Quantifying SARS-CoV-2 Infection Risk Within the Google/Apple Exposure Notification Framework to Inform Quarantine Recommendations.

Most early Bluetooth-based exposure notification apps use three binary classifications to recommend quarantine following SARS-CoV-2 exposure: a window of infectiousness in the transmitter, ≥15 minutes duration, and Bluetooth attenuation below a threshold. However, Bluetooth attenuation is not a reliable measure of distance, and infection risk is not a binary function of distance, nor duration, nor timing. We model uncertainty in the shape and orientation of an exhaled virus-containing plume and in inhalation parameters, and measure uncertainty in distance as a function of Bluetooth attenuation. We calculate expected dose by combining this with estimated infectiousness based on timing relative to symptom onset. We calibrate an exponential dose-response curve based on infection probabilities of household contacts. The probability of current or future infectiousness, conditioned on how long postexposure an exposed individual has been symptom-free, decreases during quarantine, with shape determined by incubation periods, proportion of asymptomatic cases, and asymptomatic shedding durations. It can be adjusted for negative test results using Bayes' theorem. We capture a 10-fold range of risk using six infectiousness values, 11-fold range using three Bluetooth attenuation bins, ∼sixfold range from exposure duration given the 30 minute duration cap imposed by the Google/Apple v1.1, and ∼11-fold between the beginning and end of 14 day quarantine. Public health authorities can either set a threshold on initial infection risk to determine 14-day quarantine onset, or on the conditional probability of current and future infectiousness conditions to determine both quarantine and duration.

Stomata-Inspired Photomechanical Ion Nanochannels Modified by Azobenzene Composites.

A low-powered and highly selective photomechanical sensor system mimicking stomata in the epidermis of leaves harvested from nature is demonstrated. This device uses a light-responsive composite consisting of 4-amino-1,1'-azobenzene-3,4'-disulfonic acid monosodium salt (AZO) and poly(diallyldimethylammonium chloride) (PDDA) coated on a membrane with tens of nanometer-size pores. The ionic current change through the pore channels as a function of pore size variation is then measured. The tran-cis isomerism of AZO-PDDA during light irradiation and the operation mechanism of photomechanical ion channel sensor are discussed and analyzed using UV-vis spectroscopy and atomic force microscopy analysis. It presents the discriminative current levels to the different light wavelengths. The response time of the photoreceptor is about 0.2 s and it consumes very low operating power (≈15 nW) at 0.1 V bias. In addition, it is found that the change of the pore diameter during the light irradiation is due to the photomechanical effect, which is capable of distinguishing light intensity and wavelength.

Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

Effects of recirculation and air change per hour on COVID-19 transmission in indoor settings: A CFD study with varying HVAC parameters.

COVID-19 has already claimed over 7 million lives and has infected over 775 million people globally [1]. SARS-CoV-2, the virus that causes Covid-19, spreads primarily through droplets from infected people's airways, rendering Heating, Ventilation, and Air Conditioning (HVAC) systems critical in controlling infection risk levels in the indoor environment. To understand the dynamics of exhaled droplets and aerosols and the percentage of particles that are inhaled, escaped, recirculated, or trapped on different surfaces for a variety of environmental settings, we have presented our findings from the Computational Fluid Dynamics (CFD) modeling to investigate the impact of changing HVAC parameters in this paper. When combined with the spatial and temporal distribution of droplets, this method can be used to assess the potential risk and strengthen resilience. This finding demonstrates the viability and usefulness of CFD for modeling the distribution and dynamics of droplets and aerosols in confined environments. Our study demonstrates that raising the Air Change per Hour (ACH) from 2 to 8 reduces the risk of particle inhalation by nearly 70 %. Additionally, limiting the amount of air recirculation or increasing the amount of fresh air helps to reduce the number of airborne particles in an indoor space. To reduce the potential for respiratory droplet-related transmission and to provide relevant recommendations to the appropriate authority, the same computational approach could be applied to a wide range of ventilated indoor environments such as public buses, restaurants, exhibitions, and theaters.

