Parametric information about eye movements is sent to the ears.

Eye movements alter the relationship between the visual and auditory spatial scenes. Signals related to eye movements affect neural pathways from the ear through auditory cortex and beyond, but how these signals contribute to computing the locations of sounds with respect to the visual scene is poorly understood. Here, we evaluated the information contained in eye movement-related eardrum oscillations (EMREOs), pressure changes recorded in the ear canal that occur in conjunction with simultaneous eye movements. We show that EMREOs contain parametric information about horizontal and vertical eye displacement as well as initial/final eye position with respect to the head. The parametric information in the horizontal and vertical directions can be modeled as combining linearly, allowing accurate prediction of the EMREOs associated with oblique (diagonal) eye movements. Target location can also be inferred from the EMREO signals recorded during eye movements to those targets. We hypothesize that the (currently unknown) mechanism underlying EMREOs could impose a two-dimensional eye-movement-related transfer function on any incoming sound, permitting subsequent processing stages to compute the positions of sounds in relation to the visual scene.

Tertiary structure assessment at CASP15.

The results of tertiary structure assessment at CASP15 are reported. For the first time, recognizing the outstanding performance of AlphaFold 2 (AF2) at CASP14, all single-chain predictions were assessed together, irrespective of whether a template was available. At CASP15, there was no single stand-out group, with most of the best-scoring groups-led by PEZYFoldings, UM-TBM, and Yang Server-employing AF2 in one way or another. Many top groups paid special attention to generating deep Multiple Sequence Alignments (MSAs) and testing variant MSAs, thereby allowing them to successfully address some of the hardest targets. Such difficult targets, as well as lacking templates, were typically proteins with few homologues. Local divergence between prediction and target correlated with localization at crystal lattice or chain interfaces, and with regions exhibiting high B-factor factors in crystal structure targets, and should not necessarily be considered as representing error in the prediction. However, analysis of exposed and buried side chain accuracy showed room for improvement even in the latter. Nevertheless, a majority of groups produced high-quality predictions for most targets, which are valuable for experimental structure determination, functional analysis, and many other tasks across biology. These include those applying methods similar to those used to generate major resources such as the AlphaFold Protein Structure Database and the ESM Metagenomic atlas: the confidence estimates of the former were also notably accurate.

ConPlot: web-based application for the visualization of protein contact maps integrated with other data.

SUMMARY: Covariance-based predictions of residue contacts and inter-residue distances are an increasingly popular data type in protein bioinformatics. Here we present ConPlot, a web-based application for convenient display and analysis of contact maps and distograms. Integration of predicted contact data with other predictions is often required to facilitate inference of structural features. ConPlot can therefore use the empty space near the contact map diagonal to display multiple coloured tracks representing other sequence-based predictions. Popular file formats are natively read and bespoke data can also be flexibly displayed. This novel visualization will enable easier interpretation of predicted contact maps. AVAILABILITY AND IMPLEMENTATION: available online at www.conplot.org, along with documentation and examples. Alternatively, ConPlot can be installed and used locally using the docker image from the project's Docker Hub repository. ConPlot is licensed under the BSD 3-Clause. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Providing whole blood for an urban paramedical ambulance system.

INTRODUCTION: Hemorrhage is the second leading cause of death among urban trauma patients, and the provision of prehospital blood-based resuscitation can be lifesaving. We developed an efficient system to support blood-based resuscitation by an urban advanced life support ambulance system. METHODS: We worked with our state health department for permission for fire department paramedics to initiate blood transfusion and built protocols for field whole blood resuscitation. Our regional trauma center transfusion service provided 2 units of O positive, low-titer, leukoreduced whole blood in an internally monitored and sealed ice box weighing 10 pounds to the fire department paramedic supervisor. When notified, the supervisor transported the blood to the sites of anticipated need. Total blood use and wastage were recorded. RESULTS: Following two public hearings, we obtained state-wide approval for the initiation of emergency uncrossmatched blood transfusion by paramedics. Over a 1-year period beginning August 27, 2019, 160 units of whole blood were made available for use, and 51 units were transfused to 39 patients, 30 of whom were trauma patients. Other recipients include patients in shock from massive gastrointestinal, peripartum, or other suspected bleeding. Unused units were returned to the providing transfusion service after 1 week and used for hospital patient care without loss. The estimated cost of providing blood per mission was $0.28 and per patient transfused was $1138. CONCLUSIONS: With appropriate attention to detail, it is possible to provide whole blood to an urban paramedical ambulance system with efficient blood component usage, minimal blood wastage, and low cost.

