737 research outputs found

    Eyes wide shut? UK consumer perceptions on aviation climate impacts and travel decisions to New Zealand

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    The purview of climate change concern has implicated air travel, as evidenced in a growing body of academic literature concerned with aviation CO2 emissions. This article assesses the relevance of climate change to long haul air travel decisions to New Zealand for United Kingdom consumers. Based on 15 semi-structured open-ended interviews conducted in Bournemouth, UK during June 2009, it was found that participants were unlikely to forgo potential travel decisions to New Zealand because of concern over air travel emissions. Underpinning the interviewees’ understandings and responses to air travel’s climate impact was a spectrum of awareness and attitudes to air travel and climate change. This spectrum ranged from individuals who were unaware of air travel’s climate impact to those who were beginning to consume air travel with a ‘carbon conscience’. Within this spectrum were some who were aware of the impact but not willing to change their travel behaviours at all. Rather than implicating long haul air travel, the empirical evidence instead exemplifies changing perceptions towards frequent short haul air travel and voices calls for both government and media in the UK to deliver more concrete messages on air travel’s climate impact

    Identifying Parkinson’s Disease Through the Classification of Audio Recording Data

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    Developments in artificial intelligence can be leveraged to support the diagnosis of degenerative disorders, such as epilepsy and Parkinson’s disease. This study aims to provide a software solution, focused initially towards Parkinson’s disease, which can positively impact medical practice surrounding degenerative diagnoses. Through the use of a dataset containing numerical data representing acoustic features extracted from an audio recording of an individual, it is determined if a neural approach can provide an improvement over previous results in the area. This is achieved through the implementation of a feedforward neural network and a layer recurrent neural network. By comparison with the state-of-the-art, a Bayesian approach providing a classification accuracy benchmark of 87.1%, it is found that the implemented neural networks are capable of average accuracy of 96%, highlighting improved accuracy for the classification process. The solution is capable of supporting the diagnosis of Parkinson’s disease in an advisory capacity and is envisioned to inform the process of referral through general practice

    Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74

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    The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1

    Automated electronic medical record sepsis detection in the emergency department

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    Background. While often first treated in the emergency department (ED), identification of sepsis is difficult. Electronic medical record (EMR) clinical decision tools offer a novel strategy for identifying patients with sepsis. The objective of this study was to test the accuracy of an EMR-based, automated sepsis identification system.Methods. We tested an EMR-based sepsis identification tool at a major academic, urban ED with 64,000 annual visits. The EMR system collected vital sign and laboratory test information on all ED patients, triggering a “sepsis alert” for those with ≄2 SIRS (systemic inflammatory response syndrome) criteria (fever, tachycardia, tachypnea, leukocytosis) plus ≄1 major organ dysfunction (SBP ≀ 90 mm Hg, lactic acid ≄2.0 mg/dL). We confirmed the presence of sepsis through manual review of physician, nursing, and laboratory records. We also reviewed a random selection of ED cases that did not trigger a sepsis alert. We evaluated the diagnostic accuracy of the sepsis identification tool.Results. From January 1 through March 31, 2012, there were 795 automated sepsis alerts. We randomly selected 300 cases without a sepsis alert from the same period. The true prevalence of sepsis was 355/795 (44.7%) among alerts and 0/300 (0%) among non-alerts. The positive predictive value of the sepsis alert was 44.7% (95% CI [41.2–48.2%]). Pneumonia and respiratory infections (38%) and urinary tract infection (32.7%) were the most common infections among the 355 patients with true sepsis (true positives). Among false-positive sepsis alerts, the most common medical conditions were gastrointestinal (26.1%), traumatic (25.7%), and cardiovascular (20.0%) conditions. Rates of hospital admission were: true-positive sepsis alert 91.0%, false-positive alert 83.0%, no sepsis alert 5.7%.Conclusions. This ED EMR-based automated sepsis identification system was able to detect cases with sepsis. Automated EMR-based detection may provide a viable strategy for identifying sepsis in the ED