Comparison of Force During the Endotracheal Intubation of Commercial Simulation Manikins.

Background  Medical simulation allows clinicians to safely practice the procedural skill of endotracheal intubation. Applied force to oropharyngeal structures increases the risk of patient harm, and video laryngoscopy (VL) requires less force to obtain a glottic view. It is unknown how much force is required to obtain a glottic view using commercially available simulation manikins and if variability exists. This study compares laryngoscopy force for a modified Cormack-Lehane (CL) grade I view in both normal and difficult airway scenarios between three commercially available simulation manikins. Methods Experienced clinicians (≥2 years experience) were recruited to participate from critical care, emergency medicine, and anesthesia specialties. A C-MAC size 3 VL blade was equipped with five force resistor reading (FSR) sensors (four concave surfaces, one convex), measuring resistance (Ohms) in response to applied pressure (1-100 Newtons). The study occurred in a university simulation lab. Using a randomized sequence, 49 physicians performed intubations on three manikins (Laerdal SimMan 3GPlus, Gaumard Hal S3201, CAE Apollo) in normal and difficult airway scenarios. The outcomes were sensor mean pressure, peak force, and CL grade. Summary statistics were calculated. Generalized estimating equations (GEEs) conducted for both scenarios assessed changes in pressure measured in three manikins while accounting for correlated responses of individuals assigned in random order. Paired t-test assessed for the in-manikin difference between scenarios. STATA/BE v17 (R) was used for analysis; results interpreted at type I error alpha is 0.05.  Results Participants included 49 experienced clinicians. Mean years' experience was 4(±6.6); median prior intubations were 80 (IQR 50-400). Mean individual sensor pressure varied within scenarios depending on manikin (p<0.001). Higher mean forces were used in difficult scenarios (603.4±128.9, 611.1±101.4, 467.5±72.4 FSR) than normal (462.5±121.9, 596.0±90.5, 290.6±63.2 FSR) for each manikin (p<0.001). All manikins required more peak force in the difficult scenario (p<0.03). The highest mean forces (Laerdal, CAE, difficult scenario) were associated with the higher frequency of grade 2A views (p<0.001). The Gaumard manikin was rated most realistic in terms of force required to intubate. Conclusion Commercially available high-fidelity manikins had significant variability in laryngoscopy force in both normal and difficult airway scenarios. In difficult airway scenarios, significant variability existed in CL grade between manikin brands. Experienced clinicians rated Gaumard Hal as the most realistic force applied during endotracheal intubation.

Integrating Stereoscopic Video with Modular 3D Anatomic Models for Lateral Skull Base Training.

Introduction Current virtual reality (VR) technology allows the creation of instructional video formats that incorporate three-dimensional (3D) stereoscopic footage.Combined with 3D anatomic models, any surgical procedure or pathology could be represented virtually to supplement learning or surgical preoperative planning. We propose a standalone VR app that allows trainees to interact with modular 3D anatomic models corresponding to stereoscopic surgical videos. Methods Stereoscopic video was recorded using an OPMI Pentero 900 microscope (Zeiss, Oberkochen, Germany). Digital Imaging and Communications in Medicine (DICOM) images segmented axial temporal bone computed tomography and each anatomic structure was exported separately. 3D models included semicircular canals, facial nerve, sigmoid sinus and jugular bulb, carotid artery, tegmen, canals within the temporal bone, cochlear and vestibular aqueducts, endolymphatic sac, and all branches for cranial nerves VII and VIII. Finished files were imported into the Unreal Engine. The resultant application was viewed using an Oculus Go. Results A VR environment facilitated viewing of stereoscopic video and interactive model manipulation using the VR controller. Interactive models allowed users to toggle transparency, enable highlighted segmentation, and activate labels for each anatomic structure. Based on 20 variable components, a value of 1.1 × 10 12 combinations of structures per DICOM series was possible for representing patient-specific anatomy in 3D. Conclusion This investigation provides proof of concept that a hybrid of stereoscopic video and VR simulation is possible, and that this tool may significantly aid lateral skull base trainees as they learn to navigate a complex 3D surgical environment. Future studies will validate methodology.

Nonlinearly Frequency-Adaptive, Self-Powered, Proton-Driven Somatosensor Inspired by a Human Mechanoreceptor.

In the human skin, it has been well known that several mechanoreceptors uniquely sense external stimuli with specific frequencies and magnitudes. With regard to sensitivity, the output response shows nonlinearity depending on the frequency magnitude of the stimulus. We demonstrate a self-powered proton-driven solid-state somatosensor, which mimics a unique nonlinear response and intensity behavior of human mechanoreceptors. For this, a solid-state sensor is fabricated by combining a piezoelectric film and a proton generation device. The proton injection electrode and the Nafion layer conjugated with sulfonated graphene oxide are used for proton generation and transport. Two types of nonlinear signals from the sensor are similar to the Merkel/Ruffini (low deviation of threshold intensity), and in contrast, the behavior of Pacinian/Meissner (high deviation of threshold intensity) is simultaneously shown. The region of the most responsive frequency is also discriminated according to proton conduction. Moreover, it is asserted that unique signal patterns are obtained from the stimuli of various frequencies, such as respiration, radial artery pulse, and neck vibration, which naturally occur in the human body.

Virtual coach: the next tool in functional endoscopic sinus surgery education.

BACKGOUND: Functional endoscopic sinus surgery (FESS) can be challenging as novices become accustomed to handling endoscopes and instruments while navigating complex sinonasal anatomy. Experts demonstrate fluid and efficient motions when addressing pathology. The training process from novice to expert relies on hands-on experience in cadaveric laboratories and preceptorship models that require significant time and expense. This study aims to validate the use of a virtual coach to guide users step-by-step through a basic FESS. METHODS: Seventeen surgeons were grouped into novice (n = 10) and expert (n = 7) based on self-reported levels of surgical experience. Users were trained using the maxillary antrostomy module in the Neurorhinological Surgery (NRS) simulator combining the physical craniofacial model with virtual reality (VR)-tracked surgical instruments in the VR operating room. The virtual coach guided the user using surgical videos, auditory, and visual cues. The coach recorded data for each subject including the number of times borders of the nasal cavity were encountered and time to completion. Users graded the usefulness of the virtual coach on a Likert questionnaire. RESULTS: Face validity of our NRS simulator was replicated by user questionnaires, and construct validity replicated by differentiation between novice and expert level surgeons (p < 0.01). Novices contacted a significantly higher number of anatomic borders (n = 17) and had a longer operative time (t = 370 seconds). All users reported high scores on the benefit and usefulness of the virtual coach. CONCLUSION: The virtual coach provides a useful tool to enhance FESS education by providing objective real-time data in a novel mixed-reality surgical environment.

Combining Stereoscopic Video and Virtual Reality Simulation to Maximize Education in Lateral Skull Base Surgery.

Mastery of lateral skull base (LSB) surgery requires thorough knowledge of complex, 3-dimensional (3D) microanatomy and techniques. While supervised operation under binocular microscopy remains the training gold standard, concerns over operative time and patient safety often limit novice surgeons' stereoscopic exposure. Furthermore, most alternative educational resources cannot meet this need. Here we present proof of concept for a tool that combines 3D-operative video with an interactive, stereotactic teaching environment. Stereoscopic video was recorded with a microscope during translabyrinthine approaches for vestibular schwannoma. Digital imaging and communications in medicine (DICOM) temporal bone computed tomography images were segmented using 3D-Slicer. Files were rendered using a game engine software built for desktop virtual reality. The resulting simulation was an interactive immersion combining a 3D operative perspective from the lead surgeon's chair with virtual reality temporal bone models capable of hands-on manipulation, label toggling, and transparency modification. This novel tool may alter LSB training paradigms.

Virtual Functional Endoscopic Sinus Surgery Simulation with 3D-Printed Models for Mixed-Reality Nasal Endoscopy.

The surgeon's knowledge of a patient's individual anatomy is critical in skull base surgery. Trainees and experienced surgeons can benefit from surgical simulation; however, current models are expensive and impractical for widespread use. In this study, we report a next-generation mixed-reality surgical simulator. We segmented critical anatomic structures for 3-dimensional (3D) models to develop a modular teaching tool. We then developed a navigation tracking system utilizing a 3D-printed endoscope as a trackable virtual-reality (VR) controller and validated the accuracy on VR and 3D-printed skull models within 1 cm. We combined VR and augmented-reality visual cues with our 3D physical model to simulate sinus endoscopy and highlight segmented structures in real time. This report provides evidence that a mixed-reality simulator combining VR and 3D-printed models is feasible and may prove useful as an educational tool that is low cost and customizable.

A Self-Powered Sensor Mimicking Slow- and Fast-Adapting Cutaneous Mechanoreceptors.

Highly efficient human skin systems transmit fast adaptive (FA) and slow adaptive (SA) pulses selectively or consolidatively to the brain for a variety of external stimuli. The integrated analysis of these signals determines how humans perceive external physical stimuli. Here, a self-powered mechanoreceptor sensor based on an artificial ion-channel system combined with a piezoelectric film is presented, which can simultaneously implement FA and SA pulses like human skin. This device detects stimuli with high sensitivity and broad frequency band without external power. For the feasibility study, various stimuli are measured or detected. Vital signs such as the heart rate and ballistocardiogram can be measured simultaneously in real time. Also, a variety of stimuli such as the mechanical stress, surface roughness, and contact by a moving object can be distinguished and detected. This opens new scientific fields to realize the somatic cutaneous sensor of the real skin. Moreover, this new sensing scheme inspired by natural sensing structures is able to mimic the five senses of living creatures.

Horticultural, systems-engineering and economic evaluations of short-term plant storage techniques as a labor management tool for vegetable grafting nurseries.

This transdisciplinary study has a three-fold systems approach in evaluating a horticultural technology: 1) horticultural evaluations, 2) economic and resource analyses, and 3) systems engineering analyses, using low temperature storage as an example technology. Vegetable grafting is a technique to produce value-added seedlings but requires labor intensive nursery operations. Low temperature storage of seedlings for a short period of time can reduce peak production, but has not been evaluated at the extent demonstrated in this paper. Seedlings of 22 genotypes of Cucurbitaceae (cucurbit family) and Solanaceae (nightshade family) were evaluated for storability under selected temperatures and photosynthetic photon flux. Storability of Cucurbitaceous seedlings varied between 2 to 4 weeks at 12°C and 13 µmol m-2 s-1. Solanaceous seedlings were generally storable for 4 weeks at 12°C and 13 µmol m-2 s-1, but tomato seedlings could be stored for 4 weeks at 10°C and 5 µmol m-2 s-1. Capital and weekly operational costs of a low temperature storage system with a design that meets environmental requirements were estimated as $671 to $708 per m2 footprint and $0.79 to $2.21 per m2 footprint per week, respectively. Electricity costs per plant was less than 0.1 cents for 2 to 4 weeks of storage. Using a schedule-optimization heuristic and a logistics simulator previously developed for grafting nursery operations, six production scenarios consisting of two crops (tomato or watermelon) and three production peak patterns were examined to evaluate the impact of including low temperature storage. While the overall average costs of grafting labor were not significantly different, maximum labor demand and grafting labor cost during the peak production week were reduced by 31% to 50% and 14% to 30% by using storage, respectively. Therefore, low temperature storage can be an effective means to address the issue of labor management in grafting nurseries.

Highly Sensitive and Patchable Pressure Sensors Mimicking Ion-Channel-Engaged Sensory Organs.

