2,061 research outputs found
Magnetotelluric imaging of anisotropic crust near Fort McMurray, Alberta: implications for engineered geothermal system development
Viability for the development of an engineered geothermal system (EGS) in the oilsands region near Fort McMurray, Alberta, is investigated by studying the structure of the Precambrian basement rocks with magnetotellurics (MT). MT data were collected at 94 broad-band stations on two east–west profiles. Apparent resistivity and phase data showed little variation along each profile. The short period MT data detected a 1-D resistivity structure that could be identified as the shallow sedimentary basin underlain by crystalline basement rocks to a depth of 4–5 km. At lower frequencies a strong directional dependence, large phase splits, and regions of out-of-quadrant (OOQ) phase were detected. 2-D isotropic inversions of these data failed to produce a realistic resistivity model. A detailed dimensionality analysis found links between large phase tensor skews (∼15°), azimuths, OOQ phases and tensor decomposition strike angles at periods greater than 1 s. Low magnitude induction vectors, as well as uniformity of phase splits and phase tensor character between the northern and southern profiles imply that a 3-D analysis is not necessary or appropriate. Therefore, 2-D anisotropic forward modelling was used to generate a resistivity model to interpret the MT data. The preferred model was based on geological observations of outcropping anisotropic mylonitic basement rocks of the Charles Lake shear zone, 150 km to the north, linked to the study area by aeromagnetic and core sample data. This model fits all four impedance tensor elements with an rms misfit of 2.82 on the southern profile, and 3.3 on the northern. The conductive phase causing the anisotropy is interpreted to be interconnected graphite films within the metamorphic basement rocks. Characterizing the anisotropy is important for understanding how artificial fractures, necessary for EGS development, would form. Features of MT data commonly interpreted to be 3-D (e.g. out of OOQ phase and large phase tensor skew) are shown to be interpretable with this 2-D anisotropic model
Seagrass meadows in a globally changing environment
Seagrass meadows are valuable ecosystem service providers that are now being lost globally at an unprecedented rate, with water quality and other localised stressors putting their future viability in doubt. It is therefore critical that we learn more about the interactions between seagrass meadows and future environmental change in the anthropocene. This needs to be with particular reference to the consequences of poor water quality on ecosystem resilience and the effects of change on trophic interactions within the food web. Understanding and predicting the response of seagrass meadows to future environmental change requires an understanding of the natural long-term drivers of change and how these are currently influenced by anthropogenic stress. Conservation management of coastal and marine ecosystems now and in the future requires increased knowledge of how seagrass meadows respond to environmental change, and how they can be managed to be resilient to these changes. Finding solutions to such issues also requires recognising people as part of the social-ecological system. This special issue aims to further enhance this knowledge by bringing together global expertise across this field. The special issues considers issues such as ecosystem service delivery of seagrass meadows, the drivers of long-term seagrass change and the socio-economic consequences of environmental change to seagrass
Help yourself: The mechanisms through which a self-leadership intervention influences strain.
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Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction
The MEK inhibitors cobimetinib and trametinib are used in combination with BRAF inhibitors to treat metastatic melanoma but increase rates of hemorrhage relative to BRAF inhibitors alone. Platelets express several members of the MAPK signalling cascade including MEK1 and MEK2 and ERK1 and ERK2 but their role in platelet function and haemostasis is ambiguous as previous reports have been contradictory. It is therefore unclear if MEK inhibitors might be causing platelet dysfunction and contributing to increased hemorrhage. In the present study we performed pharmacological characterisation of cobimetinib and trametinib in vitro to investigate potential for MEK inhibitors to cause platelet dysfunction.
We report that whilst both cobimetinib and trametinib are potent inhibitors of platelet MEK activity, treatment with trametinib did not alter platelet function. Treatment with cobimetinib results in inhibition of platelet aggregation, integrin activation, alpha-granule secretion and adhesion but only at suprapharmacological concentrations. We identified that the inhibitory effects of high concentrations of cobimetinib are associated with off-target inhibition on Akt and PKC. Neither inhibitor caused any alteration in thrombus formation on collagen under flow conditions in vitro.
