Time-resolved crystallography of boric acid binding to the active site serine of the ß-lactamase CTX-M-14 and subsequent 1,2-diol esterification.

The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of ß-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the ß-lactams. Effective ß-lactamase inhibitors and mechanistic insights into their action are central in overcoming this type of resistance, and in this context boronate-based ß-lactamase inhibitors were just recently approved to treat multidrug-resistant bacteria. Using boric acid as a simplified inhibitor model, time-resolved serial crystallography was employed to obtain mechanistic insights into binding to the active site serine of ß-lactamase CTX-M-14, identifying a reaction time frame of 80-100 ms. In a next step, the subsequent 1,2-diol boric ester formation with glycerol in the active site was monitored proceeding in a time frame of 100-150 ms. Furthermore, the displacement of the crucial anion in the active site of the ß-lactamase was verified as an essential part of the binding mechanism of substrates and inhibitors. In total, 22 datasets of ß-lactamase intermediate complexes with high spatial resolution of 1.40-2.04 Å and high temporal resolution range of 50-10,000 ms were obtained, allowing a detailed analysis of the studied processes. Mechanistic details captured here contribute to the understanding of molecular processes and their time frames in enzymatic reactions. Moreover, we could demonstrate that time-resolved crystallography can serve as an additional tool for identifying and investigating enzymatic reactions.

Requirements for the Acceptance of an App for Voice Therapy-A Usability Report Based on the "Oldenburger Logopädie App" (OLA).

OBJECTIVE: The prototype "Oldenburger Logopädie App" (OLA) was designed to support voice therapy for patients with recurrent paresis, such as to accompany homework or as a short-term substitute for regular therapy due to dropouts, such as during the COVID-19 pandemic. The treating speech and language pathologists (SLPs) unlocks videos individually applicable to the respective patients, in which the SLPs instruct the individual exercises. The app can be used without information technology knowledge or detailed instructions. MATERIALS AND METHODS: The prototype's usability was evaluated through a usability test battery (AttrakDiff questionnaire, System Usability Scale, Visual Aesthetics of Websites Inventory questionnaire) and informal interviews from the perspective of patients and SLPs. RESULTS: The acceptance, usability, user experience, self-descriptiveness, and user behavior of OLA were consistently given and mostly rated as positive. Both user groups rated OLA as practical and easy to use (eg, System Usability Scale: "practical" (agree: ∅ 49.5%), "cumbersome to use" (total: strongly disagree: ∅ 60.0%). However, the monotonous layout of the app and the instructional and exercise videos should be modified in the next editing step. An overview of relevant criteria for a voice therapy app, regarding design and functions, was derived from the results. CONCLUSION: This user-oriented feedback on the usability of the voice app provides the proof of concept and the basis for the further development of the Artificial intelligence-based innovative follow-up app LAOLA. In the future, it should be possible to support the treatment of all voice disorders with such an app. For the further development of the voice app, the therapeutic content and the effectiveness of the training should also be investigated.

Towards a validated glossary of usability attributes for the evaluation of wearable robotic devices.

BACKGROUND: Despite technical advances in the field of wearable robotic devices (WRD), there is still limited user acceptance of these technologies. While usability often comes as a key factor influencing acceptance, there is a scattered landscape of definitions and scopes for the term. To advance usability evaluation, and to integrate usability features as design requirements during technology development, there is a need for benchmarks and shared terminology. These should be easily accessible and implementable by developers. METHODS: An initial set of usability attributes (UA) was extracted from a literature survey on usability evaluation in WRD. The initial set of attributes was enriched and locally validated with seven developers of WRD through an online survey and a focus group. The locally validated glossary was then externally validated through a globally distributed online survey. RESULTS: The result is the Robotics Usability Glossary (RUG), a comprehensive glossary of 41 UA validated by 70 WRD developers from 17 countries, ensuring its generalizability. 31 of the UA had high agreement scores among respondents and 27 were considered highly relevant in the field, but only 11 of them had been included as design criteria by the respondents. CONCLUSIONS: Multiple UA ought to be considered for a comprehensive usability assessment. Usability remains inadequately incorporated into device development, indicating a need for increased awareness and end-user perspective. The RUG can be readily accessed through an online platform, the Interactive Usability Toolbox (IUT), developed to provide context-specific outcome measures and usability evaluation methods. Overall, this effort is an important step towards improving and promoting usability evaluation practices within WRD. It has the potential to pave the way for establishing usability evaluation benchmarks that further endorse the acceptance of WRD.

