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Competing Interests: The authors have no financial relationships relevant to this article to disclose.

Objective: Hemorrhage is the leading cause of preventable death in civilian trauma centers and on the battlefield. One of the emerging treatment options for hemorrhage in austere environments is tranexamic acid (TXA). However, the landscape is not amenable to the current delivery standard. This study compared the pharmacokinetics of TXA via a standard 10-minute intravenous infusion (IV infusion), intravenous rapid push over 10 s (IV push), and intramuscular injection (IM) in a swine polytrauma and hemorrhagic shock model (trauma group) compared to uninjured controls (control group)., Methods: Thirty swine were randomized to the trauma or control group. Following anesthesia, the trauma group experienced a simulated blast injury and 40% controlled hemorrhage. Subjects in both groups were then randomized to receive 1 g/10 mL TXA via IV infusion, IV push, or IM. Animals were monitored for four hours with serial blood sampling. Serum TXA concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and analyzed., Results: The time to maximum TXA concentration (T max ) was not affected by trauma in IV infusion or IV push, but was affected in the IM administration with T max significantly slower than the control group ( p  = 0.016). The minimum effective serum concentration of TXA (C eff , 10 µg/mL) was reached in less than one minute with IV infusion and instantaneously with IV push. Despite lower bioavailability, the time to reach C eff (T eff ) was achieved via IM administration in less than 10 min for both groups (6.4 min trauma vs. 2.1 min control)., Conclusions: In austere prehospital environments, an alternative to intravenous infusion of a life-saving medication is desired. Administration of TXA via all three methods reached the level needed to cause substantial inhibition of fibrinolysis within 10 min. The IV push method showed similar pharmacokinetics to IV infusion of TXA but can be delivered quickly without sacrificing an access site for 10 min.

Neutrophils are recognized for their role in host defense against pathogens as well as inflammatory conditions mediated through many mechanisms including neutrophil extracellular trap (NET) formation and generation of reactive oxygen species (ROS). NETs are increasingly appreciated as a major contributor in autoimmune and inflammatory diseases such as cystic fibrosis. Myeloperoxidase (MPO), a key neutrophil granule enzyme mediates generation of hypochlorous acid which, when extracellular, can cause host tissue damage. To better understand the role played by neutrophils in inflammatory diseases, we measured and modulated myeloperoxidase activity and NETs in vivo, utilizing a rat peritonitis model. RLS-0071 is a 15 amino acid peptide that has been shown to inhibit myeloperoxidase activity and NET formation in vitro. The rat model of inflammatory peritonitis was induced with intraperitoneal injection of either P. aeruginosa supernatant or immune-complexes. After euthanasia, a peritoneal wash was performed and measured for myeloperoxidase activity and free DNA as a surrogate for measurement of NETs. P. aeruginosa supernatant caused a 2-fold increase in MPO activity and free DNA when injected IP. Immune-complexes injected IP increased myeloperoxidase activity and free DNA 2- fold. RLS-0071 injection decreased myeloperoxidase activity and NETs in the peritoneal fluid generally to baseline levels in the presence of P. aeruginosa supernatant or immune-complexes. Taken together, RLS-0071 demonstrated the ability to inhibit myeloperoxidase activity and NET formation in vivo when initiated by different inflammatory stimuli including shed or secreted bacterial constituents as well as immune-complexes., Competing Interests: Parvathi Kumar, Adrianne Enos, Brittany Lassiter, and Pamela S. Hair: employees of ReAlta Life Sciences. Neel K. Krishna is an employee and has equity ownership of ReAlta Life Sciences Kenji. M. Cunnion is an employee, has equity ownership, and membership on the board of ReAlta Life Sciences. Commercial affiliation with ReAlta Life Sciences Inc, does not alter our adherence to PLOS ONE policies on sharing data and materials.

The plasmon resonances of a concentric metallic nanoshell arise from the hybridization of primitive plasmon modes of the same angular momentum on its inner and outer surfaces. For a nanoshell with an offset core, the reduction in symmetry relaxes these selection rules, allowing for an admixture of dipolar components in all plasmon modes of the particle. This metallodielectric nanostructure with reduced symmetry exhibits a core offset-dependent multipeaked spectrum, seen in single-particle spectroscopic measurements, and exhibits significantly larger local-field enhancements on its external surface than the equivalent concentric spherical nanostructure.

Two commercial egg-type strains were beak-trimmed at 10, 10 and 63, or 10 and 84 d. There were no interactions between strain and beak trimming treatment. Pullet feed consumption was significantly reduced within the 14-d period following beak trimming at 63 or 84 d. Total pullet feed consumption (1 to 126 d) was significantly lower among birds trimmed twice than among those trimmed only at 10 d. At 126 d, body weight of pullets trimmed at 10 and 84 d or 10 and 63 d was significantly less than that of those trimmed only at 10 d. Pullet mortality was not significantly influenced by beak trimming treatments. No significant effects of beak trimming treatments on layer mortality, egg production, egg weight, egg mass, feed conversion, or egg quality were detected. Layer feed consumption was significantly greater among birds beak trimmed at 10 d than among those trimmed at 10 and 84 d. Most of the effects associated with beak trimming treatments can be attributed to the influence that beak trimming had on feed consumption.