The eardrums move when the eyes move: A multisensory effect on the mechanics of hearing.

Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.

Occupational exposures and programmatic response to COVID-19 pandemic: an emergency medical services experience.

Rigorous assessment of occupational COVID-19 risk and personal protective equipment (PPE) use is not well-described. We evaluated 9-1-1 emergency medical services (EMS) encounters for patients with COVID-19 to assess occupational exposure, programmatic strategies to reduce exposure and PPE use. We conducted a retrospective cohort investigation of laboratory-confirmed patients with COVID-19 in King County, Washington, USA, who received 9-1-1 EMS responses from 14 February 2020 to 26 March 2020. We reviewed dispatch, EMS and public health surveillance records to evaluate the temporal relationship between exposure and programmatic changes to EMS operations designed to identify high-risk patients, protect the workforce and conserve PPE. There were 274 EMS encounters for 220 unique COVID-19 patients involving 700 unique EMS providers with 988 EMS person-encounters. Use of 'full' PPE including mask (surgical or N95), eye protection, gown and gloves (MEGG) was 67%. There were 151 person-exposures among 129 individuals, who required 981 quarantine days. Of the 700 EMS providers, 3 (0.4%) tested positive within 14 days of encounter, though these positive tests were not attributed to occupational exposure from inadequate PPE. Programmatic changes were associated with a temporal reduction in exposures. When stratified at the study encounters midpoint, 94% (142/151) of exposures occurred during the first 137 EMS encounters compared with 6% (9/151) during the second 137 EMS encounters (p<0.01). By the investigation's final week, EMS deployed MEGG PPE in 34% (3579/10 468) of all EMS person-encounters. Less than 0.5% of EMS providers experienced COVID-19 illness within 14 days of occupational encounter. Programmatic strategies were associated with a reduction in exposures, while achieving a measured use of PPE.

Management of Acute Aortic Dissection During Critical Care Air Medical Transport.

Acute aortic dissection is a time-critical emergency that air medical teams must be capable of transporting. Aortic dissections can manifest a myriad of complications in which prompt recognition and tailored treatments may mitigate additional physiological burden and limit dissection flap propagation. The purpose of this review is to discuss specific critical scenarios that air medical providers may be faced with and to equip them with a pathophysiological understanding of the disease and best practices for the management of acute aortic dissections.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PURPOSE: Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. METHODS: A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. RESULTS: A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. CONCLUSION: Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.

Inclined position is associated with improved first pass success and laryngoscopic view in prehospital endotracheal intubations.

PURPOSE: In hospital-based studies, patients intubated by physicians while in an inclined position compared to supine position had a higher rate of first pass success and lower rate of peri-intubation complications. We evaluated the impact of patient positioning on prehospital endotracheal intubation in an EMS system with rapid sequence induction capability. We hypothesized that patients in the inclined position would have a higher first-pass success rate. METHODS: Prehospital endotracheal intubation cases performed by paramedics between 2012 and 2017 were prospectively collected in airway registries maintained by a metropolitan EMS system. We included all adult (age ≥ 18 years) non-traumatic, non-arrest patients who received any attempt at intubation. Patients were categorized according to initial positioning: supine or inclined. The primary outcome measure was first pass success with secondary outcomes of laryngoscopic view and challenges to intubation. RESULTS: Of the 13,353 patients with endotracheal intubation attempted by paramedics during the study period, 4879 were included for analysis. Of these, 1924 (39.4%) were intubated in the inclined position. First pass success was 86.3% among the inclined group versus 82.5% for the supine group (difference 3.8%, 95% CI: 1.5%-6.1%). First attempt laryngeal grade I view was 62.9% in the inclined group versus 57.1% for the supine group (difference 5.8%, 2.0-9.6). Challenges to intubation were more frequent in the supine group (42.3% versus 38.8%, difference 3.5%, 0.6-6.3). CONCLUSION: Inclined positioning was associated with a better grade view and higher rate of first pass success. The technique should be considered as a viable approach for prehospital airway management.

