social virtual reality. CCS Concepts: • Human-centered computing → Virtual reality; Collaborative and social computing; Empirical studies in collaborative and social computing.

Background Regular mindfulness practice has been demonstrated to be beneficial for mental health, but mindfulness can be challenging to adopt, with environmental and personal distractors often cited as challenges. Virtual reality (VR) may address these challenges by providing an immersive environment for practicing mindfulness and by supporting the user to orient attention to the present moment within a tailored virtual setting. However, there is currently a limited understanding of the ways in which VR can support or hinder mindfulness practice. Such an understanding is required to design effective VR apps while ensuring that VR-supported mindfulness is acceptable to end users. Objective This study aimed to explore how VR can support mindfulness practice and to understand user experience issues that may affect the acceptability and efficacy of VR mindfulness for users in the general population. Methods A sample of 37 participants from the general population trialed a VR mindfulness app in a controlled laboratory setting. The VR app presented users with an omnidirectional video of a peaceful forest environment with a guided mindfulness voiceover that was delivered by a male narrator. Scores on the State Mindfulness Scale, Simulator Sickness Questionnaire, and single-item measures of positive and negative emotion and arousal were measured pre- and post-VR for all participants. Qualitative feedback was collected through interviews with a subset of 19 participants. The interviews sought to understand the user experience of mindfulness practice in VR. Results State mindfulness (P<.001; Cohen d=1.80) and positive affect (P=.006; r=.45) significantly increased after using the VR mindfulness app. No notable changes in negative emotion, subjective arousal, or symptoms of simulator sickness were observed across the sample. Participants described the user experience as relaxing, calming, and peaceful. Participants suggested that the use of VR helped them to focus on the present moment by using visual and auditory elements of VR as attentional anchors. The sense of presence in the virtual environment (VE) was identified by participants as being helpful to practicing mindfulness. Interruptions to presence acted as distractors. Some uncomfortable experiences were discussed, primarily in relation to video fidelity and the weight of the VR headset, although these were infrequent and minor. Conclusions This study suggests that an appropriately designed VR app can support mindfulness practice by enhancing state mindfulness and inducing positive affect. VR may help address the challenges of practicing mindfulness by creating a sense of presence in a tailored VE; by allowing users to attend to visual and auditory anchors of their choice; and by reducing the scope of the content in users’ mind-wandering. VR has the unique capability to combine guided mindfulness practice with tailored VEs that lend themselves to support individuals to focus attention on the present moment.

Objective Deceased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large/mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, we examined the density and volume of dendritic spines in deep layer 3 auditory cortex of 20 schizophrenia and matched control subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss. Methods Primary auditory cortex deep layer 3 spine density and volume was assessed in 20 pairs of schizophrenia and matched comparison subjects in an initial and replication cohort (12 and 8 pairs) by immunohistochemistry-confocal microscopy. Targeted Mass Spectrometry was used to quantify postsynaptic density and voltage-gated calcium channel protein expression. The effect of increased voltage-gated calcium channel subunit protein expression on spine density and volume was assessed in primary rat neuronal culture. Findings Only the smallest spines are lost in deep layer 3 primary auditory cortex of schizophrenia, while larger spines are retained. Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects. Consistent with this observation, CACNB4 overexpression resulted in a lower density of smaller spines in primary neuronal cultures. Conclusion These findings require a rethinking of the over pruning hypothesis, demonstrate a link between small spine loss and a schizophrenia risk gene, and should spur more in-depth investigations of the mechanisms that govern new/small spine generation and stabilization under normal conditions as well as how this process is impaired in schizophrenia.

Cryptococcus neoformans is an encapsulated fungal pathogen with a predilection to infect persons with suppressed T-cell function. Cryptococcal mannoproteins (MP) are highly mannosylated antigens which elicit T-cell responses in infected mice and in convalescent patients. Key to the immunogenicity of MP is its capacity to bind to the conserved mannose receptor (MR), CD206, on dendritic cells (DCs). To test the role of the MR in the immune response to C. neoformans, wild-type and MR knockout (MR KO) mice were compared by using in vivo and ex vivo models of cryptococcosis. Following a pulmonary challenge with C. neoformans, MR KO mice died significantly faster than wild-type mice and had higher lung fungal burdens after 4 weeks of infection. Uptake of MP was similar when DCs obtained from wild-type and MR KO mice were compared. Additionally, MP did not upregulate the maturation markers major histocompatibility complex class II, CD86, and CD40 in either wild-type or MR KO DCs. However, MP stimulated lymphoproliferation in CD4 ؉ T cells obtained from the peripheral lymph nodes of infected wild-type but not MR KO mice. These studies demonstrate a nonredundant role for the MR in the development of CD4 ؉ T-cell responses to MP and protection from C. neoformans.Cryptococcus neoformans is an opportunistic fungal pathogen which preferentially afflicts immunocompromised persons, particularly those with AIDS or lymphoid malignancies and recipients of immunosuppressive treatments for solid organ transplants (2). The primary site of infection is generally the lungs. While exposure is thought to be common, most immunocompetent persons are able to contain the infection. However, in the absence of effective CD4 ϩ T-cell responses, the organism can disseminate and eventually cross the blood-brain barrier to produce cryptococcal meningitis (18).The inverse correlation between CD4 ϩ T-cell function and the propensity to develop cryptococcosis has prompted investigators to search for antigens which drive the cell-mediated immune response. In this regard, a family of heavily mannosylated proteins, termed mannoproteins (MP), has been identified as immunodominant antigens in mouse models of cryptococcosis and in patients who have recovered from infection (1,16,26). MP possess serine-and threonine-rich C-terminal regions which serve as sites for extensive O-linked mannosylation. Additional mannosylation may be provided via N linkages (17). These areas of O-linked and N-linked mannosylation promote the recognition of MP by host receptors for mannose, in particular, the mannose receptor (MR, CD206) and dendritic cell (DC)-specific intercellular adhesion molecule 3 grabbing nonintegrin (CD209) (17,21). DCs are the main antigenpresenting cells responsible for the uptake, processing, and presentation of MP to CD4 ϩ T cells (21, 22). Blocking receptors for mannose with mannan or deglycosylating MP results in strongly diminished T-cell responses (21,22,32).The MR is a C-type lectin receptor which recognizes terminally mannosylated molecules (24...

TCR specific activation is pivotal to dendritic epidermal T cell (DETC) function during cutaneous wound repair. However, DETC TCR ligands are uncharacterized and little is known about their expression patterns and kinetics. Using soluble DETC TCR tetramers, we demonstrate that DETC TCR ligands are not constitutively expressed in healthy tissue, but are rapidly upregulated following wounding on keratinocytes bordering wound edges. Ligand expression is tightly regulated with down-modulation following DETC activation. Early inhibition of TCR-ligand interactions using DETC TCR tetramers delays wound repair in vivo, highlighting DETC as rapid responders to injury. This first visualization of DETC TCR ligand expression provides novel information about how ligand expression impacts early stages of DETC activation and wound repair.

IntroductionThe wider application of bone marrow transplantation (BMT) has been limited, in part, by graft-versus-host disease (GVHD) complications. Human and mouse mesenchymal stem cells (MSCs) have been shown to suppress allogeneic-induced and nonspecific mitogen-induced T-cell proliferation in vitro (reviewed in detail 1,2 ). Implicated suppressive mechanisms have included interleukin (IL)-10, 3 transforming growth factor (TGF)-␤, hepatocyte growth factor, 4 indoleamine 2,3 dioxygenase (IDO), 5 nitric oxide, 6 prostaglandin (PG) E 2 , 7 increased T-regulatory cells (Tregs), 8 and activation of the PD-1-negative costimulatory pathway. 9 In vivo, there have been conflicting data regarding the potential of MSCs to suppress GVHD. [10][11][12] Multipotent adult progenitor cells (MAPCs) are nonhematopoietic stem cells that can be copurified with MSCs from BM cells. MAPCs express the pluripotent state-specific transcription factors Oct-3/4 and Rex-1, and can differentiate into cell types representative of all 3 germ layers 13,14 ; thus, MAPCs are generally believed to be a more primitive cell type than MSCs. MSCs kept for prolonged periods in culture tend to lose their differentiation capabilities and undergo senescence at approximately 20 to 40 population doublings. 15,16 In contrast to MSCs, MAPCs have an average telomere length that remained constant for up to 100 population doublings in vitro. 13 Based upon their differential potential and reduced senescence, MAPCs have been considered as a potentially desirable nonhematopoietic stem cell source for use in allogeneic BMT. In fact, a multicenter phase 1 open label clinical trial of MultiStem, based upon MAPC technology, was initiated in 2008.In this study, we sought to determine whether MAPCs might be useful for GVHD prevention. We demonstrate that murine MAPCs are potently immune suppressive in vitro and can reduce GVHD lethality in vivo when present in the spleen, a site of initial allopriming, early post-BMT. Furthermore, we identify the mechanism of action MAPCs use to elicit T-cell inhibition and reduce GVHD-induced tissue injury in vivo. Methods MiceBALB/c (H2 d ), C57BL/6 (H2 b ; termed B6), and B10.BR (H2 k ) mice were purchased from The Jackson Laboratory or the National Institutes of Health (NIH). All mice were housed in a specific pathogen-free facility in microisolator cages and used at 8 to 12 weeks of age in protocols approved by the Institutional Animal Care and Use Committee of the University of Minnesota. MAPC isolation and cultureMAPCs were isolated from B6 and BALB/c BM, as described. 13 Briefly, BM was plated in Dulbecco modified Eagle medium/MCDB containing 10 ng/mL epidermal growth factor (Sigma-Aldrich), platelet-derived growth factor-BB (R&D Systems), leukemia inhibitory factor (Chemicon International), 2% fetal calf serum (HyClone), 1ϫ selenium-insulin-transferrinethanolamine, 0.2 mg/mL linoleic acid-bovine serum albumin (BSA), 0.8 mg/mL BSA, 1ϫ chemically defined lipid concentrate, and 1ϫ ␣-mercaptoethanol (all from Sigma-Aldrich). Cells...