Studies of Pion Production Near Threshold

This work was supported by National Science Foundation Grant PHY 75-00289 and Indiana Universit

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

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Guidelines for the calibration of personnel dosimeters

This guide describes minimum acceptable performance levels for personnel dosimetry systems used at Department of Energy (DOE) facilities. The goal is to improve both the quality of radiological calibrations and the methods of comparing reported occupational doses between DOE facilities. Reference calibration techniques are defined. A standard for evaluation of personnel dosimetry systems and recommended design parameters for personnel dosimeters are also included. Approximate intervals for the radiation energies for which these guidelines are appropriate are 15 keV to 2 MeV for photons; above 0.3 MeV for beta particles; and 1 keV to 2 MeV for neutrons. An analysis of ANSI N13.11 was completed using performance evaluations of selected personnel dosimetry systems in use at DOE facilities. The results of this analysis are incorporated in the guidelines

Determination of photon conversion factors relating exposure and dose for several extremity phantom designs

This report presents the results of measurements of dosimetric properties of simple extremity phantoms suitable for use in extremity dosimeter performance testing. Two sizes of phantoms were used in this study. One size represented the forearm or lower leg and the other size represented the finger or toe. For both phantom sizes, measurements were performed on solid plastic phantoms and on phantoms containing simulated bone material to determine the effect of backscattered radiations from the bone on the surface dose. Exposure-to-dose conversion factors (C/sub x/ factors) were determined for photon energies ranging from 16 to 1250 keV (average for /sup 60/Co). The effect of the presence of a phantom was also measured for a /sup 90/Sr//sup 90/Y source. Significant differences in the measured C/sub x/ factors were found among the phantoms investigated. The factors for the finger-sized phantoms were uniformly less than for the arm-sized phantoms

Radiation standards and calibrations. FY-1981 annual report

The research program encompasses: reviewing calibration standards, regulations, and handbooks; assuring that calibration procedures used are in agreement with technically accepted methods; maintaining basic radioactive sources and instruments that serve as radiological standards; and providing traceability to the National Bureau of Standards where possible. In addition, major efforts are being expended to upgrade the 318 calibration facility. This report focuses on major accomplishments during FY-1981. However, most maintenance and quality assurance efforts involve routine support and only a summary report is provided. (PSB