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Like human language, song in songbirds is learned during an early sensitive period and is facilitated by motivation to seek out social interactions with vocalizing adults. Songbirds are therefore powerful models with which to understand the neural underpinnings of vocal learning. Social motivation and early social orienting are thought to be mediated by the oxytocin system; however, the developmental trajectory of oxytocin receptors in songbirds, particularly as it relates to song learning, is currently unknown. This gap in knowledge has hindered the development of songbirds as a model of the role of social orienting in vocal learning. In this study, we used quantitative PCR to measure oxytocin receptor expression during the sensitive period of song learning in zebra finches (Taeniopygia guttata). We focused on brain regions important for social motivation, attachment, song recognition, and song learning. We detected expression in these regions in both sexes from post-hatch day 5 to adulthood, encompassing the entire period of song learning. In this species, only males sing; we found that in regions implicated in song learning specifically, oxytocin receptor mRNA expression was higher in males than females. These sex differences were largest during the developmental phase when males attend to and memorize tutor song, suggesting a functional role of expression in learning. Our results show that oxytocin receptors are expressed in relevant brain regions during song learning, and thus provide a foundation for developing the zebra finch as a model for understanding the mechanisms underlying the role of social motivation in vocal development. This article is protected by copyright. All rights reserved.

In bariatric surgery, retraction of the liver is essential to ensure appropriate visualization of the surgical field. Many devices are currently employed for this purpose. Generally, these devices require constant use of a port, or an additional incision. Magnetic technology provides a novel solution, by allowing liver retraction during bariatric procedures that do not require a dedicated port nor an extra incision. Retrospective review of consecutive patients who underwent magnetic-assisted liver retraction during primary or revisional laparoscopic bariatric surgery at the Duke Center for Metabolic and Weight Loss Surgery between October 2016 and August 2017. The 73 cases were comprised of 29 primary sleeve gastrectomies, 24 gastric bypasses, 10 duodenal switches, 3 gastric band removals, and 7 revisions. All cases were completed laparoscopically. Mean pre-operative BMI was 43.6 kg/m2 (range 18.3–67.7 kg/m2). Mean operative times for primary cases were similar to published averages. Two patients experienced minor 30-day morbidities, neither of which were attributed to the device and did not require further interventions. There were no 30-day mortalities. Surgeons described subjective overall surgical exposure as adequate and device utilization as technically simple even for the large livers. Magnetic-assisted retraction is a novel approach that allows a safe, reproducible, incision-less technique for unconstrained, port-less intra-abdominal mobilization. The device successfully permitted optimal liver retraction during laparoscopic bariatric surgery, enhancing surgical exposure while decreasing the number of abdominal incisions.

In species with vocal learning, acquiring species-typical vocalizations relies on early social orienting. In zebra finches (Taeniopygia guttata), for example, learning song requires dynamic social interactions with a “tutor” during an early sensitive period. The oxytocin system plays a central role in social orienting across species, yet it is unknown whether this system participates in the attentional and motivational processes that support vocal learning. Here, we tested whether blocking oxytocin receptors during exposure to tutors would impact learning from those tutors. Juvenile, song-naïve males were each tutored by two unfamiliar adults. During exposure to one tutor, juveniles were treated with oxytocin receptor antagonist (OTA) and during exposure to the other, saline (control). We found that OTA significantly reduced behaviors associated with approach and attention during tutoring sessions. Next, using an operant assay in which exposure to the two songs was balanced, we found that the juveniles preferred the control song over the OTA song. The developmental trajectory of preference for the control song resembled the pattern shown by father-reared birds choosing to hear their father’s song. Finally, the adult songs of the tutored birds more closely resembled control song than OTA song. The magnitude of this difference was significantly predicted by the early preference for the control song. Overall, oxytocin antagonism during exposure to a tutor seemed to bias juveniles against that tutor and his song. Our results suggest that oxytocin receptors play a role in socially-guided vocal learning in zebra finches, perhaps by affecting attention and motivation during tutoring.

