Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Molecular Interactions between Lecithin and Bile Salts/Acids in Oils and Their Effects on Reverse Micellization

It has been known that the addition of bile salts to lecithin organosols induces the formation of reverse wormlike micelles and that the worms are similar to long polymer chains that entangle each other to form viscoelastic solutions. In this study, we further investigated the effects of different bile salts and bile acids on the growth of lecithin reverse worms in cyclohexane and <i>n</i>-decane. We utilized rheological and small-angle scattering techniques to analyze the properties and structures of the reverse micelles. All of the bile salts can transform the originally spherical lecithin reverse micelles into wormlike micelles and their rheological behaviors can be described by the single-relaxation-time Maxwell model. However, their efficiencies to induce the worms are different. In contrast, before phase separation, bile acids can induce only short cylindrical micelles that are not long enough to impart viscoelasticity. We used Fourier transform infrared spectroscopy to investigate the interactions between lecithin and bile salts/acids and found that different bile salts/acids employ different functional groups to form hydrogen bonds with lecithin. Such effects determine the relative positions of the bile salts/acids in the headgroups of lecithin, thus resulting in varying efficiencies to alter the effective critical packing parameter for the formation of wormlike micelles. This work highlights the importance of intermolecular interactions in molecular self-assembly

Gold-ore Metallogeny of the Yenisey Ridge: Geological-Structural Province, Structural Types of ore Fields

В статье рассмотрено геологическое положение и генезис золоторудных месторождений Енисейского кряжа - одной из богатейших золотоносных провинций мира. На основании статистического анализа выявлена превалирующая приуроченность золотоносных объектов к кординской и удерейской свитам рифея. Месторождения распространены в зонах смятия и приразломного метаморфизма в области флексурного перегиба рифейских толщ интрудированных массами гранитоидов. Рудоносные гидротермы генетически связаны с зонами ультраметаморфизма и гранитообразования. Главными типами структур рудных полей являются зоны смятия: в S-образных дизъюнктивах на крыльях линейных антиклиналей, осложняющих крылья компенсационных синклиналей в контактах с гранитоидами; в контактовой области (несогласия) нижнепротерозойских и рифейских толщ; в троговых бассейнах осадконакопления. Особое место в золотоносных проявлениях Енисейского кряжа занимают нефелиновые интрузии. Их промышленное значение требует изучения. Возраст золотого оруденения Енисейского кряжа соответствует интервалу 847- 605 млн лет. Возможно, в некоторых месторождениях проявлялась стадия перераспределения золоторудной минерализации в девонское время (364-368 млн лет).The article describes the geological location and the genesis of gold-ore deposits of the Yenisey Ridge - one of the richest gold-bearing world provinces. Prevailing confideness of gold-bearing projects to the Korda and the Uderey Riphean suites is revealed on the basis of statistical analysis. Deposits are developed in folding and fault metamorphism zones in the area of flexure bending of Riphean strata by intruding granitoid masses. Ore-bearing hydrotherms are genetically associated with ultramorphism and granite formation zones. The main types of structures of ore fields are folding zones: in S-shaped disjunctive faults at the limbs of line anticlines; complicating the limbs of compensational synclines in contacts with granitoids; in the contact area (non-conformity) of Lower Proterozoic and Riphean strata; in trough sedimentation basins. Nepheline intrusions take a specific position in gold-bearing occurrences of the Yenisey Ridge. Their commercial value requires study. The age of gold mineralization of the Yenisey Ridge corresponds to the range of 847-605 MA. In some deposits there probably was a stage of re-distribution of gold-ore mineralization during the Devonian Age (364-368 MA)

Gold-ore Metallogeny of the Yenisey Ridge: Geological-Structural Province, Structural Types of ore Fields

