Rapid Prototyping Assisted Design and Development of Inter-Vertebral Implants

This paper presents a case study of applying rapid prototyping in assisting in the design and development of inter-vertebral implants for spine fusions. The major process of design and implant development, its biological and mechanical requirements, the approach for developing a 3D reconstructive vertebral anatomy model, the inter-vertebral implant CAD model, and the integration with a finite element analysis for the implant's structural analysis are presented. The process of 3D Printing of the vertebral anatomy and the inter-vertebral implant is described. The application of the prototyping model in assisting in the inter-vertebral anatomic fitting, in guiding the implant's geometric design, in helping with the virtual surgical planning, and in understanding the implant's mechanical properties and structural stability are discussed.Mechanical Engineerin

Delineating the operational envelope of mobile and conventional EDA sensing on key body locations

Electrodermal activity (EDA) is an important affective indicator, measured conventionally on the fingers with desktop sensing instruments. Recently, a new generation of wearable, battery-powered EDA devices came into being, encouraging the migration of EDA sensing to other body locations. To investigate the implications of such sensor/location shifts in psychophysiological studies we performed a validation experiment. In this experiment we used startle stimuli to instantaneously arouse the sympathetic system of n = 23 subjects while sitting. Startle stimuli are standard but minimal stressors, and thus ideal for determining the sensor and location resolution limit. The experiment revealed that precise measurement of small EDA responses on the fingers and palm is feasible either with conventional or mobile EDA sensors. By contrast, precise measurement of small EDA responses on the sole is challenging, while on the wrist even detection of such responses is problematic for both EDA modalities. Given that affective wristbands have emerged as the dominant form of EDA sensing, researchers should beware of these limitations

Evaluating smartphone-based user interface designs for a 2D psychological questionnaire

This study explored various user interface designs to transition a two dimensional (2D) questionnaire from its paper-and-pencil testing format to the mobile platform. The current administration of the test limits its usage beyond the lab environment. Creating a mobile version would facilitate ubiquitous administration of the test. Yet, the mobile design must be at least as good as its paper-based counterpart in terms of input accuracy and user interaction efforts. We developed four user interface designs, each of which featured a specific interaction approach. These approaches included displaying the 2D space of the questionnaire in its original form (M1), inputting one variable at a time on the 2D space (M2), dissolving the 2D space into two one-dimensional ordinal scales (M3), and orienting the input selections to the diagonal axes (M4). The designs were tested by a total of 34 participants, aged 18 to 52 years. The study results find the first three interaction approaches (M1-M3) effective but the fourth approach inefficient. Furthermore, the results indicate that the two-tap designs (M2 and M3) are equally as good as the one-tap design (M1)

Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

ABSTRACT Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern

High-Titer Neutralizing Antibodies against the SARS-CoV-2 Delta Variant Induced by Alhydroxyquim-II-Adjuvanted Trimeric Spike Antigens

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained, and cross-variant SARS-CoV-2 neutralizing antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a Toll-Like Receptor (TLR) 7/8 small-molecule agonist chemisorbed on aluminum hydroxide (Alhydrogel). Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titer NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralizing against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titers against multiple SARS-CoV-2 variants; notably, high titers against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern. IMPORTANCE There is an urgent need for next-generation COVID-19 vaccines that are safe, demonstrate high protective efficacy against SARS-CoV-2 variants and can be manufactured at scale. We describe a vaccine candidate (CoVac-II) that is based on stabilized, trimeric spike antigen produced in an optimized, scalable and chemically defined production process. CoVac-II demonstrates strong and persistent immunity after vaccination of mice, and is highly immunogenic in multiple animal models, including rabbits and horses. We further show that prior immunity can be boosted using a recombinant spike antigen from the Beta variant; importantly, plasma from boosted mice effectively neutralize multiple SARS-CoV-2 variants in vitro, including Delta. The strong humoral and Th1-biased immunogenicity of CoVac-II is driven by use of Alhydroxiquim-II (AHQ-II), the first adjuvant in an authorized vaccine that acts through the dual Toll-like receptor (TLR)7 and TLR8 pathways, as part of the Covaxin vaccine. Our data suggest AHQ-II/spike protein combinations could constitute safe, affordable, and mass-manufacturable COVID-19 vaccines for global distribution