Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

External exercise information provides no immediate additional performance benefit to untrained individuals in time trial cycling.

OBJECTIVE: To determine the importance of the provision of external exercise information to the setting of the pacing strategy, in subjects unfamiliar with a cycling task. DESIGN: Twenty-two healthy, untrained cyclists (VO(2max), 50 ± 9 mL-(1)·kg-(1)·min-(1)) were randomly assigned to a control (CON) group or an experimental (EXP) group and two successive 4 km time trials (TT) were performed, separated by a 17 min recovery. The CON group received distance knowledge and distance feedback; the EXP group received neither, but knew that each TT was to be of the same distance. RESULTS: No significant difference in completion time (p>0.05) was observed between the groups for either time to complete TT one (TT1) (CON=443 ± 33 s versus EXP=471 ± 63 s) or time to complete TT two (time trial 2) (CON=461 ± 37 s versus EXP=501 ± 94 s). No significant difference in the final RPE was observed between groups. However, a significant interaction for RPE (rating of perceived exertion)×TT in the CON was observed (F7,70=5.32, p<0.05), with significantly higher RPE values in the final kilometre of TT2 (p<0.05). CONCLUSION: The lack of any performance improvement in either group, despite the differences in exercise information received, indicates both a reliance on the afferent feedback for setting a pacing strategy and slow learning effect from practice in subjects unfamiliar with the task. The modification in RPE profile observed in the CON, despite no performance improvement, suggests exercise perception based changes may pre-empt work rate based changes and thus not immediately translate to improved performance.

Effect of hip position on gravity effect torque.

Hip position has been hypothesized to influence gravity effect torque (GET) at the knee during isokinetic testing; however, no data exist to support or refute this hypothesis. Therefore, the purposes of this study were 1) to determine if a significant difference exists between GET in seated and supine positions, 2) to determine the effect of the supine and seated GET on isokinetic peak torque values, and 3) to determine the relationship between hamstring flexibility and GET. Gravity effect torque was recorded in supine and seated positions. Peak torque values in flexion and extension were obtained on a isokinetic dynamometer at 1.047 and 5.235 rads.s-1 (60 and 300 degrees.s-1, respectively). Hamstring flexibility was assessed by the active knee extension test (AKET). The mean seated GET value was 5.64 Nm higher than the mean supine GET value (F(1,82) = 97.85, P = 0.0001). Significant correlations existed between hamstring flexibility and GET values measured in the seated and supine positions (r = 0.45, P = 0.0001, and r = 0.30, P = 0.0058, respectively). Significant differences in peak torque values occurred for three of the four isokinetic conditions when using different GET values (P-value 0.0002-0.0049). Although mean differences in peak torque values were only 2.43-4.23 Nm, these differences may translate to significant errors in the isokinetic measurement of the injured population undergoing rehabilitation. Furthermore, every attempt should be made to improve the validity of isokinetic testing. Therefore, we recommend the supine position for GET determination.