New concepts for use in low-energy cardiac defibrillation

The presence of three-dimensional rotating action potential waves, called scroll waves, in the heart causes ventricular fibrillation. Recently, there has been interest in developing low-energy methods, consisting of applying an electric field to terminate these waves, as a means of defibrillation. The success of these methods often depends on the orientation of the waves. We present computer simulations of a method that applies multiple electrical fields in a hemispherical shell system representative of the ventricles of the heart. Scroll waves in this system persist when the filament (the curve around which the wave rotates) connects the inside and outside surfaces. Our scheme for applying electric fields aims to disconnect these filaments from the surfaces. Once the filaments no longer connect the inside and outside surfaces, they contract and disappear, terminating the scroll wave. Importantly, as opposed to most existing schemes, the idea on which this scheme is based is applicable irrespective of how many scroll waves are present, where they are located, or where they are in their rotation. We discuss the success of this scheme both for different numbers of waves and for different wave orientations and present potential failure mechanisms. The effects of other conditions, such as the stability of the waves and heart geometry, remain to be studied. In the future, the presented low-energy method for termination of scroll waves may be a useful means of cardiac defibrillation

Are "visitor effects" overestimated? Behaviour in captive lemurs is mainly driven by co-variation with time and weather

The potential influence of visitors on behaviour of captive animals is well known. However, little research on “visitor effects” has also evaluated time of day and weather, which can affect behaviour directly and often also co-vary with visitor numbers. Here, we examine visitor effects on captive ring-tailed lemurs Lemur catta in a walk-through enclosure, where potential for visitor effects is especially high, while specifically considering weather and time of day (between 10:00 hr when lemurs were released into their outdoor enclosure and 16:00 hr when then returned to overnight accommodation). Time, weather and visitor variables interacted in complex ways, but time and weather exerted the strongest effect on behaviour. Weather strongly affected resting, feeding/foraging, and locomotion. Sunbathing was highest in mornings; locomotion increased in afternoons. Visitor numbers were negatively associated with feeding/foraging and sunbathing; visitor activity was positively associated with locomotion and alertness. Crucially, however, “visitor effects” were small both overall and in relation to underlying effects of time/weather. Univariate models suggested visitors accounted for ~20% of behavioural variation; after time/weather had been included this dropped to ~6-8%. We conclude that underlying visitor : time and visitor : weather correlations can lead to overestimation of visitor effects and offer recommendations for future work

A Microbial Mutualist Within Host Individuals Increases Parasite Transmission Between Host Individuals: Evidence From a Field Mesocosm Experiment

The interactions among host-associated microbes and parasites can have clear consequences for disease susceptibility and progression within host individuals. Yet, empirical evidence for how these interactions impact parasite transmission between host individuals remains scarce. We address this scarcity by using a field mesocosm experiment to investigate the interaction between a systemic fungal endophyte, Epichloë coenophiala, and a fungal parasite, Rhizoctonia solani, in leaves of a grass host, tall fescue (Lolium arundinaceum). Specifically, we investigated how this interaction impacted transmission of the parasite under field conditions in replicated experimental host populations. Epichloë-inoculated populations tended to have greater disease prevalence over time, though this difference had weak statistical support. More clearly, Epichloë-inoculated populations experienced higher peak parasite prevalences than Epichloë-free populations. Epichloë conferred a benefit in growth; Epichloë-inoculated populations had greater aboveground biomass than Epichloë-free populations. Using biomass as a proxy, host density was correlated with peak parasite prevalence, but Epichloë still increased peak parasite prevalence after controlling for the effect of biomass. Together, these results suggest that within-host microbial interactions can impact disease at the population level. Further, while Epichloë is clearly a mutualist of tall fescue, it may not be a defensive mutualist in relation to Rhizoctonia solani

Two randomized trials of effect of live attenuated influenza vaccine on pneumococcal colonization

The human nasopharynx is frequently colonized by Streptococcus pneumoniae (the pneumococcus), serving as the reservoir for transmission, a state which necessarily precedes invasive pneumococcal infection. Influenza infection increases pneumococcal colonization density and dysregulates host immune responses, increasing the risk of secondary bacterial pneumonia and death

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

Abstract The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log 10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules. Trial registration The study was registered on EudraCT (2014-004634-26) Funding The study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council

Abstracts of the 3rd Annual Graduate Entry Research in Medicine Conference

This book contains the abstracts of the papers presented at The 3rd Annual Graduate Entry Research in Medicine Conference (GERMCON 2020) Organized by Warwick Medical School, University of Warwick in collaboration with Swansea University Medical School, Swansea University, Wales, UK held on 12–18 October 2020. This was especially important for Graduate Entry Medical (GEM) students, who have less opportunity and time to engage in research due to their accelerated medical degree. Conference Title: 3rd Annual Graduate Entry Research in Medicine ConferenceConference Acronym: GERMCON 2020Conference Date: 12–18 October 2020Conference Location: Online (Virtual Mode)Conference Organizer: Warwick Medical School, University of Warwick, UKCo-organizer: Swansea University Medical School, Swansea University, Wales, UK Other Abstract Book of GERMCON: Abstracts of the 4th Annual Graduate Entry Research in Medicine Conferenc

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration isrctn.org Identifier: ISRCTN16912075