Lacustrine stromatolites: Useful structures for environmental interpretation – an example from the Miocene Ebro Basin

The significance of stromatolites as depositional environmental indicators and the underlying causes of lamination in the lacustrine realm are poorly understood. Stromatolites in a ca 600 m thick Miocene succession in the Ebro Basin are good candidates to shed light on these issues because they are intimately related to other lacustrine carbonate and sulphate facies, grew under variable environmental conditions and show distinct lamination patterns. These stromatolites are associated with wave-related, clastic-carbonate laminated limestones. Both facies consist of calcite and variable amounts of dolomite. Thin planar stromatolites (up to 10 cm thick and less than 6 m long) occurred in very shallow water. These stromatolites represented first biological colonization after: (i) subaerial exposure in the palustrine environment (i.e. at the beginning of deepening cycles); or (ii) erosion due to surge action, then coating very irregular surfaces on laminated limestones (i.e. through shallowing or deepening cycles). Sometimes they are associated with evaporative pumping. Stratiform stromatolites (10 to 30 cm high and tens of metres long) and domed stromatolites (10 to 30 cm high and long) developed in deeper settings, between the surge periods that produced hummocky cross-stratification and horizontal lamination offshore. Changes in stromatolite lamina shape, and thus in the growth forms through time, can be attributed to changes in water depth, whereas variations in lamina continuity are linked to water energy and sediment supply. Growth of the stromatolites resulted from in situ calcite precipitation and capture of minor amounts of fine-grained carbonate particles. Based on texture, four types of simple laminae are distinguished. The simple micrite and microsparite laminae can be grouped into light and dark composite laminae, which represent, respectively, high and low Precipitation/Evaporation ratio periods. Different lamination patterns provide new ideas for the interpretation of microbial laminations as a function of variations in climate-dependent parameters (primarily the Precipitation/Evaporation ratio) over variable timescales

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy