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Abstract Background IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis. Methods Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals. Results We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis. Conclusion Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.

Abstract Background The drug treatment field tends to place emphasis on the individual rather than the individual in social context. While there are a growing number of studies indicating that drug-using intimate partners are likely to play an important role in determining treatment options, little attention has been given to the experience and complex treatment needs of illicit drug-using (heroin, cocaine, crack) couples. Methods This exploratory study used in-depth interviews and ethnographic engagement to better understand the relationship between interpersonal dynamics and the treatment experience of ten relatively stable drug-using couples in Hartford, CT. Semi-structured and open-ended qualitative interviews were conducted with each couple and separately with each partner. Whenever possible, the day-to-day realities and contexts of risk were also observed via participant and non-participant observation of these couples in the community. A grounded theory approach was used to inductively code and analyze nearly 40 transcripts of 60–90 minute interviews as well as fieldnotes. Results This study builds on a concept of complex interpersonal dynamics among drug users. Interpersonal dynamics of care and collusion were identified: couples cared for each other and colluded to acquire and use drugs. Care and collusion operate at the micro level of the risk environment. Treatment barriers and inadequacies were identified as part of the risk environment at the meso or intermediate level of analysis, and larger social forces such as gender dynamics, poverty and the "War on Drugs" were identified at the macro level. Interpersonal dynamics posed problems for couples when one or both partners were interested in accessing treatment. Structural barriers presented additional obstacles with the denial of admittance of both partners to treatment programs which had a sole focus on the individual and avoided treating couples. Conclusion Detoxification and treatment facilities need to recognize the complex interplay between interpersonal dynamics which shape the treatment experience of couples, and which are also shaped by larger structural dynamics, including barriers in the treatment system. Improvements to the treatment system in general will go a long way in improving treatment for couples. Couples-specific programming also needs to be developed.

Abstract Background Romantic partnerships between drug-using couples, when they are recognized at all, tend to be viewed as dysfunctional, unstable, utilitarian, and often violent. This study presents a more nuanced portrayal by describing the interpersonal dynamics of 10 heroin and cocaine-using couples from Hartford, Connecticut. Results These couples cared for each other similarly to the ways that non-drug-using couples care for their intimate partners. However, most also cared by helping each other avoid the symptoms of drug withdrawal. They did this by colluding with each other to procure and use drugs. Care and collusion in procuring and using drugs involved meanings and social practices that were constituted and reproduced by both partners in an interpersonal dynamic that was often overtly gendered. These gendered dynamics could be fluid and changed over time in response to altered circumstances and/or individual agency. They also were shaped by and interacted with long-standing historical, economic and socio-cultural forces including the persistent economic inequality, racism and other forms of structural violence endemic in the inner-city Hartford neighborhoods where these couples resided. As a result, these relationships offered both risk and protection from HIV, HCV and other health threats (e.g. arrest and violence). Conclusion A more complex and nuanced understanding of drug-using couples can be tapped for its potential in shaping prevention and intervention efforts. For example, drug treatment providers need to establish policies which recognize the existence and importance of interpersonal dynamics between drug users, and work with them to coordinate detoxification and treatment for both partners, whenever possible, as well as provide additional couples-oriented services in an integrated and comprehensive drug treatment system.

Objective: One important factor in adolescents' development of problem alcohol use is their family environment. Yet, the mechanisms that relate parenting to youth alcohol use are not well characterized. This study employed a naturalistic laboratory-based approach to observe parenting behaviors (support, structure, criticism) and adolescents' physiological and emotional responses to parent-adolescent interactions to examine associations with adolescent alcohol use.Method: Fifty eight 10-16year olds and their parents completed a 10minute Parent Adolescent Interaction Task (PAIT) in which they discussed a mutually highly-rated conflict topic. Parental support, structure, and criticism were coded from the interaction. Adolescents' heart rate (HR), blood pressure (BP), reported emotions, and salivary cortisol were assessed before, during, and after the interaction.Results: Findings indicated that lower parental structure and support were associated with youth's greater diastolic BP and anger arousal in response to the PAIT. Furthermore, higher HR, systolic BP, and cortisol responses to the interaction were associated with youth's alcohol use.Conclusions: Findings suggest that heightened emotional and physiological responses to parent-adolescent conflict interactions in youth may be one pathway by which parenting is associated with adolescent alcohol use and risk for abuse. [ABSTRACT FROM AUTHOR]

Objective: Functional vascular imaging is a critical method for early detection and prevention of disease. Established non-contact vascular imaging techniques capture predominantly structural information. In this study, a novel non-contact label-free in vivo Photon Absorption Remote Sensing (PARS) microscope is developed for structural and functional vascular imaging., Methods: The presented in vivo PARS microscope captures the endogenous absorption of green (532nm) light to form a complete picture of vasculature and surrounding tissues. Imaging system repeatability is enhanced through robust transient absorption signal extraction, and state-of-the-art real-time alignment methods., Results: Detailed imaging of vascular structure is demonstrated through in vivo microscopy of two established animal models: mouse ear and chicken embryo. Preliminary functional contrast is realized through video rate imaging of red blood cell dynamics in the capillary networks of chicken embryos., Conclusion: The presented in vivo PARS microscope successfully captures detailed structural and functional vascular contrast., Significance: This innovative non-contact label-free imaging technique holds promise as a tool for preventative medical care, as functional change often precedes structural change.

The Homo sapiens Chromosomal Location Ontology (HSCLO) is designed to facilitate the integration of human genomic features into biomedical knowledge graphs from releases GRCh37 and GRCh38 at multiple resolutions. HSCLO comprises two distinct versions, HSCLO37 and HSCLO38, each tailored to its respective human genome release. This ontology supports the efficient integration and analysis of human genomic data across scales ranging from entire chromosomes to individual base pairs, thereby enhancing data retrieval and interoperability within large-scale biomedical datasets. Unlike existing ontologies that primarily focus on genomic feature identification or annotation, HSCLO is specifically engineered to optimize the interoperability and scalability of genomic data within biomedical knowledge graphs. The utility and performance of HSCLO are demonstrated through a case study involving the integration of high-resolution chromatin interaction data, which reveals significant improvements in query efficiency and data linkage. HSCLO represents a valuable resource for advancing research in disease genetics, personalized medicine, and other domains that require complex genomic data integration., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Over the past decade, there has been substantial growth in both the quantity and complexity of available biomedical data. In order to more efficiently harness this extensive data and alleviate challenges associated with integration of multi-omics data, we developed Petagraph, a biomedical knowledge graph that encompasses over 32 million nodes and 118 million relationships. Petagraph leverages more than 180 ontologies and standards in the Unified Biomedical Knowledge Graph (UBKG) to embed millions of quantitative genomics data points. Petagraph provides a cohesive data environment that enables users to efficiently analyze, annotate, and discern relationships within and across complex multi-omics datasets supported by UBKG's annotation scaffold. We demonstrate how queries on Petagraph can generate meaningful results across various research contexts and use cases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Echolocating big brown bats ( Eptesicus fuscus ) detect changes in ultrasonic echo delay with an acuity as sharp as 1 µs or less. How this perceptual feat is accomplished in the nervous system remains unresolved. Here, we examined the precision of latency registration (latency jitter) in neural population responses as a possible mechanism underlying the bat's hyperacuity. We recorded local field potentials in the cochlear nucleus and inferior colliculus of anesthetized big brown bats to sequences of sounds consisting of a simulated frequency-modulated broadcast followed, at various echo delays, by a four-echo cascade. Latencies of the first negative response peak to the broadcast and to the first echo in the cascade were shorter in the cochlear nucleus than in the inferior colliculus, but latency jitter of this peak was comparable in both brainstem nuclei. Mean latency jitter, averaged over all stimulus conditions, was 51 µs in the cochlear nucleus and 56 µs in the inferior colliculus. Latency jitter to the successive echoes in the echo cascades was larger, with means of 125 µs and 111 µs, respectively. These values are lower than values commonly reported for single-neuron latency variability in bats and other mammals, and they approach within an order of magnitude the big brown bat's psychophysical performance. Latency jitter for synchronized population responses on a scale of microseconds reduces the gap between neurophysiological and behavioral measures of acuity. Further systems-level analysis is necessary for understanding neural mechanisms of perception. NEW & NOTEWORTHY Echolocating big brown bats resolve time delays with a sharp precision of 1 µs or less. How this hyperacuity is accomplished in the auditory system is unknown. We now report that the precision of latency registration (latency jitter) in population activity from two brainstem nuclei in response to simulated echolocation sounds is in the range of tens of microseconds. These values are smaller than observed in single neuron responses and approach the bat's psychophysical acuity.

Glenis Long championed the application of quantitative psychophysical methods to understand comparative hearing abilities across species. She contributed the first psychophysical studies of absolute and masked hearing sensitivities in an auditory specialist, the echolocating horseshoe bat. Her data demonstrated that this bat has hyperacute frequency discrimination in the 83-kHz range of its echolocation broadcast. This specialization facilitates the bat's use of Doppler shift compensation to separate echoes of fluttering insects from concurrent echoes of non-moving objects. In this review, we discuss another specialization for hearing in a species of echolocating bat that contributes to perception of echoes within a complex auditory scene. Psychophysical and behavioral studies with big brown bats show that exposures to long duration, intense wideband or narrowband ultrasonic noise do not induce significant increases in their thresholds to echoes and do not impair their ability to orient through a naturalistic sonar scene containing multiple distracting echoes. Thresholds of auditory brainstem responses also remain low after intense noise exposures. These data indicate that big brown bats are not susceptible to temporary threshold shifts as measured in comparable paradigms used with other mammals, at least within the range of stimulus parameters that have been tested so far. We hypothesize that echolocating bats have evolved a decreased susceptibility to noise-induced hearing losses as a specialization for echolocation in noisy environments., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Echolocating big brown bats (Eptesicus fuscus) broadcast downward frequency-modulated sweeps covering the ultrasonic range from 100-23 kHz in two harmonics. They perceive target range from the time delay between each broadcast and its returning echo. Previous experiments indicated that the bat's discrimination acuity for broadcast-echo delay declines when the lowest frequencies (23-35 kHz) in the first harmonic of an echo are removed. This experiment examined whether echo detection is similarly impaired. Results show that detection thresholds for echoes missing these lowest frequencies are raised. Increased thresholds for echoes differing in spectra facilitates the bat's ability to discriminate against clutter., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Echolocating big brown bats (Eptesicus fuscus) broadcast frequency modulated (FM) ultrasonic pulses containing two prominent harmonic sweeps (FM1, FM2). Both harmonics typically return as echoes at the same absolute time delay following the broadcast, making them coherent. Electronically splitting FM1 and FM2 allows their time delays to be controlled separately, making them non-coherent. Earlier work shows that big brown bats discriminate coherent from split harmonic, non-coherent echoes and that disruptions of harmonic coherence produce blurry acoustic images. A psychophysical experiment on two trained big brown bats tested the hypothesis that detection thresholds for split harmonic, non-coherent echoes are higher than those for coherent echoes. Thresholds of the two bats for detecting 1-glint echoes with coherent harmonics were around 35 and 36 dB sound pressure level, respectively, while thresholds for split harmonic echoes were about 10 dB higher. When the delay of FM2 in split harmonic echoes is shortened by 75 μs to offset neural amplitude-latency trading and restore coherence in the auditory representation, thresholds decreased back down to those estimated for coherent echoes. These results show that echo detection is affected by loss of harmonic coherence, consistent with the proposed broader role of coherence across frequencies for auditory perception., (© 2023 Acoustical Society of America.)

