284 research outputs found
Individual participant data meta-analysis of new-onset and worsening diabetes mellitus in large-scale randomized double-blind trials of statin therapy
Revisiting ocean carbon sequestration by direct injection: A global carbon budget perspective
In this study we look beyond the previously studied effects of oceanic CO2 injections on atmospheric and oceanic reservoirs and also account for carbon cycle and climate feedbacks between the atmosphere and the terrestrial biosphere. Considering these additional feedbacks is important since backfluxes from the terrestrial biosphere to the atmosphere in response to reducing atmospheric CO2 can further offset the targeted reduction. To quantify these dynamics we use an Earth system model of intermediate complexity to simulate direct injection of CO2 into the deep ocean as a means of emissions mitigation during a high CO2 emission scenario. In three sets of experiments with different injection depths, we simulate a 100-year injection period of a total of 70 GtC and follow global carbon cycle dynamics over another 900 years. In additional parameter perturbation runs, we varied the default terrestrial photosynthesis CO2 fertilization parameterization by ±50 % in order to test the sensitivity of this uncertain carbon cycle feedback to the targeted atmospheric carbon reduction through direct CO2 injections. Simulated seawater chemistry changes and marine carbon storage effectiveness are similar to previous studies. As expected, by the end of the injection period avoided emissions fall short of the targeted 70 GtC by 16–30 % as a result of carbon cycle feedbacks and backfluxes in both land and ocean reservoirs. The target emissions reduction in the parameter perturbation simulations is about 0.2 and 2 % more at the end of the injection period and about 9 % less to 1 % more at the end of the simulations when compared to the unperturbed injection runs.
An unexpected feature is the effect of the model's internal variability of deep-water formation in the Southern Ocean, which, in some model runs, causes additional oceanic carbon uptake after injection termination relative to a control run without injection and therefore with slightly different atmospheric CO2 and climate. These results of a model that has very low internal climate variability illustrate that the attribution of carbon fluxes and accounting for injected CO2 may be very challenging in the real climate system with its much larger internal variability
Vibrational properties and thermodynamical stabilities of alloys and compounds
Die Eigenschaften von Festkörper werden mit der Genauigkeit von Dichtefunktionaltheorie (DFT) modelliert. Dabei wurde insbesondere, der Beitrag der Schwingungen zur Freien Energie berücksichtigt.
Die Mo3Al2C(1-x) Verbindung ist von besonderem Interesse, da diese supraleitende Eigenschaften aufweist, aber die Kristallstruktur keine Inversionsymmetry beinhaltet. Durch Phononenrechnungen wurde festgestellt, dass die Verbindung ohne Kohlenstoffleerstellen dynamisch instabil ist, d.h. um Stabilität zu erreichen muss x größer als 0 sein.
Kupfer ist ein technologisch wichtiger Härtezusatz zu Stahl. Für ein konzentrationsabhängiges Model des Fe-Cu Phasendiagrammes wurde die "Cluster Expansion" (CE) Methode gewählt. Basierend auf einer großen Anzahl von Inputstrukturen, die mit spin-polarisierten DFT berechnet wurden, wurde mit CE die effektiven Clusterwechselwirkungsenergien (ECIs) des dazugehörigen Satzes von Figuren ermittelt. Durch Berücksichtigung der Freien Energie der Schwingungen wurden die ECI’s auch temperatur-abhängig. Die Löslichkeit wurde anhand von Monte Carlo Rechnungen ermittelt.Properties of solids are modelled with density functional theory (DFT) accuracy. The role of vibrational free energies for phase stabilities is investigated by studying two types of materials.
Mo3Al2C(1-x) is of interest because it is superconducting without a center of inversion. It was found, that the stoichiometric compound is dynamically unstable whereas carbon vacancies stabilise the phonon dispersions.