Several studies have suggested that women in science are less productive than men, and that this gap contributes to their under-representation in the ranks of senior researchers. However, few studies have examined the role of mentoring, and in particular mentor gender, on the productivity of female scientists early in their careers. Such efforts are limited by the difficulties of unambiguously linking mentees to their mentors and measuring the research productivity resulting from those relationships. Here we use our novel author disambiguation solution to investigate the role of self-identified gender in mentorship of 12,932 trainees who either successfully or unsuccessfully applied to the National Institutes of Health for research fellowships between fiscal years 2011 and 2017, applying a multi-dimensional framework to assess productivity. We found that, after normalizing for the funding level of mentors, the productivity of female and male mentees is indistinguishable; it is also independent of the gender of the mentor, other than in measures of clinical impact, where women mentored by women outperform other mentee-mentor dyads.

SummaryMaternal immune activation (MIA) increases likelihood of altered neurodevelopmental outcomes. Maternal cytokines are proposed to affect fetal brain development in mice; however, the contribution of fetal immunity to neurodevelopmental disorders is largely unexplored. Here, we show that MIA mediated by Toll-like receptor 3 (TLR3), but not other TLRs, induces a specific set of behavioral phenotypes including decreased sociability and increased restricted repetitive behavior in offspring. Accordingly, these behavioral phenotypes were absent when offspring were deficient for Trif, the downstream adapter molecule of TLR3. Using single-cell RNA sequencing, we identified clusters of border-associated macrophages that were significantly enriched in the fetal brain following TLR3-MIA, and these clusters were diminished in Trif−/− fetal brains.Moreover, we found that triggering TLR3-TRIF in offspring can occur through transplacental viral infection, resulting in altered behavioral phenotypes. Collectively, our data indicate that fetal innate immunity contributes to MIA-induced atypical behaviors in mice.

Reliability and safety of engineered systems often extends to a system composed of autonomous and heterogeneous systems. Systems integration enables formation of larger system of systems with greater, encompassing scope and goals. Nuclear power station reliability and safety involves an extensive system of systems. Failures at Chernobyl and Fukushima underscore the rare but catastrophic ripple-effect of a failed system within a system of systems conceptual model. Modeling and simulation of systems with various scenarios increases confidence in conceptual models, particularly scenarios that are too costly or risky to assess by other means. This research implements a system of systems conceptual model of a notional Fukishima-like disaster using a Live-Virtual-Constructive simulation framework. Focusing on a conceptual model involving an unmanned aerial system intervention, the research illustrates the framework's utility and effectiveness for assessing system reliability and safety within the conceptual model. Novel use of a screening experiment demonstrates the framework's capability to rapidly identify critical factors and their significance. A framework encompassing live, virtual, and constructive simulations provides a generalized capability to compose, simulate, and evaluate from multiple perspectives the suitability of various systems and conceptual models to accomplish a broad range of emergency response missions including the one investigated here.

Corrosion of reinforcing steel reduces the capacity of reinforced concrete structures by reducing the reinforcement area and decreasing the bond between the reinforcement and the surrounding concrete. Currently the assessment of reinforced concrete structures is based largely on visual inspections, which do not provide quantitative data about structural behaviour. This research program investigates the use of distributed fibre optic strain sensors to measure the effects of corrosion on reinforced concrete beam behaviour. Six beams with varying levels of corrosion are instrumented with fibre optic sensors and tested in three point bending. The percentage of reinforcement area lost due to corrosion has a disproportionate impact on the percentage reduction in beam capacity, however these results are a function of the testing parameters and may not be applicable to structures in the field. The fibre optic measurements are used to identify regions of reinforcement-concrete bond loss and the effect of that bond loss on beam behaviour.

