108 AUROTHIOMALATE INHIBITS COX-2 EXPRESSION AND PGE2 PRODUCTION IN CHONDROCYTES BY INCREASING MKP-1 EXPRESSION AND DECREASING p38 AND JNK PHOSPHORYLATION

The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels. Opportunities for innovation in dyslipidaemia treatment should address the substantial risk of lipid-associated cardiovascular events among patients optimally treated per guidelines but who cannot achieve LDL-C goals and who could benefit from additional LDL-C-lowering therapy or experience side effects of statins. Fresh approaches are needed to identify promising drug targets early and develop them efficiently. The Cardiovascular Round Table of the European Society of Cardiology (ESC) convened a workshop to discuss new lipid-lowering strategies for cardiovascular risk reduction. Opportunities to improve treatment approaches and the efficient study of new therapies were explored. Circulating biomarkers may not be fully reliable proxy indicators of the relationship between treatment effect and clinical outcome. Mendelian randomization studies may better inform development strategies and refine treatment targets before Phase 3. Trials should match the drug to appropriate lipid and patient profile, and guidelines may move towards a precision-based approach to individual patient management. Stakeholder collaboration is needed to ensure continued innovation and better international coordination of both regulatory aspects and guidelines. It should be noted that risk may also be addressed through increased attention to other risk factors such as smoking, hypertension, overweight, and inactivity

Quantum transport effects in semiconductors

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The role of multiple weak lithologies in the deformation of cover units in the northwestern segment of the zagros fold-and-thrust belt

The geometry, kinematics and dynamics of fold-and-thrust belts are strongly influenced by the mechanical behaviour of the basal decollement. However, many fold-and-thrust belts also include mechanically weak lithologies such as evaporites and marls or mudstones at different levels within the shortened stratigraphy. The kinematics and dynamic evolution of these thrust belts are controlled by the mechanical behaviour both of the basal decollement and of the weak units embedded within the overlying stratigraphic succession. In the Zagros fold-and-thrust belt (ZFTB), the shortened sedimentary cover is between 7 and 12 km thick and mechanically weak lithologies compartmentalize the stratigraphic column at shallow and intermediate levels. In this paper, satellite, field and seismic data from the Kurdistan Region of Iraq are used to identify structures of different sizes and surface traces. The observations are used to underline the role of mechanically weak horizons within the Zagros stratigraphy and the decoupling of deformation both laterally and with depth in the belt. The decoupling between shallow and deeper structures observed in seismic profiles from the Kurdistan Region of Iraq is also reported from field observations from the Iranian part of the Zagros fold-and-thrust belt, where folds with different surface traces occur. Decoupling between shallow and deep layers by incompetent lithologies at intermediate depths (e.g. marls, mudstones and evaporites) results in the formation of disharmonic folds. The geometry, size and location of such folds may differ between outcropping and subsurface structures. Decoupling may have a significant impact on hydrocarbon exploration in different parts of the Zagros fold-and-thrust belt due to potential offsets between outcropping and subsurface structures and their associated traps