The vestigial pinna-orienting system in humans briefly suppresses superior auricular muscle activity during reflexive orienting toward auditory stimuli.

The vestigial pinna-orienting system in humans is capable of increasing the activity of several auricular muscles in response to lateralized transient auditory stimuli. For example, transient increases in electromyographic activity in the posterior auricular muscle (PAM) to an attention-capturing stimulus have been documented. For the current study, surface electromyograms (EMGs) were recorded from the PAMs and superior auricular muscles (SAMs) of 10 normal-hearing participants. During the experiments, lateralized transient auditory stimuli, such as a crying baby, a shattering vase, or the participant's first names, were presented. These transient stimuli were either presented in silence or when participants actively listened to a podcast. Although ipsilateral PAM activity increased in response to transient stimuli, the SAM displayed the opposite behavior, i.e., a brief, ipsilateral suppression of activity. This suppression of ipsilateral SAM activity was more frequent on the right (75%) than left side (35%), whereas an ipsilateral PAM increase was roughly equal in prevalence on the two sides (left: 90%, right: 95%). During the active listening task, SAM suppression on the right ear was significantly larger in response to ipsilateral stimuli, compared with contralateral ones (P = 0.002), whereas PAM activity increased significantly (P = 0.002). Overall, this study provides evidence of a systematic transient suppression of the SAM during exogenous attention. This could suggest a more complex system than previously assumed, as the presence of synchronized excitatory and inhibitory components in different auricular muscles points toward a coordinated attempt at reflexively orienting the pinna toward a sound.NEW & NOTEWORTHY This study provides evidence that two auricular muscles in humans, the posterior and superior auricular muscles (PAM, SAM), react fundamentally different to lateralized transient auditory stimuli, especially during active listening. Although the PAM reacts with a transient increase in ipsilateral activity, ongoing ipsilateral SAM activity is briefly suppressed at the same time. This indicates the presence of a more complex and nuanced pinna-orienting system, with synchronized excitatory and inhibitory components in humans, than previously suspected.

Virus filter scalability: Demonstration of consistent viral clearance across laboratory and manufacturing scales.

Virus removal filtration processes in biopharmaceutical manufacturing are developed, optimized and validated for viral clearance using laboratory scale filters. Thus, the scalability of these filters is critical for accurately extrapolating filtration performance and reliably extending viral clearance to manufacturing scale. Virus removal filter manufacturers generally validate scalability of filtration performance based on various filtration parameters, and virus removal capability is extended to manufacturing scale filters using inert, size-appropriate particles such as gold nanoparticles to avoid the risks associated with using mammalian viruses in large feed volumes. In this study, we use bacteriophage PP7 as a parvovirus model to directly demonstrate viral clearance on Planova™ BioEX virus removal filters across all scales, including manufacturing scale. Filters with hollow fibers from three spinning series with filter sizes ranging from 0.0003 to 4.0 m2 were tested for virus removal, flux, and protein recovery performance using BSA spiked with PP7. Complete viral clearance was observed across all filter sizes with PP7 LRV of ≥4.7 or higher. Flux and protein recovery were also consistent. These results demonstrate the scalability of filtration performance and consistent virus removal at all sizes, supporting the use of laboratory scale filters to validate viral clearance at manufacturing scales.

Speech induced binaural beats: Electrophysiological assessment of binaural interaction.

This paper introduces and evaluates a speech signal manipulation scheme that generates transient speech induced binaural beats (SBBs). These SBBs can only be perceived when different signals are presented dichotically (to both ears). Event-related potentials were recorded in 22 normal-hearing subjects. Dichotic stimulus presentation reliably evoked auditory late responses (ALRs) in all subjects using such manipulated signals. As control measurements, diotic stimulation modalities were presented to confirm that the ALRs were not evoked by the speech signal itself or that the signal manipulation scheme created audible artifacts. Since diotic measurements evoked no ALRs, responses from dichotic stimulation are a pure correlate of binaural interaction. While there are several auditory stimuli (mostly modulated sinusoids or noise) that share this characteristic, none of them are based on running speech. Because SBBs can be added to any arbitrary speech signal, they could easily be combined with psychoacoustic tests, for example speech reception thresholds, adding an objective measure of binaural interaction.

Fast acquisition of full-range auditory event-related potentials using an interleaved deconvolution approach.