Fundamental scientific advances can take decades to translate into improvements in human health. Shortening this interval would increase the rate at which scientific discoveries lead to successful treatment of human disease. One way to accomplish this would be to identify which advances in knowledge are most likely to translate into clinical research. Toward that end, we built a machine learning system that detects whether a paper is likely to be cited by a future clinical trial or guideline. Despite the noisiness of citation dynamics, as little as 2 years of postpublication data yield accurate predictions about a paper’s eventual citation by a clinical article (accuracy = 84%, F1 score = 0.56; compared to 19% accuracy by chance). We found that distinct knowledge flow trajectories are linked to papers that either succeed or fail to influence clinical research. Translational progress in biomedicine can therefore be assessed and predicted in real time based on information conveyed by the scientific community’s early reaction to a paper., Fundamental scientific advances can take decades to translate into improvements in human health. This study shows that a machine learning model can accurately predict whether an article is likely to be cited by a future clinical trial or guideline, using as little as two years of post-publication citation data.

Juvenile male zebra finches memorize and learn to sing the song of a male caregiver, or “tutor”, during a complex vocal learning process. Juveniles are highly motivated to interact socially with their tutor, and these interactions are required for effective vocal learning. It is currently unknown what neurological mechanisms underlie attraction to tutors, but social motivation and affiliation in this and other species may be mediated by oxytocin and related nonapeptides. Here, we used qPCR to quantify expression of oxytocin receptor (OTR) mRNA in the lateral septum, auditory forebrain, and regions of the song control system in zebra finches throughout post-hatch development and vocal learning. We found that zebra finches express OTR mRNA in these regions from post-hatch day 5 to adulthood, encompassing the entire period of auditory and sensorimotor learning. We also mapped the binding of 125I-ornithine vasotocin, an oxytocin receptor antagonist that binds to oxytocin receptors in songbird brain, to understand the neuroanatomical distribution of oxytocin-like action during vocal development. This study provides the groundwork for the use of zebra finches as a model for understanding the mechanisms underlying social motivation and its role in vocal development.

Nuclear disasters have severe and far-reaching consequences. Emergency managers and first responders from utility owners to local, state, and federal civil authorities and the Department of Defense (DoD) must be well prepared in order to rapidly mitigate the disaster and protect the public and environment from spreading damage. Given the high risks, modeling and simulation (M&S) plays a significant role in planning and training for the spectrum of derivate scenarios. Existing reactor models are largely legacy, stove-piped designs lacking interoperability between themselves and other M&S tools for emergency preparedness system evaluation and training. Unmanned systems present a growing area of technology promising significant improvement in response and mitigation. To bridge the gap between current and future models, we propose a conceptual model (CM) for integrating live, virtual, and constructive (LVC) models with nuclear disaster and mitigation models utilizing a system-of-systems (SoS) approach. The CM offers to synergistically enhance current reactor and dispersion simulations with intervening avatar and agent simulations. The SoS approach advances life cycle stages including concept exploration, system design, engineering, training, and mission rehearsal. Component subsystems of the CM are described along with an explanation of input/output requirements. A notional implementation is described. Finally, applications to analysis and training, an evaluation of the CM based on recently proposed criteria found in the literature, and suggestions for future research are discussed.

Corrosion of reinforcing steel is the primary deterioration mechanism for reinforced concrete structures, however its impact on structural behaviour can be difficult to assess using visual inspections. This paper investigates the potential for using distributed fibre optic sensors to monitor the impact of corrosion to supplement visual inspections. Tension tests were conducted on bare reinforcement and reinforced concrete specimens subjected to accelerated corrosion. The distributed fibre optic strain data provided insights into the concrete-reinforcement bond performance of corroded specimens and the detection of pitting corrosion appeared to be possible although challenging.