The cochlear nucleus (CN) receives ipsilateral input from the auditory nerve and projects to other auditory brainstem nuclei. Little is known about CN processing of signals used for echolocation. This study recorded multiple unit activity in the CN of anesthetized big brown bats (Eptesicus fuscus) to ultrasonic frequency-modulated (FM) sweeps differing in sweep direction. FM up-sweeps evoke larger peak amplitudes at shorter onset latencies and with smaller amplitude-latency trading ratios than FM down-sweeps. Variability of onset latencies is in the tens of microsecond ranges, indicating sharp temporal precision in the CN for coding of FM signals., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: The echolocating bat is used as a model for studying the auditory nervous system because its specialized sensory capabilities arise from general mammalian auditory percepts such as pitch and sound source localization. These percepts are mediated by precise timing within neurons and networks of the lower auditory brainstem, where the gap junction protein Connexin36 (CX36) is expressed. Gap junctions and electrical synapses in the central nervous system are associated with fast transmission and synchronous patterns of firing within neuronal networks. The purpose of this study was to identify areas where CX36 was expressed in the bat cochlear nucleus to shed light on auditory brainstem networks in a hearing specialist animal model., Methods: We investigated the distribution of CX36 RNA throughout the cochlear nucleus complex of the echolocating big brown bat, Eptesicus fuscus, using in situ hybridization. As a qualitative comparison, we visualized Gjd2 gene expression in the cochlear nucleus of transgenic CX36 reporter mice, species that hear ultrasound but do not echolocate., Results: In both the bat and the mouse, CX36 is expressed in the anteroventral and in the dorsal cochlear nucleus, with more limited expression in the posteroventral cochlear nucleus. These results are generally consistent with previous work based on immunohistochemistry., Conclusion: Our data suggest that the anatomical substrate for CX36-mediated electrical neurotransmission is conserved in the mammalian CN across echolocating bats and non-echolocating mice., (© 2023. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Background: Recent work has shown inpatient length of stay (LOS) following shoulder arthroplasty to hold the second strongest association with overall cost (after implant cost itself). In particular, a preoperative understanding for the patients at risk of extended inpatient stays (≥3 days) can allow for counseling, optimization, and anticipating postoperative adverse events., Methods: A multicenter retrospective review was performed of 5410 anatomic (52%) and reverse (48%) total shoulder arthroplasties done at 2 large, tertiary referral health systems. The primary outcome was extended inpatient LOS of at least 3 days, and over 40 preoperative sociodemographic and comorbidity factors were tested for their predictive ability in a multivariable logistic regression model based on the patient cohort from institution 1 (derivation, N = 1773). External validation was performed using the patient cohort from institution 2 (validation, N = 3637), including area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values., Results: A total of 814 patients, including 318 patients (18%) in the derivation cohort and 496 patients (14%) in the validation cohort, experienced an extended inpatient LOS of at least 3 days. Four hundred forty-five (55%) were discharged to a skilled nursing or rehabilitation facility. Following parameter selection, a multivariable logistic regression model based on the derivation cohort (institution 1) demonstrated excellent preliminary accuracy (AUC: 0.826), with minimal decrease in accuracy under external validation when tested against the patients from institution 2 (AUC: 0.816). The predictive model was composed of only preoperative factors, in descending predictive importance as follows: age, marital status, fracture case, ASA (American Society of Anesthesiologists) score, paralysis, electrolyte disorder, body mass index, gender, neurologic disease, coagulation deficiency, diabetes, chronic pulmonary disease, peripheral vascular disease, alcohol dependence, psychoses, smoking status, and revision case., Conclusion: A freely-available, preoperative online clinical decision tool for extended inpatient LOS (≥ 3 days) after shoulder arthroplasty reaches excellent predictive accuracy under external validation. As a result, this tool merits consideration for clinical implementation, as many risk factors are potentially modifiable as part of a preoperative optimization strategy., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Subsequent to his breakthrough discovery of delay-tuned neurons in the bat's auditory midbrain and cortex, Albert Feng proposed that neural computations for echo delay involve intrinsic oscillatory discharges generated in the inferior colliculus (IC). To explore further the presence of these neural oscillations, we recorded multiple unit activity with a novel annular low impedance electrode from the IC of anesthetized big brown bats and Seba's short-tailed fruit bats. In both species, responses to tones, noise bursts, and FM sweeps contain long latency components, extending up to 60 ms post-stimulus onset, organized in periodic, oscillatory-like patterns at frequencies of 360-740 Hz. Latencies of this oscillatory activity resemble the wide distributions of single neuron response latencies in the IC. In big brown bats, oscillations lasting up to 30 ms after pulse onset emerge in response to single FM pulse-echo pairs, at particular pulse-echo delays. Oscillatory responses to pulses and evoked responses to echoes overlap extensively at short echo delays (5-7 ms), creating interference-like patterns. At longer echo delays, responses are separately evident to both pulses and echoes, with less overlap. These results extend Feng's reports of IC oscillations, and point to different processing mechanisms underlying perception of short vs long echo delays., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We introduce two EEG techniques, one based on conventional monopolar electrodes and one based on a novel tripolar electrode, to record for the first time auditory brainstem responses (ABRs) from the scalp of unanesthetized, unrestrained big brown bats. Stimuli were frequency-modulated (FM) sweeps varying in sweep direction, sweep duration, and harmonic structure. As expected from previous invasive ABR recordings, upward-sweeping FM signals evoked larger amplitude responses (peak-to-trough amplitude in the latency range of 3-5 ms post-stimulus onset) than downward-sweeping FM signals. Scalp-recorded responses displayed amplitude-latency trading effects as expected from invasive recordings. These two findings validate the reliability of our noninvasive recording techniques. The feasibility of recording noninvasively in unanesthetized, unrestrained bats will energize future research uncovering electrophysiological signatures of perceptual and cognitive processing of biosonar signals in these animals, and allows for better comparison with ABR data from echolocating cetaceans, where invasive experiments are heavily restricted., (© 2022. The Author(s).)

Background: As bundled payment models continue to spread, understanding the primary drivers of cost excess helps providers avoid penalties and ensure equal health care access. Recent work has shown discharge to rehabilitation and skilled nursing facilities (SNFs) to be a primary cost driver in total joint arthroplasty, and an accurate preoperative risk calculator for shoulder arthroplasty would not only help counsel patients in clinic during shared decision-making conversations but also identify high-risk individuals who may benefit from preoperative optimization and discharge planning., Methods: Anatomic and reverse total shoulder arthroplasty cohorts from 2 geographically diverse, high-volume centers were reviewed, including 1773 cases from institution 1 (56% anatomic) and 3637 from institution 2 (50% anatomic). The predictive ability of a variety of candidate variables for discharge to SNF/rehabilitation was tested, including case type, sociodemographic factors, and the 30 Elixhauser comorbidities. Variables surviving parameter selection were incorporated into a multivariable logistic regression model built from institution 1's cohort, with accuracy then validated using institution 2's cohort., Results: A total of 485 (9%) shoulder arthroplasties overall were discharged to post-acute care (anatomic: 6%, reverse: 14%, P < .0001), and these patients had significantly higher rates of unplanned 90-day readmission (5% vs. 3%, P = .0492). Cases performed for preoperative fracture were more likely to require post-acute care (13% vs. 3%, P < .0001), whereas revision cases were not (10% vs. 10%, P = .8015). A multivariable logistic regression model derived from the institution 1 cohort demonstrated excellent preliminary accuracy (area under the receiver operating characteristic curve [AUC]: 0.87), requiring only 11 preoperative variables (in order of importance): age, marital status, fracture, neurologic disease, paralysis, American Society of Anesthesiologists physical status, gender, electrolyte disorder, chronic pulmonary disease, diabetes, and coagulation deficiency. This model performed exceptionally well during external validation using the institution 2 cohort (AUC: 0.84), and to facilitate convenient use was incorporated into a freely available, online prediction tool. A model built using the combined cohort demonstrated even higher accuracy (AUC: 0.89)., Conclusions: This validated preoperative clinical decision tool reaches excellent predictive accuracy for discharge to SNF/rehabilitation following shoulder arthroplasty, providing a vital tool for both patient counseling and preoperative discharge planning. Further, model parameters should form the basis for reimbursement legislation adjusting for patient comorbidities, ensuring no disparities in access arise for at-risk populations., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The transition from inpatient to outpatient shoulder arthroplasty critically depends on appropriate patient selection, both to ensure safety and to counsel patients preoperatively regarding individualized risk. Cost and patient demand for same-day discharge have encouraged this transition, and a validated predictive tool may help decrease surgeon liability for complications and help select patients appropriate for same-day discharge. We hypothesized that an accurate predictive model could be created for short inpatient length of stay (discharge at least by postoperative day 1), potentially serving as a useful proxy for identifying patients appropriate for true outpatient shoulder arthroplasty., Methods: A multicenter cohort of 5410 shoulder arthroplasties (2805 anatomic and 2605 reverse shoulder arthroplasties) from 2 geographically diverse, high-volume health systems was reviewed. Short inpatient stay was the primary outcome, defined as discharge on either postoperative day 0 or 1, and 49 patient outcomes and factors including the Elixhauser Comorbidity Index, sociodemographic factors, and intraoperative parameters were examined as candidate predictors for a short stay. Factors surviving parameter selection were incorporated into a multivariable logistic regression model, which underwent internal validation using 10,000 bootstrapped samples., Results: In total, 2238 patients (41.4%) were discharged at least by postoperative day 1, with no difference in rates of 90-day readmission (3.5% vs. 3.3%, P = .774) between cohorts with a short length of stay and an extended length of stay (discharge after postoperative day 1). A multivariable logistic regression model demonstrated high accuracy (area under the receiver operator characteristic curve, 0.762) for discharge by postoperative day 1 and was composed of 13 variables: surgery duration, age, sex, electrolyte disorder, marital status, American Society of Anesthesiologists score, paralysis, diabetes, neurologic disease, peripheral vascular disease, pulmonary circulation disease, cardiac arrhythmia, and coagulation deficiency. The percentage cutoff maximizing sensitivity and specificity was calculated to be 47%. Internal validation showed minimal loss of accuracy after bias correction for overfitting, and the predictive model was incorporated into a freely available online tool to facilitate easy clinical use., Conclusions: A risk prediction tool for short inpatient length of stay after shoulder arthroplasty reaches very good accuracy despite requiring only 13 variables and was derived from an underlying database with broad geographic diversity in the largest institutional shoulder arthroplasty cohort published to date. Short inpatient length of stay may serve as a proxy for identifying patients appropriate for same-day discharge, although perioperative care decisions should always be made on an individualized and holistic basis., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Big brown bats echolocate using wideband frequency-modulated (FM) ultrasonic pulses, perceiving target range from echo delay and target size from echo amplitude. Echolocation pulses contain two prominent down-sweeping harmonics (FM1, ∼55-22 kHz; FM2, ∼100-55 kHz), which are affected differently by propagation to the target and back to the bat. Previous work demonstrates that big brown bats utilize the low frequencies in FM1 for target ranging, while FM2 only contributes if FM1 is also present. The present experiments test the hypothesis that the bat's ability to discriminate echo amplitude is also affected by selectively attenuating FM1 or FM2 in target or nontarget echoes. Bats were trained to perform an amplitude discrimination task with virtual echo targets located 83 cm away. Echo delay was fixed and echo amplitude was varied, while either FM1 or FM2 was attenuated by highpass or lowpass filtering. Bats' performance decreased when lower frequencies were attenuated in target echoes and when higher frequencies were attenuated in nontarget echoes. Performance was reversed in the opposite filtering conditions. The bat's ability to distinguish between virtual targets varying in amplitude at the same simulated range indicates a high level of focused attention for perceptual isolation of target from non-target echoes.

Background: The variability of coronavirus disease 2019 (COVID-19) illness severity has puzzled clinicians and has sparked efforts to better predict who would benefit from rapid intervention. One promising biomarker for in-hospital morbidity and mortality is cardiac troponin (cTn)., Methods: A retrospective study of 1331 adult patients with COVID-19 admitted to the Rush University System in Illinois, USA was performed. Patients without cTn measurement during their admission or a history of end stage renal disease or stage 5 chronic kidney disease were excluded. Using logistic regression adjusted for baseline characteristics, pre-existing comorbidities, and other laboratory markers of inflammation, cTn was assessed as a predictor of 60-day mortality and severe COVID-19 infection, consisting of a composite of 60-day mortality, need for intensive care unit, or requiring non-invasive positive pressure ventilation or intubation., Results: A total of 772 patients met inclusion criteria. Of these, 69 (8.9%) had mild cTn elevation (> 1 to < 2x upper limit of normal (ULN)) and 46 (6.0%) had severe cTn elevation (≥ 2x ULN). Regardless of baseline characteristics, comorbidities, and initial c-reactive protein, lactate dehydrogenase, and ferritin, when compared to the normal cTn group, mild cTn elevation and severe cTn elevation were predictors of severe COVID-19 infection (adjusted OR [aOR] aOR 3.00 [CI: 1.51 - 6.29], P < 0.01; aOR 9.96 [CI: 2.75 - 64.23], P < 0.01, respectively); severe cTn elevation was a predictor of in-hospital mortality (aOR 2.42 [CI: 1.10 - 5.21], P < 0.05) and 60-day mortality (aOR 2.45 [CI: 1.13 - 5.25], P < 0.05)., Conclusion: In our cohort, both mild and severe initial cTn elevation were predictors of severe COVID-19 infection, while only severe cTn elevation was predictive of 60-day mortality. First cTn value on hospitalization is a valuable longitudinal prognosticator for COVID-19 disease severity and mortality., (Copyright © 2021. Published by Elsevier Inc.)

Study Objective: Chest computed tomography (chest CT) is routinely obtained to assess disease severity in COVID-19. While pulmonary findings are well-described in COVID-19, the implications of cardiovascular findings are less well understood. We evaluated the impact of cardiovascular findings on chest CT on the adverse composite outcome (ACO) of hospitalized COVID-19 patients., Setting/participants: 245 COVID-19 patients who underwent chest CT at Rush University Health System were included., Design: Cardiovascular findings, including coronary artery calcification (CAC), aortic calcification, signs of right ventricular strain [right ventricular to left ventricular diameter ratio, pulmonary artery to aorta diameter ratio, interventricular septal position, and inferior vena cava (IVC) reflux], were measured by trained physicians., Interventions/main Outcome Measures: These findings, along with pulmonary findings, were analyzed using univariable logistic analysis to determine the risk of ACO defined as intensive care admission, need for non-invasive positive pressure ventilation, intubation, in-hospital and 60-day mortality. Secondary endpoints included individual components of the ACO., Results: Aortic calcification was independently associated with an increased risk of the ACO (odds ratio 1.86, 95% confidence interval (1.11-3.17) p  < 0.05). Aortic calcification, CAC, abnormal septal position, or IVC reflux of contrast were all significantly associated with 60-day mortality and major adverse cardiovascular events. IVC reflux was associated with in-hospital mortality ( p  = 0.005)., Conclusion: Incidental cardiovascular findings on chest CT are clinically important imaging markers in COVID-19. It is important to ascertain and routinely report cardiovascular findings on CT imaging of COVID-19 patients as they have potential to identify high risk patients., Competing Interests: The authors have no conflicts of interest to disclose. The authors have no competing interests. The Conflict of Interest Form is attached., (© 2021 Published by Elsevier Inc.)