This work relates to recent advances in the field of auditory event-related potentials (ERP), specifically deconvolution-based ERP acquisition and single-trial processing. An efficient stimulus sequence optimization method for ERP deconvolution is proposed, achieving consistent noise attenuation within a broad designated frequency range. Furthermore, a stimulus presentation paradigm for the fast, interleaved acquisition of auditory brainstem, middle-latency and late responses featuring alternating periods of high-rate deconvolution sequences, and subsequent low-rate stimulation is investigated in 20 normal hearing subjects. Deconvolved sequence responses containing early and middle-latency ERP components are fused with subsequent late responses using a time-frequency resolved weighted averaging method based on cross-trial regularity, yielding a uniform signal-to-noise ratio of the full-range auditory ERP across investigated timescales. Obtained average ERP waveforms exhibit morphologies consistent with both literature values and reference recordings acquired in 15 normal hearing subjects using a prior art approach to full-range auditory ERP acquisition, with all prominent waves being visible in the grand average waveforms. Results suggest the proposed interleaved stimulus presentation and associated ERP processing methodology to be suitable for the fast, reliable extraction of full-range auditory processing correlates in future ERP studies.

Toward a taxonomic model of attention in effortful listening.

In recent years, there has been increasing interest in studying listening effort. Research on listening effort intersects with the development of active theories of speech perception and contributes to the broader endeavor of understanding speech perception within the context of neuroscientific theories of perception, attention, and effort. Due to the multidisciplinary nature of the problem, researchers vary widely in their precise conceptualization of the catch-all term listening effort. Very recent consensus work stresses the relationship between listening effort and the allocation of cognitive resources, providing a conceptual link to current cognitive neuropsychological theories associating effort with the allocation of selective attention. By linking listening effort to attentional effort, we enable the application of a taxonomy of external and internal attention to the characterization of effortful listening. More specifically, we use a vectorial model to decompose the demand causing listening effort into its mutually orthogonal external and internal components and map the relationship between demanded and exerted effort by means of a resource-limiting term that can represent the influence of motivation as well as vigilance and arousal. Due to its quantitative nature and easy graphical interpretation, this model can be applied to a broad range of problems dealing with listening effort. As such, we conclude that the model provides a good starting point for further research on effortful listening within a more differentiated neuropsychological framework.

Adapting virus filtration to continuous processing: Effects of product and process variability on filtration performance.

Virus filtration (VF) is an important unit operation in the manufacture of biotherapeutics that provides robust removal of potential virus contaminants. Small virus removal can be impacted by the low operating pressures and potential depressurization events that are often associated with continuous operations where increased operational flexibility for higher loading at low flux and low pressure is required. In this study, we evaluated the impact of low flux (7 LMH) and pressure interruptions on minute virus of mice (MVM) removal. We used long-term filtrations conducted to a target throughput of 1000 L/m2 with four different monoclonal antibodies on small-scale hollow fiber virus filters with a hydrophilic modified polyvinylidene fluoride membrane. These conditions are certainly challenging for any VF operation and ensuring robust viral clearance under such conditions is critical to the design and implementation of continuous VF. Planova BioEX filters effectively removed MVM at 4 log or greater when run continuously for up to 6 days. Interestingly, pressure increases associated with filter fouling over the duration of long-term filtrations were shown to be reflective of load material variability and could be remediated by implementation of an inline prefilter. Pressure interruptions had minimal impact on overall MVM logarithmic reduction value. Effective virus removal was achieved with pressure increases being largely product-specific, which demonstrates the capability of the virus filter to remove virus independent of pressure increases that are expected to occur with increased protein load.

The role of attention in immersion: The two-competitor model.

Currently, we face an exponentially increasing interest in immersion, especially sensory-driven immersion, mainly due to the rapid development of ideas and business models centered around a digital virtual universe as well as the increasing availability of affordable immersive technologies for education, communication, and entertainment. However, a clear definition of 'immersion', in terms of established neurocognitive concepts and measurable properties, remains elusive, slowing research on the human side of immersive interfaces. To address this problem, we propose a conceptual, taxonomic model of attention in immersion. We argue (a) modeling immersion theoretically as well as studying immersion experimentally requires a detailed characterization of the role of attention in immersion, even though (b) attention, while necessary, cannot be a sufficient condition for defining immersion. Our broader goal is to characterize immersion in terms that will be compatible with established psychophysiolgical measures that could then in principle be used for the assessment and eventually the optimization of an immersive experience. We start from the perspective that immersion requires the projection of attention to an induced reality, and build on accepted taxonomies of different modes of attention for the development of our two-competitor model. The two-competitor model allows for a quantitative implementation and has an easy graphical interpretation. It helps to highlight the important link between different modes of attention and affect in studying immersion.

