Multiple models for outbreak decision support in the face of uncertainty.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

Transport features predict if a molecule is odorous.

In studies of vision and audition, stimuli can be chosen to span the visible or audible spectrum; in olfaction, the axes and boundaries defining the analogous odorous space are unknown. As a result, the population of olfactory space is likewise unknown, and anecdotal estimates of 10,000 odorants have endured. The journey a molecule must take to reach olfactory receptors (ORs) and produce an odor percept suggests some chemical criteria for odorants: a molecule must 1) be volatile enough to enter the air phase, 2) be nonvolatile and hydrophilic enough to sorb into the mucous layer coating the olfactory epithelium, 3) be hydrophobic enough to enter an OR binding pocket, and 4) activate at least one OR. Here, we develop a simple and interpretable quantitative model that reliably predicts whether a molecule is odorous or odorless based solely on the first three criteria. Applying our model to a database of all possible small organic molecules, we estimate that at least 40 billion possible compounds are odorous, six orders of magnitude larger than current estimates of 10,000. With this model in hand, we can define the boundaries of olfactory space in terms of molecular volatility and hydrophobicity, enabling representative sampling of olfactory stimulus space.

On the Role of Theory and Modeling in Neuroscience.

In recent years, the field of neuroscience has gone through rapid experimental advances and a significant increase in the use of quantitative and computational methods. This growth has created a need for clearer analyses of the theory and modeling approaches used in the field. This issue is particularly complex in neuroscience because the field studies phenomena that cross a wide range of scales and often require consideration at varying degrees of abstraction, from precise biophysical interactions to the computations they implement. We argue that a pragmatic perspective of science, in which descriptive, mechanistic, and normative models and theories each play a distinct role in defining and bridging levels of abstraction, will facilitate neuroscientific practice. This analysis leads to methodological suggestions, including selecting a level of abstraction that is appropriate for a given problem, identifying transfer functions to connect models and data, and the use of models themselves as a form of experiment.

NeuroML-DB: Sharing and characterizing data-driven neuroscience models described in NeuroML.

As researchers develop computational models of neural systems with increasing sophistication and scale, it is often the case that fully de novo model development is impractical and inefficient. Thus arises a critical need to quickly find, evaluate, re-use, and build upon models and model components developed by other researchers. We introduce the NeuroML Database (NeuroML-DB.org), which has been developed to address this need and to complement other model sharing resources. NeuroML-DB stores over 1,500 previously published models of ion channels, cells, and networks that have been translated to the modular NeuroML model description language. The database also provides reciprocal links to other neuroscience model databases (ModelDB, Open Source Brain) as well as access to the original model publications (PubMed). These links along with Neuroscience Information Framework (NIF) search functionality provide deep integration with other neuroscience community modeling resources and greatly facilitate the task of finding suitable models for reuse. Serving as an intermediate language, NeuroML and its tooling ecosystem enable efficient translation of models to other popular simulator formats. The modular nature also enables efficient analysis of a large number of models and inspection of their properties. Search capabilities of the database, together with web-based, programmable online interfaces, allow the community of researchers to rapidly assess stored model electrophysiology, morphology, and computational complexity properties. We use these capabilities to perform a database-scale analysis of neuron and ion channel models and describe a novel tetrahedral structure formed by cell model clusters in the space of model properties and features. This analysis provides further information about model similarity to enrich database search.

Transcutaneous Bilirubin Monitoring in Preterm Infants of 23 to 34 Weeks' Gestation.