Direct Band Gap Semiconductors with Two- and Three-Dimensional Triel-Phosphide Frameworks (Triel=Al, Ga, In).

Recently, several ternary phosphidotrielates and -tetrelates have been investigated with respect to their very good ionic conductivity, while less focus was pointed towards their electronic structures. Here, we report on a novel series of compounds, in which several members possess direct band gaps. We investigated the known compounds Li3AlP2, Li3GaP2, Li3InP2, and Na3InP2 and describe the synthesis and the crystal structure of novel Na3In2P3. For all mentioned phosphidotrielates reflectance UV-Vis measurements reveal direct band gaps in the visible light region with decreasing band gaps in the series: Li3AlP2 (2.45 eV), Li3GaP2 (2.18 eV), Li3InP2 (1.99 eV), Na3InP2 (1.37 eV), and Na3In2P3 (1.27 eV). All direct band gaps are confirmed by quantum chemical calculations. The unexpected property occurs despite different structure types. As a common feature all compounds contain EP4 tetrahedra, which share exclusively vertices for E=In and vertices as well as edges for E=Al and Ga. The structure of the novel Na3In2P3 is built up by a polyanionic framework of six-membered rings of corner-sharing InP4 tetrahedra. As a result, the newly designed semiconductors with direct band gaps are suitable for optoelectronic applications, and they can provide significant guidance for the design of new functional semiconductors.

Mixed methods usability evaluation of an assistive wearable robotic hand orthosis for people with spinal cord injury.

BACKGROUND: Robotic hand orthoses (RHO) aim to provide grasp assistance for people with sensorimotor hand impairment during daily tasks. Many of such devices have been shown to bring a functional benefit to the user. However, assessing functional benefit is not sufficient to evaluate the usability of such technologies for daily life application. A comprehensive and structured evaluation of device usability not only focusing on effectiveness but also efficiency and satisfaction is required, yet often falls short in existing literature. Mixed methods evaluations, i.e., assessing a combination of quantitative and qualitative measures, allow to obtain a more holistic picture of all relevant aspects of device usability. Considering these aspects already in early development stages allows to identify design issues and generate generalizable benchmarks for future developments. METHODS: We evaluated the short-term usability of the RELab tenoexo, a RHO for hand function assistance, in 15 users with tetraplegia after a spinal cord injury through a comprehensive mixed methods approach. We collected quantitative data using the Action Research Arm Test (ARAT), the System Usability Scale (SUS), and timed tasks such as the donning process. In addition, qualitative data were collected through semi-structured interviews and user observations, and analyzed with a thematic analysis to enhance the usability evaluation. All insights were attributed and discussed in relation to specifically defined usability attributes such as comfort, ease of use, functional benefit, and safety. RESULTS: The RELab tenoexo provided an immediate functional benefit to the users, resulting in a mean improvement of the ARAT score by 5.8 points and peaking at 15 points improvement for one user (clinically important difference: 5.7 points). The mean SUS rating of 60.6 represents an adequate usability, however, indicating that especially the RHO donning (average task time = 295 s) was perceived as too long and cumbersome. The participants were generally very satisfied with the ergonomics (size, dimensions, fit) of the RHO. Enhancing the ease of use, specifically in donning, increasing the provided grasping force, as well as the availability of tailoring options and customization were identified as main improvement areas to promote RHO usability. CONCLUSION: The short-term usability of the RELab tenoexo was thoroughly evaluated with a mixed methods approach, which generated valuable data to improve the RHO in future iterations. In addition, learnings that might be transferable to the evaluation and design of other RHO were generated, which have the potential to increase the daily life applicability and acceptance of similar technologies.

Temperature-dependent photo-elastic coefficient of silicon at 1550 nm.

This paper presents a study on the temperature dependent photo-elastic coefficient in single-crystal silicon with (100) and (110) orientations at a wavelength of 1550 nm. The measurement of the photo-elastic coefficient was performed using a polarimetric scheme across a wide temperature range from 5 to 300 K. The experimental setup employed high-sensitivity techniques and incorporated automatic beam path correction, ensuring precise and accurate determination of the coefficient's values. The results show excellent agreement with previous measurements at room temperature, specifically yielding a value of [Formula: see text] 1/Pa for the (100) orientation. Interestingly, there is a significant difference in photo-elasticity between the different crystal orientations of approximately [Formula: see text]. The photo-elastic coefficient's absolute value increases by approximately 40% with decreasing temperature down to 5 K. These findings provide valuable insights into the photo-elastic properties of silicon and its behavior under varying mechanical stress, particularly relevant for optomechanical precision experiments like cryogenic gravitational wave detectors and microscale optomechanical quantum sensors.