Echolocating big brown bats ( Eptesicus fuscus ) perceive their surroundings by broadcasting frequency-modulated (FM) ultrasonic pulses and processing returning echoes. Bats echolocate in acoustically cluttered environments containing multiple objects, where each broadcast is followed by multiple echoes at varying time delays. The bat must decipher this complex echo cascade to form a coherent picture of the entire acoustic scene. Neurons in the bat's inferior colliculus (IC) are selective for specific acoustic features of echoes and time delays between broadcasts and echoes. Because of this selectivity, different subpopulations of neurons are activated as the bat flies through its environment, while the physical scene itself remains unchanging. We asked how a neural representation based on variable single-neuron responses could underlie a cohesive perceptual representation of a complex scene. We recorded local field potentials from the IC of big brown bats to examine population coding of echo cascades similar to what the bat might encounter when flying alongside vegetation. We found that the temporal patterning of a simulated broadcast followed by an echo cascade is faithfully reproduced in the population response at multiple stimulus amplitudes and echo delays. Local field potentials to broadcasts and echo cascades undergo amplitude-latency trading consistent with single-neuron data but rarely show paradoxical latency shifts. Population responses to the entire echo cascade move as a unit coherently in time as broadcast-echo cascade delay changes, suggesting that these responses serve as an index for the formation of a cohesive perceptual representation of an acoustic scene. NEW & NOTEWORTHY Echolocating bats navigate through cluttered environments that return cascades of echoes in response to the bat's broadcasts. We show that local field potentials from the big brown bat's auditory midbrain have consistent responses to a simulated echo cascade varying across echo delays and stimulus amplitudes, despite different underlying individual neuronal selectivities. These results suggest that population activity in the midbrain can build a cohesive percept of an auditory scene by aggregating activity over neuronal subpopulations.

Background: To investigate sex differences in coronavirus disease 2019 (COVID-19) outcomes in a large Illinois-based cohort. Methods: A multicenter retrospective cohort study compared males versus females with COVID-19 infections from March 1, 2020, to June 21, 2020, in the Rush University System. We analyzed sex differences in rates of hospitalization, intensive care unit (ICU) admission, vasopressor use, endotracheal intubation, and death in this cohort. A multivariable model correcting for age and sum of comorbidities was used to explore associations between sex and COVID-19-related outcomes. Results: There were 8108 positive COVID-19 patients-4300 (53.0%) females and 3808 (47.0%) males. Males had higher rates of hospitalization (19% vs. 13%; p  < 0.001), ICU transfer (8% vs. 4%; p  < 0.001), vasopressor support (4% vs. 2%; p  < 0.001), and endotracheal intubation (5% vs. 2%; p  < 0.001). Of those who died, 92 were males and 64 were females (2% vs. 1%; p  = 0.003). A multivariable model correcting for age and sum of comorbidities showed a significant association between male sex and mortality in the total cohort (odds ratio, 1.96; 95% confidence interval, 1.34-2.90; p  = 0.001). Conclusion: Male sex was independently associated with death, hospitalization, ICU admissions, and need for vasopressors or endotracheal intubation, after correction for important covariates.

We challenged four big brown bats to maneuver through abrupt turns in narrow corridors surrounded by dense acoustic clutter. We quantified bats' performance, sonar beam focus, and sensory acquisition rate. Performance was excellent in straight corridors, with sonar beam aim deviating less than 5° from the corridor midline. Bats anticipated an upcoming abrupt turn to the right or left by slowing flight speed and shifting beam aim to "look" proactively into one side of the corridor to identify the new flightpath. All bats mastered the right turn, but two bats consistently failed the left turn. Bats increased their sensory acquisition rate when confronting abrupt turns in both successful and failed flights. Limitations on biosonar performance reflected failures to switch beam aim and to modify a learned spatial map, rather than failures to update acquisition rate., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Computational models of animal biosonar seek to identify critical aspects of echo processing responsible for the superior, real-time performance of echolocating bats and dolphins in target tracking and clutter rejection. The Spectrogram Correlation and Transformation (SCAT) model replicates aspects of biosonar imaging in both species by processing wideband biosonar sounds and echoes with auditory mechanisms identified from experiments with bats. The model acquires broadband biosonar broadcasts and echoes, represents them as time-frequency spectrograms using parallel bandpass filters, translates the filtered signals into ten parallel amplitude threshold levels, and then operates on the resulting time-of-occurrence values at each frequency to estimate overall echo range delay. It uses the structure of the echo spectrum by depicting it as a series of local frequency nulls arranged regularly along the frequency axis of the spectrograms after dechirping them relative to the broadcast. Computations take place entirely on the timing of threshold-crossing events for each echo relative to threshold-events for the broadcast. Threshold-crossing times take into account amplitude-latency trading, a physiological feature absent from conventional digital signal processing. Amplitude-latency trading transposes the profile of amplitudes across frequencies into a profile of time-registrations across frequencies. Target shape is extracted from the spacing of the object's individual acoustic reflecting points, or glints, using the mutual interference pattern of peaks and nulls in the echo spectrum. These are merged with the overall range-delay estimate to produce a delay-based reconstruction of the object's distance as well as its glints. Clutter echoes indiscriminately activate multiple parts in the null-detecting system, which then produces the equivalent glint-delay spacings in images, thus blurring the overall echo-delay estimates by adding spurious glint delays to the image. Blurring acts as an anticorrelation process that rejects clutter intrusion into perceptions., Competing Interests: The authors have declared that no competing interests exist.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

We used a novel microendoscope system to record simultaneously optical activity (fluorescence of a calcium indicator dye) and electrical activity (multi-unit activity and local field potentials) from the dorsal inferior colliculus of the echolocating bat, Carollia perspicillata. Optically recorded calcium responses to wide-band noise and to frequency-modulated bursts were recorded at probe depths down to 1300 µm, with the majority of active sites encountered at more shallow depths down to 800 µm. Calcium activity exhibited long latencies, within the time span of 50-100 ms after stimulus onset, significantly longer than onset latencies of either multi-unit activity or local field potentials. Latencies and amplitude/latency trading of these electrical responses were consistent with those seen in standard electrophysiological recordings, confirming that the microendoscope was able to record both neural and optical activity successfully. Optically recorded calcium responses rose and decayed slowly and were correlated in time with long-latency negative deflections in local field potentials. These data suggest that calcium-evoked responses may reflect known, sustained inhibitory interactions in the inferior colliculus.

