Finally, the tagging approach used is unlikely to adequately capture rare variants (minor allele frequency <0.05), and so the possibility that there are important rare susceptibility variants acting together cannot be excluded.
Adequately powered rare variant mapping studies using these new, denser, GWAS chips are therefore going to be very expensive.
Our solution, which we call Deep Drilling with iterative Mapping (DDiMAP), is a multi-pronged approach that includes the use of sufficient numbers of tumor cells to adequately sample rare events, ultra-deep sequencing (>10,000×) of regions of aSHM/kataegis, and maintaining subclonal specific sequences throughout the entire process for multiple uses.
We asked: 1) how adequately are units with rare plant hotspots protected?
For example, Natura 2000, the world's largest network of protected areas, fails to cover adequately the distribution of rare and endangered aquatic species, and lacks of appropriate spatial design to make conservation for freshwater biodiversity effective.
It is not hard to paint lips adequately, but it is rare and difficult to paint them well.
Second, because CNS relapse remains a rare complication, adequately powering a study is costly and difficult.
Regarding safety, the trial was adequately sized to identify rare AEs, i.e. those that may not have been detected in previous clinical studies, (incidence 1: 1,000) with a probability of > 99% and very rare events (incidence 1: 10,000) with a probability of > 75%.
Limitations of this analysis are that AEs were not independently adjudicated and the post hoc design of this analysis was not adequately powered to detect very rare AEs (incidence <0.01%), nor were the duration of the trials long enough to observe rare AEs with a long course of development (eg, cancers).
But the studies did not include enough cases to adequately assess risk of many rare defects; nor did they include information on how long women were taking antidepressants or at what doses.