OBJECTIVE: The study aimed to evaluate the validity of transcutaneous bilirubin (TcB) measurements at three sites in premature infants born at 230/7 to 346/7 weeks' gestational age (GA) compared with total serum bilirubin (TSB) measurements. STUDY DESIGN: A prospective study was conducted at Banner - University Medical Center Phoenix, where informed consent was obtained from the infant's parent or legally authorized representative. Cohort A was comprised of infants 230/7 to 286/7 weeks' GA and Cohort B contained subjects 290/7 to 346/7 weeks' GA. Baseline TSB measurements were collected at approximately 24 hours of life, as the standard of care and the TcB measurements were obtained from the sternum, interscapular, and buttock areas at approximately ± 30 minutes from collection of the TSB. Statistical analysis of measurements including sensitivity, specificity, positive, and negative predictive values, and the area under the receiver operator characteristic curve (AUROC) were performed. RESULTS: A total of 166 infants were included in the study population. Cohort A consisted of 41 subjects and Cohort B contained 125 subjects. The results showed that baseline TcB measurements from the interscapular area were the most sensitive and specific with TSB levels >5.0 mg/dL in Cohort A. Baseline TcB measurements from the sternum demonstrated greatest sensitivity and specificity when the TSB level was >8.0 mg/dL in Cohort B. In general, each of the three sites in both cohorts demonstrated excellent AUROCs and negative predictive values. CONCLUSION: The use of a TcB meter in preterm infants can be a reliable noninvasive screening tool for hyperbilirubinemia, and it may be beneficial in decreasing painful stimuli and iatrogenic blood loss when used as an adjunct to TSB monitoring. KEY POINTS: · Interscapular TcB is sensitive/specific in 23 to 29 weeks' GA.. · Sternal TcB is sensitive/specific in 29 to 35 weeks' GA.. · TcB readings are reliable in preterm infants.. · TcB is reliable when serum bilirubin is >5.0 mg/dL..

The Adaptive Olfactory Measure of Threshold (ArOMa-T): a rapid test of olfactory function.

Many widely used psychophysical olfactory tests have limitations that can create barriers to adoption. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and prior experience with the odor. Conversely, classic threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially available tests are slow and may require a trained administrator, making them impractical for use in situations where time is at a premium or self-administration is required. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T)-a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant delivery card-in a non-clinical sample of individuals (n = 534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 7.5% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold lower for females) and age (~8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, this study suggests the ArOMa-T can determine odor detection thresholds. Additional validation studies are needed to confirm the value of ArOMa-T in clinical or field settings where rapid and portable assessment of olfactory function is needed.

Changes in pairwise correlations during running reshape global network state in the main olfactory bulb.

Neural codes for sensory inputs have been hypothesized to reside in a broader space defined by ongoing patterns of spontaneous activity. To understand the structure of this spontaneous activity in the olfactory system, we performed high-density recordings of neural populations in the main olfactory bulb of awake mice. We observed changes in pairwise correlations of spontaneous activity between mitral and tufted (M/T) cells when animals were running, which resulted in an increase in the entropy of the population. Surprisingly, pairwise maximum entropy models that described the population activity using only assumptions about the firing rates and correlations of neurons were better at predicting the global structure of activity when animals were stationary as compared to when they were running, implying that higher order (3rd, 4th order) interactions governed population activity during locomotion. Taken together, we found that locomotion alters the functional interactions that shape spontaneous population activity at the earliest stages of olfactory processing, one synapse away from the sensory receptors in the nasal epithelium. These data suggest that the coding space available for sensory representations responds adaptively to the animal's behavioral state.NEW & NOTEWORTHY The organization and structure of spontaneous population activity in the olfactory system places constraints of how odor information is represented. Using high-density electrophysiological recordings of mitral and tufted cells, we found that running increases the dimensionality of spontaneous activity, implicating higher order interactions among neurons during locomotion. Behavior, thus, flexibly alters neuronal activity at the earliest stages of sensory processing.

Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System.

BACKGROUND & AIMS: Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system. METHODS: A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria. RESULTS: A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers. CONCLUSIONS: The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms.

Parsing Sage and Rosemary in Time: The Machine Learning Race to Crack Olfactory Perception.

Color and pitch perception are largely understandable from characteristics of physical stimuli: the wavelengths of light and sound waves, respectively. By contrast, understanding olfactory percepts from odorous stimuli (volatile molecules) is much more challenging. No intuitive set of molecular features is up to the task. Here in Chemical Senses, the Ray lab reports using a predictive modeling framework-first breaking molecular structure into thousands of features and then using this to train a predictive statistical model on a wide range of perceptual descriptors-to create a tool for predicting the odor character of hundreds of thousands of available but previously uncharacterized molecules (Kowalewski et al. 2021). This will allow future investigators to representatively sample the space of odorous molecules as well as identify previously unknown odorants with a target odor character. Here, I put this work into the context of other modeling efforts and highlight the urgent need for large new datasets and transparent benchmarks for the field to make and evaluate modeling breakthroughs, respectively.

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Experience-dependent tuning of early olfactory processing in the adult honey bee, Apis mellifera.