Big brown bats transmit wideband FM biosonar sounds that sweep from 55 to 25 kHz (first harmonic, FM1) and from 110 to 50 kHz (second harmonic, FM2). FM1 is required to perceive echo delay for target ranging; FM2 contributes only if corresponding FM1 frequencies are present. We show that echoes need only the lowest FM1 broadcast frequencies of 25 to 30 kHz for delay perception. If these frequencies are removed, no delay is perceived. Bats begin echo processing at the lowest frequencies and accumulate perceptual acuity over successively higher frequencies, but they cannot proceed without the low-frequency starting point in their broadcasts. This reveals a solution to pulse-echo ambiguity, a serious problem for radar or sonar. In dense, extended biosonar scenes, bats have to emit sounds rapidly to avoid collisions with near objects. But if a new broadcast is emitted when echoes of the previous broadcast still are arriving, echoes from both broadcasts intermingle, creating ambiguity about which echo corresponds to which broadcast. Frequency hopping by several kilohertz from one broadcast to the next can segregate overlapping narrowband echo streams, but wideband FM echoes ordinarily do not segregate because their spectra still overlap. By starting echo processing at the lowest frequencies in frequency-hopped broadcasts, echoes of the higher hopped broadcast are prevented from being accepted by lower hopped broadcasts, and ambiguity is avoided. The bat-inspired spectrogram correlation and transformation (SCAT) model also begins at the lowest frequencies; echoes that lack them are eliminated from processing of delay and no longer cause ambiguity., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Beaches around the world continuously adjust to daily and seasonal changes in wave and tide conditions, which are themselves changing over longer time-scales. Different approaches to predict multi-year shoreline evolution have been implemented; however, robust and reliable predictions of shoreline evolution are still problematic even in short-term scenarios (shorter than decadal). Here we show results of a modelling competition, where 19 numerical models (a mix of established shoreline models and machine learning techniques) were tested using data collected for Tairua beach, New Zealand with 18 years of daily averaged alongshore shoreline position and beach rotation (orientation) data obtained from a camera system. In general, traditional shoreline models and machine learning techniques were able to reproduce shoreline changes during the calibration period (1999-2014) for normal conditions but some of the model struggled to predict extreme and fast oscillations. During the forecast period (unseen data, 2014-2017), both approaches showed a decrease in models' capability to predict the shoreline position. This was more evident for some of the machine learning algorithms. A model ensemble performed better than individual models and enables assessment of uncertainties in model architecture. Research-coordinated approaches (e.g., modelling competitions) can fuel advances in predictive capabilities and provide a forum for the discussion about the advantages/disadvantages of available models.

Mines and caves provide essential roosting places for bats, but often they are obstructed to prevent entry by humans. To allow bats to access their roosts, metal corrugated culvert pipes are sometimes installed. Wildlife surveys indicate, however, that bats may abandon caves having corrugated culvert entrances. Culverts may be confusing to bats due to the complex patterns of echoes returned by the regular, ring-like corrugations. We tested the hypothesis that a circular tunnel composed of successive hoops is difficult for big brown bats (Eptesicus fuscus) to navigate. Experiments challenged bats with flights through a tunnel of round plastic hoops or a corridor flanked left and right by rows of plastic hanging chains. The bats swerved sideways and left the pathway on more flights in the hoop tunnel compared to only rarely in the chain corridor. Even during successful flights through the hoops, bats changed the temporal patterning of their echolocation pulses to compress them into more sonar sound groups. From prior research, this active reaction is an indicator of a perceptually more difficult task. To allow bats access to mines through culverts without affecting their echolocation behavior, smoothing or masking the regular corrugations inside with concrete may be effective.

During nightly foraging activity, echolocating bats drink by flying low over the water surface and dipping the lower jaw while avoiding further bodily contact with the water. This task poses different sensorimotor challenges than flying in the open to forage for insects. Of interest is how bats adjust the timing of their echolocation pulses to accommodate the surrounding scene, from the progressively nearer water surface itself to objects at longer distances. Drinking behavior has been described in only a few of the roughly 1,000 echolocating bat species, and in none of the 110 species in the Indian subcontinent. Here, we describe how bats emitting frequency-modulated (FM) echolocation pulses behaved while drinking from a swimming pool in urban northeast India. At least two different bat species were present, using 1st-harmonic frequencies sweeping down to about 35 Hz ("low frequency") and down to about 50 kHz ("high frequency"), separable at a 40 kHz boundary. Over entire drinking maneuvers, intervals between broadcast pulses accommodate both the proximate task of registering the water surface while drinking and registering echoes from the farther reaches of the scene. During approach to the water, both low and high frequency bats emit longer, more stable interpulse intervals that matched the time interval covering echo arrival-times out to the frequency-dependent maximum operating range. High frequency bats use shorter interpulse intervals than low frequency bats, consistent with the shorter operating range at higher frequencies. Bats then accelerate their pulse rate to guide the dive down to drinking, with low frequency bats continuing to decrease pulse intervals and high frequency bats maintaining a more steady interval during the drinking buzz. The circumstance that both groups were engaged in the same task made this a natural experiment on the behavior during approach., Competing Interests: The authors have declared that no competing interests exist.

Numerous bat species emit wideband frequency-modulated signals for echolocation to hunt prey and avoid obstacles. Research investigating the behavioral and physiological responses of bats to echoes typically includes analysis of acoustic signals from microphones and/or microphone arrays, using time difference of arrival between array elements or the microphones to locate flying bats (azimuth and elevation). This has provided insight into transmission adaptations such as pulse duration and duty cycle with respect to target distance, clutter, and interferers. Microphones recording transmitted signals and echoes near a stationary bat provide sound pressure as a function of time but no directional information. In this work, the authors propose a spatial audio/soundfield microphone array to both track bats in flight and pinpoint the directions of echoes received by a bat. The authors introduce an ultrasonic (20-80 kHz) tetrahedral soundfield microphone to capture bat sounds up to 80 kHz. A spatial audio decoding technique called high angular resolution planewave expansion (HARPEx) supplies angle and elevation estimates, either for a flying bat based on the bat pulses or for targets based on echoes. Experiments using the soundfield microphone and HARPEx show that the approach accurately estimates the sound direction of arrival in both scenarios.

