Visual Stability of Objects and Environments Viewed through Head-Mounted Displays

Virtual Environments (aka Virtual Reality) is again catching the public imagination and a number of startups (e.g. Oculus) and even not-so-startup companies (e.g. Microsoft) are trying to develop display systems to capitalize on this renewed interest. All acknowledge that this time they will get it right by providing the required dynamic fidelity, visual quality, and interesting content for the concept of VR to take off and change the world in ways it failed to do so in past incarnations. Some of the surprisingly long historical background of the technology that the form of direct simulation that underlies virtual environment and augmented reality displays will be briefly reviewed. An example of a mid 1990's augmented reality display system with good dynamic performance from our lab will be used to illustrate some of the underlying phenomena and technology concerning visual stability of virtual environments and objects during movement. In conclusion some idealized performance characteristics for a reference system will be proposed. Interestingly, many systems more or less on the market now may actually meet many of these proposed technical requirements. This observation leads to the conclusion that the current success of the IT firms trying to commercialize the technology will depend on the hidden costs of using the systems as well as the development of interesting and compelling content

Discontinuity Detection for Analysis of Telerobot Trajectories

To identify spatial and temporal discontinuities in telerobot movement in order to describe the shift in operators control and error correction strategies from continuous control to move-and-wait strategies. This shift was studied under conditions of simulated increasingly time-delayed teleoperation. The ultimate goal is to determine if the time delay associated with the shift is invariant with independently imposed control difficulty. We expect this shift to manifest itself as changes in the number of discontinuity of movement path. We proposed an approach to spatial and temporal discontinuity detection algorithm for analysis of teleoperated trajectory in three dimensional space. The algorithm provides a simple and potentially objective method for detecting the discontinuity during telerobot operation and evaluating the difficulty of rotational coordinate condition in teleoperation

Clearing the complexity: immune complexes and their treatment in lupus nephritis

Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control

Misalignment Effect Function Measurement for Oblique Rotation Axes: Counterintuitive Predictions and Theoretical Extensions

The Misalignment Effect Function (MEF) describes the decrement in manual performance associated with a rotation between operators' visual display frame of reference and that of their manual control. It now has been empirically determined for rotation axes oblique to canonical body axes and is compared with the MEF previously measured for rotations about canonical axes. A targeting rule, called the Secant Rule, based on these earlier measurements is derived from a hypothetical process and shown to describe some of the data from three previous experiments. It explains the motion trajectories determined for rotations less than 65deg in purely kinematic terms without the need to appeal to a mental rotation process. Further analysis of this rule in three dimensions applied to oblique rotation axes leads to a somewhat surprising expectation that the difficulty posed by rotational misalignment should get harder as the required movement is shorter. This prediction is confirmed. Geometry underlying this rule also suggests analytic extensions for predicting more generally the difficulty of making movements in arbitrary directions subject to arbitrary misalignments

A Flow Cytometric Assay to Detect Functional Ganglionic Acetylcholine Receptor Antibodies by Immunomodulation in Autoimmune Autonomic Ganglionopathy

Autoimmune Autonomic Ganglionopathy (AAG) is an uncommon immune-mediated neurological disease that results in failure of autonomic function and is associated with autoantibodies directed against the ganglionic acetylcholine receptor (gnACHR). The antibodies are routinely detected by immunoprecipitation assays, such as radioimmunoassays (RIA), although these assays do not detect all patients with AAG and may yield false positive results. Autoantibodies against the gnACHR exert pathology by receptor modulation. Flow cytometric analysis is able to determine if this has occurred, in contrast to the assays in current use that rely on immunoprecipitation. Here, we describe the first high-throughput, non-radioactive flow cytometric assay to determine autoantibody mediated gnACHR immunomodulation. Previously identified gnACHR antibody seronegative and seropositive sera samples (RIA confirmed) were blinded and obtained from the Oxford Neuroimmunology group along with samples collected locally from patients with or without AAG. All samples were assessed for the ability to cause gnACHR immunomodulation utilizing the prototypical gnACHR expressing cell line, IMR-32. Decision limits were calculated from healthy controls, and Receiver Operating Characteristic (ROC) curves were constructed after unblinding all samples. One hundred and ninety serum samples were analyzed; all 182 expected negative samples (from healthy controls, autonomic disorders not thought to be AAG, other neurological disorders without autonomic dysfunction and patients with Systemic Lupus Erythematosus) were negative for immunomodulation (<18%), as were the RIA negative AAG and unconfirmed AAG samples. All RIA positive samples displayed significant immunomodulation. There were no false positive or negative samples. There was perfect qualitative concordance as compared to RIA, with an Area Under ROC of 1. Detection of Immunomodulation by flow cytometry for the identification of gnACHR autoantibodies offers excellent concordance with the gnACHR antibody RIA, and overcomes many of the shortcomings of immunoprecipitation assays by directly measuring the pathological effects of these autoantibodies at the cellular level. Further work is needed to determine the correlation between the degree of immunomodulation and disease severity