Resuscitative Airway Management for Massive Gastrointestinal Hemorrhage.

Massive upper gastrointestinal hemorrhage represents a highly morbid, resource intensive disease entity that requires rapid diagnostic and therapeutic delivery in parallel with mobilization of in-hospital providers for definitive intervention. This report details a unique case demonstrating exceptional collaboration spanning multiple healthcare systems, a novel use of resuscitative endovascular balloon occlusion of the aorta, and a discussion on resuscitative airway management in the setting of massive upper gastrointestinal hemorrhage.

Frequency-specific neuromodulation of local and distant connectivity in aging and episodic memory function.

A growing literature has focused on the brain's ability to augment processing in local regions by recruiting distant communities of neurons in response to neural decline or insult. In particular, both younger and older adult populations recruit bilateral prefrontal cortex (PFC) as a means of compensating for increasing neural effort to maintain successful cognitive function. However, it remains unclear how local changes in neural activity affect the recruitment of this adaptive mechanism. To address this problem, we combined graph theoretical measures from functional MRI with diffusion weighted imaging and repetitive transcranial magnetic stimulation (rTMS) to resolve a central hypothesis: how do aged brains flexibly adapt to local changes in cortical activity? Specifically, we applied neuromodulation to increase or decrease local activity in a cortical region supporting successful memory encoding (left dorsolateral PFC or DLPFC) using 5 or 1 Hz rTMS, respectively. We then assessed a region's local within-module degree, or the distributed between-module degree (BMD) between distant cortical communities. We predicted that (1) local stimulation-related deficits may be counteracted by boosting BMD between bilateral PFC, and that this effect should be (2) positively correlated with structural connectivity. Both predictions were confirmed; 5 Hz rTMS increased local success-related activity and local increases in PFC connectivity, while 1 Hz rTMS decreases local activity and triggered a more distributed pattern of bilateral PFC connectivity to compensate for this local inhibitory effect. These results provide an integrated, causal explanation for the network interactions associated with successful memory encoding in older adults. Hum Brain Mapp 38:5987-6004, 2017. © 2017 Wiley Periodicals, Inc.

Right Atrial Collapse With Hepatic Hydrothorax in Advanced Liver Disease.

Cardiac chamber collapse secondary to extrapericardial causes is rare. Focused cardiac ultrasound (FoCUS) in the emergency department can rapidly yield important clinical information and guide management in patients presenting with dyspnea, hypotension, or other cardiopulmonary complaints of uncertain etiology. We report a case of newly-diagnosed cirrhosis with massive ascites and large pleural effusions that distorted normal cardiac anatomy and venous return, in which FoCUS was essential in differentiating underlying pathology of this sick patient and guiding therapy.

Validation of a Low-cost Optic Nerve Sheath Ultrasound Phantom: An Educational Tool.

