The Method of Moral Hypothesis

Moral philosophy has become interested again in particular, substantive questions of right and wrong. In an effort to divine answers to such questions, philosophers often employ the following method: general rules are floated as potential principles of morality; the principles are regarded as confirmed insofar as they match our pre-theoretical intuitions about particular cases; and otherwise infirmed. Such principles, if sufficiently confirmed, are then used to overturn other, ‘aberrant’ moral intuitions that do not square with the rule. The aim of this work is to indict this ‘method of moral hypothesis’, and with it the moral theory project which relies on it. I argue that the method trades on an unsustainable picture of moral epistemology; that the motivations for engaging in it are without merit; and that its attractions as a systematizing tool are illusory. In chapter one, I examine some recent ‘etiological’ skeptical challenges to moral knowledge; and argue that such challenges succeed only against a particular sort of moral epistemology—the kind to which the moral theory project is wedded. I conclude that we should reject this epistemology, and the project with it. Chapter two aims to vindicate the charges of Pessimists about moral testimony—those who claim that testimony cannot transmit moral knowledge. I argue that one barrier to moral-knowledge transmission by testimony is its inability to transfer moral-conceptual ‘know-how’; more generally that the ‘Humean reasons’ which support testimony are insufficient to support moral knowledge; and that, for parallel reasons, the theory project cannot produce moral knowledge. Chapter three attacks a picture of justification which makes the theory project seem pressing. In its place, I argue for an alternative picture, on which justification is infected with certain pragmatic, contextual factors. This alternative undermines one of the motivations for the theory project: finding an ultimate justification for our moral beliefs. In chapter four, I unify these arguments; and argue that, in general, we are correct to reject any summarizing principle which conflicts with a strongly held, pre-theoretical moral verdict. This negates one of the central ambitions of the theory project. Its other motivations are, I argue, equally misplaced

Managing blood pressure in older adults

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Intensive Blood Pressure Lowering in Patients With Renal Impairment and Lacunar Stroke

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The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

Acknowledgments: DA would like to thank the University of Aberdeen for providing an Elphinstone Scholarship to support her PhD project. The authors also thank Dr Neil Scott for giving advice on statistical analysis, Professor Jesse Dawson and Karen Shields for recruiting participants at the Queen Elizabeth University Hospital.Peer reviewedPublisher PD

Automatic Spatial Estimation of White Matter Hyperintensities Evolution in Brain MRI using Disease Evolution Predictor Deep Neural Networks

Funds from the Indonesia Endowment Fund for Education (LPDP), Ministry of Finance, Republic of Indonesia (MFR); Row Fogo Charitable Trust (Grant No. BRO-D.FID3668413)(MCVH); Wellcome Trust (patient recruitment, scanning, primary study Ref No. WT088134/Z/09/A); Fondation Leducq (Perivascular Spaces Transatlantic Network of Excellence); EU Horizon 2020 (SVDs@Target); and the MRC UK Dementia Research Institute at the University of Edinburgh (Wardlaw programme) are gratefully acknowledged. The Titan Xp used for this research was donated by the NVIDIA Corporation.Peer reviewedPublisher PD

ADAMTS-1 and Syndecan-4 intersect in the regulation of cell migration and angiogenesis

ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1: an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper

Long-term morphological changes of symptomatic lacunar infarcts and surrounding white matter on structural MRI

The contributing studies were funded by the Chief Scientist Office of the Scottish Executive (grant 217 NTU R37933), the Wellcome Trust (grants 075611 and WT088134/Z/09/A), and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE (Scottish Imaging Network, A Platform for Scientific Excellence) collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). This work was supported by European Union Horizon 2020 (EU H2020), PHC- 03 to 15, project No. 666881, SVDs@Target, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref No. 16 CVD 05. Dr Loos was supported by the Dutch Alzheimer Foundation.Peer reviewedPublisher PD

Clinically confirmed stroke with negative diffusion-weighted imaging magnetic resonance imaging. Longitudinal study of clinical outcomes, stroke recurrence, and systematic review

Makin, Stephen D J Doubal, Fergus N Dennis, Martin S Wardlaw, Joanna M eng 088134/Z/09/A/Wellcome Trust/United Kingdom Observational Study Research Support, Non-U.S. Gov't 2015/10/01 06:00 Stroke. 2015 Nov;46(11):3142-8. doi: 10.1161/STROKEAHA.115.010665. Epub 2015 Sep 29.Peer reviewedPublisher PD