192 research outputs found

    Unextractable fossil fuels in a 1.5 °C world

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    Parties to the 2015 Paris Agreement pledged to limit global warming to well below 2 °C and to pursue efforts to limit the temperature increase to 1.5 °C relative to pre-industrial times1. However, fossil fuels continue to dominate the global energy system and a sharp decline in their use must be realized to keep the temperature increase below 1.5 °C (refs. 2,3,4,5,6,7). Here we use a global energy systems model8 to assess the amount of fossil fuels that would need to be left in the ground, regionally and globally, to allow for a 50 per cent probability of limiting warming to 1.5 °C. By 2050, we find that nearly 60 per cent of oil and fossil methane gas, and 90 per cent of coal must remain unextracted to keep within a 1.5 °C carbon budget. This is a large increase in the unextractable estimates for a 2 °C carbon budget9, particularly for oil, for which an additional 25 per cent of reserves must remain unextracted. Furthermore, we estimate that oil and gas production must decline globally by 3 per cent each year until 2050. This implies that most regions must reach peak production now or during the next decade, rendering many operational and planned fossil fuel projects unviable. We probably present an underestimate of the production changes required, because a greater than 50 per cent probability of limiting warming to 1.5 °C requires more carbon to stay in the ground and because of uncertainties around the timely deployment of negative emission technologies at scale

    Randomised crossover trial of rate feedback and force during chest compressions for paediatric cardiopulmonary resuscitation

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    Objective: To determine the effect of visual feedback on rate of chest compressions, secondarily relating the forces used. / Design: Randomised crossover trial. / Setting: Tertiary teaching hospital. / Subjects: Fifty trained hospital staff. / Interventions: A thin sensor-mat placed over the manikin's chest measured rate and force. Rescuers applied compressions to the same paediatric manikin for two sessions. During one session they received visual feedback comparing their real-time rate with published guidelines. / Outcome measures: Primary: compression rate. Secondary: compression and residual forces. / Results: Rate of chest compressions (compressions per minute (compressions per minute; cpm)) varied widely (mean (SD) 111 (13), range 89–168), with a fourfold difference in variation during session 1 between those receiving and not receiving feedback (108 (5) vs 120 (20)). The interaction of session by feedback order was highly significant, indicating that this difference in mean rate between sessions was 14 cpm less (95% CI −22 to −5, p=0.002) in those given feedback first compared with those given it second. Compression force (N) varied widely (mean (SD) 306 (94); range 142–769). Those receiving feedback second (as opposed to first) used significantly lower force (adjusted mean difference −80 (95% CI −128 to −32), p=0.002). Mean residual force (18 N, SD 12, range 0–49) was unaffected by the intervention. / Conclusions: While visual feedback restricted excessive compression rates to within the prescribed range, applied force remained widely variable. The forces required may differ with growth, but such variation treating one manikin is alarming. Feedback technologies additionally measuring force (effort) could help to standardise and define effective treatments throughout childhood

    Eureka and beyond: mining's impact on African urbanisation

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    This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

    Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

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    Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

    Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery

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    Publisher Copyright: © 2015 Ozolina et al.Background: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.publishersversionPeer reviewe

    Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

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    INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

    Involvement of the Metabotropic Glutamate Receptor mGluR5 in NMDA Receptor-Dependent, Learning-Facilitated Long-Term Depression in CA1 Synapses

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    Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent synaptic plasticity to the coupling of weak afferent stimulation, which is subthreshold for the induction of plasticity, with a spatial learning experience. The metabotropic glutamate receptor subtype 5 (mGluR5) is critically involved in enabling the persistency of multiple forms of hippocampal synaptic plasticity. We compared the effects of pharmacological allosteric antagonism of mGluR5 in learning-facilitated plasticity with plasticity that had been induced solely by patterned afferent stimulation of the Schaffer collateral pathway to the CA1 stratum radiatum of adult freely behaving rats. Intracerebroventricular injection of the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) had no effect on basal synaptic transmission but significantly prevented both long-term depression (LTD) elicited by electrical stimulation and LTD facilitated by novel object-place configuration learning. NMDA receptor antagonism also prevented learning-facilitated LTD. Habituation to the objects was prevented by MPEP application. Whereas reexposure to the object-place configuration (after 7 days) failed to facilitate LTD in control animals, those who had been treated previously with MPEP expressed LTD, suggesting that inhibition of learning contributed to the initial prevention of LTD. These data support a pivotal role for mGluR5 in both hippocampal LTD and the acquisition of object-place configurations

    Mechanisms Involved in Nicotinic Acetylcholine Receptor-Induced Neurotransmitter Release from Sympathetic Nerve Terminals in the Mouse Vas Deferens

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    Prejunctional nicotinic acetylcholine receptors (nAChRs) amplify postganglionic sympathetic neurotransmission, and there are indications that intraterminal Ca2+ stores might be involved. However, the mechanisms by which nAChR activation stimulates neurotransmitter release at such junctions is unknown. Rapid local delivery (picospritzing) of the nAChR agonist epibatidine was combined with intracellular sharp microelectrode recording to monitor spontaneous and field-stimulation-evoked neurotransmitter release from sympathetic nerve terminals in the mouse isolated vas deferens. Locally applied epibatidine (1 µM) produced ‘epibatidine-induced depolarisations’ (EIDs) that were similar in shape to spontaneous excitatory junction potentials (SEJPs) and were abolished by nonselective nAChR antagonists and the purinergic desensitizing agonist α,β-methylene ATP. The amplitude distribution of EIDs was only slightly shifted towards lower amplitudes by the selective α7 nAChR antagonists α-bungarotoxin and methyllcaconitine, the voltage-gated Na+ channel blocker tetrodotoxin or by blocking voltage-gated Ca2+ channels with Cd2+. Lowering the extracellular Ca2+ concentration reduced the frequency of EIDs by 69%, but more surprisingly, the Ca2+-induced Ca2+ release blocker ryanodine greatly decreased the amplitude (by 41%) and the frequency of EIDs by 36%. Ryanodine had no effect on electrically-evoked neurotransmitter release, paired-pulse facilitation, SEJP frequency, SEJP amplitude or SEJP amplitude distribution. These results show that activation of non-α7 nAChRs on sympathetic postganglionic nerve terminals induces high-amplitude junctional potentials that are argued to represent multipacketed neurotransmitter release synchronized by intraterminal Ca2+-induced Ca2+ release, triggered by Ca2+ influx directly through the nAChR. This nAChR-induced neurotransmitter release can be targeted pharmacologically without affecting spontaneous or electrically-evoked neurotransmitter release
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