Systematic review of the behavioural assessment of pain in cats

Objectives The objectives were to review systematically the range of assessment tools used in cats to detect the behavioural expression of pain and the evidence of their quality; and to examine behavioural metrics (considering both the sensory and affective domains) used to assess pain. Methods A search of PubMed and ScienceDirect, alongside articles known to the authors, from 2000 onwards, for papers in English was performed. This was followed by a manual search of the references within the primary data sources. Only peer-reviewed publications that provided information on the assessment tool used to evaluate the behavioural expression of pain in cats, in conscious animals (not anaesthetised cats), were included. Results No previous systematic reviews were identified. One hundred papers were included in the final assessment. Studies were primarily related to the assessment of pain in relation to surgical procedures, and no clear distinction was made concerning the onset of acute and chronic pain. Ten broad types of instrument to assess pain were identified, and generally the quality of evidence to support the use of the various instruments was poor. Only one specific instrument (UNESP-Botucatu scale) had published evidence of validity, reliability and sensitivity at the level of a randomised control trial, but with a positive rather than placebo control, and limited to its use in the ovariohysterectomy situation. The metrics used within the tools appeared to focus primarily on the sensory aspect of pain, with no study clearly discriminating between the sensory and affective components of pain. Conclusions and relevance Further studies are required to provide a higher quality of evidence for methods used to assess pain in cats. Furthermore, a consistent definition for acute and chronic pain is needed. Tools need to be validated that can detect pain in a range of conditions and by different evaluators (veterinary surgeons and owners), which consider both the sensory and emotional aspects of pain

Interactions of Generated Weather Raster and Soil Profiles in Simulating Adaptive Crop Management and Consequent Yields for Five Major Crops throughout a Region in Southern Germany

Klimaanpassung und MitigationThe ability of bioeconomic simulation modelling to realistically predict agricultural adaptation is limited by the degree of detail in crucial model components. Model robustness must be tested before localized calibrations can be applied to regions of heterogenous environmental conditions. The agent-based model FARMACTOR was used to simulate the timing of field management actions (planting, harvest etc.) in response to environmental conditions, and consequent yields of winter wheat, barley and rapeseed, spring barley and silage maize as the predominant crops in a distinct region of Germany, by linking weather data and the crop growth simulation model EXPERT-N. The integrated models were calibrated to observed experimental data and official phenological observations and then run from 1990 to 2009, forced with climate data from ERA-interim Reanalyses data which was downscaled with the Weather and Research Forecast (WRF) model to a 12 X 12 km² grid. Variability in regional soils was replicated with 10 different soil profiles mapped at 1/25,000 scale. The nature of the forcing climate data dictates temporal aggregation for analysis, so that validity is examined by comparing mean simulated planting and harvest dates and yields to official records in the area. The mean predicted planting dates are very close to observations over the period, within a few days of observations, but show less variance. Harvest dates are accurately predicted as well, within one to two weeks, and the variances are closer to observations. Predicted winter wheat yields are well simulated in comparison to observed data, but maize yields are underestimated, while winter and spring barley and winter rapeseed yields are greater than observed district ("Landkreis") yields. The degree of variance in simulated yields is acceptable in wheat, winter barley and maize, but excessive in spring barley and winter rapeseed. Cross-sectional examination of yields shows that the different soil profiles are responsible for more yield variance than simulated weather cells in all crops. While the coupled models appear accurate in predicting crop management dates and physiological development, the inaccuracy in yields in all crops except winter wheat calls into question the reliability of the integrated models when applied, as is, outside of calibration conditions. That soil parameterization is responsible for more variance than generated weather is helpful in seeking to improve performance and encouraging in terms of the method of weather generation. Reliable extension of the coupled models to include all soils in an area together with artificial spatial climatic variability may require regionalized calibration to increase crop model stability

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.

BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665

Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum

Neuromyelitis optica (NMO) predominantly affects women, some in childbearing age, and requires early therapeutic intervention to prevent disabling relapses. We report an anti-AQP4 antibody-seropositive patient who became pregnant seven months after low-dose (100 mg) rituximab application. Pregnancy showed no complications, and low-dose rituximab restarted two days after delivery resulted in neurological stability for 24 months. Remarkably, her otherwise healthy newborn presented with anti-AQP4 antibody and reduced B lymphocyte counts in umbilical cord blood, which normalized three months later. Confirming and extending previous reports, our case suggests that low-dose rituximab might be compatible with pregnancy and prevent rebound NMO disease activity postpartum

Modelling the response of phytoplankton in a shallow lake (Loch Leven, UK) to changes in lake retention time and water temperature.

The phytoplankton community of Loch Leven in 2005 was modelled and subjected to a combination of different flushing rates and water temperatures in order to assess the lake’s sensitivity to these two climatic drivers. Whilst the simulated annual mean total chlorophyll a proved relatively insensitive to these changes, at the species level marked changes were recorded. Some species responded positively to increased temperature (e.g. Aulacoseira), some negatively (e.g. Asterionella), whilst others were negatively affected by increased flow (e.g. Aphanocapsa) and others enhanced (e.g. Stephanodiscus). However, this relationship with flow was season dependent with, for example, a simulated increase in summer inflows actually benefiting some species through increased nutrient supply, whereas an equivalent increase in flow in wetter seasons would have negatively affected those species (i.e. through flushing loss). Overall, the simulations showed that the range of species types simulated in the community was sufficient for one species to always benefit from the changing niches created by the multiple climatic drivers applied in this study. The level of exploitation by such a species was only constrained by the nutrient carrying capacity of the system, which led to the overall dampened response in the total chlorophyll a measure, both at the annual and season scale. Thus, whilst overall biomass showed relatively little reaction to the two climatic drivers tested, the phytoplankton community composition responded markedly

Modelling interaction with economic models of search

Understanding how people interact when searching is central to the study of Interactive Information Retrieval (IIR). Most of the prior work has either been conceptual, observational or empirical. While this has led to numerous insights and findings regarding the interaction between users and systems, the theory has lagged behind. In this paper, we extend the recently proposed search economic theory to make the model more realistic. We then derive eight interaction based hypotheses regarding search behaviour. To validate the model, we explore whether the search behaviour of thirty-six participants from a lab based study is consistent with the theory. Our analysis shows that observed search behaviours are in line with predicted search behaviours and that it is possible to provide credible explanations for such behaviours. This work describes a concise and compact representation of search behaviour providing a strong theoretical basis for future IIR research