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Competing Interests: The authors disclose no conflicts of interest.

Study Objective: We compare high-velocity nasal insufflation, a form of high-flow nasal cannula, with noninvasive positive-pressure ventilation in the treatment of undifferentiated respiratory failure with respect to therapy failure, as indicated by requirement for endotracheal intubation or cross over to the alternative therapy., Methods: This was a multicenter, randomized trial of adults presenting to the emergency department (ED) with respiratory failure requiring noninvasive positive-pressure ventilation. Patients were randomly assigned to high-velocity nasal insufflation (initial flow 35 L/min; temperature 35°C (95°F) to 37°C (98.6°F); FiO 2 1.0) or noninvasive positive-pressure ventilation using an oronasal mask (inspiratory positive airway pressure 10 cm H 2 O; expiratory positive airway pressure 5 cm H 2 O). The primary outcome was therapy failure at 72 hours after enrollment. A subjective outcome of crossover was allowed as a risk mitigation to support deferment of informed consent. Noninferiority margins were set at 15 and 20 percentage points, respectively., Results: A total of 204 patients were enrolled and included in the analysis, randomized to high-velocity nasal insufflation (104) and noninvasive positive-pressure ventilation (100). The intubation rate (high-velocity nasal insufflation=7%; noninvasive positive-pressure ventilation=13%; risk difference=-6%; 95% confidence interval -14% to 2%) and any failure of the assigned arm (high-velocity nasal insufflation=26%; noninvasive positive-pressure ventilation=17%; risk difference 9%; confidence interval -2% to 20%) at 72 hours met noninferiority. The effect on PCO 2 over time was similar in the entire study population and in patients with baseline hypercapnia. Vital signs and blood gas analyses improved similarly over time. The primary limitation was the technical inability to blind the clinical team., Conclusion: High-velocity nasal insufflation is noninferior to noninvasive positive-pressure ventilation for the treatment of undifferentiated respiratory failure in adult patients presenting to the ED., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE Experimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology. In this study, the authors sought to adapt a midline FPI to postnatal day (PND) 17 and 35 rats. The authors hypothesized that scaling the craniectomy size based on skull dimensions would result in a reproducible injury comparable to the standard midline FPI in adult rats. METHODS PND17 and PND35 rat skulls were measured, and trephines were scaled based on skull size. Custom trephines were made. Rats arrived on PND10 and were randomly assigned to one of 3 cohorts: PND17, PND35, and 2 months old. Rats were subjected to midline FPI, and the acute injury was characterized. The right reflex was recorded, injury-induced apnea was measured, injury-induced seizure was noted, and the brains were immediately examined for hematoma. RESULTS The authors' hypothesis was supported; scaling the trephines based on skull size led to a reproducible injury in the PND17 and PND35 rats that was comparable to the injury in a standard 2-month-old adult rat. The midline FPI suppressed the righting reflex in both the PND17 and PND35 rats. The injury induced apnea in PND17 rats that lasted significantly longer than that in PND35 and 2-month-old rats. The injury also induced seizures in 73% of PND17 rats compared with 9% of PND35 rats and 0% of 2-month-old rats. There was also a significant relationship between the righting reflex time and presence of seizure. Both PND17 and PND35 rats had visible hematomas with an intact dura, indicative of diffuse injury comparable to the injury observed in 2-month-old rats. CONCLUSIONS With these procedures, it becomes possible to generate brain-injured juvenile rats (pediatric [PND17] and adolescent [PND35]) for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented.