В статье рассмотрено геологическое положение и генезис золоторудных месторождений Енисейского кряжа - одной из богатейших золотоносных провинций мира. На основании статистического анализа выявлена превалирующая приуроченность золотоносных объектов к кординской и удерейской свитам рифея. Месторождения распространены в зонах смятия и приразломного метаморфизма в области флексурного перегиба рифейских толщ интрудированных массами гранитоидов. Рудоносные гидротермы генетически связаны с зонами ультраметаморфизма и гранитообразования. Главными типами структур рудных полей являются зоны смятия: в S-образных дизъюнктивах на крыльях линейных антиклиналей, осложняющих крылья компенсационных синклиналей в контактах с гранитоидами; в контактовой области (несогласия) нижнепротерозойских и рифейских толщ; в троговых бассейнах осадконакопления. Особое место в золотоносных проявлениях Енисейского кряжа занимают нефелиновые интрузии. Их промышленное значение требует изучения. Возраст золотого оруденения Енисейского кряжа соответствует интервалу 847- 605 млн лет. Возможно, в некоторых месторождениях проявлялась стадия перераспределения золоторудной минерализации в девонское время (364-368 млн лет).The article describes the geological location and the genesis of gold-ore deposits of the Yenisey Ridge - one of the richest gold-bearing world provinces. Prevailing confideness of gold-bearing projects to the Korda and the Uderey Riphean suites is revealed on the basis of statistical analysis. Deposits are developed in folding and fault metamorphism zones in the area of flexure bending of Riphean strata by intruding granitoid masses. Ore-bearing hydrotherms are genetically associated with ultramorphism and granite formation zones. The main types of structures of ore fields are folding zones: in S-shaped disjunctive faults at the limbs of line anticlines; complicating the limbs of compensational synclines in contacts with granitoids; in the contact area (non-conformity) of Lower Proterozoic and Riphean strata; in trough sedimentation basins. Nepheline intrusions take a specific position in gold-bearing occurrences of the Yenisey Ridge. Their commercial value requires study. The age of gold mineralization of the Yenisey Ridge corresponds to the range of 847-605 MA. In some deposits there probably was a stage of re-distribution of gold-ore mineralization during the Devonian Age (364-368 MA)

Effects of Alkali Cations and Halide Anions on the Self-Assembly of Phosphatidylcholine in Oils

The interactions between ions and phospholipids are closely associated with the structures and functions of cell membrane. Instead of conventional aqueous systems, we systematically investigated the effects of inorganic ions on the self-assembly of lecithin, a zwitterionic phosphatidylcholine, in cyclohexane. Previous studies have shown that addition of inorganic salts with specific divalent and trivalent cations can transform lecithin organosols into organogels. In this study, we focused on the effect of monovalent alkali halides. Fourier transform infrared spectroscopy was used to demonstrate that the binding strength of the alkali cations with the phosphate of lecithin is in the order Li⁺ > Na⁺ > K⁺. More importantly, the cation–phosphate interaction is affected by the paired halide anions, and the effect follows the series I^– > Br^– > Cl^–. The salts of stronger interactions with lecithin, including LiCl, LiBr, LiI, and NaI, were found to induce cylindrical micelles sufficiently long to form organogels, while others remain organosols. A mechanism based on the charge density of ions and the enthalpy change of the ion exchange between alkali halides and lecithin headgroup is provided to explain the contrasting interactions and the effectiveness of the salts to induce organogelation

Ultrafast Lasers and Solids in Highly Excited States: Results of Hydrodynamics and Molecular Dynamics Simulations

Action of ultrafast optical and X-ray lasers on metals is considered. It is known that under certain conditions surface structures appear as result of irradiation. Generation of nano-structures is usually associated with excitation of surface plasmons. But often structures do not have forms of ripples, and their spacial scales are order of magnitude less than optical wavelength. In the paper full description of surface nano-structures is given for the case of single shot laser action onto well polished boundaries. Plasmon effects are insignificant for this case and also for X-ray pulses. It is shown that structures are formed after laser illumination in a process of mechanical spallation of ultrathin surface layer of molten metal. Spallation is accompanied by a strong foaming of melt, breaking of foam, and freezing of foam remnants. Those remnants form chaotic nano-structures observed in experiments

Ultrashort laser -matter interaction at moderate intensities: two-temperature relaxation, foaming of stretched melt, and freezing of evolving nanostructures

ABSTRACT Interaction of ultrashort laser pulse with metals is considered. Ultrafast heating in our range of absorbed fluences F abs &gt; 10 mJ/cm 2 transfers matter into two-temperature (2T) state and induces expressed thermomechanical response. To analyze our case, where 2T, thermomechanical, and multidimensional (formation of surface structures) effects are significant, we use density functional theory (DFT), solutions of kinetic equations in τ -approximation, 2T-hydrodynamics, and molecular dynamics simulations. We have studied transition from light absorption in a skin layer to 2T state, and from 2T stage to hydrodynamical motions. We describe (i) formation of very peculiar (superelasticity) acoustic wave irradiated from the laser heated surface layer and (ii) rich complex of surface phenomena including fast melting, nucleation of seed bubbles in hydrodynamically stretched fluid, evolution of vapor-liquid mixture into very spatially extended foam, mechanical breaking of liquid membranes in foam (foam disintegration), strong surface tension oscillations driven by breaking of membranes, non-equilibrium freezing of overcooled molten metals, transition to nano-domain solid, and formation of surface nanostructures