Biological ion channels have led to much inspiration because of their unique and exquisite operational functions in living cells. Specifically, their extreme and dynamic sensing abilities can be realized by the combination of receptors and nanopores coupled together to construct an ion channel system. In the current study, we demonstrated that artificial ion channel pressure sensors inspired by nature for detecting pressure are highly sensitive and patchable. Our ion channel pressure sensors basically consisted of receptors and nanopore membranes, enabling dynamic current responses to external forces for multiple applications. The ion channel pressure sensors had a sensitivity of ∼5.6 kPa(-1) and a response time of ∼12 ms at a frequency of 1 Hz. The power consumption was recorded as less than a few µW. Moreover, a reliability test showed stability over 10 000 loading-unloading cycles. Additionally, linear regression was performed in terms of temperature, which showed no significant variations, and there were no significant current variations with humidity. The patchable ion channel pressure sensors were then used to detect blood pressure/pulse in humans, and different signals were clearly observed for each person. Additionally, modified ion channel pressure sensors detected complex motions including pressing and folding in a high-pressure range (10-20 kPa).

Impact of road environment on drivers' behaviors in dilemma zone: Application of agent-based simulation.

At a signalized intersection, there exists an area where drivers become indecisive as to either stop their car or proceed through when the traffic signal turns yellow. This point, called a dilemma zone, has remained a safety concern for drivers due to the great possibility of a rear-end or right-angle crash occurring. In order to reduce the risk of car crashes at the dilemma zone, Institute of Transportation Engineers (ITE) recommended a dilemma zone model. The model, however, fails to provide precise calculations on the decision of drivers because it disregards the supplemental roadway information, such as whether a red light camera is present. Hence, the goal of this study was to incorporate such roadway environmental factors into a more realistic driver decision-making model for the dilemma zone. A driving simulator was used to determine the influence of roadway conditions on decision-making of real drivers. Following data collection, each driver's decision outcomes were implemented in an Agent-Based Simulation (ABS) so as to analyze behaviors under realistic road environments. The experimental results revealed that the proposed dilemma zone model was able to accurately predict the decisions of drivers. Specifically, the model confirmed the findings from the driving simulator study that the changes in the roadway environment reduced the number of red light violations at an intersection.

Stem cell dynamics in an experimental model of stroke.

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin(+) NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin(+) NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.

Characterization and molecular cloning of a novel endoglucanase from Trichoderma sp. C-4.

A fungal strain, C-4, was isolated from etiolated leaves. Based on taxonomic studies, the fungus C-4 can be classified as a strain of Trichoderma species. When strain C-4 was cultured in Mandels' medium at 28 degrees C for 6 days, the enzyme activities detected in the broth corresponded to 8.2 U/ml (28.1 U/mg) carboxymethylcellulase activity. An endoglucanase (EG; F-I-II) was purified from the culture filtrate of the strain through a four-step procedure-chromatography on Sephacryl S-200, DEAE-Sephadex A-50, Con A-Sepharose, and Chromatofocusing on Mono-P (HPLC). The molecular weight of this EG, which was called C4endoII, was determined to be about 51 kDa. The optimum temperature and pH of C4endoII were 50 degrees C and 5.0, respectively. Incubation at 50 degrees C for 24 h did not destroy the cellulose degradation activity. Amino acid sequence analysis revealed the N-terminal sequence of an internal peptide of C4endoII to be Phe-Ala-Gly-Ile-Asn-Ile-Ala-Gly-Phe-Asp-Phe, which is homologous to EGII from Trichoderma reesei. A C4endoII cDNA (C4endoII) was cloned from a cDNA library constructed using the mRNA of the strain cultivated in a cellulase-induction medium. The deduced protein sequence of C4endoII was 417 amino acids long and had a putative signal sequence of 21 amino acids with a predicted cleavage site after Ala-21. A single potential N-glycosylation site was present in the amino acid sequence.