Antinociceptive and Cardiorespiratory Effects of a Single Dose of Dexmedetomidine in Laboratory Mice Subjected to Craniotomy under General Anaesthesia with Isoflurane and Carprofen or Meloxicam

Pain refinement represents an important aspect of animal welfare in laboratory animals. Refining analgesia regimens in mice undergoing craniotomy has been sparsely investigated. Here, we sought to investigate the effect of dexmedetomidine in combination with other analgesic drugs on intraoperative anti-nociceptive effects and cardiorespiratory stability. All mice were anaesthetised with isoflurane and received local lidocaine infiltration at the surgical site. Mice were randomised into treatment groups consisting of either carprofen 5 mg kg−1 or meloxicam 5 mg kg−1 with or without dexmedetomidine 0.1 mg kg−1 administered subcutaneously. Intra-anaesthetic heart rates, breathing rates, isoflurane requirements, and arterial oxygen saturations were continuously monitored. We found that administration of dexmedetomidine significantly improved heart and breathing rate stability during two of four noxious stimuli (skin incision and whisker stimulation) compared to non-dexmedetomidine-treated mice and lowered isoflurane requirements throughout anaesthesia by 5–6%. No significant differences were found between carprofen and meloxicam. These results demonstrate that dexmedetomidine reduces nociception and provides intra-anaesthetic haemodynamic and respiratory stability in mice. In conclusion, the addition of dexmedetomidine to anaesthetic regimes for craniotomy offers a refinement over current practice for laboratory mice

Machine learning reveals interhemispheric somatosensory coherence as indicator of anesthetic depth

The goal of this study was to identify features in mouse electrocorticogram recordings that indicate the depth of anesthesia as approximated by the administered anesthetic dosage. Anesthetic depth in laboratory animals must be precisely monitored and controlled. However, for the most common lab species (mice) few indicators useful for monitoring anesthetic depth have been established. We used electrocorticogram recordings in mice, coupled with peripheral stimulation, in order to identify features of brain activity modulated by isoflurane anesthesia and explored their usefulness in monitoring anesthetic depth through machine learning techniques. Using a gradient boosting regressor framework we identified interhemispheric somatosensory coherence as the most informative and reliable electrocorticogram feature for determining anesthetic depth, yielding good generalization and performance over many subjects. Knowing that interhemispheric somatosensory coherence indicates the effectively administered isoflurane concentration is an important step for establishing better anesthetic monitoring protocols and closed-loop systems for animal surgeries

Oscillating Fracture in Rubber

We have found an oscillating instability of fast-running cracks in thin rubber sheets. A well-defined transition from straight to oscillating cracks occurs as the amount of biaxial strain increases. Measurements of the amplitude and wavelength of the oscillation near the onset of this instability indicate that the instability is a Hopf bifurcation

Wound botulism in injectors of drugs: upsurge in cases in England during 2004.

Wound infections due to Clostridium botulinum were not recognised in the UK and Republic of Ireland before 2000. C. botulinum produces a potent neurotoxin which can cause paralysis and death. In 2000 and 2001, ten cases were clinically recognised, with a further 23 in 2002, 15 in 2003 and 40 cases in 2004. All cases occurred in heroin injectors. Seventy cases occurred in England; the remainder occurred in Scotland (12 cases), Wales (2 cases) and the Republic of Ireland (4 cases). Overall, 40 (45%) of the 88 cases were laboratory confirmed by the detection of botulinum neurotoxin in serum, or by the isolation of C. botulinum from wounds. Of the 40 cases in 2004, 36 occurred in England, and of the 12 that were laboratory confirmed, 10 were due to type A. There was some geographical clustering of the cases during 2004, with most cases occurring in London and in the Yorkshire and Humberside region of northeast England

Neurons in the Nucleus papilio contribute to the control of eye movements during REM sleep

Rapid eye movements (REM) are characteristic of the eponymous phase of sleep, yet the underlying motor commands remain an enigma. Here, we identified a cluster of Calbindin-D28K-expressing neurons in the Nucleus papilio (NPCalb), located in the dorsal paragigantocellular nucleus, which are active during REM sleep and project to the three contralateral eye-muscle nuclei. The firing of opto-tagged NPCalb neurons is augmented prior to the onset of eye movements during REM sleep. Optogenetic activation of NPCalb neurons triggers eye movements selectively during REM sleep, while their genetic ablation or optogenetic silencing suppresses them. None of these perturbations led to a change in the duration of REM sleep episodes. Our study provides the first evidence for a brainstem premotor command contributing to the control of eye movements selectively during REM sleep in the mammalian brain