Unraveling Sodium-Ion Dynamics in Honeycomb-Layered Na2MgxZn2-xTeO6 Solid Electrolytes with Solid-State NMR.

All-solid-state sodium-ion batteries (SIBs) have the potential to offer large-scale, safe, cost-effective, and sustainable energy storage solutions by supplementing the industry-leading lithium-ion batteries. However, for the enhanced bulk properties of SIB components (e.g., solid electrolytes), a comprehensive understanding of their atomic-scale structure and the dynamic behavior of sodium (Na) ions is essential. Here, we utilize a robust multinuclear (23Na, 125Te, 25Mg, and 67Zn) magnetic resonance approach to explore a novel Mg/Zn homogeneously mixed-cation honeycomb-layered oxide Na2MgxZn2-xTeO6 solid solution series. These new intermediate compounds exhibit tailorable bulk Na-ion conductivity (σ) with the highest σ = 0.14 × 10-4 S cm-1 for Na2MgZnTeO6 at room temperature suitable for SIB solid electrolyte applications as observed by powder electrochemical impedance spectroscopy (EIS). A combination of powder X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and field emission scanning electron microscopy (FESEM) reveals highly crystalline phase-pure compounds in the P6322 space group. We show that the Mg/Zn disorder is random within the honeycomb layers using 125Te nuclear magnetic resonance (NMR) and resolve multiple Na sites using two-dimensional (triple-quantum magic-angle spinning (3QMAS)) 23Na NMR. The medium-range disorder in the honeycomb layer is revealed through the combination of 25Mg and 67Zn NMR, complemented by electronic structure calculations using density functional theory (DFT). Furthermore, we expose very fast local Na-ion hopping processes (hopping rate, 1/τNMR = 0.83 × 109 Hz) by using a laser to achieve variable high-temperature (∼860 K) 23Na NMR, which are sensitive to different Mg/Zn ratios. The Na2MgZnTeO6 with maximum Mg/Zn disorder displays the highest short-range Na-ion dynamics among all of the solid solution members.

Design and validation of a novel online platform to support the usability evaluation of wearable robotic devices.

Wearable robotic devices (WRD) are still struggling to fulfill their vast potential. Inadequate daily life usability is one of the main hindrances to increased technology acceptance. Improving usability evaluation practices during the development of WRD could help address these limitations. In this work, we present the design and validation of a novel online platform aiming to fill this gap, the Interactive Usability Toolbox (IUT). This platform consists of a public website that offers an interactive, context-specific search within a database of 154 user research methods and educational information about usability. In a dedicated study, the effect of this platform to support usability evaluation was investigated. Twelve WRD experts were asked to complete the task of defining usability evaluation protocols for two specific use cases. The platform was provided to support one of the use cases. The quality and composition of the proposed protocols were assessed by (i) two blinded reviewers, (ii) the participants themselves, and (iii) the study coordinators. We showed that using the IUT significantly affected the proposed evaluation focus, shifting protocols from mainly effectiveness-oriented to more user-focused studies. The protocol quality, as rated by the external reviewers, remained equivalent to those designed with conventional strategies. A mixed-method usability evaluation of the platform yielded an overall positive image, with detailed suggestions for further improvements. The IUT is expected to positively affect the evaluation and development of WRD through its educational value, the context-specific recommendations supporting ongoing benchmarking endeavors, and highlighting the value of qualitative user research.

Usability of an exosuit in domestic and community environments.

