Development of the CHARIOT Research Register for the Prevention of Alzheimer’s Dementia and Other Late Onset Neurodegenerative Diseases

Identifying cognitively healthy people at high risk of developing dementia is an ever-increasing focus. These individuals are essential for inclusion in observational studies into the natural history of the prodromal and early disease stages and for interventional studies aimed at prevention or disease modification. The success of this research is dependent on having access to a well characterised, representative and sufficiently large population of individuals. Access to such a population remains challenging as clinical research has, historically, focussed on patients with dementia referred to secondary and tertiary services. The primary care system in the United Kingdom allows access to a true prodromal population prior to symptoms emerging and specialist referral. We report the development and recruitment rates of the CHARIOT register, a primary care-based recruitment register for research into the prevention of dementia. The CHARIOT register was designed specifically to support recruitment into observational natural history studies of pre-symptomatic or prodromal dementia stages, and primary or secondary prevention pharmaceutical trials or other prevention strategies for dementia and other cognitive problems associated with ageing.Participants were recruited through searches of general practice lists across the west and central London regions. Invitations were posted to individuals aged between 60 and 85 years, without a diagnosis of dementia. Upon consent, a minimum data set of demographic and contact details was extracted from the patient's electronic health record.To date, 123 surgeries participated in the register, recruiting a total of 24,509 participants-a response rate of 22.3%. The age, gender and ethnicity profiles of participants closely match that of the overall eligible population. Higher response rates tended to be associated with larger practices (r = 0.34), practices with a larger older population (r = 0.27), less socioeconomically disadvantaged practices (r = 0.68), and practices with a higher proportion of White patients (r = 0.82).Response rates are comparable to other registers reported in the literature, and indicate good interest and support for a research register and for participation in research for the prevention of age-related neurodegenerative diseases and dementia. We consider that the simplicity of the approach means that this system is easily scalable and replicable across the UK and internationally

MATHEMATICAL MODELS: PLANNING TOOLS FOR THE GREAT LAKES 1

The Great Lakes Basin Commission has initiated a Framework Study to assess the present and projected water- and related land-resource problems and demands in the Great Lakes Basin. Poorly defined objectives; incomplete and inconsistent data arrays; unknown air, biota, water, and sediment interactions; and multiple planning considerations for interconnected, large lake systems hinder objective planning. To incorporate mathematical modeling as a planning tool for the Great Lakes, a two-phase program, comprising a feasibility and design study followed by contracted and in-house modeling, data assembly, and plan development, has been initiated. The models will be used to identify sensitivities of the lakes to planning and management alternatives, insufficiencies in the data base, and inadequately understood ecosystem interactions. For the first time objective testing of resource-utilization plans to identify potential conflicts will provide a rational and cost-effective approach to Great Lakes management. Because disciplines will be interrelated, the long-term effects of planning alternatives and their impacts on neighboring lakes and states can be evaluated. Testing of the consequences of environmental accidents and increased pollution levels can be evaluated, and risks to the resource determined. Examples are cited to demonstrate the use of such planning tools.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73455/1/j.1752-1688.1972.tb05143.x.pd

Self-synchronization and dissipation-induced threshold in collective atomic recoil lasing

Networks of globally coupled oscillators exhibit phase transitions from incoherent to coherent states. Atoms interacting with the counterpropagating modes of a unidirectionally pumped high-finesse ring cavity form such a globally coupled network. The coupling mechanism is provided by collective atomic recoil lasing, i.e., cooperative Bragg scattering of laser light at an atomic density grating, which is self-induced by the laser light. Under the rule of an additional friction force, the atomic ensemble is expected to undergo a phase transition to a state of synchronized atomic motion. We present the experimental investigation of this phase transition by studying the threshold behavior of this lasing process

Real-time analysis of single influenza virus replication complexes reveals large promoter-dependent differences in initiation dynamics

The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; further, little is known about cRNA promoter conformations. To probe the RNA conformations adopted during initial replication, we monitored single, surface-immobilized vRNA and cRNA initiation complexes in real-time. Our results show that, while the 3′ terminus of the vRNA promoter exists in dynamic equilibrium between pre-initiation and initiation conformations, the cRNA promoter exhibited very limited dynamics. Two residues in the proximal 3′ region of the cRNA promoter (residues absent in the vRNA promoter) allowed the cRNA template strand to reach further into the active site, limiting promoter dynamics. Our results highlight promoter-dependent differences in influenza initiation mechanisms, and advance our understanding of virus replication

"I am in favour of organ donation, but I feel you should opt-in"—qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England

\ua9 The Author(s) 2024. Background: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. Methods: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. Results: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. Conclusions: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. Trial registration: National Institute of Health Research (NIHR) [IRAS 275992]

Sequential superradiant scattering from atomic Bose-Einstein condensates

We theoretically discuss several aspects of sequential superradiant scattering from atomic Bose-Einstein condensates. Our treatment is based on the semiclassical description of the process in terms of the Maxwell-Schroedinger equations for the coupled matter-wave and optical fields. First, we investigate sequential scattering in the weak-pulse regime and work out the essential mechanisms responsible for bringing about the characteristic fan-shaped side-mode distribution patterns. Second, we discuss the transition between the Kapitza-Dirac and Bragg regimes of sequential scattering in the strong-pulse regime. Finally, we consider the situation where superradiance is initiated by coherently populating an atomic side mode through Bragg diffraction, as in studies of matter-wave amplification, and describe the effect on the sequential scattering process.Comment: 9 pages, 4 figures. Submitted to Proceedings of LPHYS'06 worksho

Scheduling Irrigations Using Climate-Crop-Soil Data

Recent studies of surface irrigation systems (16,21,29) 4 indicate that irrigation scheduling practices, tithing and amount applied, have not changed significantly from those observed about 25 yr ago by Israelson, et al. (11). Attempts to relate observed irrigation efficiencies to field, soil, crop, and management characteristics generally have not been successful because the factors causing the large variations in timing and amount of water applied at each irrigation are so diverse that the resulting irrigation efficiencies appear to be random events with a broad, uniform distribution. The potential for better irrigation water management has; however, increased substantially during the past 15 yr because of better water control and measurement facilities (24), improved system design criteria (2), more reliable methods for estimating evapotranspiration (13), increased knowledge of each crop's response to soil moisture levels (9), and commercially available soil moisture instrumentation for timing irrigations (10)

Single-molecule FRET for virology : 20 years of insight into protein structure and dynamics

Although viral protein structure and replication mechanisms have been explored extensively with X-ray crystallography, cryo-electron microscopy, and population imaging studies, these methods are often not able to distinguish dynamic conformational changes in real time. Single-molecule fluorescence resonance energy transfer (smFRET) offers unique insights into interactions and states that may be missed in ensemble studies, such as nucleic acid or protein structure, and conformational transitions during folding, receptor–ligand interactions, and fusion. We discuss the application of smFRET to the study of viral protein conformational dynamics, with a particular focus on viral glycoprotein dynamics, viral helicases, proteins involved in HIV reverse transcription, and the influenza RNA polymerase. smFRET experiments have played a crucial role in deciphering conformational changes in these processes, emphasising the importance of smFRET as a tool to help elucidate the life cycle of viral pathogens and identify key anti-viral targets

Classical and quantum chaos in a circular billiard with a straight cut

We study classical and quantum dynamics of a particle in a circular billiard with a straight cut. This system can be integrable, nonintegrable with soft chaos, or nonintegrable with hard chaos, as we vary the size of the cut. We use a quantum web to show differences in the quantum manifestations of classical chaos for these three different regimes.Comment: LaTeX2e, 8 pages including 3 Postscript figures and 4 GIF figures, submitted to Phys. Rev.

Subterranean sympatry : an investigation into diet using stable isotope analysis

In the Western Cape three species of mole-rat occur in sympatry, however, little is known about differences in their dietary preferences. Dietary composition of the three species; the common mole-rat (Cryptomys hottentotus hottentotus), the Cape mole-rat (Georychus capensis) and the Cape dune mole-rat (Bathyergus suillus) were examined using stable isotope analysis. Blood, fur and claw samples were collected from 70 mole-rats, in addition to several potential food items, to assess food selection of the three species under natural conditions. Overall there was a significant difference in the isotopic composition (d13C and d15N) between all three species and significant differences in their diet composition. There were also significant differences between tissues in all three species suggesting temporal variation in diet. The small size and colonial lifestyle of C. h. hottentotus allows it to feed almost 100% on bulbs, while the solitary and larger species G. capensis and B. suillus fed to a greater extent on other resources such as grasses and clover. B. suillus, the largest of the species, had the most generalized diet. However, overall all species relied most heavily upon geophytes and consumed the same species suggesting competition for resources could exist. We also showed a high level of individual variation in diet choices. This was most pronounced in B. suillus and G. capensis and less so in C. h. hottentotus. We demonstrate that stable isotope analysis can successfully be applied to examine dietary patterns in subterranean mammals and provide insights into foraging patterns and dietary variation at both the inter and intra population level.G. Robb was funded by a University of Pretoria Post-doctoral fellowship. N. Bennett and fieldwork costs were funded through the Department of Science and Technology and National Research Foundation SARChI Chair of Mammal Behavioural Ecology and Physiology.http://www.plosone.orgab201