A new perspective on metformin therapy in type 1 diabetes

Metformin is quite frequently used off-label in type 1 diabetes to limit insulin dose requirement. Guidelines recommend that it can improve glucose control in those who are overweight and obese but evidence in support of this is limited. Recently-published findings from the REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL) trial suggest that metformin therapy in type 1 diabetes can reduce atherosclerosis progression, weight and LDL-cholesterol levels. This provides a new perspective on metformin therapy in type 1 diabetes and suggests a potential role for reducing the long-term risk of cardiovascular disease

Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms

Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes

Party, democracy and representation : the political consequences of Brexit

The narrow victory of the leave campaign at the 2016 referendum on UK membership of the EU introduced a new constitutional divide into British politics; still, the political impact of the referendum remains difficult to assess. The binary identities that emerged after the poll overlapped imprecisely with existing political loyalties. There were also crucial territorial dimensions to post-referendum politics. While England and Wales delivered majorities for leave, in Northern Ireland and Scotland there was majority support for continued EU membership. Moreover, in Scotland, Brexit raised the prospect of a sequel to the 2014 referendum on Scottish independence. Parliamentarians, a majority of whom had advocated remain, struggled to implement the referendum result. By exposing the distance between the electorate and their representatives, and setting in opposition competing popular, parliamentary and territorial mandates, the impact of Brexit went beyond electoral concerns, bringing into focus questions of legitimacy, representation and sovereignty that are the focus of this chapter. The ‘high’ political consequences of Brexit are assessed first. The constitutional challenges raised by Brexit in a Scottish context are then explored. The final section considers the degree to which Brexit was an example of the rise of forms of political ‘populism’.Postprin

The “ABC model”: a non-hydrostatic toy model for use in convective-scale data assimilation investigations

In developing methods for convective-scale data assimilation (DA) it is necessary to consider the full range of motions governed by the compressible Navier-Stokes equations (including non-hydrostatic and ageostrophic flow). These equations describe motion on a wide range of time-scales with non-linear coupling. For the purpose of developing new DA techniques that suit the convective-scale problem it is helpful to use so-called ‘toy models’ that are easy to run, and contain the same types of motion as the full equation set. Such a model needs to permit hydrostatic and geostrophic balance at large-scales, but to allow imbalance at small-scales, and in particular, it needs to exhibit intermittent convection-like behaviour. Existing ‘toy models’ are not always sufficient for investigating these issues. A simplified system of intermediate complexity derived from the Euler equations is presented, which supports dispersive gravity and acoustic modes. In this system the separation of time scales can be greatly reduced by changing the physical parameters. Unlike in existing toy models, this allows the acoustic modes to be treated explicitly, and hence inexpensively. In addition, the non-linear coupling induced by the equation of state is simplified. This means that the gravity and acoustic modes are less coupled than in conventional models. A vertical slice formulation is used which contains only dry dynamics. The model is shown to give physically reasonable results, and convective behaviour is generated by localised compressible effects. This model provides an affordable and flexible framework within which some of the complex issues of convective-scale DA can later be investigated. The model is called the “ABC model” after the three tunable parameters introduced: A (the pure gravity wave frequency), B (the modulation of the divergent term in the continuity equation), and C (defining the compressibility)

Politics, the constitution and the independence movement in Scotland since devolution

This article explores the course of Scottish politics since the establishment of the devolved parliament in 1999. It begins by considering the political roots of devolution before assessing the extent to which the electoral successes of the Scottish National Party (SNP) at the 2007 and 2011 devolved elections indicated a rise in support for Scottish independence. The focus then shifts to the political consequences of the 2014 independence referendum, in particular the relationship between the ‘Yes’ campaign and the SNP, as well as the changing social composition of the SNP's electoral support. The article concludes by examining the attempts of the SNP, and the wider independence movement, to secure a second independence referendum before reviewing recent political developments in Scotland.Publisher PDFPeer reviewe

SGLT2 inhibitors in type 1 diabetes: knocked down, but up again?

No abstract available

A method for merging flow-dependent forecast error statistics from an ensemble with static statistics for use in high resolution variational data assimilation

The background error covariance matrix, B, is often used in variational data assimilation for numerical weather prediction as a static and hence poor approximation to the fully dynamic forecast error covariance matrix, Pf. In this paper the concept of an Ensemble Reduced Rank Kalman Filter (EnRRKF) is outlined. In the EnRRKF the forecast error statistics in a subspace defined by an ensemble of states forecast by the dynamic model are found. These statistics are merged in a formal way with the static statistics, which apply in the remainder of the space. The combined statistics may then be used in a variational data assimilation setting. It is hoped that the nonlinear error growth of small-scale weather systems will be accurately captured by the EnRRKF, to produce accurate analyses and ultimately improved forecasts of extreme events

Ancient Egypt 1922 Part 4

Part 4 of the 1922 Ancient Egypt books. Contents include the Shellal mosaic, Old World cubit in America, the Constantinople obelisk, the rise of prices in Egypt, dualism in African religions, and Egyptian mathematics.https://knowledge.e.southern.edu/kweeks_coll/1021/thumbnail.jp

Ancient Egypt 1920 Part 4

Part 4 of the 1920 Ancient Egypt books. Contents include Coptic twists and plaits, the sphinxes of Tanis, Alexandrian world maps, passages of Aleppo Citadel, and Kheker friezes.https://knowledge.e.southern.edu/kweeks_coll/1013/thumbnail.jp