Traumatic brain injury (TBI) is induced by mechanical forces which initiate a cascade of secondary injury processes, including inflammation. Therapies which resolve the inflammatory response may promote neural repair without exacerbating the primary injury. Specific derivatives of omega-3 fatty acids loosely grouped as specialized pro-resolving lipid mediators (SPMs) and termed resolvins promote the active resolution of inflammation. In the current study, we investigate the effect of two resolvin molecules, RvE1 and AT-RvD1, on post-traumatic sleep and functional outcome following diffuse TBI through modulation of the inflammatory response. Adult, male C57BL/6 mice were injured using a midline fluid percussion injury (mFPI) model (6-10min righting reflex time for brain-injured mice). Experimental groups included mFPI administered RvE1 (100ng daily), AT-RvD1 (100ng daily), or vehicle (sterile saline) and counterbalanced with uninjured sham mice. Resolvins or saline were administered daily for seven consecutive days beginning 3days prior to TBI to evaluate proof-of-principle to improve outcome. Immediately following diffuse TBI, post-traumatic sleep was recorded for 24h post-injury. For days 1-7 post-injury, motor outcome was assessed by rotarod. Cognitive function was measured at 6days post-injury using novel object recognition (NOR). At 7days post-injury, microglial activation was quantified using immunohistochemistry for Iba-1. In the diffuse brain-injured mouse, AT-RvD1 treatment, but not RvE1, mitigated motor and cognitive deficits. RvE1 treatment significantly increased post-traumatic sleep in brain-injured mice compared to all other groups. RvE1 treated mice displayed a higher proportion of ramified microglia and lower proportion of activated rod microglia in the cortex compared to saline or AT-RvD1 treated brain-injured mice. Thus, RvE1 treatment modulated post-traumatic sleep and the inflammatory response to TBI, albeit independently of improvement in motor and cognitive outcome as seen in AT-RvD1-treated mice. This suggests AT-RvD1 may impart functional benefit through mechanisms other than resolution of inflammation alone., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Juvenile traumatic brain injury (TBI) leaves survivors facing a potential lifetime of cognitive, somatic and emotional symptoms. A recent study published in Experimental Neurology (Kamper et al., 2013) explored the chronic consequences of focal brain injury induced in the juvenile animal, extending their previous observations out to 6months post-injury. The results demonstrate transient, persistent, and late onset behavioral dysfunction, which are associated with subtle evidence for enduring histopathology. In line with investigations about chronic traumatic encephalopathy from brain injury initiated in the adult, juvenile TBI establishes signs of a chronic brain disorder, with unique considerations relative to ongoing developmental processes. This commentary discusses the challenges in evaluating aging with injury in the juvenile population, the current methods of juvenile TBI, and what can be anticipated for the future of the field., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Measurement of tree root systems by conventional methods is a Herculean task. The electrical capacitance method offers a rapid and non-destructive alternative, but it has largely been restricted to herbaceous species. The Dalton Model has been the main concept for understanding equivalent root circuitry; it proposed that roots were cylindrical capacitors with epidermis and xylem being the external and internal electrodes. Capacitance (C) therefore varied in proportion to root surface area (A), mass (M), length (L) and relative permittivity of the plant tissue ε(r). We used the capacitance method on forest and plantation trees (13 to circa 100 y.o.) in situ to test hypotheses derived from implicit assumptions about tree-root-soil circuitry. We concluded: C was not confounded by intermingled root systems; C was strongly related to diameter at breast height (DBH); C was less strongly related to DBH for multiple species at the same site; and C was a poor indicator of DBH, M and L across species, ages and sites. We proposed that ε(r) was proportional to root tissue density ρ and fitted a model with P < 0.05 and R(2) = 0.70 when the three immature (13 y.o.) trees were excluded. There was no significant difference (P = 0.28) between the parameters of the tree model (excluding the immature trees) and one of the same form fitted to data from bean (Vicia faba L.; R(2) = 0.55). Together, the data sets suggested (R(2) = 0.94; n = 26) that there may exist a general relationship of this form applied over two orders of magnitude of L.