Cu enrichment of steel makes it harder and the task is to derive the solubility of Cu in Fe. For alloy modelling the Cluster Expansion (CE) was chosen. From spin-polarised DFT calculations the effective cluster interactions (ECI's) and corresponding figures were derived. When vibrational free energies were included the ECI's became temperature dependent. At each temperature a separate CE needed to be done. The solubility was determined by Monte Carlo simulations
I can see clearly now: Survey results from neonatal staff on mydriatic use in retinopathy or prematurity screening
Aims:
Very preterm infants require mydriatic eye drops in preparation for retinopathy of prematurity examination. Mydriatic dosing needs to provide adequate pupil dilation for the examination and yet, avoid adverse effects. Although the relative frequency of mydriatic administration is high, there is no established or preferred mydriatic regimen in the Australia and New Zealand.
The aim of surveying neonatal health care professionals is to establish the variation in mydriatic regimens and to estimate the frequency of common to rare adverse drug events after mydriatic administration.
Methods:
A questionnaire was emailed to selected nursing and management staff at Neonatal Intensive Care Units (NICU) listed in the Directory of NICU within Australia and New Zealand, 2017, the target survey participant being staff who administer the mydriatic eye drops during the retinopathy of prematurity eye examination.
Results:
Forty six neonatal staff from all major regions in Australia and New Zealand participated in the survey. The majority of participants were nursing staff who administered the mydriatics. Just over half of the staff prepare their own phenylephrine and cyclopentolate eye drops and approximately a quarter used either Cyclomydril® or a combination of phenylephrine and tropicamide.
In-house compounded phenylephrine, cyclopentolate and tropicamide eye drops were diluted in the majority of cases. Staff that used the proprietary product Cyclomydril® used it undiluted (90%). Fifty four percent of staff reported that they administered one set of drops, compared to 41% gave two sets of drops and 5% administered 3 drops. No staff member reported administering more than 3 drops.
The majority of staff administered a standard drop from the end of a minim or syringe (78%). A microdrop needle and an IV cannula (with the needle removed) were used to administer a microdrop in the remainder (22%).
Neonatal staff reported seeing hypertension, tachycardia, bradycardia, apnoea, feed intolerance, abdominal distension, necrotising enterocolitis, death, seizure and skin blanching after mydriatic administration.
Conclusions:
There is a wide variety of mydriatic combinations used in Australia and New Zealand and a range in frequency of adverse drug events seen after mydriatic administration
Lack of evidence and consequential harm caused by mydriatic regimens used in retinopathy of prematurity screening.
Approximately 3,500 infants in New Zealand and Australia are screened annually for retinopathy of prematurity (ROP). To view the retina and diagnose ROP, adequate pupil dilation with mydriatic medicines is required.
Although mydriatic drops are in common use in NICUs, there is no established or preferred mydriatic regimen in New Zealand and Australia. A literature review revealed that there is very limited literature involving only pilot studies on which international mydriatic guidelines are based. Results from these pilot studies suggest that there is very little benefit in administering larger doses when smaller doses are effective.
A survey of New Zealand and Australian neonatal nursing staff identified 11 different mydriatic regimens, highlighting the need for robust evidence to guide clinical practice. Within these 11 mydriatic regimens, there was up to a 27-fold difference in total dose. Only 22% of the respondents indicated using a microdrop to reduce the total dose. The larger the total dose of mydriatic medicines, the higher the risk for adverse events. Adverse events that neonatal nurses reported after mydriatic administration were; hypertension, tachycardia, apnoea, feed intolerance, abdominal distension, necrotising enterocolitis, death and periorbital pallor.
