530 research outputs found

    Capturing the short-term variability of carbon dioxide emissions from sedimentary rock weathering in a remote mountainous catchment, New Zealand

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    Weathering of organic carbon contained in sedimentary rocks (petrogenic OC, OCpetro) is an important control on the concentrations of carbon dioxide (CO2) and oxygen in the atmosphere. Of particular significance are steep mountainous catchments, where high rates of physical erosion introduce OCpetro to the surface, where oxygen in air and water can help drive oxidative weathering reactions, yet measurements of CO2 emissions from OCpetro oxidation are still scarce. Here, we use in situ gas accumulation chambers and show that CO2 fluxes, and their environmental controls, can be determined during a stand-alone, short-term (8 days) field campaign, applied to a remote setting. In the rapidly eroding Waiapu River catchment, New Zealand, dominated by mudstones, we measured high rates of CO2 release (222–1590 mgC m−2 d−1) in five accumulation chambers in the near-surface of naturally fractured and bedded rock outcrops. The corresponding CO2 concentrations are very high (pCO2 ~4700–27,100 ppmv), and such values could influence acid-hydrolysis reactions during chemical weathering of co-occurring silicate minerals. The CO2 is radiocarbon depleted (fraction modern, F14C = 0.0122–0.0547), confirming it is petrogenic in origin. Stable carbon isotopes suggest a source from OCpetro, but δ13C values of the CO2 are lower by ~3.5–3.7 ± 0.1 ‰ from those of OCpetro (−25.9 ± 0.1 ‰), consistent with isotope fractionation associated with microbial respiration of OCpetro. Over 6 days of measurement, we find that CO2 fluxes respond quickly to changes in temperature and humidity, indicating an environmental regulation that is captured by our short-term installation. The approaches applied here mean that future research can now seek to constrain the climatic, lithological and biological controls on OCpetro oxidation across regional to global scales

    Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis

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    Objective To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica

    Small-Molecule Ligands that Bind the RET Receptor Activate Neuroprotective Signals Independent of but Modulated by Coreceptor GFR alpha 1

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    Glial cell line-derived neurotrophic factor (GDNF) binds the GFR alpha 1 receptor, and the GDNF-GFR alpha 1 complex binds to and activates the transmembrane RET tyrosine kinase to signal through intracellular Akt/Erk pathways. To dissect the GDNF-GFR alpha 1-RET signaling complex, agents that bind and activate RET directly and independently of GFR alpha 1 expression are valuable tools. In a focused naphthalenesulfonic acid library from the National Cancer Institute database, we identified small molecules that are genuine ligands binding to the RET extracellular domain. These ligands activate RET tyrosine kinase and afford trophic signals irrespective of GFR alpha 1 coexpression. However, RET activation by these ligands is constrained by GFR alpha 1, likely via an allosteric mechanism that can be overcome by increasing RET ligand concentration. In a mouse model of retinitis pigmentosa, monotherapy with a small-molecule RET agonist activates survival signals and reduces neuronal death significantly better than GDNF, suggesting therapeutic potential. SIGNIFICANCE STATEMENT A genuine ligand of RET receptor ectodomain was identified, which acts as an agonist. Binding and agonism are independent of a coreceptor glial cell line-derived neurotrophic factor family receptor a, which is required by the natural growth factor glial cell line-derived neurotrophic factor, and are selective for cells expressing RET. The lead agent protects neurons from death in vivo. This work validates RET receptor as a druggable therapeutic target and provides for potential leads to evaluate in neurodegenerative states. We also report problems that arise when screening chemical libraries.Peer reviewe

    Manipulative therapy and/or NSAIDs for acute low back pain: design of a randomized controlled trial [ACTRN012605000036617]

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    BACKGROUND: Acute low back pain is a common condition resulting in pain and disability. Current national and international guidelines advocate general practitioner care including advice and paracetamol (4 g daily in otherwise well adults) as the first line of care for people with acute low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and spinal manipulative therapy (SMT) are advocated in many guidelines as second line management options for patients with acute low back pain who are not recovering. No studies have explored the role of NSAIDs and/or SMT in addition to first line management for acute low back pain. The primary aim of this study is to investigate if NSAIDs and/or SMT in addition to general practitioner advice and paracetamol results in shorter recovery times for patients with acute low back pain. The secondary aims of the study are to evaluate whether the addition of SMT and/or NSAIDs influences pain, disability and global perceived effect at 1, 2, 4 and 12 weeks after onset of therapy for patients with significant acute low back pain. METHODS/DESIGN: This paper presents the rationale and design of a randomised controlled trial examining the addition of NSAIDs and/or SMT in 240 people who present to their general practitioner with significant acute low back pain

    PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP) should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses) results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN) for recovery from acute LBP.</p> <p>Methods/Design</p> <p>The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol), PRN paracetamol (plus placebo time-contingent paracetamol) or a double placebo study arm. The primary outcome will be time (days) to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives.</p> <p>Discussion</p> <p>The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP.</p> <p>Trail registration</p> <p>ACTRN12609000966291.</p

    Adverse childhood experience and adult persistent pain and disability: protocol for a systematic review and meta-analysis

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    A growing body of research highlights the pervasive harms of adverse childhood experiences (ACEs) on health throughout the life-course. However, findings from prior reviews and recent longitudinal studies investigating the association between types of ACEs and persistent pain have yielded inconsistent findings in the strength and direction of associations. The purpose of this review is to appraise and summarize evidence on the relationship between ACEs and persistent pain and disability outcomes in adulthood. The specific aims are (1) to determine whether there is a relationship between exposure to ACE and persistent pain and disability in adults and (2) to determine whether unique and cumulative ACEs exposures (number and type) increase the risk of developing persistent pain and disability in adulthood

    Charged Particle Pseudorapidity Distributions in Au+Al, Cu, Au, and U Collisions at 10.8 A\cdotGeV/c

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    We present the results of an analysis of charged particle pseudorapidity distributions in the central region in collisions of a Au projectile with Al, Cu, Au, and U targets at an incident energy of 10.8~GeV/c per nucleon. The pseudorapidity distributions are presented as a function of transverse energy produced in the target or central pseudorapidity regions. The correlation between charged multiplicity and transverse energy measured in the central region, as well as the target and projectile regions is also presented. We give results for transverse energy per charged particle as a function of pseudorapidity and centrality.Comment: 31 pages + 12 figures (compressed and uuencoded by uufiles), LATEX, Submitted to PR
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