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Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes.

Research has shown principals have the second highest impact on student achievement, only surpassed by the level of instruction. This being the case, it is critical to have the most effective leaders serving in the principal role who are committed to continuing to grow and evolve to meet the needs of their students. This case study was designed to determine what central office supports are in place for principal development in a central Texas school district and identify recommendations for further action and study. Emerging research on central office supports for principal growth points to clear guidance on specific structures. Key themes in the research include the role of the principal supervisor, a focus on instructional leadership, principal collaboration, and job-embedded coaching. Through a mixed-methods approach, the researcher gained insights into the specific structures and perceptions of impact from the perspectives of principals as well as central office leaders in one school district. This study affirms several components found in the research around supporting principal development, specifically related to the role of the principal supervisor and clearly defined expectations. Further, this study highlights the impact of job-embedded coaching with a principal supervisor and illuminates the need for further research around principal collaboratives.

We propose a new conceptual framework (computational validity) for translation across species and populations based on the computational similarity between the information processing underlying parallel tasks. Translating between species depends not on the superficial similarity of the tasks presented, but rather on the computational similarity of the strategies and mechanisms that underlie those behaviours. Computational validity goes beyond construct validity by directly addressing questions of information processing. Computational validity interacts with circuit validity as computation depends on circuits, but similar computations could be accomplished by different circuits. Because different individuals may use different computations to accomplish a given task, computational validity suggests that behaviour should be understood through the subject's point of view; thus, behaviour should be characterized on an individual level rather than a task level. Tasks can constrain the computational algorithms available to a subject and the observed subtleties of that behaviour can provide information about the computations used by each individual. Computational validity has especially high relevance for the study of psychiatric disorders, given the new views of psychiatry as identifying and mediating information processing dysfunctions that may show high inter-individual variability, as well as for animal models investigating aspects of human psychiatric disorders. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Whole-genome expression profiling revealed Escherichia coli MG1655 genes induced by growth on mucus, conditions designed to mimic nutrient availability in the mammalian intestine. Most were nutritional genes corresponding to catabolic pathways for nutrients found in mucus. We knocked out several pathways and tested the relative fitness of the mutants for colonization of the mouse intestine in competition with their wild-type parent. We found that only mutations in sugar pathways affected colonization, not phospholipid and amino acid catabolism, not gluconeogenesis, not the tricarboxylic acid cycle, and not the pentose phosphate pathway. Gluconate appeared to be a major carbon source used by E. coli MG1655 to colonize, having an impact on both the initiation and maintenance stages. N-acetylglucosamine and N-acetylneuraminic acid appeared to be involved in initiation, but not maintenance. Glucuronate, mannose, fucose, and ribose appeared to be involved in maintenance, but not initiation. The in vitro order of preference for these seven sugars paralleled the relative impact of the corresponding metabolic lesions on colonization: gluconate > N-acetylglucosamine > N-acetylneuraminic acid = glucuronate > mannose > fucose > ribose. The results of this systematic analysis of nutrients used by E. coli MG1655 to colonize the mouse intestine are intriguing in light of the nutrientniche hypothesis, which states that the ecological niches within the intestine are defined by nutrient availability. Because humans are presumably colonized with different commensal strains, differences in nutrient availability may provide an open niche for infecting E. coli pathogens in some individuals and a barrier to infection in others.

Neurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders. Previous work from our lab has shown that a mouse model of 16p11.2 hemideletion (del/+) exhibits male-specific behavioral phenotypes. We, therefore, aimed to investigate with magnetic resonance imaging (MRI), whether del/+ animals also exhibited a sex-specific neuroanatomical endophenotype. Using the Allen Mouse Brain Atlas, we analyzed the expression patterns of the 27 genes within the 16p11.2 region to identify which gene expression patterns spatially overlapped with brain structural changes. MRI was performed ex vivo and the resulting images were analyzed using Voxel-based morphometry for T1-weighted sequences and tract-based spatial statistics for diffusion-weighted images. In a subsequent step, all available in situ hybridization (ISH) maps of the genes involved in the 16p11.2 hemideletion were aligned to Waxholm space and clusters obtained by sex-specific group comparisons were analyzed to determine which gene(s) showed the highest expression in these regions. We found pronounced sex-specific changes in male animals with increased fractional anisotropy in medial fiber tracts, especially in those proximate to the striatum. Moreover, we were able to identify gene expression patterns spatially overlapping with male-specific structural changes that were associated with neurite outgrowth and the MAPK pathway. Of note, previous molecular studies have found convergent changes that point to a sex-specific dysregulation of MAPK signaling. This convergent evidence supports the idea that ISH maps can be used to meaningfully analyze imaging data sets.