BACKGROUND: Exosuits have been shown to reduce metabolic cost of walking and to increase gait performance when used in clinical environment. Currently, these devices are transitioning to private use to facilitate independent training at home and in the community. However, their acceptance in unsupervised settings remains unclear. Therefore, the aim of this study was to investigate end-user perspectives and the adoption of an exosuit in domestic and community settings. METHODS: We conducted a mixed-method study to investigate the usability and user experience of an exosuit, the Myosuit. We leveraged on a cohort of seven expert users, who had the device available at home for at least 28 days. Each participant completed two standardized questionnaires (SUS and QUEST) and one personalized, custom questionnaire. Furthermore, a semi-structured interview with each participant was recorded, verbatim transcribed and analyzed using descriptive thematic analysis. Data collected from device sensors quantified the frequency of use. RESULTS: A mean SUS score of 75.4 out of 100 was reported. Five participants scored above the threshold for above-average usability. Participants also expressed high satisfaction with most of the technical features in the QUEST with an average score of 4.1 (3.86-4.71) out of 5. Participants used the Myosuit mainly for walking outside and exercising at home. However, the frequency of use did not meet the recommendations for physical activity established by the World Health Organization. Five participants used the Myosuit approximately once per week. The two other participants integrated the device in their daily life and used the Myosuit to a greater extent (approx. five times per week). Major factors that prevented an extensive use of the technology were: (i) difficulties in donning that led to (ii) lack of independence and (iii) lack of motivation in exercising. CONCLUSIONS: Although usable for various activities and well perceived, the adoption of the exosuit in domestic and community settings is yet limited. Use outside the clinic poses further challenges that should be considered when developing new wearable robots. Primarily, design should meet the users' claim for independence and increased adjustability of the device.

Rapid and efficient room-temperature serial synchrotron crystallography using the CFEL TapeDrive.

Serial crystallography at conventional synchrotron light sources (SSX) offers the possibility to routinely collect data at room temperature using micrometre-sized crystals of biological macromolecules. However, SSX data collection is not yet as routine and currently takes significantly longer than the standard rotation series cryo-crystallography. Thus, its use for high-throughput approaches, such as fragment-based drug screening, where the possibility to measure at physio-logical temperatures would be a great benefit, is impaired. On the way to high-throughput SSX using a conveyor belt based sample delivery system - the CFEL TapeDrive - with three different proteins of biological relevance (Klebsiella pneumoniae CTX-M-14 ß-lactamase, Nectria haematococca xylanase GH11 and Aspergillus flavus urate oxidase), it is shown here that complete datasets can be collected in less than a minute and only minimal amounts of sample are required.

A Novel Mixed-Method Approach to Identify Needs and Requirements for Upper Limb Assistive Technology for Persons after Stroke.

Following stroke, a significant portion of individuals suffer from upper limb impairments and struggle with activities of daily living. Dedicated assistive technology (AT), such as robotic hand orthoses (RHO), can help facilitate upper limb usage and allow users to regain independence in their daily lives. Often, users' needs and requirements are neglected in AT design, thereby contributing to poor technology acceptance. In this work, we propose and apply a mixed-method focus group combining qualitative and quantitative components to gather user expectations in view of a user-centred redesign of a RHO. Three main themes emerged from a thematic analysis of two focus groups (n=5): Experience after stroke, desired design features, and reflections and realisations. Participants listed device features they would look for in AT and ranked them relative to what they deem important and necessary for a satisfactory device. Participants primarily looked for AT that is effective, intuitive and easy to use. These insights complement traditional technical design requirements for RHO by considering user desires, aspects unfortunately often neglected in the early design process. This work provides guidelines allowing for the optimization of AT design to better match the needs of persons after stroke and improve technology acceptance.

An Analysis of Intention Detection Strategies to Control Advanced Assistive Technologies at the CYBATHLON.

With the increasing range of functionalities of advanced assistive technologies (AAT), reliable control and initiation of the desired actions become increasingly challenging for users. In this work, we present an analysis of current practices, user preferences, and usability of AAT intention detection strategies based on a survey among participants with disabilities at the CYBATHLON 2020 Global Edition. We collected data from 35 respondents, using devices in various disciplines and levels of technology maturity. We found that conventional, direct inputs such as buttons and joysticks are used by the majority of AAT (71.4%) due to their simplicity and learnability. However, 22 respondents (62.8%) reported a desire for more natural control using muscle or non-invasive brain signals, and 37.1% even reported an openness to invasive strategies for potentially improved control. The usability of the used strategies in terms of the explored attributes (reliability, mental effort, required learning) was mainly perceived positively, whereas no significant difference was observed across intention detection strategies and device types. It can be assumed that the strategies used during the CYBATHLON realistically represent options to control an AAT in a dynamic, physically and mentally demanding environment. Thus, this work underlines the need for carefully considering user needs and preferences for the selection of intention detection strategies in a context of use outside the laboratory.

Refined Chelator Spacer Moieties Ameliorate the Pharmacokinetics of PSMA-617.

