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Comparing isoflurane and desflurane: A prospective randomised blinded clinical trial in horses undergoing elective surgery
Get PDFBackground: The recovery period is associated with the greatest risk of injury for horses undergoing anaesthesia. Recovery quality and duration can be influenced by the volatile agent. Methods: This prospective, randomised blinded clinical investigation recruited 101 healthy client-owned horses undergoing elective surgery at one UK equine hospital. Anaesthesia was standardised, and horses were randomly assigned to receive desflurane or isoflurane for maintenance. Horses were ventilated to normocapnia and received dobutamine to maintain mean arterial blood pressure above 60 mmHg. All the patients received romifidine intravenously prior to recovery, which was timed and video recorded to allow offline blinded evaluation by two experienced clinicians. Results: There was no significant difference between groups in haemodynamic support during anaesthesia or recovery quality. Desflurane horses recovered faster and made fewer attempts to stand. Limitations: Nonlinearity and lack of validation of the recovery scale limit reliability; however, in the absence of a validated instrument, this scoring system is widely used. Conclusion: Haemodynamic support required during anaesthesia and recovery quality were similar between agents. Desflurane horses recovered faster and required fewer attempts to stand, suggesting that this anaesthetic may lead to fewer recovery injuries and optimise workflow in the equine theatre
Leadership Development in Saudi Arabia: Impact of the Tatweer Programme
Get PDFThis study examines the impact of the Tatweer programme on leadership development practices in Saudi Arabia. Data were collected from two schools that participated in the Tatweer programme. Semi-structured interviews were conducted with 14 participants, including junior teachers, senior teachers and principals. The results indicate that the Tatweer programme supports the Saudi Ministry of Education's objective to decentralise the educational system and has contributed to enhancing the leadership skills of the participating schools. However, the Tatweer programme’s selective participation system creates a significant divide between Tatweer and non-Tatweer schools, depriving the latter of this opportunity to participate in school leadership development. The findings of the study also suggest that the Tatweer programme is not widely supported by Tatweer school teachers, reducing the impact of the initiative
Modelling and validating the time-temperature-ageing superposition principle in bitumen via molecular dynamics simulations
No full textThe durability and performance of asphalt pavements are dominantly determined by the viscoelastic properties of bitumen. Time-temperature-ageing superposition principle (TTASP) theory can effectively reflect the effects of ageing and temperature on the viscoelastic properties of bitumen. However, obtaining the parameters of TTASP experimentally is time-consuming and challenging. Accurate and rapid acquisition of the parameters of TTASP is needed. In this paper, molecular dynamics (MD) simulations are used to explore the volumetric properties of bitumen, verifying the TTASP and obtaining its parameters from a molecular computational perspective. The bitumen molecules were developed in the MD according to the proportion of the lab-measured bitumen. The TTASP parameters were derived and calibrated via fractional free volume theory, considering the model size effect influenced by the number of molecules. The degree of bitumen oxidised ageing was investigated in the MD via the carbonyl groups. The proposed method effectively verifies the rationality of Time-temperature superposition principle (TTSP) and TTASP theories at nanoscale, accurately predicting volumetric and TTASP parameters. This precise and efficient approach can be used to forecasts the viscoelastic properties and ageing behaviour of bitumen, ensuring reliable predictions consistent with experimental results
Effect of aggregate type and hydrated lime on long-term ageing of asphalt mixtures
No full textThe ageing process of asphalt binders reduces the lifespan of flexible pavements while causing stiffness related cracks that damage the structure. The effects of oxidative ageing on aggregates at the binder or mastic scale have received extensive research but studies are limited regarding oxidative ageing at the mixture level. This research investigates how aggregate selection and filler replacement with hydrated lime affects asphalt mixture ageing. Long-term ageing tests were conducted on asphalt concrete specimens made from granite and limestone aggregates with and without hydrated lime addition. This research analyzed the effects of using hydrated lime substitutes for 1% and 2% of aggregate weight on asphalt ageing behavior. The semi-circular bending (SCB), indirect tensile strength (ITS), and indirect tensile stiffness modulus (ITSM) tests were used to evaluate the mechanical performance of the specimens. A Dynamic Shear Rheometer (DSR) and Fourier Transform Infrared Spectroscopy (FTIR) were used to perform rheological and chemical analyses on the recovered binders. Results show that 2% hydrated lime replacement improved stiffness modulus of granite mixtures by up to 40%, and limestone mixtures by up to 20%. Fracture toughness (SCB test) after ageing at 20 °C increased by up to 15% with hydrated lime addition, while hydrated lime reduced the ITS ageing index by approximately 10–18% compared to mixtures without lime. Bitumen binders recovered from granite mixtures containing hydrated lime were up to 18% softer (lower ageing indices) than those with only granite filler. FTIR analysis also showed that carbonyl and sulfoxide ageing indices were reduced by up to 12%, confirming the effectiveness of hydrated lime in slowing oxidation. These findings demonstrate that hydrated lime enhances long-term performance and ageing resistance of asphalt mixtures, particularly those with granite aggregate