The white-throated sparrow (Zonotrichia albicollis) represents a powerful model in behavioral neuroendocrinology because it occurs in two plumage morphs that differ with respect to steroid-dependent social behaviors. Birds of the white-striped (WS) morph engage in more territorial aggression than do birds of the tan-striped (TS) morph, and the TS birds engage in more parenting behavior. This behavioral polymorphism is caused by a chromosomal inversion that has captured many genes, including estrogen receptor alpha (ERα). In this study, we tested the hypothesis that morph differences in aggression might be explained by differential sensitivity to estradiol (E2). We administered E2 non-invasively to non-breeding white-throated sparrows and quantified aggression toward a conspecific 10 min later. E2 administration rapidly increased aggression in WS birds but not TS birds, consistent with our hypothesis that differential sensitivity to E2 may at least partially explain morph differences in aggression. To query the site of E2 action in the brain, we administered E2 and quantified Egr-1 expression in brain regions in which expression of ERα is known to differ between the morphs. E2 treatment decreased Egr-1 immunoreactivity in nucleus taeniae of the amygdala, but this effect did not depend on morph. Overall, our results support a role for differential effects of E2 on aggression in the two morphs, but more research will be needed to determine the neuroanatomical site of action.

Objectives:The 12-lead electrocardiogram (ECG) can capture valuable information in the prehospital setting. By the time patients are assessed by an emergency department (ED) physician, their symptoms and any ECG changes may have resolved. We sought to determine whether the prehospital electrocardiogram (pECG) could influence ED management and how often the pECG was available to and reviewed by the ED physician.Methods:A retrospective medical record review was conducted on a random sample of patients ≥ 18 years who had a prehospital 12-lead ECG and were transported to one of two tertiary care centres. Data were recorded onto a standardized data extraction tool. Three investigators independently compared the pECG to the first ECG obtained in the ED after patient arrival at the hospital. Any abnormalities not present on the ED ECG were adjudicated to ascertain whether they had the potential to change ED management.Results:Of 115 ambulance runs selected, 47 had no pECG attached to the ambulance call record (ACR) and another 5 were excluded (one ST elevation myocardial infarction, one cardiac arrest, three ACR missing). Of the 63 pECGs reviewed, 16 (25%) showed changes not apparent on the initial ED ECG (κ = 0.83; 95% CI 0.74–0.93), of which 12 had differences that might influence ED management (κ = 0.76; 95% CI 0.72–0.82). Only one hospital record contained a copy of the pECG, despite the current protocol that paramedics print two copies of the pECG on arrival in the ED (one copy for the ACR and one to be handed to the medical personnel). None of 110 ED charts documented that the pECG was reviewed by the ED physician.Conclusion:The pECG has the potential to influence ED management. Improvement in paramedic and physician documentation and a formal pECG handover process appear necessary.

In a post-Fukushima world, defense nuclear disaster planners must recognize and be ready for urgent requests for military support to mitigate the impacts of a civilian nuclearpower plant disaster. At both Chernobyl and Fukushima nuclear power plants, explosions, leakage, and paramount concerns of the spread of radiation around the world lead to urgent requests for local and international military support to disaster mitigation efforts.

Iron's chemical structure and its ability to initiate one-electron reactions are properties that cause it to play a major role in the production and metabolism of oxygen free radicals in biological systems. Oxygen free radicals are conjectured to cause cardiac failure in individuals afflicted with disorders of iron overload. We report on the use of both acyloins and aldehydes as markers of oxidative stress in a murine model of chronic iron-overload cardiomyopathy. Twenty mice were randomized to four treatment groups: (1) control (0.2 mL normal saline ip/mouse/d); (2) 100 mg iron (0.05 mL iron dextran/mouse/d); (3) 200 mg iron (0.1 mL iron dexxtran/mouse/d); (4) 400 mg iron (0.2 mL iron dextran/mouse/d). Significant dose-dependent increases in both total heart aldehyde and total heart acyloin concentrations were found. Furthermore, a significant positive correlation existed between the dose of iron administered and each quantified aldehyde and acyloin found in the heart.

Considerable progress has occurred toward our understanding of the molecular basis for vascular morphogenesis, maturation, and stabilization. A major reason for this progress has been the development of novel in vitro systems to investigate these processes in 3D extracellular matrices. In this chapter, we present models of human endothelial cell (EC) tube formation and EC-pericyte tube co-assembly using serum-free defined conditions in 3D collagen matrices. We utilize both human venous and arterial ECs and show that both cell types readily form tubes and induce pericyte recruitment and both ECs and pericytes work together to remodel the extracellular matrix environment by assembling the vascular basement membrane, a key step in capillary tube network maturation and stabilization. Importantly, we have shown that these events occur under serum-free defined conditions using the hematopoietic stem cell cytokines, SCF, IL-3, and SDF-1α and also including FGF-2. In contrast, the combination of VEGF and FGF-2 fails to support vascular tube morphogenesis or pericyte-induced tube maturation under the same serum-free defined conditions. Furthermore, we present novel assays whereby we have developed both human ECs and pericytes to induce specific genes using a doxycycline-regulated lentiviral system. In this manner, we can upregulate the expression of wild-type or mutant gene products at any stage of vascular morphogenesis or maturation in 3D matrices. These in vitro experimental approaches will continue to identify key molecular requirements and signaling pathways that control fundamental events in tissue vascularization under normal or pathologic conditions. Furthermore, these models will provide new insights into the development of novel disease therapeutic approaches where vascularization is an important pathogenic component and create new ways to assemble capillary tube networks with associated pericytes for tissue engineering applications.

Considerable progress has occurred toward our understanding of the molecular basis for vascular morphogenesis, maturation, and stabilization. A major reason for this progress has been the development of novel in vitro systems to investigate these processes in 3D extracellular matrices. In this chapter, we present models of human endothelial cell (EC) tube formation and EC-pericyte tube co-assembly using serum-free defined conditions in 3D collagen matrices. We utilize both human venous and arterial ECs and show that both cell types readily form tubes and induce pericyte recruitment and both ECs and pericytes work together to remodel the extracellular matrix environment by assembling the vascular basement membrane, a key step in capillary tube network maturation and stabilization. Importantly, we have shown that these events occur under serum-free defined conditions using the hematopoietic stem cell cytokines, SCF, IL-3, and SDF-1α and also including FGF-2. In contrast, the combination of VEGF and FGF-2 fails to support vascular tube morphogenesis or pericyte-induced tube maturation under the same serum-free defined conditions. Furthermore, we present novel assays whereby we have developed both human ECs and pericytes to induce specific genes using a doxycycline-regulated lentiviral system. In this manner, we can upregulate the expression of wild-type or mutant gene products at any stage of vascular morphogenesis or maturation in 3D matrices. These in vitro experimental approaches will continue to identify key molecular requirements and signaling pathways that control fundamental events in tissue vascularization under normal or pathologic conditions. Furthermore, these models will provide new insights into the development of novel disease therapeutic approaches where vascularization is an important pathogenic component and create new ways to assemble capillary tube networks with associated pericytes for tissue engineering applications.

An important advance using in vitro EC tube morphogenesis and maturation models has been the development of systems using serum-free defined media. Using this approach, the growth factors and cytokines which are actually necessary for these events can be determined. The first model developed by our laboratory was such a system where we showed that phorbol ester was needed in order to promote survival and tube morphogenesis in 3D collagen matrices. Recently, we have developed a new system in which the hematopoietic stem cell cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and stromal derived factor-1α (SDF-1α) were added in conjunction with FGF-2 to promote human EC tube morphogenesis in 3D collagen matrices under serum-free defined conditions. This new model using SCF, IL-3, SDF-1α, and FGF-2 also works well following the addition of pericytes where EC tube formation occurs, pericytes are recruited to the tubes, and vascular basement membrane matrix assembly occurs following EC-pericyte interactions. In this chapter, we describe several in vitro assay models that we routinely utilize to investigate the molecular requirements that are critical to EC tube formation and maturation events in 3D extracellular matrix environments.