Prostate-specific membrane antigen (PSMA) binding tracers are promising agents for the targeting of prostate tumors. To further optimize the clinically established radiopharmaceutical PSMA-617, novel PSMA ligands for prostate cancer endoradiotherapy were developed. A series of PSMA binding tracers that comprise a benzyl group at the chelator moiety were obtained by solid-phase synthesis. The compounds were labeled with 68Ga or 177Lu. Competitive cell-binding assays and internalization assays were performed using the cell line C4-2, a subline of the PSMA positive cell line LNCaP (human lymph node carcinoma of the prostate). Positron emission tomography (PET) imaging and biodistribution studies were conducted in a C4-2 tumor bearing BALB/c nu/nu mouse model. All 68Ga-labeled ligands were stable in human serum over 2 h; 177Lu-CA030 was stable over 72 h. The PSMA ligands revealed inhibition potencies [Ki] (equilibrium inhibition constants) between 4.8 and 33.8 nM. The percentage of internalization of the injected activity/106 cells of 68Ga-CA028, 68Ga-CA029, and 68Ga-CA030 was 41.2 ± 2.7, 44.3 ± 3.9, and 53.8 ± 5.4, respectively; for the comparator 68Ga-PSMA-617, 15.5 ± 3.1 was determined. Small animal PET imaging of the compounds showed a high tumor-to-background contrast. Organ distribution studies revealed high specific uptake in the tumor, that is, approximately 34.4 ± 9.8% of injected dose per gram (%ID/g) at 1 h post injection for 68Ga-CA028. At 1 h p.i., 68Ga-CA028 and 68Ga-CA030 demonstrated lower kidney uptake than 68Ga-PSMA-617, but at later time points, kidney time-activity curves converge. In line with the preclinical data, first diagnostic PET imaging using 68Ga-CA028 and 68Ga-CA030 revealed high-contrast detection of bone and lymph node lesions in patients with metastatic prostate cancer. The novel PSMA ligands, in particular CA028 and CA030, are promising agents for targeting PSMA-positive tumor lesions as shown in the preclinical evaluation and in a first patient, respectively. Thus, clinical translation of 68Ga-CA028 and 68Ga/177Lu-CA030 for diagnostics and endoradiotherapy of prostate cancer in larger cohorts of patients is warranted.

Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor.

Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.

A survey on the influence of CYBATHLON on the development and acceptance of advanced assistive technologies.

BACKGROUND: Advanced assistive technologies (AAT) aim to exploit the vast potential of technological developments made in the past decades to improve the quality of life of people with disabilities. Combining complex robotic technologies with the unique needs of people with disabilities requires a strong focus on user-centered design to ensure that the AAT appropriately addresses the daily life struggles of target users. The CYBATHLON aims to promote this mindset by empowering the AAT target users ("pilots") to compete on race tracks that represent approximations of daily life obstacles. The objective of this work was to investigate the AAT technology development, usability, and user involvement (i.e., application of user-centered design) in the context of the CYBATHLON. METHODS: With an online survey targeting the pilots and technical leads of teams preparing for the CYBATHLON 2020 Global Edition, we investigated to what extent the pilots were involved in device development and how this influences the perceived usability of the showcased AAT. Furthermore, the effects of user-centered design variables on the individual race performances were analyzed. RESULTS: A total of 81 responses from 35 pilots and 46 technical leads were collected in the two weeks prior to the event. Of all teams partaking in the included disciplines of the CYBATHLON 2020 Global Edition, 81.8% (36 of 44) were included in the study. User-centered design appeared to be a prevalent practice among the teams, as 85.7% of all pilots reported a certain level of involvement. However, only 25.5% of the pilots reported daily life usage, despite QUEST usability scores of both respondent groups showing moderate to high satisfaction with the respected AAT across all investigated disciplines. An explorative linear mixed model indicated that daily life usage (p < 0.05) and prolonged user involvement (e.g., more than 2 years, p < 0.001) have a significant positive effect on the race performance at the competition. CONCLUSIONS: We conclude that the CYBATHLON positively fulfills its conceptual goals of promoting active participation and inclusion of people with disabilities in the design and evaluation of AAT, thereby stimulating the development of promising novel technological solutions. Also, our data could underline the value of the competition as a benchmark, highlighting remaining usability limitations or technology adoption hurdles.

Intention Detection Strategies for Robotic Upper-Limb Orthoses: A Scoping Review Considering Usability, Daily Life Application, and User Evaluation.