In many mammals, upward-sweeping frequency-modulated (FM) sounds (up-chirps) evoke larger auditory brainstem responses than downward-sweeping sounds (down-chirps). To determine if similar effects occur in FM echolocating bats, auditory evoked responses (AERs) in big brown bats in response to up-chirps and down-chirps at different chirp durations and levels were recorded. Even though down-chirps are the biologically relevant stimulus for big brown bats, up-chirps typically evoked larger peaks in the AER, but with some exceptions at the shortest chirp durations. The up-chirp duration that produced the largest AERs and the greatest differences between up-chirps and down-chirps varied between individual bats and stimulus levels. Cross-covariance analyses using the entire AER waveform confirmed that amplitudes were typically larger to up-chirps than down-chirps at supra-threshold levels, with optimal durations around 0.5-1 ms. Changes in response latencies with stimulus levels were consistent with previous estimates of amplitude-latency trading. Latencies tended to decrease with increasing up-chirp duration and increase with increasing down-chirp duration. The effects of chirp direction on AER waveforms are generally consistent with those seen in other mammals but with small differences in response patterns that may reflect specializations for FM echolocation.

This paper presents results from an ex-vivo study of intradermal jet injections, which is an attractive method to achieve both needle-free and fractional dose delivery of vaccines. Due to the fact that fluid properties of many novel therapeutics and vaccines can vary significantly, a key parameter for our study is the fluid viscosity, whilst the main focus is on determining the best correlation between the delivered volume and geometrical dimensions of the fluid deposit. For this we use a combination of top-view (skin wheal), underside (below the dermis), and cross-section (true skin bleb) perspectives and find that the top-view alone, as done in clinical practice, is insufficient to estimate the volume deposited in the dermis. Overall, the best correlation is found between the injection volume and cross-sectional diameter, however there is significant variation amongst the different fluids. For mean injection volumes of 60 μL the mean bleb diameter is ≈8 mm, with mean aspect ratio h¯/d=0.38, indicating the blebs are mostly oblate. However, the shape varies with viscosity and the higher viscosity does not spread laterally to the same degree as lower viscosity fluids. In addition, our high-speed video observations of the injection process, reveal some interesting dynamics of the jet injection method, and we modeled the bleb growth with an exponential saturation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Echolocating big brown bats emit frequency-modulated (FM) sounds covering ultrasonic frequencies in two harmonic sweeps (FM1 from 50-60 kHz sweeping down to 20-25 kHz, FM2 from 100-110 kHz sweeping down to 45 kHz). Using a complex interplay of acoustic cues, the bats perceive object distance from echo delay and object shape from echo spectra. Typical natural targets-flying insects-return discrete reflections, called glints, from prominent body parts (e.g., head, wings). Insect sizes are mostly 0.5 cm to about 3.5 cm, corresponding to reflected time separations of 30 to 210 μs. When closely spaced reflections overlap, they interfere to create a characteristic echo spectrum containing repetitive peaks and nulls. Time spacing of these glints (Δ t ) is transposed into spectral ripples at frequency intervals (Δ f = 1/Δ t ) from about 30 kHz down to 5 kHz. The bat's perception of rippled echoes as a distinct class was tested in two-alternative forced-choice discrimination experiments with a standard stimulus of 100 μs glint separation (10 kHz ripples), in the middle of natural ripple separations (30 kHz to 5 kHz). Stimuli were electronically generated virtual targets with simulated 2-glint sizes from smaller than 0.5 cm to larger than 3.5 cm. Bats perceived insect-sized virtual objects (glint delays of 36-300 μs) as similar to the 100-μs standard, while smaller or larger virtual objects were perceived as not similar. Insect-sized echoes contained a pattern of microscale spectral ripples that stood apart from the coarser, macroscale spectral features of smaller objects or the temporally separate reflections of larger objects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In complex biosonar scenes, the delay of echoes represents the spatial distribution of objects in depth. To avoid overlap of echo streams from successive broadcasts, individual echolocation sounds should only be emitted after all echoes of previous sounds have returned. However, close proximity of obstacles demands rapid pulse updates for steering to avoid collisions, which often means emitting a new sound before all of the previous echoes have returned. When two echo streams overlap, there is ambiguity about assigning echoes to the corresponding broadcasts. In laboratory tests of flight in dense, cluttered scenes, four species of echolocating bats exhibited different patterns of pulse emissions to accommodate potential pulse-echo ambiguity. Miniopterus fuliginosus emitted individual FM pulses only after all echoes of previous pulses had returned, with no alternating between long and short intervals. Pipistrellus abramus and Eptesicus fuscus alternated between emitting long FM pulse intervals to receive all echoes before the next pulse, and short intervals to update the rapidly changing scene while accepting partial overlap of successive echo streams. Rhinolophus ferrumequinum nippon transmitted CF/FM pulses in alternating short and long intervals, usually two to four closely spaced sounds that produced overlapping echo streams, followed by a longer interval that separated echo streams. Rhinolophus f. nippon is a statistical outlier from the three FM species, which are more similar to each other. The repeated overlap of CF/FM echo streams suggests that CF components have a distinct role in rejection of clutter and mitigation of ambiguity., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)