The findings indicate the need for further evidence to support the dosing of mydriatics in neonates. There is a need for a RCT to investigate the use of low dose cyclopentolate and phenylephrine by comparing a standard drop to a microdrop. Results from the RCT will provide evidence for international guidelines, and therefore guide clinical practice
(Mis)conceptions about modeling of negative emissions technologies
Intentionally removing carbon from the atmosphere with negative emission technologies (NETs) will be important to achieve net-zero emissions by mid-century and to limit global warming to 2 °C or even 1.5 °C (IPCC 2018). Model scenarios that consider NETs as part of mitigation pathways are still largely restricted to afforestation and bioenergy with carbon capture and storage (BECCS), while the '[f]easibility and sustainability of [NETs] use could be enhanced by a portfolio of options deployed at substantial, but lesser scales, rather than a single option at very large scale' (IPCC 2018, p 19). Here, we show the results from an anonymous expert survey, including 32 Earth-System-Model (ESM) experts and 18 Integrated-Assessment-Model (IAM) experts, about the role of NETs in future climate policies and about how well the various technologies are represented in current models. We find that they strongly support the view that technology portfolios are required to achieve negative emissions, however, the responses show that the number and range of NETs that can be assessed in IAMs is small and that IAMs and ESMs are rather applied to analyze technologies separately than in combination. IAM experts in particular consider BECCS as part of a future NETs portfolio; but at the same time, all experts judge the constraints BECCS would face regarding future overall feasibility and more particularly regarding resource competition to be the highest. Regarding the assessment of constraints the ESM experts are much more skeptical than the IAM experts; they also think that the BECCS carbon removal pathways are less sufficiently represented in ESMs compared to what the IAM experts thinks about the representation in their models. Despite the perceived need for NETs portfolios, the range of NETs which can be assessed in IAMs is rather small and ocean NETs have, so far, mostly been overlooked by the IAM experts
Integrated Assessment of Carbon Dioxide Removal
To maintain the chance of keeping the average global temperature increase below 2 degrees C and to limit long-term climate change, removing carbon dioxide from the atmosphere (carbon dioxide removal, CDR) is becoming increasingly necessary. We analyze optimal and cost-effective climate policies in the dynamic integrated assessment model (IAM) of climate and the economy (DICE2016R) and investigate (1) the utilization of (ocean) CDR under different climate objectives, (2) the sensitivity of policies with respect to carbon cycle feedbacks, and (3) how well carbon cycle feedbacks are captured in the carbon cycle models used in state-of-the-art IAMs. Overall, the carbon cycle model in DICE2016R shows clear improvements compared to its predecessor, DICE2013R, capturing much better long-term dynamics and also oceanic carbon outgassing due to excess oceanic storage of carbon from CDR. However, this comes at the cost of a (too) tight short-term remaining emission budget, limiting the model suitability to analyze low-emission scenarios accurately. With DICE2016R, the compliance with the 2 degrees C goal is no longer feasible without negative emissions via CDR. Overall, the optimal amount of CDR has to take into account (1) the emission substitution effect and (2) compensation for carbon cycle feedbacks
Meeting climate targets by direct CO2 injections: what price would the ocean have to pay?
We investigate the climate mitigation potential and collateral effects of direct injections of captured CO2 into the deep ocean as a possible means to close the gap between an intermediate CO2 emissions scenario and a specific temperature target, such as the 1.5 ∘C target aimed for by the Paris Agreement. For that purpose, a suite of approaches for controlling the amount of direct CO2 injections at 3000 m water depth are implemented in an Earth system model of intermediate complexity.
Following the representative concentration pathway RCP4.5, which is a medium mitigation CO2 emissions scenario, cumulative CO2 injections required to meet the 1.5 ∘C climate goal are found to be 390 Gt C by the year 2100 and 1562 Gt C at the end of simulations, by the year 3020. The latter includes a cumulative leakage of 602 Gt C that needs to be reinjected in order to sustain the targeted global mean temperature.
CaCO3 sediment and weathering feedbacks reduce the required CO2 injections that comply with the 1.5 ∘C target by about 13 % in 2100 and by about 11 % at the end of the simulation.
With respect to the injection-related impacts we find that average pH values in the surface ocean are increased by about 0.13 to 0.18 units, when compared to the control run. In the model, this results in significant increases in potential coral reef habitats, i.e., the volume of the global upper ocean (0 to 130 m depth) with omega aragonite > 3.4 and ocean temperatures between 21 and 28 ∘C, compared to the control run. The potential benefits in the upper ocean come at the expense of strongly acidified water masses at depth, with maximum pH reductions of about −2.37 units, relative to preindustrial levels, in the vicinity of the injection sites. Overall, this study demonstrates that massive amounts of CO2 would need to be injected into the deep ocean in order to reach and maintain the 1.5 ∘C climate target in a medium mitigation scenario on a millennium timescale, and that there is a trade-off between injection-related reductions in atmospheric CO2 levels accompanied by reduced upper-ocean acidification and adverse effects on deep-ocean chemistry, particularly near the injection sites
Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease
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