Measuring proliferation in breast cancer: practicalities and applications

Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy

The Effects of Mental Fatigue on Physical Performance: A Systematic Review.

Background: Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity. It has recently been suggested that mental fatigue can affect physical performance. Objective: Our objective was to evaluate the literature on impairment of physical performance due to mental fatigue and to create an overview of the potential factors underlying this effect. \ud Methods: Two electronic databases, PubMed and Web of Science (until 28 April 2016), were searched for studies designed to test whether mental fatigue influenced performance of a physical task or influenced physiological and/or perceptual responses during the physical task. Studies using short (<30 min) self-regulatory depletion tasks were excluded from the review. Results: A total of 11 articles were included, of which six were of strong and five of moderate quality. The general finding was a decline in endurance performance (decreased time to exhaustion and self-selected power output/velocity or increased completion time) associated with a higher than normal perceived exertion. Physiological variables traditionally associated with endurance performance (heart rate, blood lactate, oxygen uptake, cardiac output, maximal aerobic capacity) were unaffected by mental fatigue. Maximal strength, power, and anaerobic work were not affected by mental fatigue. Conclusion: The duration and intensity of the physical task appear to be important factors in the decrease in physical performance due to mental fatigue. The most important factor responsible for the negative impact of mental fatigue on endurance performance is a higher perceived exertion

Fractional Flow Reserve Evaluated as Metric of Coronary Stenosis — A Mathematical Model Study

Introduction: Coronary arterial stenosis may impair myocardial perfusion with myocardial ischemia and associated morbidity and mortality as result. The myocardial fractional flow reserve (FFR) is clinically used as a stenosis-specific index. Aim: This study aims to identify the relation between the FFR and the degree of coronary arterial stenosis using a simple mathematical model of the coronary circulation. Methods: A mathematical model of the coronary circulation, including an arterial stenosis of variable degree, was developed. The relation between the FFR and the degree of stenosis (defined as the fractional cross sectional area narrowing) was investigated, including the influence of the aortic and venous pressures and the capillary resistance. An additional study concerning 22 patients with coronary artery disease permits comparison of clinical data and in silico findings. Results: The FFR shows an S-shaped relationship with the stenosis index. We found a marked influence of venous and aortic pressure and capillary resistance. The FFR is accompanied by a clinically relevant co-metric (FFRC), defined by the Pythagorean sum of the two pressures in the definition formula for FFR. In the patient group the FFRC is strongly related to the post-stenotic pressure (R = 0.91). The FFRC requires establishment of a validated cut-off point using future trials. Conclusion: The S-shaped dependence of FFR on the severity of the stenosis makes the FFR a measure of the ordinal scale. The marked influences of the aortic and venous pressures and the capillary resistance on the FFR will be interpreted as significant variations in intra- and inter-individual clinical findings. These fluctuations are partly connected to the neglect of considering the FFRC. At otherwise identical conditions the FFR as measured at baseline differs from the value obtained during hyperemic conditions. This expected observation requires further investigation, as the current hyperemia based evaluation fails to take advantage of available baseline data