Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3 years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Women’s Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD

Spatial distribution of phytoplankton cells in small elongated lakes subject to weak diurnal wind forcing

The horizontal distribution of phytoplankton in a medium-size canyon type reservoir, forced by weak winds of 3-4 ms-¹, is largely driven by the interaction of the large-scale circulation and processes regulating the vertical distribution of algal cells in the water column. These drivers, in turn, are subject to diurnal variations, making our understanding of the horizontal distribution of phytoplankton a challenging task. A three-dimensional physical--ecological model is used to understand the spatial distribution of algae and the role of diurnal variations in the physical-biological drivers. The model was used to demonstrate that the large-scale circulation induced during the day is more efficient generating patchiness than the circulation existing at night, when convectively driven turbulence homogenizes the upper layers. Different spatial distributions develop for different populations and under different forcing scenarios, characterized in terms of the directionality of wind forcing, wind magnitude and the lags between winds and diel heat fluxes. The time scales needed so that algal biomass in the surface exhibit significant longitudinal gradients-Tp-will vary depending on the algal group, and its ability to regulate its vertical position. These scales are shorter for those species that either migrate actively in the water column or exhibit positive buoyancy (Cryptophytes or Positive buoyant algae). In El Gergal, these scales TP are on the order of a few days. Synoptic changes in the meteorological forcing, like the passing of a front, could potentially change the longitudinal distribution of algal biomass if they persist for periods of time longer than Tp.Javier Vidal, Anna Rigosi, Andrea Hoyer, Carmelo Escot, Francisco J. Rued