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Background Statins are the first-line pharmaceutical agent in the management of hypercholesterolemia and cardiovascular (CV) risk reduction, and the most commonly prescribed class of drugs worldwide. Studies describing CV risk reduction independent of LDL-cholesterol lowering have evoked an interest in the pleiotropic mechanisms of statins’ benefits. We recently demonstrated that administration of statins in animal models lowers aldosterone levels and observed an association between statin use and reduced aldosterone levels in two human cohorts, with lipophilic statins displaying a greater effect than hydrophilic statins. Therefore, we designed a randomized, placebo-controlled, double-blinded intervention study to assess whether statin treatment lowers aldosterone in a type-dependent manner in humans, with simvastatin (lipophilic) showing a greater effect than pravastatin (hydrophilic). Methods/design One hundred five healthy participants will be recruited from the general population to enroll in a 12-week, randomized, placebo-controlled, double-blinded, 3-arm clinical trial. Ninety participants are anticipated to complete the protocol. After baseline assessment of aldosterone levels, participants will be randomized to daily simvastatin, pravastatin, or placebo. Aldosterone levels will be assessed after 2 days on study drug and again after 6 weeks and 12 weeks on study drug. Prior to each aldosterone assessment, participants will consume an isocaloric sodium and potassium-controlled run-in diet for 5 days. Assessments will occur on an inpatient research unit to control for diurnal, fasting, and posture conditions. The primary outcome will compare 12-week angiotensin II-stimulated serum aldosterone by study drug. Secondary outcomes will compare baseline and 12-week 24-h urine aldosterone by study drug. Discussion Results from this rigorous study design should provide strong support that statins lower aldosterone levels in humans. These results may explain some of the beneficial effects of statins that are not attributed to the LDL-lowering effect of this important class of medications. Results would demonstrate that statin lipophilicity is an important attribute in lowering aldosterone levels. The outcomes of this program will have implications for the design of studies involving statin medications, as well as for the differential use of classes of statins. Trial registration ClinicalTrials.gov; NCT02871687 ; First Posted August 18, 2016.

The duration of tree seedling persistence in the understory varies greatly between forests and across environmental conditions within a forest ecosystem. To examine species‐level variation in understory persistence and passage to the sapling life stage, we followed 5236 seedlings in single‐tree canopy gaps and closed canopy conditions over three years and simulated seedling passage times and the number of seedlings required to produce one 1.5‐m tall sapling of five common tree species in a hemlock–hardwood forest of Massachusetts, USA. Averaged across species, it took 26 years in gaps and 31 years under closed canopies to go from a first‐year seedling to a 1.5‐m sapling. Across species, the average number of seedlings needed for one sapling was 294 in gaps and 2674 in closed canopy environments. We observed high interspecific variation in passage times and number required for one sapling. Betula congeners and Pinus strobus took less time and significantly fewer individuals than Acer rubrum and Tsuga canadensis, which are generally regarded as more tolerant of understory conditions. The largest intraspecific difference in gaps versus closed canopy environments was for Quercus rubra, where we estimated the number of seedlings required to produce one sapling in closed canopies to be 172 times higher than in gaps. Stem breakage also increased the number of seedlings needed per sapling, especially in closed canopy environments. We evaluated our estimates in the lab by aging cross‐sections obtained from seedlings in gap and closed canopy conditions. Compared to our empirical age‐to‐height relationships, most simulations tended to underpredict seedling age for a given height, suggesting that passage times may be even longer than our simulations indicated. Our study shows that trees can persist for decades in the seedling life stage, highlighting a need for better‐parameterized recruitment processes in demographic forecasting.

Simon Jenkins (The Savile witch-hunt sets us on a path to paranoia, 24 October) could not declare that Savile is \"dead, damned, gone forever\", or talk in terms of \"honest mistakes\" or \"restrictions likely to be out of all proportion to the harm they seek to avert\" if he had any serious understanding of the damage done to individuals by sexual abuse, particularly in childhood.

[Margaret McGlade] enjoyed hill-walking with friends and family, and was a founder member of a 25-year-old book group, which focused on women's writings. Friends remember her wise counsel, strong principles, tenacious determination, sharp intellect and personal warmth. Her Irish roots meant a lot to Margaret - of her 42 Christmases after leaving Draperstown, only two were spent away from \"home\".

So Richard Dawkins laments that Tube announcements are apparently made by a \"young woman they pulled out of...

Ian Jack (Royal wedding supplement, 30 April) fails to mention the feminist objections to Charles and Diana's wedding, which proved to be the most accurate in both their analysis and their prediction of the likely outcome.

I am writing to complain about my husband's total unpreparedness for the current weather conditions.

It is laudable of Claire Messud to try to convince us that Americans are normal people (Do They Mean Us?, May 4), but I doubt if her words will have much effect.

I was delighted to learn from Alexander McCall Smith's article that Barbara Pym's Excellent Women is to be reissued (\"Very Barbara Pym\", April 5). I first met her when we were both in the WRNS and working at the Admiralty at the end of the war - we became great friends.