A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice

Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models. There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 %) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 %). No statistical differences were detected in regards to administration route (P <= 0.94). This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia

A Model for the Analysis of Caries Occurrence in Primary Molar Tooth Surfaces

Recently methods of caries quantification in the primary dentition have moved away from summary ‘whole mouth’ measures at the individual level to methods based on generalised linear modelling (GLM) approaches or survival analysis approaches. However, GLM approaches based on logistic transformation fail to take into account the time-dependent process of tooth/surface survival to caries. There may also be practical difficulties associated with casting parametric survival-based approaches in a complex multilevel hierarchy and the selection of an optimal survival distribution, while non-parametric survival methods are not generally suitable for the assessment of supplementary information recorded on study participants. In the current investigation, a hybrid semi-parametric approach comprising elements of survival-based and GLM methodologies suitable for modelling of caries occurrence within fixed time periods is assessed, using an illustrative multilevel data set of caries occurrence in primary molars from a cohort study, with clustering of data assumed to occur at surface and tooth levels. Inferences of parameter significance were found to be consistent with previous parametric survival-based analyses of the same data set, with gender, socio-economic status, fluoridation status, tooth location, surface type and fluoridation status-surface type interaction significantly associated with caries occurrence. The appropriateness of the hierarchical structure facilitated by the hybrid approach was also confirmed. Hence the hybrid approach is proposed as a more appropriate alternative to primary caries modelling than non-parametric survival methods or other GLM-based models, and as a practical alternative to more rigorous survival-based methods unlikely to be fully accessible to most researchers

On the trace of the antipode and higher indicators

We introduce two kinds of gauge invariants for any finite-dimensional Hopf algebra H. When H is semisimple over C, these invariants are respectively, the trace of the map induced by the antipode on the endomorphism ring of a self-dual simple module, and the higher Frobenius-Schur indicators of the regular representation. We further study the values of these higher indicators in the context of complex semisimple quasi-Hopf algebras H. We prove that these indicators are non-negative provided the module category over H is modular, and that for a prime p, the p-th indicator is equal to 1 if, and only if, p is a factor of dim H. As an application, we show the existence of a non-trivial self-dual simple H-module with bounded dimension which is determined by the value of the second indicator.Comment: additional references, fixed some typos, minor additions including a questions and some remark

Validation of Results from Knowledge Discovery: Mass Density as a Predictor of Breast Cancer

The purpose of our study is to identify and quantify the association between high breast mass density and breast malignancy using inductive logic programming (ILP) and conditional probabilities, and validate this association in an independent dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set the Aleph ILP system to generate 10,000 rules per malignant finding with a recall >5% and precision >25%. Aleph reported the best rule for each malignant finding. A total of 80 unique rules were learned. A radiologist reviewed all rules and identified potentially interesting rules. High breast mass density appeared in 24% of the learned rules. We confirmed each interesting rule by calculating the probability of malignancy given each mammographic descriptor. High mass density was the fifth highest ranked predictor. To validate the association between mass density and malignancy in an independent dataset, we collected data from 180 consecutive breast biopsies performed between 2005 and 2007. We created a logistic model with benign or malignant outcome as the dependent variable while controlling for potentially confounding factors. We calculated odds ratios based on dichomotized variables. In our logistic regression model, the independent predictors high breast mass density (OR 6.6, CI 2.5–17.6), irregular mass shape (OR 10.0, CI 3.4–29.5), spiculated mass margin (OR 20.4, CI 1.9–222.8), and subject age (β = 0.09, p < 0.0001) significantly predicted malignancy. Both ILP and conditional probabilities show that high breast mass density is an important adjunct predictor of malignancy, and this association is confirmed in an independent data set of prospectively collected mammographic findings

Landscape determinants of European roller foraging habitat: implications for the definition of agri-environmental measures for species conservation

Across much of Europe, farmland birds are declining more than those in other habitats. From a conservation perspective, identifying the primary preferred habitats could help improve the foraging conditions of target species and, consequently, enhance their breeding success and survival. Here, we investigated the ranging behaviour and foraging habitat selection of the European roller (Coracias garrulus) during the breeding season in an agricultural landscape of South Iberia. The occurrence of foraging rollers was predicted to gradually increase with decreasing distance from the nest and increasing availability of perches, such as fences and electric wires. Traditional olive groves and stubble fields were positively and negatively associated with the occurrence of rollers, respectively. Additionally, analysis of hunting strikes showed that rollers highly prefer foraging in fallows rather than cereal or stubble fields. Prey surveys revealed that fallows had the highest abundance of grasshoppers, rollers’ preferred prey during chick-rearing. Pair home-ranges, obtained from 95% fixed Kernel estimators averaged 70.9 ha (range = 34–118 ha) and most foraging trips (80%) occurred in the close vicinity of the nest (<500 m). Number of chicks fledged was not affected by mean foraging distances travelled during the chick-rearing period. Overall, our results suggest that traditional extensive practices of cereal cultivation, with large areas of low-intensity grazed fallows, represent a high-quality foraging habitat for rollers and should be promoted through agri-environmental schemes within at least 1-km radius from the nest. These recommendations are targeted at the roller, but have been shown to apply broadly to several other steppe-bird species

Challenges, solutions and research priorities for sustainable rangelands

Australia’s rangeland communities, industries, and environment are under increasing pressures from anthropogenic activities and global changes more broadly. We conducted a horizon scan to identify and prioritise key challenges facing Australian rangelands and their communities, and outline possible avenues to address these challenges, with a particular focus on research priorities. We surveyed participants of the Australian Rangeland Society 20th Biennial Conference, held in Canberra in September 2019, before the conference and in interactive workshops during the conference, in order to identify key challenges, potential solutions, and research priorities. The feedback was broadly grouped into six themes associated with supporting local communities, managing natural capital, climate variability and change, traditional knowledge, governance, and research and development. Each theme had several sub-themes and potential solutions to ensure positive, long-term outcomes for the rangelands. The survey responses made it clear that supporting ‘resilient and sustainable rangelands that provide cultural, societal, environmental and economic outcomes simultaneously’ is of great value to stakeholders. The synthesis of survey responses combined with expert knowledge highlighted that sustaining local communities in the long term will require that the inherent social, cultural and natural capital of rangelands are managed sustainably, particularly in light of current and projected variability in climate. Establishment of guidelines and approaches to address these challenges will benefit from: (i) an increased recognition of the value and contributions of traditional knowledge and practices; (ii) development of better governance that is guided by and benefits local stakeholders; and (iii) more funding to conduct and implement strong research and development activities, with research focused on addressing critical knowledge gaps as identified by the local stakeholders. This requires strong governance with legislation and policies that work for the rangelands. We provide a framework that indicates the key knowledge gaps and how innovations may be implemented and scaled out, up and deep to achieve the resilience of Australia’s rangelands. The same principles could be adapted to address challenges in rangelands on other continents, with similar beneficial outcomes

Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients 60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials

Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed