Publications by authors named "Edward Long"

Purpose: To determine how time to surgical debridement and fixation affects infection and complication rate in type I open distal radius fractures by comparing patients treated within 24 hours with those treated >24 hours post-injury.

Methods: A retrospective review identified 62 patients who sustained a type I open distal radius fracture that was treated surgically. Patients were stratified into groups based on time to surgical intervention.

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Pharmacological induction of fetal hemoglobin (HbF) expression is an effective therapeutic strategy for the management of beta-hemoglobinopathies such as sickle cell disease. DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-aza) and 5-aza-2'-deoxycytidine (decitabine) have been shown to induce fetal hemoglobin expression in both preclinical models and clinical studies, but are not currently approved for the management of hemoglobinopathies. We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364.

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The purpose of this work was to use various molecular imaging techniques to non-invasively assess GSK2849330 (anti HER3 ADCC and CDC enhanced 'AccretaMab' monoclonal antibody) pharmacokinetics and pharmacodynamics in human xenograft tumor-bearing mice. Immuno-PET biodistribution imaging of radiolabeled 89Zr-GSK2849330 was assessed in mice with HER3 negative (MIA-PaCa-2) and positive (CHL-1) human xenograft tumors. Dose dependency of GSK2849330 disposition was assessed using varying doses of unlabeled GSK2849330 co-injected with 89Zr-GSK2849330.

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The aim of this study is to investigate aerosol plume geometries of pressurised metered dose inhalers (pMDIs) using a high-speed laser image system with different actuator nozzle materials and designs. Actuators made from aluminium, PET and PTFE were manufactured with four different nozzle designs: cone, flat, curved cone and curved flat. Plume angles and spans generated using the designed actuator nozzles with four solution-based pMDI formulations were imaged using Oxford Lasers EnVision system and analysed using EnVision Patternate software.

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Purpose: This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators.

Methods: Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.

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Purpose: To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs).

Methods: Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials.

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An experimental investigation into the interaction that occurs between an impacting water droplet and a granular bed of loose graded sand has been carried out. High-speed imaging, three-dimensional time-resolved particle tracking, and photogrammetric surface profiling have been used to examine individual impact events. The focus of the study is the quantification and trajectory analysis of the particles ejected from the sand bed, along with measurement of the change in bed morphology.

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Purpose: To investigate the influence of different actuator materials and nozzle designs on the electrostatic charge properties of a series of solution metered dose inhaler (pMDI) aerosols.

Methods: Actuators were manufactured with flat and cone nozzle designs using five different materials from the triboelectric series (Nylon, Polyethylene terephthalate, Polyethylene-High density, Polypropylene copolymer and Polytetrafluoroethylene). The electrostatic charge profiles of pMDI containing beclomethasone dipropionate (BDP) as model drug in HFA-134a propellant, with different concentrations of ethanol were studied.

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Concentrations of 119 pharmaceuticals and personal care products (PPCPs) and 13 perfluoroalkyl substances (PFASs) in marine sediments measured throughout Puget Sound (n = 10) and Bellingham Bay (n = 30), Washington, USA, are reported. These data are among the first measurements of PPCPs and PFASs in marine sediments from the Pacific Northwest and provide a comparison to previous measurements of these chemicals in influent, effluent, and biosolids from municipal wastewater treatment plants throughout the region. The concentrations of both PPCPs and PFASs in sediments from Puget Sound and Bellingham Bay ranged from very low to non-detectable for most compounds.

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Soluble epoxide hydrolase (sEH, EPHX2) metabolizes eicosanoid epoxides, including epoxyeicosatrienoic acids (EETs) to the corresponding dihydroxyeicosatrienoic acids (DHETs), and leukotoxin (LTX) to leukotoxin diol (LTX diol). EETs, endothelium-derived hyperpolarizing factors, exhibit potentially beneficial properties, including anti-inflammatory effects and vasodilation. A novel, potent, selective inhibitor of recombinant human, rat and mouse sEH, GSK2256294A, exhibited potent cell-based activity, a concentration-dependent inhibition of the conversion of 14,15-EET to 14,15-DHET in human, rat and mouse whole blood in vitro, and a dose-dependent increase in the LTX/LTX diol ratio in rat plasma following oral administration.

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The role of T cells in chronic obstructive pulmonary disease (COPD) is not well understood. We have previously demonstrated that chronic cigarette smoke exposure can lead to the accumulation of CD4(+) and CD8(+) T cells in the alveolar airspaces in a mouse model of COPD, implicating these cells in disease pathogenesis. However, whether specific inhibition of T cell responses represents a therapeutic strategy has not been fully investigated.

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The Washington State Department of Ecology annually conducts sediment quality monitoring in Puget Sound as a component of the Puget Sound Ecosystem Monitoring Program. Sediment samples are analyzed to determine the concentrations of about 170 chemical and physical variables. A Sediment Chemistry Index (SCI) was derived using the State of Washington Sediment Management Standards to account for the presence and concentrations of mixtures of toxicants.

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Data from toxicity tests of the pore water extracted from Puget Sound sediments were compiled from surveys conducted from 1997 to 2009. Tests were performed on 664 samples collected throughout all of the eight monitoring regions in the Sound, an area encompassing 2,294.1 km(2).

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Recently, patients with tobacco smoke induced emphysema have been shown to exhibit classical signs of T cell mediated autoimmunity characterized by autoantibody production and Th1 type responses. As the recently described Th17 type subset has been found to play a role in the pathogenesis of a number of autoimmune diseases previously considered to be Th1 driven, we sought to examine whether a Th17 type response was associated with airspace enlargement in a murine model of emphysema. Six to eight months exposure of mice to inhalation of mainstream cigarette smoke led to progressive airspace enlargement as defined by morphometric analysis.

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The Escherichia coli SOS response to DNA damage is modulated by the RecA protein, a recombinase that forms an extended filament on single-stranded DNA and hydrolyzes ATP. The RecA K72R (recA2201) mutation eliminates the ATPase activity of RecA protein. The mutation also limits the capacity of RecA to form long filaments in the presence of ATP.

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Members of the papain family of cysteine proteases (cathepsins) mediate late stage processing of MHC class II-bound invariant chain (Ii), enabling dissociation of Ii, and binding of antigenic peptide to class II molecules. Recognition of cell surface class II/Ag complexes by CD4(+) T cells then leads to T cell activation. Herein, we demonstrate that a pan-active cathepsin inhibitor, SB-331750, attenuated the processing of whole cell Ii p10 to CLIP by Raji cells, and DBA/1, SJL/J, and C57BL/6 splenocytes.

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The bioavailability of sediment-associated contaminants is poorly understood. Often, a triad of chemical concentration measurements, laboratory sediment toxicity tests, and benthic infaunal community condition is used to assess whether contaminants are present at levels of ecological concern. Integration of these 3 lines of evidence is typically based on best professional judgment by experts; however, the level of consistency among expert approach and interpretation has not been determined.

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The lower Passaic River in northern New Jersey (USA) has been heavily industrialized since the mid-nineteenth century and its shoreline and aquatic habitats degraded or destroyed. Similar to other urban systems, Passaic River sediments, both surface and buried, historically have contained elevated levels of numerous contaminants that may pose risks to ecological receptors and humans. Sediments from 15 stations in the lower Passaic River and 3 reference stations in the Mullica River in southern New Jersey were sampled in 1999 and characterized for chemical contamination, toxicity, and impairment of the benthic community.

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High-density perfusion cultivation of mammalian cells can result in elevated bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2) exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH control. Recognizing the limitations to the practicality of gas sparging for CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the source was investigated.

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Matching chemical and toxicological data of surficial sediments from Sydney Harbour, Australia, and vicinity, were collected to evaluate predictive abilities of Effects Range-Low (ERL), Effects Range-Median (ERM) and other sediment quality guidelines (SQGs). Samples (n=103) containing a wide range of chemicals and concentrations were subjected to a battery of 4-6 toxicity tests. ERLs and functionally equivalent low-range SQGs were highly predictive of non-toxicity when not exceeded, as incidences of toxicity were 0-8%.

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Fine-grained sediments contaminated with complex mixtures of organic and inorganic chemical contaminants can be toxic in laboratory tests and/or cause adverse impacts to resident benthic communities. Effects-based, sediment quality guidelines (SQGs) have been developed over the past 20 years to aid in the interpretation of the relationships between chemical contamination and measures of adverse biological effects. Mean sediment quality guideline quotients (mSQGQ) can be calculated by dividing the concentrations of chemicals in sediments by their respective SQGs and calculating the mean of the quotients for the individual chemicals.

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An internally consistent dataset comprising 103 surficial estuarine sediment samples were collected from Sydney Harbour, Australia and locations south of Sydney. This paper describes the chemical characteristics of the dataset and evaluates its suitability for use in evaluating biological effects-based sediment quality guidelines (SQGs). The sediments contained mixtures of chemicals, the most prevalent chemical classes being metals and polycyclic aromatic hydrocarbons, whereas sediments from coastal lakes/estuaries south of Sydney had low concentrations of contaminants.

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A survey was designed and conducted to determine the severity, spatial patterns, and spatial extent of degraded sediment quality in Puget Sound (Washington State, USA). A weight of evidence compiled from results of chemical analyses, toxicity tests, and benthic infaunal analyses was used to classify the quality of sediments. Sediment samples were collected from 300 locations within a 2363 km(2) area extending from the US/Canada border to the inlets of southern Puget Sound and Hood Canal.

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Laboratory survival tests were conducted with an indigenous infaunal amphipod, Corophium colo, on 103 sediment samples from Sydney Harbor (NSW, Australia) and vicinity, containing a wide range of chemicals and concentrations. The present study describes the sensitivity of C. colo to the sediments and compares the results to data for North American amphipods (Rhepoxynius abronius and Ampelisca abdita) previously used to establish and validate sediment-quality guidelines (SQGs).

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