Experience-dependent plasticity in the central nervous system allows an animal to adapt its responses to stimuli over different time scales. In this study, we explored the impacts of adult foraging experience on early olfactory processing by comparing naturally foraging honey bees, Apis mellifera, with those that experienced a chronic reduction in adult foraging experience. We placed age-matched sets of sister honey bees into two different olfactory conditions, in which animals were allowed to forage ad libitum In one condition, we restricted foraging experience by placing honey bees in a tent in which both sucrose and pollen resources were associated with a single odor. In the second condition, honey bees were allowed to forage freely and therefore encounter a diversity of naturally occurring resource-associated olfactory experiences. We found that honey bees with restricted foraging experiences had altered antennal lobe development. We measured the glomerular responses to odors using calcium imaging in the antennal lobe, and found that natural olfactory experience also enhanced the inter-individual variation in glomerular response profiles to odors. Additionally, we found that honey bees with adult restricted foraging experience did not distinguish relevant components of an odor mixture in a behavioral assay as did their freely foraging siblings. This study highlights the impacts of individual experience on early olfactory processing at multiple levels.

Robotic Transabdominal Cerclage vs Laparotomy: A Comparison of Obstetric and Surgical Outcomes.

STUDY OBJECTIVE: To compare obstetric and surgical outcomes of transabdominal cerclage (TAC) via laparotomy (TAC-LAP) versus robotic-assisted (TAC-RA) approaches. DESIGN: Retrospective cohort study. SETTING: An academic medical center. PATIENTS: Sixty-nine women with acquired or congenital cervical insufficiency. INTERVENTIONS: All women underwent TAC either by laparotomy or robotic-assisted approaches by 2 primary surgeons between January 2003 and July 2018. Women with a preconceptional TAC without a subsequent pregnancy were excluded. MEASUREMENTS AND MAIN RESULTS: A total of 69 women met inclusion criteria in the 15-year study period with 40 in the historical TAC-LAP group and 29 in the TAC-RA group. Gestational age at delivery was similar in the 2 groups (36 weeks 3 days vs 37 weeks; median difference -1 day, 95% confidence interval [CI] -6 to 2, p = .36). There were no differences in birth weight, Apgar scores, neonatal intensive care unit admission, or neonatal survival. Estimated blood loss and length of stay were significantly greater in the TAC-LAP group (50 mL vs 20 mL; median difference 25, 95% CI 5-40, p = .007 and 76 hours vs 3 hours; median difference 71, 95% CI 65-75, p <.001, respectively). Operative time was significantly shorter in the TAC-LAP group (65 minutes vs 132 minutes; median difference -64.7, 95% CI -79 to -49, p <.001). There was one intra-operative complication and 4 minor postoperative complications in the TAC-LAP group and none observed in the TAC-RA group. All outcomes were similar when comparing postconceptional TAC alone, except there was no longer a difference in blood loss. When comparing pre- versus postconceptional robotic TAC, there were no differences in surgical outcomes. CONCLUSION: Robotic TAC has similar favorable obstetric outcomes to traditional laparotomy and is associated with reduced blood loss and shorter hospital stays. Despite longer operative times, the robotic group did not experience any intra-operative or postoperative complications, which speaks to the benefits of this minimally invasive approach to TAC.

QTc Prolongation Associated With Psychiatric Medications: A Retrospective Cross-Sectional Study of Adult Inpatients.

OBJECTIVE: The aim of our study was to assess the impact of psychiatric medications and concomitant risk factors on the prevalence of QTc prolongation and torsades de pointes (TdP) in hospitalized subjects. We examined the association between individual risk scores and QTc prolongation and proposed an evidence-based protocol for electrocardiogram monitoring on psychotropic medications. METHOD: Electrocardiograms (ECGs) of subjects hospitalized over a 1-year period were analyzed for QTc prolongation, associated risk factors, and use of medications. Analysis was performed using logistic regression to identify independent predictors of QTc prolongation, and the Pearson χ test was used for risk score assessment. RESULTS: A total of 1249 ECGs of 517 subjects were included in this study. Eighty-seven subjects had QTcB intervals greater than 470 milliseconds for females and greater than 450 milliseconds for males. Twelve (2.3%) subjects had QTcB of 500 milliseconds or greater, or greater than 60 milliseconds of change from baseline. Of these subjects, only 1 case of QTc interval change was related to routine use of psychiatric medications. There were no incidents of TdP. Age, diabetes, hypokalemia, overdose, diphenhydramine, and haloperidol were significant independent predictors of QTc prolongation. Risk scores were significantly correlated with QTc prolongation (P = 0.001). CONCLUSION: Our retrospective review study found that the occurrence of TdP and QTc prolongation was low in this subject population. QT abnormalities were associated with known risk factors, and risk scores correlated well with QTc prolongation. Providers can use the protocol proposed in this study, which incorporates risk scores and the CredibleMeds classification system to determine the need for ECG monitoring and to guide treatment.