Evaluation of accuracy of invasive and non-invasive blood pressure monitoring in relation to carotid artery pressure in anaesthetised ponies

Invasive blood pressure measurement (IBP) using peripheral arteries is a commonly used technique in equine anaesthesia, although the accuracy has not been demonstrated. Non-invasive blood pressure monitoring (NIBP) may be indicated for field anesthesia, short procedures and foal anaesthesia. In the present report, the agreement of various IBP and NIBP measuring sites compared to carotid artery pressure was tested in anaesthetised experimental ponies. Six ponies were anaesthetised in lateral recumbency with sevoflurane and received either saline or dexmedetomidine boli followed by constant rate infusion (CRI). Invasive blood pressure measurements were obtained simultaneously from the carotid, facial and metatarsal arteries. NIBP measurements over both median arteries, metatarsal and middle coccygeal arteries were performed in random order. All blood pressure readings obtained were compared to carotid pressure by Bland-Altman analysis. Non-invasive blood pressure measurements had larger bias and poorer limits of agreement compared to IBP measurements. NIBP measurement from the coccygeal artery had the best repeatability and best limits of agreement of all NIBP positions and was not affected by the use of dexmedetomidine. The facial artery had smaller limits of agreement with dexmedetomidine treatment. There was no difference between the facial and metatarsal arteries during dexmedetomidine treatment in MAP and DAP. Systolic arterial pressures from the metatarsal artery showed larger bias and larger limits of agreement compared to facial artery. In conclusion, NIBP measurement from the tail artery is a reliable alternative to direct arterial blood pressure measurement. Both the metatarsal and facial arteries have acceptable agreement with carotid artery pressure so the choice can be based on the logistics of the procedure

The DLV System for Knowledge Representation and Reasoning

This paper presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to $\Delta^P_3$-complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof. Furthermore, we illustrate the general architecture of the DLV system which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.Comment: 56 pages, 9 figures, 6 table

Modeling the climate response to a massive methane release from gas hydrates

[1] The climate response to a massive release of methane from gas hydrates is simulated in two 2500-year-long numerical experiments performed with a three-dimensional, global coupled atmosphere-sea ice-ocean model of intermediate complexity. Two different equilibrium states were used as reference climates; the first state with preindustrial forcing conditions and the second state with a four times higher atmospheric CO2 concentration. These climates were perturbed by prescribing a methane emission scenario equivalent to that computed for the Paleocene/Eocene thermal maximum (PETM; similar to 55.5 Ma), involving a sudden release of 1500 Gt of carbon into the atmosphere in 1000 years. In both cases, this produced rapid atmospheric warming (up to 10°C at high latitudes) and a reorganization of the global overturning ocean circulation. In the ocean, maximum warming (2-4°C) occurred at intermediate depths where methane hydrates are stored in the upper slope sediments, suggesting that further hydrate instability could result from the prescribed scenario

Error-prone protein synthesis recapitulates early symptoms of Alzheimer disease in aging mice

Age-related neurodegenerative diseases (NDDs) are associated with the aggregation and propagation of specific pathogenic protein species (e.g., Aβ, α-synuclein). However, whether disruption of synaptic homeostasis results from protein misfolding per se rather than accumulation of a specific rogue protein is an unexplored question. Here, we show that error-prone translation, with its frequent outcome of random protein misfolding, is sufficient to recapitulate many early features of NDDs, including perturbed Ca2+ signaling, neuronal hyperexcitability, and mitochondrial dysfunction. Mice expressing the ribosomal ambiguity mutation Rps9 D95N exhibited disrupted synaptic homeostasis resulting in behavioral changes reminiscent of early Alzheimer disease (AD), such as learning and memory deficits, maladaptive emotional responses, epileptiform discharges, suppressed circadian rhythmicity, and sleep fragmentation, accompanied by hippocampal NPY expression and cerebral glucose hypometabolism. Collectively, our findings suggest that random protein misfolding may contribute to the pathogenesis of age-related NDDs, providing an alternative framework for understanding the initiation of AD. Keywords: Alzheimer; CP: Neuroscience; error-prone translation; neurodegenerative diseases; pathogenesis; protein misfolding; synaptic homeostasi