Evaluation of Human and AutomationRobotics Integration Needs for Future Human Exploration Missions

NASA employs Design Reference Missions (DRMs) to define potential architectures for future human exploration missions to deep space, the Moon, and Mars. While DRMs to these destinations share some components, each mission has different needs. This paper focuses on the human and automation/robotic integration needs for these future missions, evaluating them with respect to NASA research gaps in the area of space human factors engineering. The outcomes of our assessment is a human and automation/robotic (HAR) task list for each of the four DRMs that we reviewed (i.e., Deep Space Sortie, Lunar Visit/Habitation, Deep Space Habitation, and Planetary), a list of common critical HAR factors that drive HAR design

Three Dimensional Tracking in Augmented Environments: User Performance Trade-Offs Between System Latency and Update Rate

Three-dimensional tracking performance was measured as a function of system latency (35-335 msec) and update rate (10-30 Hz). Twelve subjects used a custom, see-through head mounted stereo display to control the position of a virtual response cursor with hand and body movements. User performance trade-offs between latency and update rate were measured with objective and subjective measures and a possible performance model was evaluated. The results indicate that earlier findings suggesting that latency influenced tracking performance more than did update rate, could be due to previous studies having tested latency over a larger dynamic range. Iso-performance contours are used to compare objective performance with subjective perception and performance judgments

An Antibody-Based Leukocyte-Capture Microarray for the Diagnosis of Systemic Lupus Erythematosus

The diagnosis of Systemic Lupus Erythematosus (SLE) is challenging due to its heterogeneous clinical presentation and the lack of robust biomarkers to distinguish it from other autoimmune diseases. Further, currently used laboratory tests do not readily distinguish active and inactive disease. Several groups have attempted to apply emerging high throughput profiling technologies to diagnose and monitor SLE. Despite showing promise, many are expensive and technically challenging for routine clinical use. The goal of this work is to develop a better diagnostic and monitoring tool for SLE. We report a highly customisable antibody microarray that consists of a duplicate arrangement of 82 antibodies directed against surface antigens on peripheral blood mononuclear cells (PMBCs). This high-throughput array was used to profile SLE patients (n = 60) with varying disease activity, compared to healthy controls (n = 24), patients with rheumatoid arthritis (n = 25), and other autoimmune diseases (n = 28). We used a computational algorithm to calculate a score from the entire microarray profile and correlated it with SLE disease activity. Our results demonstrate that leukocyte-capture microarray profiles can readily distinguish active SLE patients from healthy controls (AUROC = 0.84). When combined with the standard laboratory tests (serum anti-dsDNA, complements C3 and C4), the microarrays provide significantly increased discrimination. The antibody microarrays can be enhanced by the addition of other markers for potential application to the diagnosis and stratification of SLE, paving the way for the customised and accurate diagnosis and monitoring of SLE

Future Exploration Missions' Tasks Associated with the Risk of Inadequate Design of Human and Automation/Robotic Integration

NASA's Human Research Program (HRP) funds research efforts aimed at mitigating various human health and performance risks, including the Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI). As such, within HRP, the Human Factors and Behavioral Performance (HFBP) Element tasked an evaluation of future HARI needs in order to scope and focus the HARI risk research plan. The objective was to provide a systematic understanding of the critical factors associated with effective HARI that will be necessary to achieve the future mission goals for near- and deep-space exploration. Future mission goals are specified by NASA Design Reference Missions (DRMs) that are pertinent to the HRP. The outcome of this evaluation is a set of NASA-relevant HARI tasks, factors, and interactions required for exploration-class missions

High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma

Aims: Mesothelin (MSLN) is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma, pancreatic and ovarian cancer. It is also a target for novel personalised therapies, including antibodies, antibody–drug conjugates and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would best respond to anti-mesothelin therapies and guide decisions in therapeutic strategy. This study aimed to assess the intensity and distribution of MSLN immunostaining in mesothelioma, and to determine the prognostic value of MSLN expression by histochemical-score (H-score). Methods and results: The MN1 anti-MSLN antibody was used to stain a formalin-fixed paraffin-embedded tissue microarray of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. MSLN positivity, the staining intensity, distribution of staining and H-score were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six per cent of epithelioid tumours were MSLN-positive (with expression in > 5% tumour cells). Of MSLN-expressing epithelioid tumours, 70.4% had moderate (2+) or strong (3+) intensity MSLN immunostaining, although only 37% of samples had staining in ≥ 50% of tumour cells. In multivariate analysis, MSLN H-score as a continuous variable and an H-score ≥ 33 were independent predictors of improved survival (P = 0.04 and P < 0.001, respectively). Conclusions: MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells