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Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing \"ivermectin\" and either \"covid\" or \"sars\" in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).

This mini-review focuses on the mechanisms of how severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) affects the brain, with an emphasis on the role of the spike protein in patients with neurological symptoms. Following infection, patients with a history of neurological complications may be at a higher risk of developing long-term neurological conditions associated with the α-synuclein prion, such as Parkinson’s disease and Lewy body dementia. Compelling evidence has been published to indicate that the spike protein, which is derived from SARS-CoV-2 and generated from the vaccines currently being employed, is not only able to cross the blood–brain barrier but may cause inflammation and/or blood clots in the brain. Consequently, should vaccine-induced expression of spike proteins not be limited to the site of injection and draining lymph nodes there is the potential of long-term implications following inoculation that may be identical to that of patients exhibiting neurological complications after being infected with SARS-CoV-2. However, further studies are needed before definitive conclusions can be made.

Taking a fresh look at anti-slavery debates in the late eighteenth and early nineteenth centuries, this book uncovers the structure, dynamics and flexibility of transatlantic abolitionism during the Age of Revolution. It reframes the abolition movement as a broad international network of activists across metropolitan centres and remote outposts.

Transatlantic Abolitionism in the Age of Revolution offers a fresh exploration of anti-slavery debates in the late eighteenth and early nineteenth centuries. It challenges traditional perceptions of early anti-slavery activity as an entirely parochial British, European or American affair, and instead reframes the abolition movement as a broad international network of activists across a range of metropolitan centres and remote outposts. Interdisciplinary in approach, this book explores the dynamics of transatlantic abolitionism, along with its structure, mechanisms and business methods, and in doing so, highlights the delicate balance that existed between national and international interests in an age of massive political upheaval throughout the Atlantic world. By setting slave trade debates within a wider international context, Professor Oldfield reveals how popular abolitionism emerged as a political force in the 1780s, and how it adapted itself to the tumultuous events of the late eighteenth and early nineteenth centuries.

This exciting interdisciplinary volume, featuring contributions from a group of leading international scholars, reflects on the long history of representations of transatlantic slaves and slavery, encompassing a broad chronological range, from the eighteenth century to the present day.

A new type of interlace, the three-dimensional (3D) audio display, is being developed to enhance cockpit displays in military aircraft. In order to synthesize a sound's location in space, head-related transfer functions are measured for many sound source positions (in space) and incorporated in digital filters, which are then used to synthesize location. However, most military aircraft have communication systems that are band-limited in frequency response, as are most recently designed auditory displays currently used in military applications. The present study investigated the effects of limiting signal bandwidth on sound localization. Results show that broadband signals encompassing frequencies from 0 to (at least) 13 kHz are required in order for listeners to accurately localize signals actually presented from a range of spatial locations. These results have clear implications for the design and implementation of 3D spatial synthesis systems in military aircraft. Communications systems should be capable of carrying broadband signals and acoustic signals used in 3D audio displays should also be broadband in nature.

We investigated the time participants took to perform a visual search task for targets outside the visual field of view using a helmet-mounted display. We also measured the effectiveness of visual and auditory cues to target location. The auditory stimuli used to cue location were noise bursts previously recorded from the ear canals of the participants and were either presented briefly at the beginning of a trial or continually updated to compensate for head movements. The visual cue was a dynamic arrow that indicated the direction and angular distance from the instantaneous head position to the target. Both visual and auditory spatial cues reduced search time dramatically, compared with unaided search. The updating audio cue was more effective than the transient audio cue and was as effective as the visual cue in reducing search time. These data show that both spatial auditory and visual cues can markedly improve visual search performance. Potential applications for this research include highly visual environments, such as aviation, where there is risk of overloading the visual modality with information.

The influence of elevated CO2 on the development of the shoot apex and on subsequent vegetative growth and grain yield investigated using rice (Oryza sativa L. cv Jarrah) grown in flooded soil at either 350 or 700 microliter CO2 L-1. At 8 d after planting (DAP), elevated CO2 increased the height and diameter of the apical dome and lengths of leaf primordia and tiller buds but had no effect on their numbers. By 16 DAP, there were five tiller buds in the apex at 700 microliter CO2 L-1 compared with only three tiller buds at 350 microliter CO2 L-1. These changes in development of the shoot apex at high CO2 were forerunners to faster development of the vegetative shoot at elevated CO2 between 11 and 26 DAP as evidenced by increases in the relative growth rates of the shoot and tillers. Accelerated development at high CO2 was responsible for the 42% increase in tiller number at the maximum tillering stage and the 57% enhancement of grain yield at the final harvest. The link between high CO2 effects on development during the first 15 DAP and final tiller number and grain yield was demonstrated by delaying exposure of plants to high CO2 for 15 d. The delay totally inhibited the tillering response to high CO2, and the increase in grain yield of 20% arose from a greater number of grains per panicle. Consequently, it can be concluded that accelerated development in the shoot apex early in development is crucial for obtaining maximum increases in grain yield at elevated atmospheric CO2 concentrations

The growth in computing resources at scientific computing centers has created new challenges for system software. These multi-teraflop systems often exceed the capabilities of the system software and require new approaches to accommodate these large processor counts. The costs associated with development and maintenance of this software are also significant impediments, which are compounded by a lack of interoperability because of site-specific enhancements. The Scalable System Software project seeks to address these issues through a component based approach to system software development. An overview of this design and the benefits of such an approach will be discussed in this paper.