Emergency Department-Based Physical Function Measures for Falls in Older Adults and Outcomes: A Secondary Analysis of GAPcare.

BACKGROUND AND PURPOSE: Falls are the leading reason for injury-related emergency department (ED) visits for older adults. The Geriatric Acute and Post-acute Fall Prevention Intervention (GAPcare), an in-ED intervention combining a medication therapy management session delivered by a pharmacist and a fall risk assessment and plan by a physical therapist, reduced ED revisits at 6 months among older adults presenting after a fall. Our objective was to evaluate the relationship between measures of function obtained in the ED and clinical outcomes. METHODS: This was a secondary analysis of data from GAPcare, a randomized controlled trial conducted from January 2018 to October 2019 at 2 urban academic EDs. Standardized measures of function (Timed Up and Go [TUG] test, Barthel Activity of Daily Living [ADL], Activity Measure for Post Acute Care [AM-PAC] 6 clicks) were collected at the ED index visit. We performed a descriptive analysis and hypothesis testing (chi square test and analysis of variance) to assess the relationship of functional measures with outcomes (ED disposition, ED revisits for falls, and place of residence at 6 months). Emergency department disposition status refers to discharge location immediately after the ED evaluation is complete (eg, hospital admission, original residence, skilled nursing facility). RESULTS AND DISCUSSION: Among 110 participants, 55 were randomized to the GAPcare intervention and 55 received usual care. Of those randomized to the intervention, 46 received physical therapy consultation. Median age was 81 years; participants were predominantly women (67%) and White (94%). Seventy-three (66%) were discharged to their original residence, 14 (13%) were discharged to a skilled nursing facility and 22 (20%) were admitted. There was no difference in ED disposition status by index visit Barthel ADLs (P = .371); however, TUG times were faster (P = .016), and AM-PAC 6 clicks score was higher among participants discharged to their original residence (P ≤ .001). Participants with slower TUG times at the index ED visit were more likely to reside in nursing homes by six months (P = .002), while Barthel ADL and AM-PAC 6 clicks did not differ between those residing at home and other settings. CONCLUSIONS: Measures of function collected at the index ED visit, such as the AM-PAC 6 clicks and TUG time, may be helpful at predicting clinical outcomes for older adults presenting for a fall. Based on our study findings, we suggest a novel workflow to guide the use of these clinical measures for ED patients with falls.

Improvement in Parkinson Disease Symptoms After Treatment for COVID-19 with Monoclonal Antibodies.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by motor symptoms, such as bradykinesia, and non-motor symptoms, such as fatigue, which can be a particularly disabling feature of the disease. METHODS: We conducted a retrospective chart review on a patient who reported improvement in baseline PD symptoms after COVID-19 treatment. RESULTS: The patient is a 76-year-old male with a six-year history of PD who developed a COVID-19 infection, underwent treatment with COVID-19 monoclonal antibodies, and experienced a remarkable improvement in his pre-COVID PD symptoms, most notably his gait and fatigue. Prior to COVID, he rated his fatigue as '9 out of 10,' which worsened to 10 out of 10 during his COVID infection, and post-COVID treatment, his fatigue improved to '3 out of 10'. PRINCIPAL CONCLUSIONS: We described an unexpected improvement in baseline PD symptoms for a patient treated with COVID-19 monoclonal antibodies. Further investigation will be essential to understand the mechanisms underlying this phenomenon.

[New perspectives in orthopedics : Developments through neurotechnology and metaverse]. / Neue Perspektiven in der Orthopädie : Entwicklungen durch Neurotechnologie und Metaversum.