    Arbuscular mycorrhizal response to adverse soil conditions

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    Adverse conditions are a pervasive feature in both natural as well as agronomic soils. The soil environment is constantly changing with regard to moisture, temperature and nutrition. In addition, soil properties such as fertility, pH and aeration are often changed to improve crop yields. Soils have been unintentionally contaminated as a result of accidents that occur during agronomic operations or intentionally contaminated in mining or manufacturing operations by disposal of chemicals that are toxic to plants and micro-organisms. Mycorrhizal associations in terrestrial ecosystems influence organic and inorganic nutrient relationships, water relations and carbon cycling in plants. Relatively little is known about factors that control the vigour and extent of mycorrhization. This lack of understanding arises in large part from the difficulty of studying the intact association, which is a functionally and anatomically distinct structure comprising two biologically different organisms, e.g., plants and arbuscular mycorrhizae (AM) fungi. The formation and function of mycorrhizal relationships are affected by edaphic conditions such as soil composition, moisture, temperature, pH, cation exchange capacity. They are also affected by anthropogenic stressers such as heavy metals, pesticides and soil compaction. An organism's response to stress may involve interactions among various avoidance and tolerance mechanisms (Taylor, 1978; Tingey and Taylor, 1982; Tingey and Anderson, 1991). Stress avoidance mechanisms influence the amount and rate at which stress will reach the target site in the plant. Stress tolerance is defined as resistance via an ability "to come to thermodynamic equilibrium to the stress" without being killed (Levitt, 1980). In this chapter, we shall review the effects of a number of soil-associated stressers, including soil moisture, temperature, pH, heavy metals, agricultural practices and pesticides on AM development and function and host plant tolerance to these stresses. Several publications have reviewed the impact of various stresses on plant-mycorrhizal interactions (Anderson and Rygiewicz, 1991; Read, 1991; Van Duin et al, 1991; Sylvia and Williams, 1992), which provide additional information on this subject

    Influence of adverse soil conditions on the formation and function of Arbuscular mycorrhizas

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    The majority of plants have mycorrhizal fungi associated with them. Mycorrhizal fungi are ecologically significant because they form relationships in and on the roots of a host plant in a symbiotic association. The host plant provides the fungus with soluble carbon sources, and the fungus provides the host plant with an increased capacity to absorb water and nutrients from the soil. Adverse conditions are a pervasive feature in both natural and agronomic soils. The soil environment is constantly changing with regard to moisture, temperature and nutrient availability. In addition, soil properties are often manipulated to improve crop yields. In many cases, soils may be contaminated through disposal of chemicals that are toxic to plants and microorganisms. The formation and function of mycorrhizal relationships are affected by edaphic conditions such as soil composition, moisture, temperature, pH, cation exchange capacity, and also by anthropogenic stressors including soil compaction, metals and pesticides. Arbuscular mycorrhizal fungi are of interest for their reported roles in alleviation of diverse soil-associated plant stressors, including those induced by metals and polychlorinated aliphatic and phenolic pollutants. Much mycorrhizal research has investigated the impact of extremes in water, temperature, pH and inorganic nutrient availability on mycorrhizal formation and nutrient acquisition. Evaluation of the efficacy of plant–mycorrhizal associations to remediate soils contaminated with toxic materials deserves increased attention. Before the full potential benefits of arbuscular mycorrhizal fungi to reclaim contaminated soils can be realized, research advances are needed to improve our understanding of the physiology of mycorrhizae subjected to adverse physical and chemical conditions. This paper will review literature and discuss the implications of soil contamination on formation and function of arbuscular mycorrhizal associations

    ZnII(atsm) is protective in amyotrophic lateral sclerosis model mice via a copper delivery mechanism

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    AbstractMutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete metallation of SOD1 confers abnormal folding, aggregation and biochemical properties, and improving the metallation state of SOD1 provides a viable therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant SOD1 have been demonstrated recently. The aim of the current study was to determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4-methylthiosemicarbazonato)zincII [ZnII(atsm)]. Treatment resulted in an improvement in locomotor function and survival of the mice. However, biochemical analysis of spinal cord tissue collected from the mice revealed that the treatment did not increase overall Zn levels in the spinal cord nor the Zn content of SOD1. In contrast, overall levels of Cu in the spinal cord were elevated in the ZnII(atsm)-treated SOD1G37R mice and the Cu content of SOD1 was also elevated. Further experiments demonstrated transmetallation of ZnII(atsm) in the presence of Cu to form the Cu-analogue CuII(atsm), indicating that the observed therapeutic effects for ZnII(atsm) in SOD1G37R mice may in fact be due to in vivo transmetallation and subsequent delivery of Cu

    Increased typhoon activity in the Pacific deep tropics driven by Little Ice Age circulation changes

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    Author Posting. © The Author(s), 2020. This is the author's version of the work. It is posted here by permission of Nature Research for personal use, not for redistribution. The definitive version was published in Bramante, J. F., Ford, M. R., Kench, P. S., Ashton, A. D., Toomey, M. R., Sullivan, R. M., Karnauskas, K. B., Ummenhofer, C. C., & Donnelly, J. P. (2020). Increased typhoon activity in the Pacific deep tropics driven by Little Ice Age circulation changes. Nature Geoscience, 13, 806–811. doi:10.1038/s41561-020-00656-2.The instrumental record reveals that tropical cyclone activity is sensitive to oceanic and atmospheric variability on inter-annual and decadal scales. However, our understanding of the influence of climate on tropical cyclone behaviour is restricted by the short historical record and the sparseness of prehistorical reconstructions, particularly in the western North Pacific, where coastal communities suffer loss of life and livelihood from typhoons annually. Here, to explore past regional typhoon dynamics, we reconstruct three millennia of deep tropical North Pacific cyclogenesis. Combined with existing records, our reconstruction demonstrates that low-baseline typhoon activity prior to 1350 ce was followed by an interval of frequent storms during the Little Ice Age. This pattern, concurrent with hydroclimate proxy variability, suggests a centennial-scale link between Pacific hydroclimate and tropical cyclone climatology. An ensemble of global climate models demonstrates a migration of the Pacific Walker circulation and variability in two Pacific climate modes during the Little Ice Age, which probably contributed to enhanced tropical cyclone activity in the tropical western North Pacific. In the next century, projected changes to the Pacific Walker circulation and expansion of the tropics will invert these Little Ice Age hydroclimate trends, potentially reducing typhoon activity in the deep tropical Pacific.This work was supported by the Strategic Environmental Research and Development Program (SERDP RC-2336). C.C.U. acknowledges support from NSF under AGS-1602455. We thank student intern D. Carter for extensive labwork on core LTD3. We acknowledge the WCRP’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modelling groups for producing and making available their model output. CMIP5 model output was provided by the WHOI CMIP5 Community Storage Server via their website: http://cmip5.whoi.edu/. Any use of trade, firm or product names is for descriptive purposes only and does not imply endorsement by the US Government.2021-05-1

    Hyaluronic Acid Enhances Gene Delivery into the Cochlea

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    Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98453/1/hum%2E2011%2E086.pd

    Unexpected Long-Term Variability in Jupiter's Tropospheric Temperatures

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    An essential component of planetary climatology is knowledge of the tropospheric temperature field and its variability. Previous studies of Jupiter hinted at periodic behavior that was non-seasonal, as well as dynamical relationships between tropospheric and stratospheric temperatures. However, these observations were made over time frames shorter than Jupiter's orbit or they used sparse sampling. We derived upper-tropospheric (300-mbar) temperatures over 40 years, extending those studies to cover several orbits of Jupiter, revealing unexpected results. Periodicities of 4, 7 8-9 and 10-14 years were discovered that involved different latitude bands and seem disconnected from seasonal changes in solar heating. Anti-correlations of variability in opposite hemispheres were particularly striking at 16, 22 and 30 degrees from the equator. Equatorial temperature variations are also anticorrelated with those 60-70 km above. Such behavior suggests a top-down control of equatorial tropospheric temperatures from stratospheric dynamics. Realistic future global climate models must address the origins of these variations in preparation for their extension to a wider array of gas-giant exoplanets.Comment: Primary file: 16 pages, 5 figures. Supplemental File (attached): 12 pages, 3 figures, 1 tabl
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