The theory of evolution was advanced by Darwin in 1859, prior to Mendel’s experiments demonstrating the particulate nature of inheritance. The modern synthesis was formulated in the early 1940s, well before the conce...The theory of evolution was advanced by Darwin in 1859, prior to Mendel’s experiments demonstrating the particulate nature of inheritance. The modern synthesis was formulated in the early 1940s, well before the concept of coded information was understood. This paper outlines four mathematical challenges to the modern synthesis, which are based on current understanding of the proposed mechanisms of evolutionary change within the constraints of experimental molecular biology.展开更多
Someone or the other is always pointing to a published study to justify a point of view or the need for a change in what we do or how we live. There are so many such studies, many reported in top-notch journals, repor...Someone or the other is always pointing to a published study to justify a point of view or the need for a change in what we do or how we live. There are so many such studies, many reported in top-notch journals, reporting results inconsistent across and often inconsistent within. It is in the interest of increasing the credibility of science, and to safeguard the general public living with its overt and covert influence, to filter good science from bad. Some inferences are good, even when counter-intuitive or seemingly inconsistent, and are likely to withstand scrutiny and some others may represent marginal effects in the aggregate not entirely useful for individual choices or decisions, and are often non-reproducible. The New York Times featured an article in August 2018 debunking some of the reported studies supporting testing for Vitamin D deficiencies and the recommendation of large supplemental doses of Vitamin D. Some of these Vitamin D claims, among other claims, were reported as not holding up on replication in controlled trials [1]. We have noted in Ref. [2] that we need to be wary as individuals about reported signals detected in studies using stochastic data, even when these aggregate signals are of a large magnitude. We demonstrated discordance rates of 30% or higher between subject level assessments of effect and the conclusion drawn in the aggregate. Here we will provide a computation of this discordant proportion as well as post-hoc assessments of aggregate inferences, with emphasis on evaluating studies with time-to-event endpoints such as those in cancer trials. Similar evaluations for continuous, binomial data and correlations are also provided. We also discuss the use of response thresholds.展开更多
文摘The theory of evolution was advanced by Darwin in 1859, prior to Mendel’s experiments demonstrating the particulate nature of inheritance. The modern synthesis was formulated in the early 1940s, well before the concept of coded information was understood. This paper outlines four mathematical challenges to the modern synthesis, which are based on current understanding of the proposed mechanisms of evolutionary change within the constraints of experimental molecular biology.
文摘Someone or the other is always pointing to a published study to justify a point of view or the need for a change in what we do or how we live. There are so many such studies, many reported in top-notch journals, reporting results inconsistent across and often inconsistent within. It is in the interest of increasing the credibility of science, and to safeguard the general public living with its overt and covert influence, to filter good science from bad. Some inferences are good, even when counter-intuitive or seemingly inconsistent, and are likely to withstand scrutiny and some others may represent marginal effects in the aggregate not entirely useful for individual choices or decisions, and are often non-reproducible. The New York Times featured an article in August 2018 debunking some of the reported studies supporting testing for Vitamin D deficiencies and the recommendation of large supplemental doses of Vitamin D. Some of these Vitamin D claims, among other claims, were reported as not holding up on replication in controlled trials [1]. We have noted in Ref. [2] that we need to be wary as individuals about reported signals detected in studies using stochastic data, even when these aggregate signals are of a large magnitude. We demonstrated discordance rates of 30% or higher between subject level assessments of effect and the conclusion drawn in the aggregate. Here we will provide a computation of this discordant proportion as well as post-hoc assessments of aggregate inferences, with emphasis on evaluating studies with time-to-event endpoints such as those in cancer trials. Similar evaluations for continuous, binomial data and correlations are also provided. We also discuss the use of response thresholds.