The combination of neurotechnology and metaverse holds high potentials for orthopedics, as it offers a broad spectrum of possibilities to overcome the limits of traditional medical care. The vision of a medical metaverse providing the infrastructure as a link for innovative technologies opens up new opportunities for therapy, medical collaborations and practical, personalized training for aspiring physicians. However, risks and challenges, such as security and privacy, health-related issues, acceptance by patients and doctors, as well as technical hurdles and access to the technologies, remain. Hence, future research and development is paramount. Nonetheless, due to technological progress, the exploration of new research areas, and the improved availability of the technologies paired with cost reduction, the prospects for neurotechnology and metaverse in orthopedics are promising.

Serial virus filtration: A case study evaluating the product-dependent impact of control strategies on process efficiency.

The production of biopharmaceutical products carries an inherent risk of contamination by adventitious viruses. Historically, these manufacturing processes have incorporated a dedicated virus filtration step to ensure product safety. However, challenging process conditions can lead to passage of small viruses to the permeate pool and an overall decrease in the desired virus logarithmic reduction value (LRV) for the process. The implementation of serial virus filtration has improved the robustness of such processes, albeit concerns about increased operating times and process complexity have limited its implementation. This work focused on optimizing a serial filtration process and identifying process control strategies to provide maximum efficiency while ensuring proper controls for process complexity. Constant TMP was identified as the optimal control strategy, which combined with the optimal filter ratio, resulted in a robust and faster virus filtration process. To demonstrate this hypothesis, data with two filters connected in series (1:1 filter ratio) are presented for a representative non-fouling molecule. Similarly, for a fouling product, the optimal setup was a combination of a filter connected in series to two filters operated in parallel (2:1 filter ratio). The optimized filter ratios bring cost- and time-savings benefits to the virus filtration step, thereby offering improved productivity. The results of risk and cost analyses performed as part of this study combined with the control strategy, offer companies a toolbox of strategies to accommodate products with different filterability profiles in their downstream processes. This work demonstrates that the safety advantages of performing filters in series can be achieved with minimal increases in time, cost, and risk.

Assessment of Vestigial Auriculomotor Activity to Acoustic Stimuli Using Electrodes In and Around the Ear.

Recently, it has been demonstrated that electromyographic (EMG) activity of auricular muscles in humans, especially the postauricular muscle (PAM), depends on the spatial location of auditory stimuli. This observation has only been shown using wet electrodes placed directly on auricular muscles. To move towards a more applied, out-of-the-laboratory setting, this study aims to investigate if similar results can be obtained using electrodes placed in custom-fitted earpieces. Furthermore, with the exception of the ground electrode, only dry-contact electrodes were used to record EMG signals, which require little to no skin preparation and can therefore be applied extremely fast. In two experiments, auditory stimuli were presented to ten participants from different spatial directions. In experiment 1, stimuli were rapid onset naturalistic stimuli presented in silence, and in experiment 2, the corresponding participant's first name, presented in a "cocktail party" environment. In both experiments, ipsilateral responses were significantly larger than contralateral responses. Furthermore, machine learning models objectively decoded the direction of stimuli significantly above chance level on a single trial basis (PAM: ≈ 80%, in-ear: ≈ 69%). There were no significant differences when participants repeated the experiments after several weeks. This study provides evidence that auricular muscle responses can be recorded reliably using an almost entirely dry-contact in-ear electrode system. The location of the PAM, and the fact that in-ear electrodes can record comparable signals, would make hearing aids interesting devices to record these auricular EMG signals and potentially utilize them as control signals in the future.

Assessment of post-excitatory long-interval cortical inhibition in adult attention-deficit/hyperactivity disorder.

In order to further examine cortical impairment in adult ADHD patients and to test the hypothesis of a disturbed neuronal inhibition in adults with ADHD, late auditory evoked potentials were measured. By using paired-chirp auditory late responses, we compared 15 adults with ADHD with 15 control subjects, focusing on the inhibition elicited by the stimuli. Besides amplitude measurements, a time-frequency phase coherence study using the wavelet phase synchronization stability (WPSS) was performed. ADHD was diagnosed according to DSM-IV criteria. All ADHD subjects were without medication and did not suffer from any further axis I disorder. WPSS analysis revealed impaired auditory inhibition for ADHD patients for interstimulus intervals (ISI) between 500 and 1,100 ms as compared with healthy controls. By analyzing the WPSS in the interval from 80 ms to 220 ms, mean inhibition of the test chirp was found to be 6% in the ADHD group and 38.5% in the control subjects (p = 0.01). Moreover, overall smaller amplitudes in the N100 and P200 waves at all ISI were found (p = 0.04 and p = 0.02). However, reproducibility indices in the amplitude measurements were low, thus supporting the use of the instantaneous phase-based analysis method. The results support the hypothesis of reduced intracortical inhibition as a correlate of disturbed brain function in adults with ADHD.