Land use (and land management) change is seen as the primary factor responsible for changes in sediment and nutrient delivery to water bodies. Understanding how sediment and nutrient (or constituent) concentrations vary with land use is critical to understanding the current and future impact of land use change on aquatic ecosystems. Access to appropriate land-use based water quality data is also important for calculating reliable load estimates using water quality models. This study collated published and unpublished runoff, constituent concentration and load data for Australian catchments. Water quality data for total suspended sediments (TSS), total nitrogen (TN) and total phosphorus (TP) were collated from runoff events with a focus on catchment areas that have a single or majority of the contributing area under one land use. Where possible, information on the dissolved forms of nutrients were also collated. For each data point, information was included on the site location, land use type and condition, contributing catchment area, runoff, laboratory analyses, the number of samples collected over the hydrograph and the mean constituent concentration calculation method. A total of ∼750 entries were recorded from 514 different geographical sites covering 13 different land uses. We found that the nutrient concentrations collected using "grab" sampling (without a well defined hydrograph) were lower than for sites with gauged auto-samplers although this data set was small and no statistical analysis could be undertaken. There was no statistically significant difference (p<0.05) between data collected at plot and catchment scales for the same land use. This is most likely due to differences in land condition over-shadowing the effects of spatial scale. There was, however, a significant difference in the concentration value for constituent samples collected from sites where >90% of the catchment was represented by a single land use, compared to sites with <90% of the upstream area represented by a single land use. This highlights the need for more single land use water quality data, preferably over a range of spatial scales. Overall, the land uses with the highest median TSS concentrations were mining (∼50,000mg/l), horticulture (∼3000mg/l), dryland cropping (∼2000mg/l), cotton (∼600mg/l) and grazing on native pastures (∼300mg/l). The highest median TN concentrations are from horticulture (∼32,000μg/l), cotton (∼6500μg/l), bananas (∼2700μg/l), grazing on modified pastures (∼2200μg/l) and sugar (∼1700μg/l). For TP it is forestry (∼5800μg/l), horticulture (∼1500μg/l), bananas (∼1400μg/l), dryland cropping (∼900mg/l) and grazing on modified pastures (∼400μg/l). For the dissolved nutrient fractions, the sugarcane land use had the highest concentrations of dissolved inorganic nitrogen (DIN), dissolved organic nitrogen (DON) and dissolved organic phosphorus (DOP). Urban land use had the highest concentrations of dissolved inorganic phosphorus (DIP). This study provides modellers and catchment managers with an increased understanding of the processes involved in estimating constituent concentrations, the data available for use in modelling projects, and the conditions under which they should be applied. Areas requiring more data are also discussed., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Llangorse Lake is the largest natural lake in South Wales, UK, and is of European conservation importance. The site has a long history of eutrophication problems and, in recent years, significant efforts have been made to meet water quality restoration targets at this site by reducing the input of phosphorus (P) from external sources. Although the lake has improved substantially in quality since the late 1970s, it is still not meeting its ecological targets. Phosphorus concentrations have remained high and there has been little reduction in algal biomass. Management decisions to reduce P input were originally based on the widely held assumption that shallow lakes are P-limited in summer. However, this study clearly shows that this is not always the case; Llangorse Lake, at least, is strongly nitrogen (N) limited over the summer months. As a result, bio-available P released from the sediments cannot be used by the phytoplankton population. So, it accumulates in the water column, causing very high concentrations to occur in late summer. This puts the lake at very high risk of developing algal blooms when N availability increases, usually in early autumn. The study also found that the hydrology of the lake was strongly affected by sub-surface flow. This suggested that nutrients and water could be delivered to the lake from areas beyond the topographically defined surface water catchment. These findings have widespread implications for the successful management of external inputs to lakes, which currently tends to focus on management of the surface water catchment only. The results are discussed in relation to the restoration and management of nitrogen-limited lakes, and of those that are significantly affected by sub-surface flow.

