A principal odor map unifies diverse tasks in olfactory perception.

Mapping molecular structure to odor perception is a key challenge in olfaction. We used graph neural networks to generate a principal odor map (POM) that preserves perceptual relationships and enables odor quality prediction for previously uncharacterized odorants. The model was as reliable as a human in describing odor quality: On a prospective validation set of 400 out-of-sample odorants, the model-generated odor profile more closely matched the trained panel mean than did the median panelist. By applying simple, interpretable, theoretically rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors.

Transient loss and recovery of oral chemesthesis, taste and smell with COVID-19: A small case-control series.

Transient loss of smell is a common symptom of influenza and other upper respiratory infections. Loss of taste is possible but rare with these illnesses, and patient reports of 'taste loss' typically arise from a taste / flavor confusion. Thus, initial reports from COVID-19 patients of loss of taste and chemesthesis (i.e., chemical somatosensation like warming or cooling) were met with skepticism until multiple studies confirmed SARS-CoV-2 infections could disrupt these senses. Many studies have been based on self-report or on single time point assessments after acute illness was ended. Here, we describe intensive longitudinal data over 28 days from adults aged 18-45 years recruited in early 2021 (i.e., prior to the Delta and Omicron SARS-CoV-2 waves). These individuals were either COVID-19 positive or close contacts (per U.S. CDC criteria at the time of the study) in the first half of 2021. Upon enrollment, all participants were given nose clips, blinded samples of commercial jellybeans (Sour Cherry and Cinnamon), and scratch-n-sniff odor identification test cards (ScentCheckPro), which they used for daily assessments. In COVID-19 cases who enrolled on or before Day 10 of infection, Gaussian Process Regression showed two distinct measures of function - odor identification and odor intensity - declined relative to controls (exposed individuals who never developed COVID-19). Because enrollment began upon exposure, some participants became ill only after enrollment, which allowed us to capture baseline ratings, onset of loss, and recovery. Data from these four cases and four age- and sex- matched controls were plotted over 28 days to create panel plots. Variables included mean orthonasal intensity of four odors (ScentCheckPro), perceived nasal blockage, oral burn (Cinnamon jellybeans), and sourness and sweetness (Sour Cherry jellybeans). Controls exhibited stable ratings over time. By contrast, COVID-19 cases showed sharp deviations over time. Changes in odor intensity or odor identification were not explained by nasal blockage. No single pattern of taste loss or recovery was apparent, implying different taste qualities might recover at different rates. Oral burn was transiently reduced for some before recovering quickly, suggesting acute loss may be missed in datasets collected only after illness ends. Collectively, intensive daily testing shows orthonasal smell, oral chemesthesis and taste were each altered by acute SARS-CoV-2 infection. This disruption was dyssynchronous for different modalities, with variable loss and recovery rates across both modalities and individuals.

Text-based predictions of COVID-19 diagnosis from self-reported chemosensory descriptions.

BACKGROUND: There is a prevailing view that humans' capacity to use language to characterize sensations like odors or tastes is poor, providing an unreliable source of information. METHODS: Here, we developed a machine learning method based on Natural Language Processing (NLP) using Large Language Models (LLM) to predict COVID-19 diagnosis solely based on text descriptions of acute changes in chemosensation, i.e., smell, taste and chemesthesis, caused by the disease. The dataset of more than 1500 subjects was obtained from survey responses early in the COVID-19 pandemic, in Spring 2020. RESULTS: When predicting COVID-19 diagnosis, our NLP model performs comparably (AUC ROC ~ 0.65) to models based on self-reported changes in function collected via quantitative rating scales. Further, our NLP model could attribute importance of words when performing the prediction; sentiment and descriptive words such as "smell", "taste", "sense", had strong contributions to the predictions. In addition, adjectives describing specific tastes or smells such as "salty", "sweet", "spicy", and "sour" also contributed considerably to predictions. CONCLUSIONS: Our results show that the description of perceptual symptoms caused by a viral infection can be used to fine-tune an LLM model to correctly predict and interpret the diagnostic status of a subject. In the future, similar models may have utility for patient verbatims from online health portals or electronic health records.

Early in the COVID-19 pandemic, people who were infected with SARS-CoV-2 reported changes in smell and taste. To better study these symptoms of SARS-CoV-2 infections and potentially use them to identify infected patients, a survey was undertaken in various countries asking people about their COVID-19 symptoms. One part of the questionnaire asked people to describe the changes in smell and taste they were experiencing. We developed a computational program that could use these responses to correctly distinguish people that had tested positive for SARS-CoV-2 infection from people without SARS-CoV-2 infection. This approach could allow rapid identification of people infected with SARS-CoV-2 from descriptions of their sensory symptoms and be adapted to identify people infected with other viruses in the future.

Metabolic activity organizes olfactory representations.

Hearing and vision sensory systems are tuned to the natural statistics of acoustic and electromagnetic energy on earth and are evolved to be sensitive in ethologically relevant ranges. But what are the natural statistics of odors, and how do olfactory systems exploit them? Dissecting an accurate machine learning model (Lee et al., 2022) for human odor perception, we find a computable representation for odor at the molecular level that can predict the odor-evoked receptor, neural, and behavioral responses of nearly all terrestrial organisms studied in olfactory neuroscience. Using this olfactory representation (principal odor map [POM]), we find that odorous compounds with similar POM representations are more likely to co-occur within a substance and be metabolically closely related; metabolic reaction sequences (Caspi et al., 2014) also follow smooth paths in POM despite large jumps in molecular structure. Just as the brain's visual representations have evolved around the natural statistics of light and shapes, the natural statistics of metabolism appear to shape the brain's representation of the olfactory world.

Transient loss and recovery of oral chemesthesis, taste and smell with COVID-19: a small case-control series.

Anosmia is common with respiratory virus infections, but loss of taste or chemesthesis is rare. Reports of true taste loss with COVID-19 were viewed skeptically until confirmed by multiple studies. Nasal menthol thresholds are elevated in some with prior COVID-19 infections, but data on oral chemesthesis are lacking. Many patients recover quickly, but precise timing and synchrony of recovery are unclear. Here, we collected broad sensory measures over 28 days, recruiting adults (18-45 years) who were COVID-19 positive or recently exposed (close contacts per U.S. CDC criteria at the time of the study) in the first half of 2021. Participants received nose clips, red commercial jellybeans (Sour Cherry and Cinnamon), and scratch-n-sniff cards (ScentCheckPro). Among COVID-19 cases who entered the study on or before Day 10 of infection, Gaussian Process Regression showed odor identification and odor intensity (two distinct measures of function) each declined relative to controls (close contacts who never developed COVID-19), but effects were larger for intensity than identification. To assess changes during early onset, we identified four COVID-19 cases who enrolled on or prior to Day 1 of their illness â€" this allowed for visualization of baseline ratings, loss, and recovery of function over time. Four controls were matched for age, gender, and race. Variables included sourness and sweetness (Sour Cherry jellybeans), oral burn (Cinnamon jellybeans), mean orthonasal intensity of four odors (ScentCheckPro), and perceived nasal blockage. Data were plotted over 28 days, creating panel plots for the eight cases and controls. Controls exhibited stable ratings over time. By contrast, COVID-19 cases showed sharp deviations over time. No single pattern of taste loss or recovery was apparent, implying different taste qualities might recover at different rates. Oral burn was transiently reduced for some before recovering quickly, suggesting acute loss may be missed in data collected after acute illness ends. Changes in odor intensity or odor identification were not explained by nasal blockage. Collectively, intensive daily testing shows orthonasal smell, oral chemesthesis and taste were each altered by acute COVID-19 infection, and this disruption was dyssynchronous for different modalities, with variable loss and recovery rates across modalities and individuals.

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.

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.

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.

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.

Gaze stability in youth athletes: A normative observational study.

BACKGROUND: The Gaze Stabilization Test (GST) assesses vestibulo-ocular reflex (VOR) function by determining the maximum head velocity at which an individual can accurately perceive a fixed-size visual target. There is limited information about gaze stability performance in youth athletes. OBJECTIVE: The purpose of this study is to describe baseline performance of athletes ages 17 years and under on a computerized GST and explore the influence of demographic characteristics on performance. METHODS: Baseline GST and demographic data were acquired via retrospective chart review. RESULTS: The sample included 106 athletes aged 8 to 17 years (mean 13.9 years±1.79; 78% male). The median values for baseline GST function were 180 (IQR: 150-210) degrees per second (d/sec) in the leftward direction, and 190 d/sec (IQR: 160-220) in the rightward direction. There were no significant effects of sex/gender or concussion history on GST performance. CONCLUSIONS: The GST is one of many tools available for clinicians to use in a multi-modal approach to concussion management. Understanding how healthy young athletes perform can assist clinicians in determining vestibular impairment, formulating the exercise prescription, and estimating physiologic recovery.

A behavioral paradigm for measuring perceptual distances in mice.

Perceptual similarities between a specific stimulus and other stimuli of the same modality provide valuable information about the structure and geometry of sensory spaces. While typically assessed in human behavioral experiments, perceptual similarities-or distances-are rarely measured in other species. However, understanding the neural computations responsible for sensory representations requires the monitoring and often manipulation of neural activity, which is more readily achieved in non-human experimental models. Here, we develop a behavioral paradigm that enables the quantification of perceptual similarity between sensory stimuli using mouse olfaction as a model system.

The perception of odor pleasantness is shared across cultures.

Humans share sensory systems with a common anatomical blueprint, but individual sensory experience nevertheless varies. In olfaction, it is not known to what degree sensory perception, particularly the perception of odor pleasantness, is founded on universal principles,1-5 dictated by culture,6-13 or merely a matter of personal taste.6,8-10,12,14 To address this, we asked 225 individuals from 9 diverse nonwestern cultures-hunter-gatherer to urban dwelling-to rank the monomolecular odorants from most to least pleasant. Contrary to expectations, culture explained only 6% of the variance in pleasantness rankings, whereas individual variability or personal taste explained 54%. Importantly, there was substantial global consistency, with molecular identity explaining 41% of the variance in odor pleasantness rankings. Critically, these universal rankings were predicted by the physicochemical properties of out-of-sample molecules and out-of-sample pleasantness ratings given by a tenth group of western urban participants. Taken together, this shows human olfactory perception is strongly constrained by universal principles.

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.

Late hemotoxicity following North American rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom and crotalidae immune polyvalent Fab (ovine) antivenom reported to the North American Snakebite Sub-registry.

INTRODUCTION: Late hemotoxicity is common following rattlesnake envenomation treated with crotalidae immune polyvalent Fab (ovine) (FabAV). Initial clinical trials showed crotalidae immune F(ab')2 (equine) (Fab2AV) to be superior to FabAV in preventing late hemotoxicity, but this effect has not been demonstrated in broader populations. This study investigated late hemotoxicity in patients receiving Fab2AV or FabAV after rattlesnake envenomation. METHODS: This is a retrospective analysis of prospectively collected data from patients with snakebite reported to the ToxIC North American Snakebite Registry (NASBR) between January 1, 2019, and December 31, 2020. Inclusion criteria were rattlesnake envenomation and administration of antivenom. Patients were excluded if they received more than one type of antivenom. The primary outcome was occurrence of late hemotoxicity (platelets ≤120 k/mm3 or fibrinogen ≤170 mg/dL) in patients receiving Fab2AV and FabAV. Data collected included demographics, envenomation characteristics, laboratory values, and treatment administered. Statistics including t-test and Fisher's exact test were used. RESULTS: A total of 201 rattlesnake envenomated patients receiving antivenom were reported to the NASBR in the study period; 144 were included. 49 received Fab2AV alone, 45 received FabAV alone and 50 received both antivenoms. Baseline patient and envenomation characteristics were similar between the groups. Late hemotoxicity occurred in 2/49 patients in the Fab2AV group (4% (95% CI 0.7-12.6)) and in 19/45 patients in the FabAV group (42% (95% CI 28.4-59.0); absolute risk reduction 39.1% (95% CI 21.2-46.2) (p = 0.001). On follow up, 0 patients (0%) receiving Fab2AV were retreated with antivenom; 4 patients (9%) receiving FabAV were retreated (p = 0.049). CONCLUSIONS: In the North American Snakebite Registry, late hemotoxicity was less common in rattlesnake envenomated patients treated with Fab2AV compared to FabAV.

The Effect of an Automated Order on Postpartum Opioid Use After Uncomplicated Vaginal Deliveries.

Background: To address the opioid epidemic, physicians are encouraged to identify means of reducing patient opioid exposure. Electronic medical records (EMRs) often include default order sets with automated orders for opioid medications, which may influence how much opioids physicians prescribe. We sought to evaluate the impact of de-selecting an automated order for oxycodone-acetaminophen from an EMR order set for postpartum vaginal deliveries on inpatient opioid exposure by comparing the proportion of patients who received an opioid after an uncomplicated vaginal delivery before and after the EMR change. As secondary outcomes, the impact on average total morphine milligram equivalents (MMEs) and discharge opioid prescriptions was investigated. Materials and Methods: A quality improvement study was conducted through retrospective chart review of uncomplicated vaginal deliveries for the four quarters before and after the EMR order set change occurred. The total proportion of patients who received an opioid in the postpartum period was then determined for the preexposure and postexposure groups. The total average MME consumed for patients who received an opioid in each group was determined and the total proportion of patients who received an opioid prescription at discharge was compared. Results: A total of 5826 records of uncomplicated vaginal deliveries met the criteria for analysis. In the preintervention group, 32.9% of patients received an opioid postpartum, compared to 12.5% of patients in the postintervention group, representing a decrease of 62.0% (p < 0.001). Of those who received opioids, the preintervention mean total opioid consumption was 28.4 MME (±27.6) compared to 33.6 MME (±46.4) postintervention, and there was no significant difference in median total opioid consumption: 22.5 MME (interquartile range [IQR]: 7.5-47.5) preintervention compared with 20.8 MME (IQR: 7.5-45.0) postintervention (p = 0.902). No significant difference was found with discharge opioid prescriptions between the two groups. Conclusion: Order sets within EMR systems appear to have a significant influence on physician prescribing behaviors and removing these automated orders for opioids should be considered.

