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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Percutaneous Injection of Radiopaque Gelified Ethanol for the Treatment of Lumbar and Cervical Intervertebral Disk Herniations

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Experience and Clinical Outcome in 80 Patients


BACKGROUND AND PURPOSE: Chemonucleolysis represents a minimally invasive percutaneous technique characterized by an intradiskal injection of materials under fluoroscopic or CT guidance. Recently, a substance based on radiopaque gelified ethanol has been introduced. The purpose of this study was to describe the indications, procedure, safety, and efficacy of radiopaque gelified ethanol in the percutaneous treatment of cervical and lumbar disk herniations.
MATERIALS AND METHODS: Between September 2010 and August 2013, 80 patients (32 women and 48 men; age range, 18–75 years) were treated for 107 lumbar disk herniations (L2–L3, n = 1; L3–L4, n = 15; L4–L5, n = 53; and L5–S1, n = 38) and 9 cervical disk herniations (C4–C5, n = 2; C5–C6, n = 2; C6–C7, n = 3; and C7–D1, n = 2) by percutaneous intradiskal injection of radiopaque gelified ethanol under fluoroscopic guidance. Thirty-six patients underwent a simultaneous treatment of 2 disk herniations. Patient symptoms were resistant to conservative therapy, with little or no pain relief after 4–6 weeks of physical therapy and drugs. All patients were evaluated by the Visual Analog Scale and the Oswestry Disability Index.
RESULTS: Sixty-two of 73 (85%) patients with lumbar disk herniations and 6/7 (83%) patients with cervical disk herniations obtained significant symptom improvement, with a Visual Analog Scale reduction of at least 4 points and an Oswestry Disability Index reduction of at least 40%. Leakage of radiopaque gelified ethanol in the surrounding tissues occurred in 19 patients, however without any clinical side effects.
CONCLUSIONS: In our experience, percutaneous intradiskal injection of radiopaque gelified ethanol is safe and effective in reducing the period of recovery from disabling symptoms.

Abbreviations

CDH
 
cervical disk herniation
 
LDH
 
lumbar disk herniation
 
ODI
Oswestry Disability Index
 
RGE
 
radiopaque gelified ethanol
 
VAS
Visual Analog Scale

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