Performance Risks During Surface Extravehicular Activity and Potential Mitigation Using Multimodal Displays.

BACKGROUND: Surface extravehicular activity (sEVA) will be a critical component of future human missions to the Moon. sEVA presents novel risks to astronaut crews not associated with microgravity operations due to fundamental differences in task demands, physiology, environment, and operations of working on the lunar surface. Multimodal spacesuit informatics displays have been proposed as a method of mitigating sEVA risk by increasing operator autonomy.METHODS: A formalized literature review was conducted. In total, 95 journal articles, conference papers, and technical reports were included. Characteristics of U.S. spacesuits were reviewed, ranging from the Apollo A7L to the xEMU Z-2.5. Multimodal display applications were then reviewed and assessed for their potential in aiding sEVA operations.RESULTS: Through literature review 25 performance impairments were identified. Performance impairments caused by the spacesuit represented the greatest number of sEVA challenges. Multimodal displays were mapped to impairments and approximately 36% of performance impairments could be aided by using display interfaces.DISCUSSION: Multimodal displays may provide additional benefits for alleviating performance impairments during sEVA. Utility of multimodal displays may be greater in certain performance impairment domains, such as spacesuit-related impairments.Zhang JY, Anderson AP. Performance risks during surface extravehicular activity and potential mitigation using multimodal displays. Aerosp Med Hum Perform. 2023; 94(1):34-41.

Estimation of Subjectively Reported Trust, Mental Workload, and Situation Awareness Using Unobtrusive Measures.

OBJECTIVE: We use a set of unobtrusive measures to estimate subjectively reported trust, mental workload, and situation awareness (henceforth "TWSA"). BACKGROUND: Subjective questionnaires are commonly used to assess human cognitive states. However, they are obtrusive and usually impractical to administer during operations. Measures derived from actions operators take while working (which we call "embedded measures") have been proposed as an unobtrusive way to obtain TWSA estimates. Embedded measures have not been systematically investigated for each of TWSA, which prevents their operational utility. METHODS: Fifteen participants completed twelve trials of spaceflight-relevant tasks while using a simulated autonomous system. Embedded measures of TWSA were obtained during each trial and participants completed TWSA questionnaires after each trial. Statistical models incorporating our embedded measures were fit with various formulations, interaction effects, and levels of personalization to understand their benefits and improve model accuracy. RESULTS: The stepwise algorithm for building statistical models usually included embedded measures, which frequently corresponded to an intuitive increase or decrease in reported TWSA. Embedded measures alone could not accurately capture an operator's cognitive state, but combining the measures with readily observable task information or information about participants' backgrounds enabled the models to achieve good descriptive fit and accurate prediction of TWSA. CONCLUSION: Statistical models leveraging embedded measures of TWSA can be used to accurately estimate responses on subjective questionnaires that measure TWSA. APPLICATION: Our systematic approach to investigating embedded measures and fitting models allows for cognitive state estimation without disrupting tasks when administering questionnaires would be impractical.

NUAK1 promotes organ fibrosis via YAP and TGF-ß/SMAD signaling.

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor-ß (TGF-ß)-driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-ß-inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-ß induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-ß/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.

Myofibroblast YAP/TAZ activation is a key step in organ fibrogenesis.

Fibrotic diseases account for nearly half of all deaths in the developed world. Despite its importance, the pathogenesis of fibrosis remains poorly understood. Recently, the two mechanosensitive transcription cofactors YAP and TAZ have emerged as important profibrotic regulators in multiple murine tissues. Despite this growing recognition, a number of important questions remain unanswered, including which cell types require YAP/TAZ activation for fibrosis to occur and the time course of this activation. Here, we present a detailed analysis of the role that myofibroblast YAP and TAZ play in organ fibrosis and the kinetics of their activation. Using analyses of cells, as well as multiple murine and human tissues, we demonstrated that myofibroblast YAP and TAZ were activated early after organ injury and that this activation was sustained. We further demonstrated the critical importance of myofibroblast YAP/TAZ in driving progressive scarring in the kidney, lung, and liver, using multiple transgenic models in which YAP and TAZ were either deleted or hyperactivated. Taken together, these data establish the importance of early injury-induced myofibroblast YAP and TAZ activation as a key event driving fibrosis in multiple organs. This information should help guide the development of new antifibrotic YAP/TAZ inhibition strategies.

Patient-specific computational biomechanics of the brain without segmentation and meshing.

Motivated by patient-specific computational modelling in the context of image-guided brain surgery, we propose a new fuzzy mesh-free modelling framework. The method works directly on an unstructured cloud of points that do not form elements so that mesh generation is not required. Mechanical properties are assigned directly to each integration point based on fuzzy tissue classification membership functions without the need for image segmentation. Geometric integration is performed over an underlying uniform background grid. The verification example shows that, while requiring no hard segmentation and meshing, the proposed model gives, for all practical purposes, equivalent results to a finite element model.

High throughput paper spray mass spectrometry analysis.

BACKGROUND: Fast analysis of chemicals in samples of complex mixtures is important for many analytical applications including therapeutic drug monitoring and food safety screening. METHODS: Based on the paper spray technology developed recently, a high throughput device was developed in this work and used for evaluation of the fast quantitative analysis using paper spray mass spectrometry. RESULTS: The performance of the method was characterized with bovine blood samples spiked with sunitinib and nicotine. At optimized condition, relatively fast analysis speed of 7s/sample was achieved with relatively good LOQs (1 ng/ml) and quantitation. CONCLUSION: In an application of the method for food screening, LODs better than 1 ng/g were achieved for clenbuterol in beef.