A tale of two TrkA inhibitor trials: same target, divergent results

The divergence of a vector field at a point is the net outward flow of the flux out of a small volume through a closed surface enclosing the volume, as the volume tends to zero. More practically, divergence measures how much a vector field spreads out or diverges from a given point. For an outgoing flux, conventionally, the divergence is positive. The diverging point is often called the "source" of the field. Meanwhile, the negative divergence of a vector field at a point means that the vector...

The divergence and Stokes' theorems are a variation of Green's theorem in a higher dimension. They are also a generalization of the fundamental theorem of calculus. The divergence theorem and Stokes' theorem are in a way similar to each other; The divergence theorem relates to the dot product of a vector, while Stokes' theorem relates to the curl of a vector. Many applications in physics and engineering make use of the divergence and Stokes' theorems, enabling us to write...

The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was  generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...