Motor unit adaptation to disuse: crossing the threshold from firing rate suppression to neuromuscular junction transmission
Get PDFNeural conditioning to scenarios of muscle disuse is undoubtedly a cause of functional decrements that typically exceed losses of muscle size. Yet establishing the relative contribution of neural adaptation and the specific location in the motor pathway remains technically challenging. Several studies of healthy humans have targeted this system and have established that motor unit firing rate is suppressed following disuse, with a number of critical caveats. It is suppressed in the immobilized limb only, at relative and absolute force levels, and preferentially targets lower-threshold motor units. Concomitantly, electrophysiological investigation of neuromuscular junction transmission (NMJ) stability of lower-threshold motor units reveals minimal change following disuse. These findings contrast with numerous other methods, which show clear involvement of the NMJ but are unable to characterize the motor unit to which they belong. It is physiologically plausible that decrements observed following disuse are a result of suppressed firing rate of lower-threshold motor units and impairment of transmission of the NMJ of higher-threshold motor units. As such, motor units within the pool should be viewed in light of their varying susceptibility to disuse. (Figure presented.)
Late Quaternary population expansion in gray brocket deer [Subulo gouazoubira (G. Fisher, 1814), Cervidae, Mammalia] in Brazil
Get PDFThere is little information about the changes in the abundance of mammalian species in South America during the late Quaternary, which is a key parameter to understanding past ecological and evolutionary dynamics. Here, we describe a conspicuous increase in the abundance of the gray brocket deer (Subulo gouazoubira G. Fisher, 1814; Mammalia) during the late Quaternary in Brazil based on paleontological evidence. We studied the material retrieved from pitfall deposits in Cuvieri Cave (Brazil) representing three time intervals (Late Pleistocene, Pleistocene/Holocene transition, and Holocene). The deposits in this cave were previously characterized in terms of facies composition, chronology, and overall taxa and taphonomy. We combined previous data with taxonomic identification at the species level for deer (morphological and ancient DNA analyses), quantification of the number of individuals for large mammals (>10 kg), taphonomic analyses, and stratigraphic distribution of specimens. Our results show that while in the Late Pleistocene gray brocket deer corresponded to up to 18% of 38 individuals, in the Holocene they represented at least 82% of 78 individuals. We interpret this change in frequency as a considerable increase in abundance in the surroundings of the cave, after excluding major taphonomical biases. The causes for this phenomenon are uncertain but could have involved a surplus of food availability and predation release due to the late Quaternary extinction event
Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia
Get PDFAlthough many internalized G protein-coupled receptors (GPCRs) continue to signal, the mechanisms and outcomes of intracellular GPCR signaling are uncertain due to the challenges of measuring organelle-specific signals and of selectively antagonizing receptors in intracellular compartments. Herein, genetically encoded biosensors targeted to the plasma membrane and early endosomes were used to analyze compartmentalized signaling of protease-activated receptor 2 (PAR2); the propensity of nanoparticles (NPs) to accumulate in endosomes was leveraged to preferentially antagonize intracellular PAR2 signaling of pain. PAR2 agonists evoked sustained activation of PAR2, Gαq, and β-arrestin-1 in early endosomes and activated extracellular signal regulated kinase (ERK) in the cytosol and nucleus, measured with targeted biosensors. Fluorescent dendrimer and core-shell polymeric NPs accumulated in endosomes of HEK293T cells, colonic epithelial cells, and nociceptors, detected by confocal microscopy. NPs efficiently encapsulated and slowly released AZ3451, a negative allosteric PAR2 modulator. NP-encapsulated AZ3451, but not unencapsulated AZ3451, rapidly and completely reversed PAR2, Gαq, and β-arrestin-1 activation in early endosomes and ERK activation in the cytosol and nucleus. When administered into the mouse colon lumen, fluorescent dendrimer NPs accumulated in endosomes of colonocytes and polymeric NPs accumulated in neurons, sites of PAR2 expression. Both NP formulations of AZ3451, but not unencapsulated AZ3451, caused long-lasting analgesia and normalized aberrant behavior in preclinical models of inflammatory bowel disease. These results provide evidence that PAR2 endosomal signaling mediates pain and that nanomedicines that antagonize PAR2 in endosomes effectively relieve pain. NP-mediated delivery may improve the efficacy of other GPCR antagonists for treatment of diverse diseases
