Proposal to disregard athletics world records prior to 2005: a radical and misjudged initiative

The recent announcement that the European Athletics Council has proposed to disregard all athletics world records set prior to 20051 has caused considerable controversy and debate among the athletics community. It is a radical initiative with commendable aims to redress the consequences of past undetected doping violations that may have led to some of the least attainable world records. This proposal has now been put to the world governing body, the International Amateur Athletics Federation (IAAF), and its merits require discussion

Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse

In the isolated rat carotid artery, the endocannabinoid anandamide induces endothelium-dependent relaxation via activation of the enzyme sphingosine kinase (SK). This generates sphingosine-1-phosphate (S1P) which can be released from the cell and activates S1P receptors on the endothelium. In anaesthetised mice, anandamide has a well-characterised triphasic effect on blood pressure but the contribution of SK and S1P receptors in mediating changes in blood pressure has never been studied. Therefore, we assessed this in the current study. The peak hypotensive response to 1 and 10 mg/kg anandamide was measured in control C57BL/6 mice and in mice pretreated with selective inhibitors of SK1 (BML-258, also known as SK1-I) or SK2 ((R)-FTY720 methylether (ROMe), a dual SK1/2 inhibitor (SKi) or an S1P1 receptor antagonist (W146). Vasodilator responses to S1P were also studied in isolated mouse aortic rings. The hypotensive response to anandamide was significantly attenuated by BML-258 but not by ROMe. Antagonising S1P1 receptors with W146 completely blocked the fall in systolic but not diastolic blood pressure in response to anandamide. S1P induced vasodilation in denuded aortic rings was blocked by W146 but caused no vasodilation in endothelium-intact rings. This study provides evidence that the SK1/S1P regulatory-axis is necessary for the rapid hypotension induced by anandamide. Generation of S1P in response to anandamide likely activates S1P1 to reduce total peripheral resistance and lower mean arterial pressure. These findings have important implications in our understanding of the hypotensive and cardiovascular actions of cannabinoids

Iterative Approach to Gravitational Lensing Theory

We develop an iterative approach to gravitational lensing theory based on approximate solutions of the null geodesic equations. The approach can be employed in any space-time which is ``close'' to a space-time in which the null geodesic equations can be completely integrated, such as Minkowski space-time, Robertson-Walker cosmologies, or Schwarzschild-Kerr geometries. To illustrate the method, we construct the iterative gravitational lens equations and time of arrival equation for a single Schwarzschild lens. This example motivates a discussion of the relationship between the iterative approach, the standard thin lens formulation, and an exact formulation of gravitational lensing.Comment: 27 pages, 2 figures, submitted to Phys.Rev.D, minor revisions, new reference

Validation of a skinfold based index for tracking proportional changes in lean mass

BACKGROUND: The lean mass index (LMI) is a new empirical measure that tracks within‐subject proportional changes in body mass adjusted for changes in skinfold thickness. OBJECTIVE: To compare the ability of the LMI and other skinfold derived measures of lean mass to monitor changes in lean mass. METHODS: 20 elite rugby union players undertook full anthropometric profiles on two occasions 10 weeks apart to calculate the LMI and five skinfold based measures of lean mass. Hydrodensitometry, deuterium dilution, and dual energy x ray absorptiometry provided a criterion choice, four compartment (4C) measure of lean mass for validation purposes. Regression based measures of validity, derived for within‐subject proportional changes through log transformation, included correlation coefficients and standard errors of the estimate. RESULTS: The correlation between change scores for the LMI and 4C lean mass was moderate (0.37, 90% confidence interval −0.01 to 0.66) and similar to the correlations for the other practical measures of lean mass (range 0.26 to 0.42). Standard errors of the estimate for the practical measures were in the range of 2.8–2.9%. The LMI correctly identified the direction of change in 4C lean mass for 14 of the 20 athletes, compared with 11 to 13 for the other practical measures of lean mass. CONCLUSIONS: The LMI is probably as good as other skinfold based measures for tracking lean mass and is theoretically more appropriate. Given the impracticality of the 4C criterion measure for routine field use, the LMI may offer a convenient alternative for monitoring physique changes, provided its utility is established under various conditions

Short-term reliability of inflammatory mediators and response to exercise in the heat.

Prospective application of serum cytokines, lipopolysaccharide (LPS), and heat shock proteins (eHSPs) requires reliable measurement of these biomarkers that can signify exercise-induced heat stress in hot conditions. To accomplish this, both short-term (7 day) reliability (at rest, n = 12) and the acute responsiveness of each biomarker to exercise in the heat (pre and post 60-min cycling, 34.5°C and 70% RH, n = 20) were evaluated. Serum was analysed for the concentration of C-reactive protein (CRP), interleukin-6 (IL-6), heat shock protein 72 (eHSP72), immunoglobulin M (IgM) and LPS. Test–retest reliability was determined as the coefficient of variation (CV). Biomarkers with the least short-term within-participant variation were IL-6 (19%, ±20%; CV, ±95% confidence limits (CL)) and LPS (23%, ±13%). Greater variability was observed for IgM, eHSP72 and CRP (CV range 28–38%). IL-6 exhibited the largest increase in response to acute exercise (95%, ±11%, P = < 0.001) and although CRP had a modest CV (12%, ±7%), it increased substantially post-exercise (P = 0.02, ES; 0.78). In contrast, eHSP72 and LPS exhibited trivial changes post-exercise. It appears variation of common inflammatory markers after exercise in the heat is not always discernible from short-term (weekly) variation

Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis

We have assessed the effect of two ether glycerol lipids, 77-6 ((2S, 3R)-4-(Tetradecyloxy)-2-amino-1,3-butanediol) and 56-5 ((S)-2-Amino-3-O-hexadecyl-1-propanol), which are substrates for sphingosine kinases, on inflammatory responses. Treatment of differentiated U937 macrophage-like cells with 77-6 but not 56-5 enhanced IL-1β release; either alone or in the presence of LPS. The stimulatory effect of sphingosine or 77-6 on LPS-stimulated IL-1β release was reduced by pretreatment of cells with the caspase-1 inhibitor, Ac-YVAD-CHO, thereby indicating a role for the inflammasome. The enhancement of LPS-stimulated IL-1β release in response to sphingosine, but not 77-6, was reduced by pretreatment of cells with the cathepsin B inhibitor, CA074Me, indicating a role for lysosomal destabilization in the effect of sphingosine. Administration of 56-5 to mice increased disease progression in an experimental autoimmune encephalomyelitis model and this was associated with a considerable increase in the infiltration of CD4+ T-cells, CD11b+ monocytes and F4/80+ macrophages in the spinal cord. 56-5 and 77-6 were without effect on the degradation of myc-tagged sphingosine 1-phosphate 1 receptor in CCL39 cells. Therefore, the effect of 56-5 on EAE disease progression is likely to be independent of the inflammasome or the sphingosine 1-phosphate 1 receptor. However, 56-5 is chemically similar to platelet activating factor and the exacerbation of EAE disease progression might be linked to platelet activating factor receptor signaling

The 678 Hz acoustic immittance probe tone: a more definitive indicator of PET than the traditional 226 Hz method.

BACKGROUND: The accurate diagnosis of Eustachian tube (ET) dysfunction can be very difficult. Our aim is to determine whether a 678 Hz probe tone is a more accurate indicator of Patulous ET (PET) than the 226 Hz probe tone when used in compliance over time (COT) testing. METHODS: Twenty subjects (11 normal ET ears and 7 PET ears) were individually seated in an examination room and connected to a GSI TympStar Middle Ear Analyzer. The order of probe tone frequency (678 or 226 Hz) was randomized. Baseline "testing" COT recordings for each ear undergoing testing were completed. Subjects were instructed to occlude their contralateral nostril and to breathe forcefully in and out through their ipsilateral nostril until the test had run to completion. This process was repeated with the probe tone that had not been previously run. For the control group, each subject had one random ear tested. For the experimental group, only the affected ear(s) was tested. Wilcoxon rank rum tests were performed to determine statistical significance. RESULTS: The baseline COT measurements for the control group and PET group were similar, 0.86 mL (SD = 0.34) and 0.74 (SD = 0.33) respectively. Comparing the 226 Hz tone between groups revealed that PET patients had a median COT difference 0.19 mL higher than healthy ET patients, and for the 678 Hz tone, PET patients had a median COT difference of 0.57 mL higher than healthy ET patients. Both were deemed to be statistically significant (p = 0.002, p = 0.004 respectively). The was a statistically significant median COT difference between the 678 Hz and 226 Hz of 0.61 mL (p = 0.034) for the PET group, while the same comparison for the control group of 0.05 mL was not significant (p = 0.262), suggesting that the 678 Hz tone yields a larger response for PET than the 226 Hz tone, and no difference for the control group, thus making it less prone to artifact noise interference. CONCLUSION: The 678 Hz probe tone is a more reliable indicator of ET patency, and should be preferably used over the 226 Hz tone for future COT testing