OBJECTIVE: To validate an ocular phantom as a realistic educational tool utilizing in vivo and phantom optic nerve sheath (ONS) images obtained by ultrasound. METHODS: This prospective study enrolled 51 resident physicians from the Denver Health Residency in Emergency Medicine (EM) and 10 ultrasound fellowship-trained EM attending physicians. Participants performed optic nerve sheath diameter (ONSD) measurements on five in vivo and five phantom ocular ultrasound images and rated the realism of each image on a 5-point Likert scale. Chi-square analysis was performed to evaluate the subjective "realness" of in vivo and phantom images. RESULTS: Sixty-one participants performed ONSD measurements. Mean Likert scale values were 3.43 (95% confidence interval: 3.31-3.55) for in vivo images and 3.41 (95% confidence interval: 3.28-3.54) for phantom images. There was no statistical difference in subjective "realness" between in vivo and phantom ONSD ultrasound images among EM residents. Ultrasound fellowship-trained EM attending physicians aptly differentiated between in vivo (p < 0.01) and phantom (p < 0.01) images, as compared with EM residents. CONCLUSION: Our ocular phantom simulates in vivo posterior ocular anatomy. EM resident physicians found the phantom indistinguishable from in vivo images. Our ONS model provides an inexpensive and realistic educational tool to teach bedside ONSD sonography.

Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex.

Measurement of the input-output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects.

Structural insights into pink-eyed dilution protein (Oca2).

Recent innovations in computational structural biology have opened an opportunity to revise our current understanding of the structure and function of clinically important proteins. This study centres on human Oca2 which is located on mature melanosomal membranes. Mutations of Oca2 can result in a form of oculocutanous albinism, which is the most prevalent and visually identifiable form of albinism. Sequence analysis predicts Oca2 to be a member of the SLC13 transporter family, but it has not been classified into any existing SLC families. The modelling of Oca2 with AlphaFold2 and other advanced methods show that, like SLC13 members, it consists of a scaffold and transport domain and displays a pseudo inverted repeat topology that includes re-entrant loops. This finding contradicts the prevailing consensus view of its topology. In addition to the scaffold and transport domains, the presence of a cryptic GOLD domain is revealed that is likely responsible for its trafficking from the endoplasmic reticulum to the Golgi prior to localisation at the melanosomes. The GOLD domain harbours some known glycosylation sites. Analysis of the putative ligand binding site of the model shows the presence of highly conserved key asparagine residues that suggest Oca2 may be a Na+/dicarboxylate symporter. Known critical pathogenic mutations map to structural features present in the repeat regions that form the transport domain. Exploiting the AlphaFold2 multimeric modelling protocol in combination with conventional homology modelling allowed the building of plausible homodimers in both inward- and outward-facing conformations, supporting an elevator-type transport mechanism.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioural tasks, subjects and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than in humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Individual similarities and differences in eye-movement-related eardrum oscillations (EMREOs).

We recently discovered a unique type of low-frequency otoacoustic emission (OAE) time-locked to the onset (and offset) of saccadic eye movements and occurring in the absence of external sound (Gruters et al., 2018). How and why these eye-movement-related eardrum oscillations (EMREOs) are generated is unknown, with a role in visual-auditory integration being the likeliest candidate. Clues to both the drivers of EMREOs and their purpose can be gleaned by examining responses in normal hearing human subjects. Do EMREOs occur in all individuals with normal hearing? If so, what components of the response occur most consistently? Understanding which attributes of EMREOs are similar across participants and which show more variability will provide the groundwork for future comparisons with individuals with hearing abnormalities affecting the ear's various motor components. Here we report that in subjects with normal hearing thresholds and normal middle ear function, all ears show (a) measurable EMREOs (mean: 58.7 dB SPL; range 45-67 dB SPL for large contralateral saccades), (b) a phase reversal for contra- versus ipsilaterally-directed saccades, (c) a large peak in the signal occurring soon after saccade onset, (d) an additional large peak time-locked to saccade offset and (e) evidence that saccade duration is encoded in the signal. We interpret the attributes of EMREOs that are most consistent across subjects as the ones that are most likely to play an essential role in their function. The individual differences likely reflect normal variation in individuals' auditory system anatomy and physiology, much like traditional measures of auditory function such as auditory-evoked OAEs, tympanometry and auditory-evoked potentials. Future work will compare subjects with different types of auditory dysfunction to population data from normal hearing subjects. Overall, these findings provide important context for the widespread observations of visual- and eye-movement related signals found in cortical and subcortical auditory areas of the brain.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioral tasks, subjects, and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for.