This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.

A normal-fault network from Milne Point, Alaska, is investigated focusing on characterizing geometry, displacement, strain, and different fault interactions. The network, constrained from threedimensional seismic reflection data, comprises two generations of faults: Cenozoic north-northeast-trending faults and Jurassic west-northwest-trending faults, which highly compartmentalize Upper Triassic to Lower Cretaceous reservoirs. The west-northwest-trending faults are influenced by a similarly oriented underlying structural grain. This influence is characterized by increases in throw on several faults, strain localization, reorientation of faults and an increase in linkage maturity.Reconstructing fault plane geometries and mapping spatial variations in throw identified key characteristic features in their interactions and reactivation of pre-existing structures. Faults are divided into isolated, abutting, and splaying faults. Isolated faults exhibit a range of displacement profiles depending on the degree of restriction at fault tips. Fault splays accommodate step-like decreases in throw along larger main faults with a throw maximum at the intersection with the main fault. Throw profiles of abutting faults are divided into two groups: early stage abutting faults with throw minima at both the isolated and abutting tips, and developed abutting faults with throw maxima near the abutting tip.Developed abutting faults accumulate throw after initial abutment, locally reactivating and transferring throw onto the preexisting fault. Two abutting faults can link kinematically by Stephen Dee is a senior structural geologist at BP, working in the Integrated Subsurface Description and Modelling team and consulting on structural and geomechanics projects. He has a Ph.D. from the University of Southampton and specializes in fault and fracture interpretation, geomechanical modeling, and seal analysis.