An important advance using in vitro EC tube morphogenesis and maturation models has been the development of systems using serum-free defined media. Using this approach, the growth factors and cytokines which are actually necessary for these events can be determined. The first model developed by our laboratory was such a system where we showed that phorbol ester was needed in order to promote survival and tube morphogenesis in 3D collagen matrices. Recently, we have developed a new system in which the hematopoietic stem cell cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and stromal derived factor-1α (SDF-1α) were added in conjunction with FGF-2 to promote human EC tube morphogenesis in 3D collagen matrices under serum-free defined conditions. This new model using SCF, IL-3, SDF-1α, and FGF-2 also works well following the addition of pericytes where EC tube formation occurs, pericytes are recruited to the tubes, and vascular basement membrane matrix assembly occurs following EC-pericyte interactions. In this chapter, we describe several in vitro assay models that we routinely utilize to investigate the molecular requirements that are critical to EC tube formation and maturation events in 3D extracellular matrix environments.

Traumatic Brain Injury (TBI) is a leading cause of mortality and morbidity for children in the United States. The unavailability of pediatric cadavers makes it difficult to study and characterize the mechanical behavior of the pediatric skull. Computer based finite element modeling could provide valuable insights, but the utility of these models depends upon the accuracy of cranial material property inputs. In this study, 47 samples from one six year-old human cranium were tested to failure via four point bending to study the effects of strain rate and the structure of skull bone on modulus of elasticity and failure properties for both cranial bone and suture. The results show that strain rate does not have a statistically meaningful effect on the mechanical properties of the six year-old skull over the range of strain rates studied (average low rate of 0.045 s−1, average medium rate of 0.44 s−1, and an average high rate of 2.2 s−1), but that these properties do depend on the growth patterns and morphology of the skull. The thickness of the bone was found to vary with structure. The bending stiffness (per unit width) for tri-layer bone (12.32±5.18 Nm2/m) was significantly higher than that of cortical bone and sutures (5.58±1.46 Nm2/m and 3.70±1.88 Nm2/m respectively). The modulus of elasticity was 9.87±1.24 GPa for cranial cortical bone and 1.10±0.53 GPa for sutures. The effective elastic modulus of tri-layer bone was 3.69±0.92 GPa. Accurate models of the pediatric skull should account for the differences amongst these three distinct tissues in the six year-old skull.

Chronic iron overload is a major cause of organ failure worldwide, but its pathogenesis remains to be elucidated.To examine in an experimental murine model of iron-overload cardiomyopathy the relation between milk whey protein and, first, the production of reactive oxygen free radical species and, second, antioxidant reserve status.B6D2F1 mice were randomly assigned to four treatment groups (n=8 per treatment group): placebo control; iron only; whey only; and iron with whey. Reactive oxygen free radical species in the heart were quantified by the cytotoxic aldehydes malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and hexanal, while antioxidant reserve status was quantified by glutathione (GSH) and glutathione peroxidase (GPx) activity in the heart tissue.Significantly decreased concentrations (pmol/100 mg wet weight tissue) of MDA (2468+/-261), HNE (912+/-38) and hexanal (5385+/-927) were observed in the heart tissue of the group receiving iron with whey, in comparison with the iron-only treatment group (MDA 9307+/-387, HNE 1416+/-157, hexanal 14,874+/-2955; P0.001). Significantly increased GPx (141+/-38 IU/L) and GSH (521+/-136 IU/L) activity were observed in mice receiving iron with whey, in comparison with mice receiving iron only (GPx 100+/-10 IU/L, GSH 446+/-33 IU/L; P0.001).Mice receiving iron treatments with whey supplementation had significantly lower concentrations of cytotoxic aldehydes and significantly higher cardiac levels of GPx and GSH activity than did iron-only treated mice. Additional basic research is warranted to examine the exact mechanisms by which milk whey protein protects the heart.