Post-Hospitalisation COVID-19 Rehabilitation (PHOSP-R): a randomised controlled trial of exercise-based rehabilitation
Get PDFObjectivePost-COVID syndrome involves prolonged symptoms with multisystem and functional impairment lasting ≥12 weeks after acute coronavirus disease 2019 (COVID-19). We aimed to determine the efficacy of exercise-based rehabilitation interventions, either face-to-face or remote, compared to usual care in individuals experiencing post-COVID syndrome following a hospitalisation with acute COVID-19.DesignThis single-blind randomised controlled trial compared two exercise-based rehabilitation interventions (face-to-face or remote) to usual care in participants with post-COVID syndrome following a hospitalisation. The interventions were either a face-to-face or remote 8-week programme of individually prescribed exercise and education. The primary outcome was the change in Incremental Shuttle Walking Test (ISWT) following 8 weeks of intervention (either face-to-face or remote) compared to usual care. Other secondary outcomes were measured including health-related quality of life (HRQoL), and exploratory outcomes included lymphocyte immunotyping.Results181 participants (55% male, mean±sd age 59±12 years, length of hospital stay 12±19 days) were randomised. There was an improvement in the ISWT distance following face-to-face rehabilitation (mean 52 m, 95% CI 19–85 m; p=0.002) and remote rehabilitation (mean 34 m, 95% CI 1–66 m; p=0.047) compared to usual care alone. There were no differences between groups for HRQoL self-reported symptoms. Analysis of immune markers revealed significant increases in naïve and memory CD8+ T-cells following face-to-face rehabilitation versus usual care alone (p<0.001, n=31).ConclusionExercise-based rehabilitation improved short-term exercise capacity in post-COVID syndrome following an acute hospitalisation and showed potential for beneficial immunomodulatory effects
Constructive (in)visibility and the trafficking industrial complex: Leveraging borders for exploitation
Get PDFThis paper explores the heterogeneity of migrant visibility across space and time, analysing where and how Eritrean forced migrants travelling along the Central Mediterranean Route are made visible or disappeared at various scales and how their (in)visibility is mobilised by other actors for profit. We point to three heterogeneous forms of (in)visibility—hypervisibility, invisibilisation and selective visibility—that frame, justify and help perpetuate a system of migrant exploitation, extortion and human trafficking. Drawing from three tranches of interviews with human trafficking survivors and migrants from Eritrea, government officials, suprastate actors, CSO employees and other stakeholders in Sudan, Libya and Ethiopia conducted between March 2021 and April 2022, we explore the dynamic interplay between representation and policy in the experiences of vulnerable migrants. We develop the term constructive (in)visibility to describe the ways in which migration governance visibilises Eritrean migrants in aggregate as threats, commodities and victims, while simultaneously invisibilising them as individuals and rights bearers. Policy responses to the hypervisibility of the ‘crime’ and ‘magnitude’ of irregular migration leave migrants vulnerable to a chain of predatory actors who see and know irregular migratory routes. Selectively deployed and leveraged borders allow profiteers to benefit from the restrictions on mobility and limitations on protections of irregular migrants, while international investments in restrictionist, externalised migration policies finance actors involved or complicit in migrant smuggling and human trafficking. The mutually reinforcing cycle of constructive (in)visibilisation and repressive policy thus facilitates the establishment of what we define as a trafficking industrial complex—a necrocapitalist market in migrants—that profits from their abandonment, exposing them to abduction, extortion and death
Quantifying vector diversion effects in zoonotic systems: A modelling framework for arbovirus transmission between reservoir and dead-end hosts
Get PDFVector-borne disease transmission involves complex interactions between vectors, reservoir hosts and dead-end hosts. We present a mathematical model for the vectorial capacity that incorporates multiple host types and their interactions, focusing specifically on West Nile virus transmission by Culex pipiens mosquitoes. Our model integrates climate-dependent parameters affecting vector biology with vector control interventions to predict transmission potential under various scenarios. We demonstrate how vector control interventions targeting one host type can significantly impact transmission dynamics across all host populations. By examining the effects of different vector control tool modes of action (repellency, preprandial killing, disarming and postprandial killing), we develop target product profiles that minimise unintended consequences of vector control. Notably, we identify the optimal intervention characteristics needed to prevent repellency on dead-end hosts from inadvertently increasing transmission among reservoir hosts. This research provides valuable insights for public health officials designing targeted vector control strategies and offers a flexible modelling framework that can be adapted to other vector-borne diseases with complex host dynamics
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