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

PURPOSE: Many widely-used psychophysical tests of olfaction have limitations that can create barriers to adoption outside research settings. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and past experience with the odor. Conversely, threshold-based tests typically avoid these issues, but are labor intensive. Additionally, many commercially available olfactory tests are slow and may require a trained administrator, making them impractical for use in a short wellness visit or other broad clinical assessment. METHODS: 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 odor-delivery card -- in a non-clinical sample of individuals (n=534) at the 2021 Twins Day Festival in Twinsburg, OH. RESULTS: Participants successfully completed the test in under 3 min with a false alarm rate of 9.6% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold) and between the youngest and oldest age groups (~8.7-fold), consistent with prior work. 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. CONCLUSION: Together, these data indicate the ArOMa-T can determine odor detection thresholds. The ArOMa-T may be particularly valuable in clinical or field settings where rapid and portable assessment of olfactory function is needed.

The relationship of tidal volume and driving pressure with mortality in hypoxic patients receiving mechanical ventilation.

PURPOSE: To determine whether tidal volume/predicted body weight (TV/PBW) or driving pressure (DP) are associated with mortality in a heterogeneous population of hypoxic mechanically ventilated patients. METHODS: A retrospective cohort study involving 18 intensive care units included consecutive patients ≥18 years old, receiving mechanical ventilation for ≥3 days, with a PaO2/FiO2 ratio ≤300 mmHg, whether or not they met full criteria for ARDS. The main outcome was hospital mortality. Multiple logistic regression (MLR) incorporated TV/PBW, DP, and potential confounders including age, APACHE IVa® predicted hospital mortality, respiratory system compliance (CRS), and PaO2/FiO2. Predetermined strata of TV/PBW were compared using MLR. RESULTS: Our cohort comprised 5,167 patients with mean age 61.9 years, APACHE IVa® score 79.3, PaO2/FiO2 166 mmHg and CRS 40.5 ml/cm H2O. Regression analysis revealed that patients receiving DP one standard deviation above the mean or higher (≥19 cmH20) had an adjusted odds ratio for mortality (ORmort) = 1.10 (95% CI: 1.06-1.13, p = 0.009). Regression analysis showed a U-shaped relationship between strata of TV/PBW and adjusted mortality. Using TV/PBW 4-6 ml/kg as the referent group, patients receiving >10 ml/kg had similar adjusted ORmort, but those receiving 6-7, 7-8 and 8-10 ml/kg had lower adjusted ORmort (95%CI) of 0.81 (0.65-1.00), 0.78 (0.63-0.97) and 0.80 0.67-1.01) respectively. The adjusted ORmort in patients receiving 4-6 ml/kg was 1.26 (95%CI: 1.04-1.52) compared to patients receiving 6-10 ml/kg. CONCLUSIONS: Driving pressures ≥19 cmH2O were associated with increased adjusted mortality. TV/PBW 4-6ml/kg were used in less than 15% of patients and associated with increased adjusted mortality compared to TV/PBW 6-10 ml/kg used in 82% of patients. Prospective clinical trials are needed to prove whether limiting DP or the use of TV/PBW 6-10 ml/kg versus 4-6 ml/kg benefits mortality.

Deconstructing the mouse olfactory percept through an ethological atlas.

Odor perception in non-humans is poorly understood. Here, we generated the most comprehensive mouse olfactory ethological atlas to date, consisting of behavioral responses to a diverse panel of 73 odorants, including 12 at multiple concentrations. These data revealed that mouse behavior is incredibly diverse and changes in response to odorant identity and concentration. Using only behavioral responses observed in other mice, we could predict which of two odorants was presented to a held-out mouse 82% of the time. Considering all 73 possible odorants, we could uniquely identify the target odorant from behavior on the first try 20% of the time and 46% within five attempts. Although mouse behavior is difficult to predict from human perception, they share three fundamental properties: first, odor valence parameters explained the highest variance of olfactory perception. Second, physicochemical properties of odorants can be used to predict the olfactory percept. Third, odorant concentration quantitatively and qualitatively impacts olfactory perception. These results increase our understanding of mouse olfactory behavior and how it compares to human odor perception and provide a template for future comparative studies of olfactory percepts among species.