Why Biological Systems Suddenly Change State: An Intuitive Guide to Freidlin–Wentzell Theory

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  Stochasticity is ubiquitous in biology and neuroscience, manifesting in various forms, including ion channel noise, synaptic variability, gene regulatory fluctuations, noisy population dynamics, and more. Many biological systems spend long periods in a stable “state” and only rarely transition to another state due to noise. For instance, a neuron typically remains inactive but may occasionally trigger a spontaneous spike. Similarly, a gene can switch from the OFF state to the ON state due to rare bursts of transcription factors. Cells can also transition out of metabolic or epigenetic states, populations might shift between different ecological equilibria, and a viral infection can fluctuate between phases of control and uncontrollability. Freidlin–Wentzell theory provides a mathematically rigorous framework to study these phenomena when noise is small but nonzero . It tells you, firstly, h ow likely rare transitions are,    secondly,   h ow fast they occ...
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Normative Reference Values of Right Heart in Competitive Athletes

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Training-induced right ventricular (RV) enlargement is frequent in athletes. Unfortunately, RV dilatation is also a common phenotypic expression and one of the diagnostic criteria of arrhythmogenic RV cardiomyopathy (ARVC). The current echocardiographic reference values derived from the general population can overestimate the presence of RV dilatation in athletes. We performed a meta-analysis of the literature (J Am Soc Echocardiogr 2017;30:845-58) to derive the proper reference values for assessing RV enlargement in competitive athletes. We conducted systematic review of English-language studies in the MEDLINE, Scopus, and Cochrane databases investigating RV size and function by echocardiography and by cardiac magnetic resonance (CMR) in competitive athletes.

In total, 6,806 and 740 competitive athletes were included for the echocardiographic and CMR quantification of the RV, respectively. In this review, we present normal reference values for RV size and function to be applied in competitive athletes according to the disciplines practiced. The reference ranges reported in this review suggest that physicians should be aware that application of the current recommendations for normal population could be misleading when evaluating athletes. We suggest using these normative reference values, obtained in competitive athletes, to avoid the potential for mistakenly concluding, in this specific population, that RV size or function are abnormal.


Physicians should be aware that the application of the current recommendations for the normal population could be misleading when evaluating athletes. In the present systematic review and meta-analysis, we derived normative values for RV echocardiographic and CMR dimensions to be applied in competitive athletes to properly assess the presence and extent of RV dilatation. The extent of RV remodeling is particularly evident in athletes practicing combined disciplines. The application of the proposed cut-offs would prevent misleading interpretation of echocardiographic RV assessment and unwarranted exclusion from sports participation in athletes exhibiting physiologic RV enlargement. Conversely, measurements greatly exceeding the athlete-derived limits here reported are unlikely to represent a uniquely physiologic adaptation to training and should raise suspicion of a pathological cardiac condition.

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