Wearable robotic upper limb orthoses (ULO) are promising tools to assist or enhance the upper-limb function of their users. While the functionality of these devices has continuously increased, the robust and reliable detection of the user's intention to control the available degrees of freedom remains a major challenge and a barrier for acceptance. As the information interface between device and user, the intention detection strategy (IDS) has a crucial impact on the usability of the overall device. Yet, this aspect and the impact it has on the device usability is only rarely evaluated with respect to the context of use of ULO. A scoping literature review was conducted to identify non-invasive IDS applied to ULO that have been evaluated with human participants, with a specific focus on evaluation methods and findings related to functionality and usability and their appropriateness for specific contexts of use in daily life. A total of 93 studies were identified, describing 29 different IDS that are summarized and classified according to a four-level classification scheme. The predominant user input signal associated with the described IDS was electromyography (35.6%), followed by manual triggers such as buttons, touchscreens or joysticks (16.7%), as well as isometric force generated by residual movement in upper-limb segments (15.1%). We identify and discuss the strengths and weaknesses of IDS with respect to specific contexts of use and highlight a trade-off between performance and complexity in selecting an optimal IDS. Investigating evaluation practices to study the usability of IDS, the included studies revealed that, primarily, objective and quantitative usability attributes related to effectiveness or efficiency were assessed. Further, it underlined the lack of a systematic way to determine whether the usability of an IDS is sufficiently high to be appropriate for use in daily life applications. This work highlights the importance of a user- and application-specific selection and evaluation of non-invasive IDS for ULO. For technology developers in the field, it further provides recommendations on the selection process of IDS as well as to the design of corresponding evaluation protocols.

Implementing an interprofessional user-centered design approach to develop a bedside leg exercise device.

BACKGROUND: Early mobilization is important to improve critically ill patients' outcomes, but barriers to its implementation are common. A suitable in-bed device to exercise patients' legs might facilitate early mobilization. OBJECTIVE: The aim of this study was to develop an in-bed leg press that would facilitate early mobilization and enhance strength training of patients in acute care settings. METHODS: A user-centered design approach was applied to develop the device. The process was assessed by different instruments: the system usability scale (SUS) questionnaire, the Kano model questionnaire and interviews with end-users. RESULTS: Through several iterations of a user-centered design process, the prototype of an in-bed leg press was developed and tested. The assessment, based on SUS, Kano and interviews, indicates high usability and demonstrates the advantages of a user-centered design process. CONCLUSIONS: An interprofessional user-centered design approach was successfully implemented to develop a medical device. The early involvement of end-users resulted in a design that already shows a high degree of production readiness. The resulting device fulfilled all core requirements from a therapeutic point of view and included key features related to its practical use.

Rapid Fluorescence Lifetime Imaging Reveals That TRPV4 Channels Promote Dysregulation of Neuronal Na+ in Ischemia.

Fluorescence imaging is an indispensable method for analysis of diverse cellular and molecular processes, enabling, for example, detection of ions, second messengers, or metabolites. Intensity-based approaches, however, are prone to artifacts introduced by changes in fluorophore concentrations. This drawback can be overcome by fluorescence lifetime imaging (FLIM) based on time-correlated single-photon counting. FLIM often necessitates long photon collection times, resulting in strong temporal binning of dynamic processes. Recently, rapidFLIM was introduced, exploiting ultra-low dead-time photodetectors together with rapid electronics. Here, we demonstrate the applicability of rapidFLIM, combined with new and improved correction schemes, for spatiotemporal fluorescence lifetime imaging of low-emission fluorophores in a biological system. Using tissue slices of hippocampi of mice of either sex, loaded with the Na+ indicator ING2, we show that improved rapidFLIM enables quantitative, dynamic imaging of neuronal Na+ signals at a full-frame temporal resolution of 0.5 Hz. Induction of transient chemical ischemia resulted in unexpectedly large Na+ influx, accompanied by considerable cell swelling. Both Na+ loading and cell swelling were dampened on inhibition of TRPV4 channels. Together, rapidFLIM enabled the spatiotemporal visualization and quantification of neuronal Na+ transients at unprecedented speed and independent from changes in cell volume. Moreover, our experiments identified TRPV4 channels as hitherto unappreciated contributors to neuronal Na+ loading on metabolic failure, suggesting this pathway as a possible target to ameliorate excitotoxic damage. Finally, rapidFLIM will allow faster and more sensitive detection of a wide range of dynamic signals with other FLIM probes, most notably those with intrinsic low-photon emission.SIGNIFICANCE STATEMENT FLIM is an indispensable method for analysis of cellular processes. FLIM often necessitates long photon collection periods, requiring the sacrifice of temporal resolution at the expense of spatial information. Here, we demonstrate the applicability of the recently introduced rapidFLIM for quantitative, dynamic imaging with low-emission fluorophores in brain slices. RapidFLIM, combined with improved correction schemes, enabled intensity-independent recording of neuronal Na+ transients at unprecedented full-frame rates of 0.5 Hz. It also allowed quantitative imaging independent from changes in cell volume, revealing a surprisingly strong and hitherto uncovered contribution of TRPV4 channels to Na+ loading on energy failure. Collectively, our study thus provides a novel, unexpected insight into the mechanisms that are responsible for Na+ changes on energy depletion.

