The Signal, the History, and the Context

      What a signal does/means depends on the context.  A hormone or biomarker level in the blood is not as informative as knowing the longitudinal history of levels and  their contexts. What is the   % change of the current level- is the marker increasing or decreasing, and how fast is that occurring? Has the marker in the past been this high or higher, and then it went down?  What made it go down? What was the maximal level attained in the past? What was the maximal % change? A specific driver is having  a personal and/or family history of having illnesses related to that marker. A first layer of context is if they have other signs of illness.  A second layer of context is  provided by information about living in an environment or having been subjected to events  relevant to the illness. Context, while non-specific, may give rise to or enable the illness manifesting, if the specific driver is in place to channel it into disease.  

      For exemplification, think PSA levels and prostate cancer. While absolute PSA levels provide some information, the slope of increasing PSA is more informative.  Have they had in the past high levels like this, which then went down?  What made them go down? What were the maximal levels attained in the past? What was the maximum slope?  A driver is a personal history or a family history of prostate illness.  A first layer of context is a physical exam or imaging test revealing an enlarged prostate. A second layer of context is provided by age, ethnicity, and environmental factors such as high fat diet. Context, while non-specific,  may  give rise to or  enable disease, if the specific driver/mutations are in place to channel it into disease .

      Another example, this time from psychiatry, is that of suicidal ideation.  While absolute levels of suicidal ideation intensity provide some information, the slope of increasing suicidal ideation may be more informative regarding risk of committing suicide.  Have they had in the past high suicidal ideation comparable to this or higher, that then resolved?  What made it resolve?  What was the maximum suicidality (ideation, attempts) they had in the past? What was the maximum slope? A specific driver of behavior is a personal history or a family history of suicidal behavior, or knowing somebody who attempted or committed suicide.  A first  layer of context is a mental status exam or test revealing increased anxiety, low mood, or distorted thinking.   A second layer of context is provided by gender, age, ethnicity, and environmental factors such as stressful life events and addictions. Context, while non-specific, may  give rise to or  enable suicide, if the specific driver is in place channel it into to suicidal ideation and action. 

Alexander B. Niculescu, III, MD, PhD