Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

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Optimal Reception of Digital Data over the Gaussian Channel with Unknown Delay and Phase Jitter

Asymptotically optimum (in the sense of minimum per-symbol error rate) receiver structures for data communication over the white Gaussian channel with unknown time delay and carrier phase jitter are developed. The receiver structures apply to the following suppressed-carrier modulation systems: double sideband (DSB), quadrature amplitude modulation (QAM) with an arbitrary constellation, vestigial sideband (VSB) and single sideband. The resulting minimum error probability receivers are asymptotically equivalent to maximum-likelihood digital sequence-estimating receivers. The optimum structures implicitly derive joint maximum-likelihood estimates of the unknown parameters and of the sequence of data symbols. It is shown that the parameter estimates can be obtained from two data-directed stochastic approximation algorithms. Unlike traditional theoretical treatments of this communication situation, which have separated the highly important carrier phase and timing recovery problem from the detection problem, a unified theory is presented from which the complete ideal receiver structure can be deduced

The orbit of asteroid (317) Roxane’s satellite Olympias from Gemini, Keck, VLT and the SOR, and (22) Kalliope’s Linus from the SOR

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