The extracellular signal-regulated kinase (ERK) signaling pathway has been implicated in diverse cellular functions. ERK and its activating kinase, mitogen-activated/extracellular signal-regulated ...kinase kinase (MEK), are downstream of cell surface receptors known to be up-regulated in many malignant gliomas. We sought to investigate the role of ERK in glioma cell migration, proliferation and differentiation using the rat-derived C6 glioma cell line and the MEK inhibitor, U0126. Treatment of C6 cells with U0126 caused a significant concentration-dependent reduction in cell proliferation and migration and also induced expression of glial fibrillary acidic protein, a marker of astrocytic differentiation. These results suggest that the ERK pathway regulates glioma cell proliferation, migration and differentiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
22.
Neurotrauma and the rule of rescue Honeybul, S; Gillett, G R; Ho, K M ...
Journal of medical ethics,
12/2011, Volume:
37, Issue:
12
Journal Article
Peer reviewed
Open access
The rule of rescue describes the powerful human proclivity to rescue identified endangered lives, regardless of cost or risk. Deciding whether or not to perform a decompressive craniectomy as a ...life-saving or ‘rescue’ procedure for a young person with a severe traumatic brain injury provides a good example of the ethical tensions that occur in these situations. Unfortunately, there comes a point when the primary brain injury is so severe that if the patient survives they are likely to remain severely disabled and fully dependent. The health resource implications of this outcome are significant. By using a web-based outcome prediction model this study compares the long-term outcome and designation of two groups of patients. One group had a very severe injury as adjudged by the model and the other group a less severe injury. At 18 month follow-up there were significant differences in outcome and healthcare requirements. This raises important ethical issues when considering life-saving but non-restorative surgical intervention. The discussion about realistic outcome cannot be dichotomised into simply life or death so that the outcome for the patient must enter the equation. As in other ‘rescue situations’, the utility of the procedure cannot be rationalised on a mere cost–benefit analysis. A compromise has to be reached to determine at what point either the likely outcome would be unacceptable to the person on whom the procedure is being performed or the social utility gained from the rule of rescue intervention fails to justify the utilitarian value and justice of equitable resource allocation.
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BFBNIB, CMK, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Decompressive craniectomy is a technically straightforward procedure whereby a large section of the cranium is temporarily removed in cases where the intracranial pressure is dangerously high. While ...its use has been described for a number of conditions, it is increasingly used in the context of severe head injury. As the use of the procedure increases, a significant number of patients may survive a severe head injury who otherwise would have died. Unfortunately some of these patients will be left severely disabled; a condition likened to the RUB, an acronym for the Risk of Unacceptable Badness. Until recently it has been difficult to predict this outcome, however an accurate prediction model has been developed and this has been applied to a large cohort of patients in Western Australia. It is possible to compare the predicted outcome with the observed outcome at 18 months within this cohort. By using predicted and observed outcome data this paper considers the ethical implications in three cases of differing severity of head injury in view of the fact that it is possible to calculate the RUB for each case.
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•High order difference schemes on unstructured disordered node sets.•Weights generated by sum of anisotropic basis functions.•4th order accuracy with 25 node stencils. 8th order with 60 node stencils ...in 2D.•Applicable to parabolic, elliptic and hyperbolic PDEs in complex geometries.•Potential for h-p adaptivity.
Mesh-free methods have significant potential for simulations in complex geometries, as the time consuming process of mesh-generation is avoided. Smoothed Particle Hydrodynamics (SPH) is the most widely used mesh-free method, but suffers from a lack of consistency. High order, consistent, and local (using compact computational stencils) mesh-free methods are particularly desirable.
Here we present a novel framework for generating local high order difference operators for arbitrary node distributions, referred to as the Local Anisotropic Basis Function Method (LABFM). Weights are constructed from linear sums of anisotropic basis functions (ABFs), chosen to ensure exact reproduction of polynomial fields up to a given order. The ABFs are based on a fundamental Radial Basis Function (RBF), and the choice of fundamental RBF has small effect on accuracy, but influences stability. LABFM is able to generate high order difference operators with compact computational stencils (4th order with N≈25 nodes, 8th order with N≈60 nodes in two dimensions). At domain boundaries (with incomplete support) LABFM automatically provides one-sided differences of the same order as the internal scheme, up to 4th order. We use the method to solve elliptic, parabolic and mixed hyperbolic-parabolic partial differential equations (PDEs), showing up to 8th order convergence. The inclusion of hyperviscosity is straightforward, and can effectively provide stability when solving hyperbolic problems.
