Development of a facial expression scale using footrot and mastitis as models of pain in sheep

Management of pain in sheep is limited by the challenges of recognising and accurately quantifying pain in this species. The use of facial expression scoring to assess pain is a well-utilised, practical tool in both humans and non-human animals. The objective of this study was to develop a standardised facial expression pain scale for adult sheep, that could be used reliably and accurately to detect pain associated with naturally occurring painful diseases, such as footrot and mastitis. We also investigated whether the scale could be reliably and accurately utilised by observers after training, enabling the development of an on-farm pain assessment tool. The Sheep Pain Facial Expression Scale (SPFES) was able to correctly identify sheep suffering from disease with a high degree of accuracy (AUC; Footrot: 0.81, Mastitis: 0.80). Diseased sheep scored higher on the scale than controls on the day of disease identification (P<0.05) and diseased sheep showed changes in their facial expression after treatment (P<0.001). The abnormal facial expressions of diseased sheep reduced over time, and at recovery were in line with control sheep. Control sheep did not change their facial expression over time. Five scorers who were trained to use the developed scale also assessed the facial expressions of sheep. The scorers were blind to treatment and session. Scorers reliably (ICC: 0.86) and accurately (α = 0.86) identified changes in the facial expression of sheep with footrot over time (P<0.05), and scored control sheep consistently low over time. The SPFES offers a reliable and effective method of assessing pain in sheep after minimal training.We would like to thank the EU VII Framework Program (FP7-KBBE-2010-4) for funding this study as part of the AWIN project. Boehringer Imgelheim Ltd are thanked for providing the meloxicam used in this study.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.applanim.2016.01.00

The Assessment of Post-Vasectomy Pain in Mice Using Behaviour and the Mouse Grimace Scale

Background: Current behaviour-based pain assessments for laboratory rodents have significant limitations. Assessment of facial expression changes, as a novel means of pain scoring, may overcome some of these limitations. The Mouse Grimace Scale appears to offer a means of assessing post-operative pain in mice that is as effective as manual behavioural-based scoring, without the limitations of such schemes. Effective assessment of post-operative pain is not only critical for animal welfare, but also the validity of science using animal models. Methodology/Principal Findings: This study compared changes in behaviour assessed using both an automated system (‘‘HomeCageScan’’) and using manual analysis with changes in facial expressions assessed using the Mouse Grimace Scale (MGS). Mice (n = 6/group) were assessed before and after surgery (scrotal approach vasectomy) and either received saline, meloxicam or bupivacaine. Both the MGS and manual scoring of pain behaviours identified clear differences between the pre and post surgery periods and between those animals receiving analgesia (20 mg/kg meloxicam or 5 mg/kg bupivacaine) or saline post-operatively. Both of these assessments were highly correlated with those showing high MGS scores also exhibiting high frequencies of pain behaviours. Automated behavioural analysis in contrast was only able to detect differences between the pre and post surgery periods. Conclusions: In conclusion, both the Mouse Grimace Scale and manual scoring of pain behaviours are assessing th

Characterization of short- and long-term mechanical sensitisation following surgical tail amputation in pigs

Commercial pigs are frequently exposed to tail mutilations in the form of preventive husbandry procedures (tail docking) or as a result of abnormal behaviour (tail biting). Although tissue and nerve injuries are well-described causes of pain hypersensitivity in humans and in rodent animal models, there is no information on the changes in local pain sensitivity induced by tail injuries in pigs. To determine the temporal profile of sensitisation, pigs were exposed to surgical tail resections and mechanical nociceptive thresholds (MNT) were measured in the acute (one week post-operatively) and in the long-term (either eight or sixteen weeks post-surgery) phase of recovery. The influence of the degree of amputation on MNTs was also evaluated by comparing three different tail-resection treatments (intact, ‘short tail’, ‘long tail’). A significant reduction in MNTs one week following surgery suggests the occurrence of acute sensitisation. Long-term hypersensitivity was also observed in tail-resected pigs at either two or four months following surgery. Tail amputation in pigs appears to evoke acute and sustained changes in peripheral mechanical sensitivity, which resemble features of neuropathic pain reported in humans and other species and provides new information on implications for the welfare of animals subjected to this type of injury

Application of a handheld Pressure Application Measurement device for the characterisation of mechanical nociceptive thresholds in intact pig tails

AbstractThe assessment of nociceptive thresholds is employed in animals and humans to evaluate changes in sensitivity potentially arising from tissue damage. Its application on the intact pig tail might represent a suitable method to assess changes in nociceptive thresholds arising from tail injury, such as tail docking or tail biting. The Pressure Application Measurement (PAM) device is used here for the first time on the tail of pigs to determine the reliability of the methods and to provide novel data on mechanical nociceptive thresholds (MNT) associated with four different age groups (9, 17, 24 and 32weeks) and with proximity of the target region to the body of the animal. We recorded an overall acceptable level of intra-individual reliability, with mean values of CV ranging between 30.1 and 32.6%. Across all age groups, the first single measurement of MNT recorded at region 1 (proximal) was significantly higher (P<0.05) than the following two. This was not observed at tail regions 2 and 3 (more distal). Age had a significant effect (P<0.05) on the mean thresholds of nociception with increasing age corresponding to higher thresholds. Furthermore, a significant effect of proximity of tail region to the body was observed (P<0.05), with MNT being higher in the proximal tail region in pigs of 9, 17 and 24weeks of age. There was also a significant positive correlation (P<0.05) between mechanical nociceptive thresholds and age/body size of the animals.To the best of our knowledge, no other investigation of tail nociceptive thresholds has been performed with the PAM device or alternative methods to obtain mechanical nociceptive thresholds in intact tails of pigs of different age/body size. The reliability of the data obtained with the PAM device support its use in the measurement of mechanical nociceptive threshold in pig tails. This methodological approach is possibly suitable for assessing changes in tail stump MNTs after tail injury caused by tail docking and biting