Invasive species can alter ecosystem properties and cause state shifts in landscapes. Resource managers charged with maintaining landscapes require tools to understand implications of alternative actions (or inactions) on landscape structure and function. Simulation models can serve as a virtual laboratory to explore these alternatives and their potential impacts on a landscape. To be useful, however, managers need to participate in model development to ensure that model structure can evaluate the response of key resources to plausible actions. Here, we detail development of a state‐and‐transition simulation model (STSM) to evaluate buffelgrass (Cenchrus ciliaris L. syn Pennisetum ciliare (L.) Link) in Saguaro National Park (SNP), Arizona, USA, through collaboration between managers and researchers. We integrate expert knowledge and research to create and parameterize a stochastic, spatially explicit STSM to evaluate specific management objectives. We also develop a dynamic link between the STSM and a fire behavior model to allow exploration of potential novel processes introduced to the ecosystem by buffelgrass invasion. Our projections show that buffelgrass can be expected to increase on the landscape and that the integration of fire into the model accelerates the projected rate of invasion and increases degradation of resources of management concern. We highlight the benefit of engaging end users in the modeling process so that the model is targeted to evaluate management objectives, in this case retention of saguaro cacti (Carnegiea gigantea (Engelm.) Britton & Rose) on the landscape. Being able to integrate an external model that can help address the unique characteristics of a problem such as the introduction of fire into the SNP desert ecosystem increases the ability of simulations to address complex ecological and management questions.

Background Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. Results In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > − 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5–67.0) years and admission APACHE II score of 21.0 (16.0–32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p  < 10 −5 ). Conclusions In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.

Background High adrenergic tone appears to be associated with mortality in septic shock, while adrenergic antagonism may improve survival. In preparation for a randomized trial, we conducted a prospective, single-arm pilot study of esmolol infusion for patients with septic shock and tachycardia that persists after adequate volume expansion. Methods From April 2016 to March 2017, we enrolled patients admitted to an intensive care unit with sepsis who were receiving vasopressor infusion and were tachycardic despite adequate volume expansion. All patients received a continuous intravenous infusion of esmolol, targeted to heart rate 80–90/min, while receiving vasopressors. The feasibility outcomes were proportion of eligible patients consented, compliance with pre-infusion safety check, and compliance with the titration protocol. The primary clinical outcome was organ-failure-free days (OFFD) at 28 days. Results We enrolled 7 of 10 eligible patients. Mean age was 46 (± 19) years, and mean admission APACHE II was 28 (± 8). Median norepinephrine infusion rate at the initiation of esmolol infusion was 0.20 (0.14–0.23) μg/kg/min. Compliance with the safety check was 100%; compliance with components of the titration protocol was 98–100%. OFFD were 26 (24.5–26); all patients survived to day 90. Median peak esmolol infusion was 50 (25–50) μg/kg/min. Median peak norepinephrine infusion rate during esmolol infusion was 0.46 (0.13–0.50) μg/kg/min. Four patients achieved target heart rate. Protocol-defined stop events, suggesting possible intolerance to a given infusion rate, occurred in three patients, all of whom were receiving at least 50 μg/kg/min of esmolol. Conclusions In a pilot, single-arm study, we report the first published experience with esmolol infusion in tachycardic patients with septic shock in the United States. These findings support a phase 2 trial of esmolol infusion for septic shock. Lower infusion rates of esmolol infusion may be better tolerated and more feasible than higher infusion rates for such a trial. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT02841241) on 19 July 2016.

Clinicians working in intensive care units (ICUs) are immersed in a cacophony of alarms and a relentless onslaught of data. Within this frenetic environment, clinicians make high-stakes decisions using many data sources and are often oversaturated with information of varying quality. Traditional bedside monitors only depict static vital signs data, and these data are not easily viewable remotely. Clinicians must rely on separate nursing charts-handwritten or electric-to review physiological patterns, including signs of potential clinical deterioration. An automated physiological data viewer has been developed to provide at-a-glance summaries and to assist with prioritizing care for multiple patients who are critically ill. This study aims to evaluate a novel vital signs viewer system in a level 1 trauma center by subjectively assessing the viewer's utility in a high-volume ICU setting. ICU attendings were surveyed during morning rounds. Physicians were asked to conduct rounds normally, using data reported from nurse charts and briefs from fellows to inform their clinical decisions. After the physician finished their assessment and plan for the patient, they were asked to complete a questionnaire. Following completion of the questionnaire, the viewer was presented to ICU physicians on a tablet personal computer that displayed the patient's physiologic data (ie, shock index, blood pressure, heart rate, temperature, respiratory rate, and pulse oximetry), summarized for up to 72 hours. After examining the viewer, ICU physicians completed a postview questionnaire. In both questionnaires, the physicians were asked questions regarding the patient's stability, status, and need for a higher or lower level of care. A hierarchical clustering analysis was used to group participating ICU physicians and assess their general reception of the viewer. A total of 908 anonymous surveys were collected from 28 ICU physicians from February 2015 to June 2017. Regarding physicians' perception of whether the viewer enhanced the ability to assess multiple patients in the ICU, 5% (45/908) strongly agreed, 56.6% (514/908) agreed, 35.3% (321/908) were neutral, 2.9% (26/908) disagreed, and 0.2% (2/908) strongly disagreed. Morning rounds in a trauma center ICU are conducted in a busy environment with many data sources. This study demonstrates that organized physiologic data and visual assessment can improve situation awareness, assist clinicians with recognizing changes in patient status, and prioritize care.