LABFM is a promising new mesh-free method for the numerical solution of PDEs in complex geometries. The method is highly scalable, and for Eulerian schemes, the computational efficiency is competitive with RBF-FD for a given accuracy. A particularly attractive feature is that in the low order limit, LABFM collapses to Smoothed Particle Hydrodynamics (SPH), and there is potential for Arbitrary Lagrangian-Eulerian schemes with natural adaptivity of resolution and accuracy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Experimental observations show that the Kaye effect does not occur in a vacuum.•These results support the theory that the jet slips on an air layer.•A mechanistic model suggests that viscoelasticity ...plays a role.•Viscoelasticity allows a greater range of supporting air layers.•Shear thinning effects reduce the viscoelastic response.
The Kaye effect is a phenomenon whereby a jet of fluid poured onto a surface appears to leap on impact, rather than stagnate or coil as expected. Since it was first described in 1963, several authors have attempted to explain the mechanism by which the phenomenon occurs, although to date no complete explanation for the behaviour exists. Current evidence points towards the existence of an air layer between the jet and the heap which enables slip. We show that the Kaye effect does not occur in a vacuum, indicating that the air layer is crucial for the effect to occur. By use of control volume analysis we show that viscoelasticity plays a key role in the Kaye effect, and this role is two-fold. Firstly, viscoelasticity appears to increase air entrainment, and secondly, it reduces the pressure required to bend the jet, allowing a thicker air layer to be sustained. Shear thinning behaviour reduces this viscoelastic response. These findings provide new insight into a problem that has puzzled rheologists for over half a century.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We cross-match galaxy cluster candidates selected via their Sunyaev–Zel'dovich effect (SZE) signatures in 129.1 deg2 of the South Pole Telescope 2500d SPT-SZ survey with optically identified clusters ...selected from the Dark Energy Survey science verification data. We identify 25 clusters between 0.1 ≲ z ≲ 0.8 in the union of the SPT-SZ and redMaPPer (RM) samples. RM is an optical cluster finding algorithm that also returns a richness estimate for each cluster. We model the richness λ-mass relation with the following function 〈ln λ|M
500〉 ∝ B
λln M
500 + C
λln E(z) and use SPT-SZ cluster masses and RM richnesses λ to constrain the parameters. We find
$B_\lambda = 1.14^{+0.21}_{-0.18}$
and
$C_\lambda =0.73^{+0.77}_{-0.75}$
. The associated scatter in mass at fixed richness is
$\sigma _{\ln M|\lambda } = 0.18^{+0.08}_{-0.05}$
at a characteristic richness λ = 70. We demonstrate that our model provides an adequate description of the matched sample, showing that the fraction of SPT-SZ-selected clusters with RM counterparts is consistent with expectations and that the fraction of RM-selected clusters with SPT-SZ counterparts is in mild tension with expectation. We model the optical-SZE cluster positional offset distribution with the sum of two Gaussians, showing that it is consistent with a dominant, centrally peaked population and a subdominant population characterized by larger offsets. We also cross-match the RM catalogue with SPT-SZ candidates below the official catalogue threshold significance ξ = 4.5, using the RM catalogue to provide optical confirmation and redshifts for 15 additional clusters with ξ ∈ 4, 4.5.
Abstract The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) scoring systems have been designed for comparative audit and have been well validated in ...general and vascular surgery. The Portsmouth predictor equation (P–POSSUM) was highly predictive of mortality in a study of elective craniotomies for neurosurgery but has yet to be validated in spinal, peripheral nerve or acute cranial neurosurgery. The West Australian Categorisation of Operative Severity (WA classification) was created for all neurosurgical procedures. Case notes and laboratory results of 531 consecutive patients undergoing neurosurgery were reviewed retrospectively. All POSSUM variables were collected and the POSSUM and P–POSSUM mortality equations were applied. The observed mortality rate was 4.52% and the WA P–POSSUM predicted mortality rate was 4.58% ( p > 0.951). The WA P–POSSUM rate was more predictive than either the WA POSSUM rate (10.9%, p < 0.0001) or the previously proposed elective craniotomy P–POSSUM classification (5.8%, p < 0.198). We concluded that the P–POSSUM model with WA classification has the potential to be used in mortality audits for general neurosurgery. By quantifying preoperative risk, P–POSSUM might provide a useful denominator to observed death rates for meaningful comparison of individual neurosurgeons and between departments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We performed experiments combining three-dimensional x-ray diffraction and x-ray computed tomography to explore the relationship between microstructure and local force and strain during quasistatic ...granular compaction. We found that initial void space around a grain and contact coordination number before compaction can be used to predict regions vulnerable to above-average local force and strain at later stages of compaction. We also found correlations between void space around a grain and coordination number, and between grain stress and maximum interparticle force, at all stages of compaction. Finally, we observed grains that fracture to have an above-average initial local void space and a below-average initial coordination number. Our findings provide (1) a detailed description of microstructure evolution during quasistatic granular compaction, (2) an approach for identifying regions vulnerable to large values of strain and interparticle force, and (3) methods for identifying regions of a material with large interparticle forces and coordination numbers from measurements of grain stress and local porosity.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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