Species specific anaesthetics for fish anaesthesia and euthanasia.

There is a need to ensure that the care and welfare for fish maintained in the laboratory are to the highest standards. This extends to the use of anaesthetics for both scientific study, humane killing and euthanasia at end of life. An anaesthetic should not induce negative behaviours and fish should not seek to avoid the anaesthetic. Surprisingly little information is available to facilitate a humane choice of anaesthetic agent for fish despite over 100 years of use and the millions of fish currently held in thousands of laboratories worldwide. Using a chemotaxic choice chamber we found different species specific behavioural responses among four closely related fish species commonly held in the laboratory, exposed to three widely used anaesthetic agents. As previously found for zebrafish (Danio rerio), the use of MS-222 and benzocaine also appears to induce avoidance behaviours in medaka (Oryzias latipes); but etomidate could provide an alternative choice. Carp (Cyprinus carpio), although closely related to zebrafish showed avoidance behaviours to etomidate, but not benzocaine or MS-222; and rainbow trout (Oncorhynchus mykiss) showed no avoidance to the three agents tested. We were unable to ascertain avoidance responses in fathead minnows (Pimephales promelas) and suggest different test paradigms are required for that species

Supporting perinatal anxiety in the digital age; a qualitative exploration of stressors and support strategies

Background The period surrounding childbirth is one of profound change, which can often be experienced as stressful and overwhelming. Indeed, around 20% of women may experience significant levels of anxiety in the perinatal period. However, most women experiencing perinatal anxiety (PNA) go unrecognised and untreated. The Internet offers a potentially scalable solution to improve access to support, however a dearth of research in this area means that work is needed to better understand women’s experience of PNA, so that potential targets for intervention can be identified and possible barriers to support overcome. This study aimed to qualitatively explore women’s experience of anxiety triggers and support in the perinatal period; and gain insight into what online support is acceptable for women with PNA. Methods Women who were either pregnant or within one-year postpartum were invited to participate in focus groups across the UK. Focus groups were used to allow a diversity of perspectives to be heard, while simultaneously promoting the identification and prioritisation of important support needs and solutions. Interviews were transcribed and thematically analysed. Results Five key themes emerged in relation to women’s experience with PNA: holding unrealistic expectations of birth and motherhood; stigma; the importance of peer support; uncertainty and poor maternal confidence; and a lack of mental health support and knowledge. Perinatal women felt under-supported and poorly prepared for motherhood. A mismatch between their expectations and the reality of their experience, alongside a pressure to be the ‘perfect mum’ was the primary source of their anxiety. Furthermore, stigma associated with PNA may have exacerbated these issues and led to help-seeking avoidance. Overall, women felt these issues could be addressed via online support, through the delivery of more realistic information, providing psychoeducation about PNA symptoms and management, and the inclusion of authentic peer experiences. Thus, delivering evidence-based information and interventions online may provide a solution that is acceptable to this cohort. Conclusions This work provides unique insight into potential sources of anxiety for women in the perinatal period, while also offering potential internet-based support solutions that are likely to be acceptable and helpful for women with PNA

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Data hosting infrastructure for primary biodiversity data

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Bioinformatics 12 Suppl. 15 (2011): S5, doi:10.1186/1471-2105-12-S15-S5.Today, an unprecedented volume of primary biodiversity data are being generated worldwide, yet significant amounts of these data have been and will continue to be lost after the conclusion of the projects tasked with collecting them. To get the most value out of these data it is imperative to seek a solution whereby these data are rescued, archived and made available to the biodiversity community. To this end, the biodiversity informatics community requires investment in processes and infrastructure to mitigate data loss and provide solutions for long-term hosting and sharing of biodiversity data. We review the current state of biodiversity data hosting and investigate the technological and sociological barriers to proper data management. We further explore the rescuing and re-hosting of legacy data, the state of existing toolsets and propose a future direction for the development of new discovery tools. We also explore the role of data standards and licensing in the context of data hosting and preservation. We provide five recommendations for the biodiversity community that will foster better data preservation and access: (1) encourage the community's use of data standards, (2) promote the public domain licensing of data, (3) establish a community of those involved in data hosting and archival, (4) establish hosting centers for biodiversity data, and (5) develop tools for data discovery. The community's adoption of standards and development of tools to enable data discovery is essential to sustainable data preservation. Furthermore, the increased adoption of open content licensing, the establishment of data hosting infrastructure and the creation of a data hosting and archiving community are all necessary steps towards the community ensuring that data archival policies become standardized