That the plasma concentration of certain divalent cations change during an inflammatory insult provides a major host defense response in vertebrate animals. This study was designed to investigate the involvement of iron sequestration in invertebrate immune responses. A ferritin molecule was cloned from an echinoderm coelomocyte cDNA library. The amino acid sequence showed sequence homology with vertebrate ferritin. The cDNA contained a conserved iron responsive element sequence. Studies showed that stimulated coelomocytes released iron into in vitro culture supernatants. The amount of iron in the supernatants decreased over time when the amebocytes were stimulated with LPS or PMA. Coelomocytes increased expression of ferritin mRNA after stimulation. In vertebrates, cytokines can cause changes in iron levels in macrophages. Similarly, echinoderm macrokines produced decreases in iron levels in coelomocyte supernatant fluids. These results suggest that echinoderm ferritin is an acute phase protein and suggest that sequestration of iron is an ancient host defense response in animals.

The TATA sequence of the human, estrogen-responsive pS2 promoter is complexed in vivo with a rotationally and translationally positioned nucleosome (NUC T). Using a chromatin immunoprecipitation assay, we demonstrate that TATA binding protein (TBP) does not detectably interact with this genomic binding site in MCF-7 cells in the absence of transcriptional stimuli. Estrogen stimulation of these cells results in hyperacetylation of both histones H3 and H4 within the pS2 chromatin encompassing NUC T and the TATA sequence. Concurrently, TBP becomes associated with the pS2 promoter region. The relationship between histone hyperacetylation and the binding of TBP was assayed in vitro using an in vivo-assembled nucleosomal array over the pS2 promoter. With chromatin in its basal state, the binding of TBP to the pS2 TATA sequence at the edge of NUC T was severely restricted, consistent with our in vivo data. Acetylation of the core histones facilitated the binding of TBP to this nucleosomal TATA sequence. Therefore, we demonstrate that one specific, functional consequence of induced histone acetylation at a native promoter is the alleviation of nucleosome-mediated repression of the binding of TBP. Our data support a fundamental role for histone acetylation at genomic promoters in transcriptional activation by nuclear receptors and provide a general mechanism for rapid and reversible transcriptional activation from a chromatin template.

The tremendous importance of cytokines to immune defensive systems suggests that they have been conserved through evolution. The existence of interleukin (IL)-1-like molecules in several invertebrate groups substantiates this hypothesis. To characterize further the relationship of invertebrate IL-1-like molecules, we have used competitive binding assays to show that invertebrate coelomocytes of the starfish Asterias forbesi possess an IL-1-specific binding protein. Competitive binding experiments used radiolabeled human IL-1alpha. IL-1 bound specifically to the coelomocytes by a single high-affinity binding site (K(d) = 8.72 x 10(-10)/M). There are approximately 6000 binding sites per cell. The specificity of the receptor was confirmed by demonstrating that, among a group of cytokines and lymphokines tested, only vertebrate IL-1- or echinoderm IL-1-like molecules and the vertebrate IL-1 receptor antagonist inhibit IL-1 binding. Treatment of coelomocytes (labeled with IL-1alpha) with bivalent water-soluble crosslinkers identified a membrane protein of approximately 70 kDa to which IL-1 is specifically crosslinked., (Copyright 2000 Academic Press.)

In spite of increasing interest in metapopulation dynamics, the genetic consequences of a metapopulation structure remain poorly understood. Here we examine the metapopulation genetic structure of the colonial, facultatively sexual freshwater bryozoan Cristatella mucedo, in the Thames basin of southern England, UK. Populations from nine sites were sampled and colonies genetically characterized using random amplified polymorphic DNA (RAPD)-PCR. A total of 78 different clones was detected over all sites. Despite the large number of clones, genetic distances among clones both within and among sites were very small. Nonetheless, no clone was present at more than one site even though C. mucedo has an asexual dispersal propagule, and clones strongly clustered by sites. No consistent pattern of clonal structure was evident, with both the number and equitability of clones varying greatly among sites. Although sites were genetically distinct, population genetic regions were absent, and a Mantel test indicated that there was no relationship between geographical distances among sites and genetic distances among populations. Our results indicate that C. mucedo exists as a classical metapopulation in the Thames basin, with dispersal independent of distance and all sites contributing to the genetic diversity of the metapopulation.