An analysis of usability evaluation practices and contexts of use in wearable robotics.

BACKGROUND: User-centered design approaches have gained attention over the past decade, aiming to tackle the technology acceptance issues of wearable robotic devices to assist, support or augment human capabilities. While there is a consensus that usability is key to user-centered design, dedicated usability evaluation studies are scarce and clear evaluation guidelines are missing. However, the careful consideration and integration of user needs appears to be essential to successfully develop an effective, efficient, and satisfactory human-robot interaction. It is primarily the responsibility of the developer, to ensure that this users involvement takes place throughout the design process. METHODS: Through an online survey for developers of wearable robotics, we wanted to understand how the design and evaluation in actual daily practice compares to what is reported in literature. With a total of 31 questions, we analyzed the most common wearable robotic device applications and their technology maturity, and how these influence usability evaluation practices. RESULTS: A total of 158 responses from a heterogeneous population were collected and analyzed. The dataset representing contexts of use for augmentation (16.5%), assistance (38.0%), therapy (39.8%), as well as few other specific applications (5.7%), allowed for an insightful analysis of the influence of technology maturity on user involvement and usability evaluation. We identified functionality, ease of use, and performance as the most evaluated usability attributes and could specify which measures are used to assess them. Also, we could underline the frequent use of qualitative measures alongside the expected high prevalence of performance-metrics. In conclusion of the analysis, we derived evaluation recommendations to foster user-centered design and usability evaluation. CONCLUSION: This analysis might serve as state-of-the-art comparison and recommendation for usability studies in wearable robotics. We believe that by motivating for more balanced, comparable and user-oriented evaluation practices, we may support the wearable robotics field in tackling the technology acceptance limitations.

Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.

Chimeric antigen receptor T cells (CAR-T) targeting CD19 have achieved significant success in patients with B cell malignancies. To date, implementation of CAR-T in other indications remains challenging due to the lack of truly tumor-specific antigens as well as control of CAR-T activity in patients. CD123 is highly expressed in acute myeloid leukemia (AML) blasts including leukemia-initiating cells making it an attractive immunotherapeutic target. However, CD123 expression in normal hematopoietic progenitor cells and endothelia bears the risk of severe toxicities and may limit CAR-T applications lacking fine-tuned control mechanisms. Therefore, we recently developed a rapidly switchable universal CAR-T platform (UniCAR), in which CAR-T activity depends on the presence of a soluble adapter called targeting module (TM), and confirmed clinical proof-of-concept for targeting CD123 in AML with improved safety. As costimulation via 4-1BB ligand (4-1BBL) can enhance CAR-T expansion, persistence, and effector functions, a novel CD123-specific TM variant (TM123-4-1BBL) comprising trimeric single-chain 4-1BBL was developed for transient costimulation of UniCAR-T cells (UniCAR-T) at the leukemic site in trans. TM123-4-1BBL-directed UniCAR-T efficiently eradicated CD123-positive AML cells in vitro and in a CDX in vivo model. Moreover, additional costimulation via TM123-4-1BBL enabled enhanced expansion and persistence with a modulated UniCAR-T phenotype. In addition, the increased hydrodynamic volume of TM123-4-1BBL prolonged terminal plasma half-life and ensured a high total drug exposure in vivo. In conclusion, expanding the soluble adapter optionality for CD123-directed UniCAR-T maintains the platforms high anti-leukemic efficacy and immediate control mechanism for a flexible, safe, and individualized CAR-T therapy of AML patients.