Modeling sources of interlaboratory variability in electrophysiological properties of mammalian neurons.

Patch-clamp electrophysiology is widely used to characterize neuronal electrical phenotypes. However, there are no standard experimental conditions for in vitro whole cell patch-clamp electrophysiology, complicating direct comparisons between data sets. In this study, we sought to understand how basic experimental conditions differ among laboratories and how these differences might impact measurements of electrophysiological parameters. We curated the compositions of external bath solutions (artificial cerebrospinal fluid), internal pipette solutions, and other methodological details such as animal strain and age from 509 published neurophysiology articles studying rodent neurons. We found that very few articles used the exact same experimental solutions as any other, and some solution differences stem from recipe inheritance from advisor to advisee as well as changing trends over the years. Next, we used statistical models to understand how the use of different experimental conditions impacts downstream electrophysiological measurements such as resting potential and action potential width. Although these experimental condition features could explain up to 43% of the study-to-study variance in electrophysiological parameters, the majority of the variability was left unexplained. Our results suggest that there are likely additional experimental factors that contribute to cross-laboratory electrophysiological variability, and identifying and addressing these will be important to future efforts to assemble consensus descriptions of neurophysiological phenotypes for mammalian cell types. NEW & NOTEWORTHY This article describes how using different experimental methods during patch-clamp electrophysiology impacts downstream physiological measurements. We characterized how methodologies and experimental solutions differ across articles. We found that differences in methods can explain some, but not all, of the study-to-study variance in electrophysiological measurements. Explicitly accounting for methodological differences using statistical models can help correct downstream electrophysiological measurements for cross-laboratory methodology differences.

Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation.

OBJECTIVES: This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation. DESIGN: This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies. SETTING: A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA). INTERVENTIONS: This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing. MAIN RESULTS: One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications. CONCLUSIONS: Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.

Automatic analysis of the retinal avascular area in the rat oxygen-induced retinopathy model.

Purpose: The aim of this study was to create an algorithm to automate, accelerate, and standardize the process of avascular area segmentation in images from a rat oxygen-induced retinopathy (OIR) model. Methods: Within 6 h of birth, full-term pups born to Sprague Dawley rat dams that had undergone partial bilateral uterine artery ligation at embryonic day 19.5 were placed into a controlled oxygen environment (Oxycycler, BioSpherix, Parish, NY) at 50% oxygen for 48 h, followed by cycling between 10% and 50% oxygen every 24 h until day 15. The pups were then moved into room air until day 18.5. Ten lectin-stained retinal flat mounts were imaged in montage fashion at 10x magnification. Three masked human reviewers measured two parameters, total retinal area and peripheral avascular area, for each image using the ImageJ freehand selection tool. The outputs of each read were measured as number of pixels. The gold standard value for each image was the mean of the three human reads. Interrater agreement for the measurement of total retinal area, avascular area, and percent avascular area was calculated using type A intraclass correlation coefficients (ICCs) with a two-way random effects model. Automated avascular area identification (A3ID) is a method written in ImageJ Macro that is intended for use in the Fiji (Fiji is Just ImageJ) image processing platform. The input for A3ID is a rat retinal image, and the output is the avascular area (in pixels). A3ID utilizes a random forest classifier with a connected-components algorithm and post-processing filters for size and shape. A separate algorithm calculates the total retinal area. We compared the output of both algorithms to gold standard measurements by calculating ICCs, performing linear regression, and determining the Dice coefficients for both algorithms. We also constructed a Bland-Altman plot for A3ID output. Results: The ICC for percent peripheral avascular/total area between human readers was 0.995 (CI: 0.974-0.999), with p<0.001. The ICC between A3ID and the gold standard was calculated for three image parameters-avascular area: 0.974 (CI: 0.899-0.993), with p<0.001; total retinal area: 0.465 (CI: 0.0-0.851), with p=0.001; and the percent peripheral avascular/total area: 0.94 (CI: 0.326-0.989), with p<0.001. In the linear regression analysis, the slope for prediction of the gold standard percent peripheral avascular/total area from A3ID was 0.98, with R2=0.975. A3ID and the total retinal area algorithm achieve an average Dice coefficient of 0.891 and 0.952, respectively. The Bland-Altman analysis revealed a trend for computer underestimation of the peripheral avascular area in images with low peripheral avascular area and overestimation of peripheral avascular area in images with large peripheral avascular areas. Conclusions: A3ID reliably predicts peripheral avascular area based on rat OIR retinal images. When the peripheral avascular area is particularly high or low, hand segmentation of images may be superior.