Software for non-parametric image registration of 2-photon imaging data.

Functional 2-photon microscopy is a key technology for imaging neuronal activity. The recorded image sequences, however, can contain non-rigid movement artifacts which requires high-accuracy movement correction. Variational optical flow (OF) estimation is a group of methods for motion analysis with established performance in many computer vision areas. However, it has yet to be adapted to the statistics of 2-photon neuroimaging data. In this work, we present the motion compensation method Flow-Registration that outperforms previous alignment tools and allows to align and reconstruct even low signal-to-noise ratio 2-photon imaging data and is able to compensate high-divergence displacements during local drug injections. The method is based on statistics of such data and integrates previous advances in variational OF estimation. Our method is available as an easy-to-use ImageJ/FIJI plugin as well as a MATLAB toolbox with modular, object oriented file IO, native multi-channel support and compatibility with existing 2-photon imaging suites.

Lagrangian Motion Magnification with Landmark-Prior and Sparse PCA for Facial Microexpressions and Micromovements.

Video motion magnification methods are motion visualization techniques that aim to magnify subtle and imper-ceptibly small motions in videos. They fall into two main groups where Eulerian methods work on the pixel grid with implicit motion information and Lagrangian methods use explicitly estimated motion and modify point trajectories. The motion in high framerate videos of faces can contain a wide variety of information that ranges from microexpressions over pulse or respiratory rate to cues on speech and affective state. In his work, we propose a novel strategy for Lagrangian motion magnification that integrates landmark information from the face as well as an approach to decompose facial motions in an unsupervised manner using sparse PCA. We decompose the estimated displacements into different movement components that are subsequently amplified selectively. We propose two approaches: A landmark-based decomposition into global and local movements and a decomposition into multiple coherent motion components based on sparse PCA. Optical flow estimation is performed using a state-of-the-art deep learning-based method that we retrain on a microexpression database. Clinical relevance- This method could be applied to the annotation and analysis of micromovements for neurocognitive assessment and even novel, medical applications where micro-motions of the face might play a role.

Motion Sickness related Route Profiling for Evaluation of the Sensory Conflict in Real-Driving Studies.

The risk for passengers of an automated vehicle to suffer from motion sickness symptoms increases while performing non-driving tasks. Motion sickness, whether at sea, in the air, in a car or in virtual reality, has been studied for years, but the specific motion patterns of different vehicles and the individual physiology of passengers complicate the definition of general applicable models. Technical progress in vehicles, e.g. the development of the chassis or general digitalization, is constantly changing the influences and marginal effects of motion sickness. In recent years, increasing number of investigations concentrated on the influencing factors on motion sickness. However, the relation between emesis and vehicle dynamics itself is predominantly inadequately presented. Therefore, the results can poorly be incorporate in mathematical models of the sensory conflict theory established as leading theory in the research community. In our research, we suggest a method to prepare and present route and driving information to increase the transparency of real-world driving experiments. We used determined position-based spectrograms to simplify the understanding of the provoked acceleration as well as frequency, known as important motion sickness trigger. Standardized use of this method would support review articles about driving experiments and thus support research regarding motion sickness prediction and occurrence in vehicles.

Leveraging Mobile-Based Sensors for Clinical Research to Obtain Activity and Health Measures for Disease Monitoring, Prevention, and Treatment.

Clinical researchers are using mobile-based sensors to obtain detailed and objective measures of the activity and health of research participants, but many investigators lack expertise in integrating wearables and sensor technologies effectively into their studies. Here, we describe the steps taken to design a study using sensors for disease monitoring in older adults and explore the benefits and drawbacks of our approach. In this study, the Geriatric Acute and Post-acute Fall Prevention Intervention (GAPcare), we created an iOS app to collect data from the Apple Watch's gyroscope, accelerometer, and other sensors; results of cognitive and fitness tests; and participant-entered survey data. We created the study app using ResearchKit, an open-source framework developed by Apple for medical research that includes neuropsychological tests (e.g., of executive function and memory), gait speed, balance, and other health assessments. Data is transmitted via an Application Programming Interface (API) from the app to REDCap for researchers to monitor and analyze in real-time. Employing the lessons learned from GAPcare could help researchers create study-tailored research apps and access timely information about their research participants from wearables and smartphone devices for disease prevention, monitoring, and treatment.

