Unit bar architecture in a highly‐variable fluvial discharge regime: Examples from the Burdekin River, Australia

Unit bars are relatively large bedforms that develop in rivers over a wide range of climatic regimes. Unit bars formed within the highly-variable discharge Burdekin River in Queensland, Australia, were examined over three field campaigns between 2015 and 2017. These bars had complex internal structures, dominated by co-sets of cross-stratified and planar-stratified sets. The cross-stratified sets tended to down-climb. The development of complex internal structures was primarily a result of three processes: (i) superimposed bedforms reworking the unit bar avalanche face; (ii) variable discharge triggering reactivation surfaces; and (iii) changes in bar growth direction induced by stage change. Internal structures varied along the length and across the width of unit bars. For the former, down-climbing cross-stratified sets tended to pass into single planar cross-stratified deposits at the downstream end of emergent bars; such variation related to changes in fluvial conditions whilst bars were active. A hierarchy of six categories of fluvial unsteadiness is proposed, with these discussed in relation to their effects on unit bar (and dune) internal structure. Across-deposit variation was caused by changes in superimposed bedform and bar character along bar crests; such changes related to the three-dimensionality of the channel and bar geometry when bars were active. Variation in internal structure is likely to be more pronounced in unit bar deposits than in smaller bedform (for example, dune) deposits formed in the same river. This is because smaller bedforms are more easily washed out or modified by changing discharge conditions and their smaller dimensions restrict the variation in flow conditions that occur over their width. In regimes where unit bar deposits are well-preserved, their architectural variability is a potential aid to their identification. This complex architecture also allows greater resolution in interpreting the conditions before and during bar initiation and development

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

History of clinical transplantation

How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

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

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Revitalizing a mature oil play: Strategies for finding and producing unrecovered oil in Frio Fluvial-Deltaic reservoirs of south Texas. Technical progress report, April 1, 1996--June 30, 1996

Advanced reservoir characterization techniques have been applied to selected reservoirs in the Frio Fluvial-Deltaic Sandstone (Vicksburg Fault Zone) trend of South Texas in order to maximize the economic producibility of resources in this mature oil play. More than half of the reservoirs in this depositionally complex play have already been abandoned, and large volumes of oil may remain unproduced unless advanced characterization techniques are applied to define untapped, incompletely drained, and new pool reservoirs as suitable targets for near-term recovery methods. This project has developed interwell-scale geological facies models and has assessed engineering attributes of Frio fluvial-deltaic reservoirs in selected fields in order to characterize reservoir architecture, flow unit boundaries, and the controls that these characteristics exert on the location and volume of unrecovered mobile and residual oil. Results of these studies led to the identification of specific opportunities to exploit these heterogeneous reservoirs for incremental recovery by recompletion and strategic infill drilling