Comparative study of chemical neuroanatomy of the olfactory neuropil in mouse, honey bee, and human.

Despite divergent evolutionary origins, the organization of olfactory systems is remarkably similar across phyla. In both insects and mammals, sensory input from receptor cells is initially processed in synaptically dense regions of neuropil called glomeruli, where neural activity is shaped by local inhibition and centrifugal neuromodulation prior to being sent to higher-order brain areas by projection neurons. Here we review both similarities and several key differences in the neuroanatomy of the olfactory system in honey bees, mice, and humans, using a combination of literature review and new primary data. We have focused on the chemical identity and the innervation patterns of neuromodulatory inputs in the primary olfactory system. Our findings show that serotonergic fibers are similarly distributed across glomeruli in all three species. Octopaminergic/tyraminergic fibers in the honey bee also have a similar distribution, and possibly a similar function, to noradrenergic fibers in the mammalian OBs. However, preliminary evidence suggests that human OB may be relatively less organized than its counterparts in honey bee and mouse.

Comparison of Uninjured and Concussed Adolecent Athletes on the Concussion Balance Test (COBALT).

BACKGROUND AND PURPOSE: Dizziness and balance problems are common symptoms following sports-related concussion (SRC). Most sports require high-level balance skills that integrate the sensory inputs used for balance. Thus, a comprehensive assessment of postural control following SRC is recommended as an integral part of evaluation and management of the injury. The purpose of this exploratory study was to examine performance differences between uninjured and concussed athletes on the Concussion Balance Test (COBALT), as well as complete preliminary analyses of criterion-related validity and reliability of COBALT. METHODS: COBALT is an 8 condition test developed for both preseason and postinjury assessment using force plate technology to measure sway velocity under dynamic postural conditions that challenge the vestibular system. Retrospective COBALT data obtained through chart review for 132 uninjured athletes and 106 concussed age-matched athletes were compared. RESULTS: All uninjured athletes were able to complete the assessment, compared with only 55% of concussed athletes. Concussed athletes committed significantly more errors than uninjured athletes. Sway velocity for concussed athletes was higher (worse) than that for uninjured athletes on 2 conditions in COBALT. DISCUSSION AND CONCLUSIONS: By examining an athlete's ability to complete the protocol, error rate, and sway velocity on COBALT postinjury, the clinician can identify balance function impairment, which may help the medical team develop a more targeted treatment plan, and provide objective input regarding recovery of balance function following SRC.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A204).

High-speed odor transduction and pulse tracking by insect olfactory receptor neurons.

Sensory systems encode both the static quality of a stimulus (e.g., color or shape) and its kinetics (e.g., speed and direction). The limits with which stimulus kinetics can be resolved are well understood in vision, audition, and somatosensation. However, the maximum temporal resolution of olfactory systems has not been accurately determined. Here, we probe the limits of temporal resolution in insect olfaction by delivering high frequency odor pulses and measuring sensory responses in the antennae. We show that transduction times and pulse tracking capabilities of olfactory receptor neurons are faster than previously reported. Once an odorant arrives at the boundary layer of the antenna, odor transduction can occur within less than 2 ms and fluctuating odor stimuli can be resolved at frequencies more than 100 Hz. Thus, insect olfactory receptor neurons can track stimuli of very short duration, as occur when their antennae encounter narrow filaments in an odor plume. These results provide a new upper bound to the kinetics of odor tracking in insect olfactory receptor neurons and to the latency of initial transduction events in olfaction.