Our findings demonstrate that platelets are able to function normally when MEK activity is fully inhibited, indicating MEK activity is dispensable for normal platelet function. We conclude that the MEK inhibitors cobimetinib and trametinib do not induce platelet dysfunction and are therefore unlikely to contribute to increased incidence of bleeding reported during MEK inhibitor therapy
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Platelet signaling: a complex interplay between inhibitory and activatory networks
The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators. This article is protected by copyright. All rights reserved
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Citations, funding and influence in Energy-Policy research on Developing Economies
Energy research seeking to influence policy in low- and -middle-income countries (LMICs) is often funded by – and conceptualised by authors in - institutions from high-income countries (HICs). Research agendas and policy recommendations determined in HICs potentially yield the most influence on policymaking for LMICs. This leaves a multidimensional gap in how LMICs frame, contextualise, evidence and enact policy processes. The unique contribution of this paper is analysing the dynamics of prevalent energy research on LMICs through a multi-method approach using bibliometric, network science and regression-based techniques. An innovative data-driven framework was established using a sample of 6,636 papers from the Web of Science database, combined with journal impact data from Scimago Journal Ranking and country economic data from the World Bank. Results show the existence of a cycle of imbalances across research practices. Most papers recommending energy policy for LMICs have a first author based in a HIC, funded by a HIC institution. Total citations of articles on energy policy in LMICs increase with the GDP of the first author’s country (a 1% increase in GDP is correlated with a 0.68% increase in total citations). Funders support authors based in countries of the same income band as them, or higher. Therefore, we recommend revising research practices and HIC funding policies to place local actors and knowledge at the heart of energy policy research, enabling high-impact policymaking in LMICs
The response of the seagrass Halodule wrightii Ascherson to environmental stressors
Seagrasses are subjected to intense levels of anthropogenic disturbance as a result of the shallow nearshore waters they inhabit. Some seagrasses are known to have dynamic growth patterns, enabling them to colonize unstable shallow environments and adapt to a range of disturbances. This can result in high levels of variability in morphological and physiological attributes. The seagrass Halodule wrightii is known to be a fast-growing pioneering species with a large geographic range. The present study examines Halodule wrightii in a region under intense anthropogenic stress in order to determine what are the main environmental drivers affecting the morphology, physiology and status of these habitats. Parameters of plant morphology, physiology and status were measured either at the meadow scale (e.g. biochemistry) or at a higher frequency shoot scale (e.g. shoot width). We assigned an impact assessment index to a series of seagrass sites over a gradient of anthropogenic disturbance and found this to be explanatory of a number of the seagrass parameters measured including epiphyte cover, stable isotope δ15N and ETRmax however, it did not clearly explain shoot density, a commonly used bioindicator of environmental stress. At the shoot scale, Principal Component Analysis identified epiphyte and leaf width to have the strongest association. At the meadow scale this was shoot density, dry weight and Ek, albeit with the most impacted sites showing highest shoot density. Stable isotope (δ15N) and leaf length were most significant in explaining the variation between sites and impact category, providing a direct link between anthropogenic sources of nutrients to seagrass meadow density
Factors affecting decision making in children with complex care needs:a consensus approach to develop best practice in a UK children’s hospital
BACKGROUND: Children with complex care needs are a growing proportion of the sick children seen in all healthcare settings in the UK. Complex care needs place demands on parents and professionals who often require many different healthcare teams to work together. Care can be both materially and logistically difficult to manage, causing friction with parents. These difficulties may be reduced if common best practice standards and approaches can be developed in this area. OBJECTIVE: To develop a consensus approach to the management of complexity among healthcare professionals, we used a modified Delphi process. The process consisted of a meeting of clinical leaders to develop candidate statements, followed by two survey rounds open to all professionals in a UK children’s hospital to measure and establish consensus recommendations. RESULTS: Ninety-nine professionals completed both rounds of the survey, 69 statements were agreed. These pertained to seven thematic areas: standardised approaches to communicating with families; processes for interprofessional communication; processes for shared decision-making in the child’s best interests; role of the multidisciplinary team; managing professional–parental disagreement and conflict; the role of clinical psychologists; and staff support. Overall, the level of consensus was high, ranging from agreement to strong agreement. CONCLUSIONS: These statements provide a consensus basis that can inform standardised approaches to the management of complexity. Such approaches may decrease friction between parents, children and healthcare professionals
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