Eleanor Davies and the New Jerusalem

Eleanor Davies was a great believer in historical moments. In her first work—A Warning to the Dragon and All His Angels of 1625-she told readers that “The Lord is at the Dore.”1 This immanence of God made her watchful and purposeful, reading the signs in her daily life, counting days, weeks, and years because she believed that Christ would come again. His arrival had been predestined from the beginning of the world: “from the going forth of the Commandement, which is the beginning of the Creation to the building of the New Jerusalem, the second comming of Messiah, the Prince the Sonne of God, it shall be Seaven Weekes or Seaven Moneths.”2 For Davies, time was elastic, but history was absolute. What the biblical prophets (in this case Ezekiel) said would come to pass, really would come to pass, but their promises were oracular; they had complete authority but were also elusive. Davies accepted this. She knew that she was living in the latter days, but when it came to God’s final judgment, “the daye and houre knoweth no man.”3 God could not be known as such and what she called knowledge was a spiritual transformation that took place when “He powreth out his Spirit upon his hand-maidens,” like herself.4 This essay uses A Warning to the Dragon and Davies’ works of the 1630s and 1640s to examine her theology

Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals

Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer’s disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired patients and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer (11)C-BU99008, (18)F-FDG and (18)F-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired patients and healthy controls in regional and voxel-wise levels of astrocyte reactivity, glucose metabolism, grey matter volume and amyloid load were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). Amyloid beta (Aβ)-positive patients showed greater (11)C-BU99008 uptake compared to controls, except in the temporal lobe, whilst further increased (11)C-BU99008 uptake was observed in Mild Cognitive Impairment subjects compared to those with Alzheimer’s disease in the frontal, temporal and cingulate cortices. BPM correlations revealed that regions which showed reduced (11)C-BU99008 uptake in Aβ-positive patients compared to controls, such as the temporal lobe, also showed reduced (18)F-FDG uptake and grey matter volume, although the correlations with (18)F-FDG uptake were not replicated in the ROI analysis. BPM analysis also revealed a regionally-dynamic relationship between astrocyte reactivity and amyloid uptake: increased amyloid load in cortical association areas of the temporal lobe and cingulate cortices was associated with reduced (11)C-BU99008 uptake, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid deposition occurs later) was associated with increased (11)C-BU99008 uptake. These novel observations add to the hypothesis that while astrocyte reactivity may be triggered by early Aβ-deposition, sustained pro-inflammatory astrocyte reactivity with greater amyloid deposition may lead to astrocyte dystrophy and amyloid-associated neuropathology such as grey matter atrophy and glucose hypometabolism, although the evidence for glucose hypometabolism here is less strong

Fluids and barriers of the CNS: a historical viewpoint

Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF) into all barriers of the central nervous system (CNS), this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century

An LES Turbulent Inflow Generator using A Recycling and Rescaling Method

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The present paper describes a recycling and rescaling method for generating turbulent inflow conditions for Large Eddy Simulation. The method is first validated by simulating a turbulent boundary layer and a turbulent mixing layer. It is demonstrated that, with input specification of mean velocities and turbulence rms levels (normal stresses) only, it can produce realistic and self-consistent turbulence structures. Comparison of shear stress and integral length scale indicates the success of the method in generating turbulent 1-point and 2-point correlations not specified in the input data. With the turbulent inlet conditions generated by this method, the growth rate of the turbulent boundary/mixing layer is properly predicted. Furthermore, the method can be used for the more complex inlet boundary flow types commonly found in industrial applications, which is demonstrated by generating non-equilibrium turbulent inflow and spanwise inhomogeneous inflow. As a final illustration of the benefits brought by this approach, a droplet-laden mixing layer is simulated. The dispersion of droplets in the near-field immediately downstream of the splitter plate trailing edge where the turbulent mixing layer begins is accurately reproduced due to the realistic turbulent structures captured by the recycling/rescaling method