Speech Tracking in Complex Auditory Scenes with Differentiated In- and Out-Field-Of-View Processing in Hearing Aids.

In naturalistic auditory scenes, relevant information is rarely concentrated at a single location, but rather unpredictably scattered in- and out-field-of-view (in-/out-FOV). Although the parsing of a complex auditory scene is a fairly simple job for a healthy human auditory system, the uncertainty represents a major issue in the development of effective hearing aid (HA) processing strategies. Whereas traditional omnidirectional microphones (OM) amplify the complete auditory scene without enhancing signal-to-noise-ratio (SNR) between in- and out-FOV streams, directional microphones (DM) may greatly increase SNR at the cost of preventing HA users to perceive out-FOV information. The present study compares the conventional OM and DM HA settings to a split processing (SP) scheme differentiating between in- and out-FOV processing. We recorded electroencephalographic data of ten young, normal-hearing listeners who solved a cocktail-party-scenario-paradigm with continuous auditory streams and analyzed neural tracking of speech with a stimulus reconstruction (SR) approach. While results for all settings exhibited significantly higher SR accuracies for attended in-FOV than unattended out-FOV streams, there were distinct differences between settings. In-FOV SR performance was dominated by DM and SP and out-FOV SR accuracies were significantly higher for SP compared to OM and DM. Our results demonstrate the potential of a SP approach to combine the advantages of traditional OM and DM settings without introduction of significant compromises.

Strategies to Ensure Continuity of Care Using Telemedicine with Older Adults during COVID-19: A Qualitative Study of Physicians in Primary Care and Geriatrics.

Objectives: Our objective was to interview primary care physicians (PCPs) and geriatricians on their experiences using telemedicine during the COVID-19 pandemic to examine strategies used to maintain continuity of care with their patients, ages 65 and older. Methods: Using purposive sampling, we selected physicians based on community size (metro/suburban/rural) and practice setting (academic/community) and conducted semi-structured interviews via Zoom (mean: 30 minutes). Interviews were recorded, transcribed, coded, and analyzed using framework analysis. Results: We enrolled 33 physicians (15 PCPs and 18 geriatricians) from July to November 2020. Findings indicate that many physicians successfully bridged the digital divide by: assessing patients' technological readiness in advance, being flexible with telehealth modes, using available home or facility-based staff, educating patients on telehealth privacy and usefulness, making accommodations for disabilities, and involving caregivers. Discussion: These findings can inform future policy and practice and assist physicians in resolving addressable barriers to telehealth use among older patients.

Modeling tangential flow filtration using reverse asymmetric membranes for bioreactor harvesting.

Tangential flow filtration (TFF) has many advantages for bioreactor harvesting, as the permeate could be introduced directly to the subsequent capture step. However, membrane fouling has limited its widespread use. This is particularly problematic given the high cell densities encountered today. Here, a reverse asymmetric membrane, where the more open surface faces the feed stream and the tighter barrier layer faces the permeate stream, has been investigated. The open surface contains pores up to 40 µm in diameter while the tighter barrier layer has an average pore size of 0.4 µm. Filtration of yeast suspensions has been conducted under a range of conditions. The yeast cells are trapped in the open pore structure. The membrane stabilizes an internal porous cake that acts like a depth filter. This stabilized cake layer can remove particulate matter that would foul the barrier layer if it faced the feed stream. As filtration continues, a surface cake layer forms on the membrane surface. A resistance in series model has been developed to describe the permeate flux during TFF. The model contains three fitted parameters which can easily be determined from constant pressure normal flow filtration experiments and total recycle constant flux TFF experiments. The model can be used to estimate the capacity of the filter for a given feed stream. Our results suggest that using a reverse asymmetric membrane could avoid severe flux decline associated with fouling of the barrier layer during bioreactor harvesting.