Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of hepatocellular carcinoma (HCC), with disease progression occurring relentlessly over many years.
In the large (5,756 participants) Multi-Ethnic Study of Atherosclerosis (MESA), which evaluated risk factors for CAC progression over 2.4 years, many cardiovascular risk factors (age, male sex, hypertension, BMI, diabetes, and family history of heart attack) were associated with both the risk of developing incident CAC and increases in existing calcification (11).
Of these models, many focus on short-term dynamics such as intracellular signaling dynamics and metabolism, or acute whole-body changes in response to an event, and are not useful in characterizing progression of the disease over many years.
This approach is not the same as human septic shock because our animal model is acute and neglects the effects of disease progression on organ dysfunction over many hours, a problem encountered in many animal models of sepsis [ 35].
MDS is characterized by ineffective bone marrow hematopoiesis, leading to cytopenias [ 2], with a highly variable disease progression that ranges from a slow development over many years to a rapid progression to AML within a few months.
This is especially true for prostate cancer patients, in whom progression of bone metastasis occurs over many years.
However, since there was a temporal relation with re-infection, it could also be related to progression of existing changes induced over many years by re-infection.
Over-expression of MMPs has been correlated with progression in many tumour types, and over-expression of MMP-9 has been found in colorectal adenomas [ 15] and carcinomas [ 16, 17].
We have recently reported data that assessed the natural progression of HRQoL reporting in cystic fibrosis over many years.
But the job is to lead a hugely complex organization over many years through an unpredictable progression of shifting markets and competitive terrains.
