MicroRNAs as Therapeutic Targets and Clinical Biomarkers in Atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Atherosclerosis develops over several decades and is mediated by a complex interplay of cellular mechanisms that drive a chronic inflammatory milieu and cell-to-cell interactions between endothelial cells, smooth muscle cells and macrophages that promote plaque development and progression. While there has been significant therapeutic advancement, there remains a gap where novel therapeutic approaches can complement current therapies to provide a holistic approach for treating atherosclerosis to orchestrate the regulation of complex signalling networks across multiple cell types and different stages of disease progression. MicroRNAs (miRNAs) are emerging as important post-transcriptional regulators of a suite of molecular signalling pathways and pathophysiological cellular effects. Furthermore, circulating miRNAs have emerged as a new class of disease biomarkers to better inform clinical diagnosis and provide new avenues for personalised therapies. This review focusses on recent insights into the potential role of miRNAs both as therapeutic targets in the regulation of the most influential processes that govern atherosclerosis and as clinical biomarkers that may be reflective of disease severity, highlighting the potential theranostic (therapeutic and diagnostic) properties of miRNAs in the management of cardiovascular disease

Placental MRI Predicts Fetal Oxygenation and Growth Rates in Sheep and Human Pregnancy

Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO(2)) can transform the clinical management of high‐risk pregnancies affected by fetal growth restriction (FGR). Here, a novel MRI method assesses the feasibility of identifying normally grown and FGR fetuses in sheep and is then applied to humans. MRI scans are performed in pregnant ewes at 110 and 140 days (term = 150d) gestation and in pregnant women at 28(+3) ± 2(+5) weeks to measure feto‐placental SO(2). Birth weight is collected and, in sheep, fetal blood SO(2) is measured with a blood gas analyzer (BGA). Fetal arterial SO(2) measured by BGA predicts fetal birth weight in sheep and distinguishes between fetuses that are normally grown, small for gestational age, and FGR. MRI feto‐placental SO(2) in late gestation is related to fetal blood SO(2) measured by BGA and body weight. In sheep, MRI feto‐placental SO(2) in mid‐gestation is related to fetal SO(2) later in gestation. MRI feto‐placental SO(2) distinguishes between normally grown and FGR fetuses, as well as distinguishing FGR fetuses with and without normal Doppler in humans. Thus, a multi‐compartment placental MRI model detects low placental SO(2) and distinguishes between small hypoxemic fetuses and normally grown fetuses

Growth and Returns to New Products and Pack Varieties: The Case of UK Pharmaceuticals

We use quarterly sales data from the UK pharmaceuticals market between 2003 and 2013 and estimate the impact of new introductions, i.e., new products and pack varieties within an anatomical therapy class on business unit growth. Using a dynamic lag adjustment growth model that accounts for endogeneity of new introductions, we find that a new product contributes to 18 per cent growth of the business unit while a new pack variety leads to 7 per cent growth for the business unit in the long run. Further, we find that there is significant variation in growth by size of firm and that the marginal effect of additional products on growth is larger for smaller business units. However, the marginal effect of pack varieties does not differ by firm size