CamTech Care February 2018

CamTechCare Newsletter

February| 2018

Keeping you informed In this Newsletter MCMS update 2 Openness Awards Dosing Refinements Directors Feedback Handling Slides Cambridge Science Festival Upcoming Events 2018 Plus much more‌..

Directors Blog Welcome to another edition of CamTechCare and the Director’s Blog!

Although a little late, let us use this as an opportunity to wish you all a Happy New Year. 2018 for UBS will mainly focus on looking forward and planning for the future. Having spent much of the last two years getting used to being one department and putting in place all the infrastructure that entails we now need to start putting more effort into forward planning and looking at what’s to come.

One of the big things on the horizon of course is the opening of the Bellatrix building. During the first half of 2018 we shall be starting to map out the movements of both staff and work into that building and towards the end of the year will be in a position to start communicating some of those plans to you. As always, we are aware that plenty of stories have started circulating about this already, but at the moment let us assure you it is all just rumour and speculation!

More immediately at the end of March 2018 the Stem Cell unit, in the basement of the Gleeson building, will be closing for 2 years whilst the Gleeson Building undergoes a significant refurbishment project. We’d like to just take this opportunity to thank everyone who works in the unit for making this process as easy as it is, and all the support we’ve received in the last few months whilst this decision was being made.

Keith and Karl had the first very successful Tech Forum at the end of last year. Whilst there are a few tweaks to be made to the format (importantly someone to produce notes of what we say, as it transpires both of them aren’t very prompt with that – apologies all!) we are very pleased with how it went and look forward to the next one.

Also Keith and Alex King held our first New Starter – check-in which they both found very useful and gave an opportunity in an informal setting, to gain an insight into our recruitment processes, from advert and application forms to interviews, inductions and training. Suffice to say we had some very positive feedback and useful comments that we hope to incorporate into the process for the future. We very much enjoyed this new opportunity to meet people as they start their careers with us.

One of the questions asked related to the “benefits of working for the University”… narrowing it down to the “tangible benefits” (i.e. money saving opportunities etc.) our next UBS Roadshow will focus on that very thing.

Make sure you watch out for info on that!

And lastly, with summer approaching, if anyone has any thoughts about this year’s Summer Event please let us know by using the suggestion box!

See you all next time.

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Openness Awards Craig Brierley, Head of Research Communications, attended the UAR Openness Awards on December 4th 2017 in London. http://www.understandinganimalresearch.org.uk/news/communications-media/ openness-awards-and-paget-lecture-2017/

These annual awards are the fruition of commitment each institute has shown during the past 12 months in their Openness working with animals in research.

UAR quote“The Openness Awards celebrate five winners who have encouraged the widespread sharing of best practice in animal research communications.

Bringing together those with an interest in Openness around animal research, the fourth UAR Openness Awards celebrates a year of achievements of the Concordat on Openness on Animal Research. The evening recognises and rewards best practice in Openness around animal research, following nominations made earlier in the year. There have been some fantastic entries to the awards, and the winning entries have set a new standard for open communications.”

“Openness Awards celebrate how far the UK has come in communicating animal research.”

At these 2017 awards the University of Cambridge won the Award for Website or Use of New Media for our videos explaining how animals, including nonhuman primates, are used to understand and treat OCD. Craig was delighted to receive this award on behalf of the University, with grateful thanks to all concerned in the making of it.

Tony Davidge, from Cancer Research UK Cambridge Institute, was also highly commended for his role in introducing local school children to the ethical and practical issues associated with animal research. The work Tony has put in over the past year with students from Cambridge Academy for Science and Technology (University Technical College) many of you will have been involved in, either by hosting work experience in your facilities or providing lectures at UTC. Tony gave thanks to Theresa Langford in his speech for the work she had put in over the years, saying he had taken over the reins after she had put in much of the original work.

CamTechCare Newsletter | February 2018 | 3

Cambridge Science Festival 2018 ‘Making sense of the 3Rs of animal research’.

Find us in the Life Science Marquee on Saturday 17th March 10-16:00 The AWERB 3Rs committee and others involved in laboratory animal research and care have volunteered once again to hold an exhibit.

The Science Festival theme is: Sense, senses, sensible, sensing, sensors, sensitive, sensation, sensational If you have some ideas, and/or would like to help, please contact: Maggie Gentry mg469@cam.ac.uk

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NC3Rs - Re-use of needles: is this an indicator of a culture of care?

Dr Lucy Whitfield, Royal Veterinary College and Dr Sally Robinson, AstraZeneca, who cover the topic of re-using hypodermic needles in day-to-day practice. https://nc3rs.org.uk/news/re-use-needles-indicator-culture-care

Image, from left to right: hypodermic needle used once (magnified x 1000), hypodermic needle used five times (magnified x 1000), hypodermic needle used five times (magnified x 1000).

Source: AstraZeneca.

SOPs (Standard Operating Procedures), competence assessments and our trainers should clarify what our standards are in this regard, and that re-use of disposable hypodermic needles is unacceptable. If we can’t take the time to do a study correctly, with proper working practices, then we shouldn’t do the study.

It’s these day-to-day practices, such as injecting an animal with a used needle, that really demonstrate whether or not our culture of care is functioning as it should.

https://www.diabetesdaily.com/blog/2014/01/how-many-times-can-you-reuse-a-syringe/

CamTechCare Newsletter | February 2018 | 5

MCMS news The next MCMS update is due at the end of February. Here is a quick overview of the new features.

Adding new mice – A new function allows you to create multiple cages when adding new mice to the system.

Project licences – The maximum number of animals to be used for each protocol can now be added to the system. While this is for reference only (the database won’t send a warning if the total is close to the limit) there is a new report ‘Animal usage by protocol’ which displays the total number of animals allowed, used and remaining.

Cage list report – Another new report to be added; this is a live report showing cages, number of animals per cage, cage type and last validation date. This can be filtered by room, PPL, Colony manager etc.

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Tasking system – the ‘Save and Notify’ button will return to always being available. When used the task requester will automatically receive an email to update them on the status of the task.

Login – The session length has been extended to one hour before the user is automatically logged out of the system.

Procedure cards – Will now show the coat colour and earmark.

Weaning – it is now possible to choose how many animals to place into each cage at weaning (up to five). Also to wean mixed sex pups into the same cage if necessary.

Embryo production – Setting up pooled females (for use in stud matings) has changed; a new guide will be available on the Moodle site. Stud males and pooled females will now show an ‘S’ or ‘P’ at the cage level.

For the full list of updates to the system; check ‘What’s New in 2018.2.0’ on your Homepage when it’s released at the end of the month.

Mary Ann Haskings 12.2.18

CamTechCare Newsletter | February 2018 | 7

3Rs Relevant Publications Lab Anim. 2018 Jan 1:23677217738268. doi: 10.1177/0023677217738268. [Epub ahead of print]

On determining sample size in experiments involving laboratory animals.

Festing MF1.

Scientists using laboratory animals are under increasing pressure to justify their sample sizes using a “power analysis”. In this paper I review the three methods currently used to determine sample size: “tradition” or “common sense”, the “resource equation” and the “power analysis”. I explain how, using the “KISS” approach, scientists can make a provisional choice of sample size using any method, and then easily estimate the effect size likely to be detectable according to a power analysis. Should they want to be able to detect a smaller effect they can increase their provisional sample size and recalculate the effect size. This is simple, does not need any software and provides justification for the sample size in the terms used in a power analysis.

Methods Mol Biol. 2018;1718:423-439. doi: 10.1007/978-14939-7531-0_25.

Anesthesia and Monitoring of Animals During MRI Studies.

Tremoleda JL1, Macholl S2, Sosabowski JK2.

The use of imaging represents a major impact on the refinement and the reduction of in vivo studies in animal models, in particular for allowing longitudinal monitoring of the onset and the progression of disease within the same animal, and studying the biological effects of drug candidate and their therapeutic effectiveness. But the use of imaging procedures can affect animal physiology, and the need to anesthetize the animals for imaging entails potential health risks. During anesthesia, there is an inevitable autonomic nervous system depression which induces cardiovascular depression, respiratory depression, and hypothermia. Also other procedures associated with imaging such as animal preparation (e.g., fasting, premedication), blood sampling, and dosage/contrast agent injections can also affect physiology and animal

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welfare. All these factors are likely to have confounding effect on the outcome of the imaging studies and pose important concerns regarding the animal’s well-being, particularly when imaging immune deprived animals or diseased animals. We will discuss these challenges and considerations during imaging to maximize efficacious data while promoting animal welfare.

ALTEX. 2017 Nov 29. doi: 10.14573/altex.1708111. [Epub ahead of print]

Recommendations to improve the EU nontechnical summaries of animal experiments.

Taylor K1, Rego L1, Weber T2.

Under the new Directive 2010/63/EC, member states have to publish non-technical summaries (NTS) of the projects involving animals that they authorise.

These summaries must include information on the objectives of the project including the predicted harm and benefits and the number and types of animals to be used. Summaries should also demonstrate compliance with the 3Rs. The intention was that NTS would help increase the transparency of animal research in the EU. In this article, we review the status of the publication of NTS across member states and give some general observations on publication speed, identification, accessibility and quality. We also review in more detail the quality of reporting in a selection of NTS from Germany and the UK. We consistently found that NTS from Germany and the UK were deficient in their description of what is being done to the animals and what they might experience as a result. Using examples taken from specific NTS we highlight what we view to be good and bad examples to assist member states and researchers in producing better NTS in the future. The NTS can also be an important tool in sharing of best practice in the 3Rs and the avoidance of duplicative animal testing. For this to happen however, member states need to publish timely, ensure that NTS are accurate and, ideally, there needs to be some centralisation of the NTS.

Front Pharmacol. 2017 Nov 14;8:818. doi: 10.3389/ fphar.2017.00818. eCollection 2017.

Lab Anim. 2018 Feb;52(1):79-87. doi: 10.1177/0023677217718862. Epub 2017 Jul 11.

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis.

Quality of reporting of otorhinolaryngology articles using animal models with the ARRIVE statement.

Despite a broad spectrum of anti-arthritic drugs currently on the market, there is a constant demand to develop improved therapeutic agents. Efficient compound screening and rapid evaluation of treatment efficacy in animal models of rheumatoid arthritis (RA) can accelerate the development of clinical candidates. Compound screening by evaluation of disease phenotypes in animal models facilitates preclinical research by enhancing understanding of human pathophysiology; however, there is still a continuous need to improve methods for evaluating disease. Current clinical assessment methods are challenged by the subjective nature of scoring-based methods, time-consuming longitudinal experiments, and the requirement for better functional readouts with relevance to human disease. To address these needs, we developed a low-touch, digital platform for phenotyping preclinical rodent models of disease. As a proof-of-concept, we utilized the rat collagen-induced arthritis (CIA) model of RA and developed the Digital Arthritis Index (DAI), an objective and automated behavioral metric that does not require human-animal interaction during the measurement and calculation of disease parameters. The DAI detected the development of arthritis similar to standard in vivo methods, including ankle joint measurements and arthritis scores, as well as demonstrated a positive correlation to ankle joint histopathology. The DAI also determined responses to multiple standard-of-care (SOC) treatments and nine repurposed compounds predicted by the SMarTRTM Engine to have varying degrees of impact on RA. The disease profiles generated by the DAI complemented those generated by standard methods.

The DAI is a highly reproducible and automated approach that can be used in-conjunction with standard methods for detecting RA disease progression and conducting phenotypic drug screens.

Research involving animal models is crucial for the advancement of science, provided that experiments are designed, performed, interpreted, and reported well. In order to investigate the quality of reporting of articles in otorhinolaryngology research using animal models, a PubMed database search was conducted to retrieve eligible articles. The checklist of the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines was used to assess the quality of reporting of articles published in ear, nose and throat (ENT) and multidisciplinary journals. Two authors screened titles, abstracts, and full texts to select articles reporting otorhinolaryngology research using in vivo animal models. ENT journals ( n = 35) reported a mean of 57.1% adequately scored ARRIVE items (median: 58.3%; 95% confidence interval [CI; 53.4-60.9%]), while articles published in multidisciplinary journals ( n = 36) reported a mean of 49.1% adequately scored items (median: 50.0; 95% CI [46.2-52.0%]). Articles published in ENT journals showed better quality of reporting of animal studies based on the ARRIVE guidelines ( P < 0.05). However, adherence to the ARRIVE guidelines is generally poor in otorhinolaryngology research using in vivo animal models. The endorsement of the ARRIVE guidelines by authors, research and academic institutes, editorial offices and funding agencies is recommended for improved reporting of scientific research using animal models.

Lim MA1, Louie B2, Ford D1, Heath K1, Cha P1, Betts-Lacroix J1, Lum PY2, Robertson TL1, Schaevitz L1.

Bezdjian A1,2,3, Klis SFL1,2, Peters JPM1,2, Grolman W1,2, Stegeman I1,2.

Lab Anim. 2018 Jan 1:23677217753464. doi: 10.1177/0023677217753464. [Epub ahead of print]

Partial cage division significantly reduces aggressive behavior in male laboratory mice.

Tallent BR1,2, Law LM1,3,2, Rowe RK1,3,2, Lifshitz J1,3,2.

Aggression in mice often results in injury leading to unplanned euthanasia or the initiation of protocols to isolate animals, thereby increasing research costs and straining resources. Here, we tested if adding a partial cage divider into existing mouse cages affected aggressive-like behavior in group-housed male mice CamTechCare Newsletter | February 2018 | 9

(18 mice; 3 per cage). Mice were randomly assigned to one of two groups upon arrival to the vivarium: (1) standard cage; (2) cage with a partial cage divider.

Behavioral observation over 12 hours were conducted at day one, two, and seven after receipt at the facility in order to assess aggression during the course of establishing dominance hierarchies. Observers blinded to study design and hypothesis scored each video for the number and type of aggressive behaviors, which were summed for each hour and analyzed.

Results indicated a statistically significant decrease in aggressive behaviors of mice in cages with dividers compared to mice in standard cages. We conclude that cage dividers, which resemble burrows and provide access to common food/water, may promote rigorous research by reducing the number of animals used in a study and refining housing, thus, improving animal welfare.

Lab Anim. 2018 Feb;52(1_suppl):5-57. doi: 10.1177/0023677217744587

Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report.

Smith D1, Anderson D2, Degryse AD3, Bol C4, Criado A5, Ferrara A6, Franco NH7, Gyertyan I8, Orellana JM9, Ostergaard G10, Varga O11, Voipio HM12.

Directive 2010/63/EU introduced requirements for the classification of the severity of procedures to be applied during the project authorisation process to use animals in scientific procedures and also to report actual severity experienced by each animal used in such procedures. These requirements offer opportunities during the design, conduct and reporting of procedures to consider the adverse effects of procedures and how these can be reduced to minimize the welfare consequences for the animals. Better recording and reporting of adverse effects should also help in highlighting priorities for refinement of future similar procedures and benchmarking good practice.

Reporting of actual severity should help inform the public of the relative severity of different areas of scientific research and, over time, may show trends regarding refinement. Consistency of assignment of severity categories across Member States is a key

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requirement, particularly if re-use is considered, or the safeguard clause is to be invoked. The examples of severity classification given in Annex VIII are limited in number, and have little descriptive power to aid assignment. Additionally, the examples given often relate to the procedure and do not attempt to assess the outcome, such as adverse effects that may occur.

The aim of this report is to deliver guidance on the assignment of severity, both prospectively and at the end of a procedure. A number of animal models, in current use, have been used to illustrate the severity assessment process from inception of the project, through monitoring during the course of the procedure to the final assessment of actual severity at the end of the procedure (Appendix 1).

Scand-LAS 2018 26-28 April Kristiansand, Norway

The Organizing Committee invites you to the 48th Scand-LAS Symposium in Norway:

â&#x20AC;&#x153;Beyond legislation Best practice in animal researchâ&#x20AC;?

More information will soon be available on www.scandlas.org

Scandinavian Society for Laboratory Animal Science

CamTechCare Newsletter | February 2018 | 11

Are Mice Scared of Death?

Of Corpse They Are! Author: Aaron Dinsdale

This is a short report in response to an apparent inconsistency in how Animal Technicians are managing animals found dead in their cages and whether or not the remaining occupants are provided with a new cage and enrichment.

It is often easy for us to focus on the individual animal when found dead in its home cage. Great effort may be taken to have the incident reported, determine cause of death and make sure the cage mates of the deceased aren’t inflicted by the same health problem that caused death. Yet to the best of the University’s knowledge there is little prescription within the animal research industry of what corrective measures should be taken with the remaining occupants of the cage to reduce necrophobic related stress.

It would seem the general consensus between technicians is for animals to receive a new cage if one of their fellow occupants is discovered dead as it has been perceived leaving the occupants with the “scent of the dead” will have negative implications on welfare. The following information supports this ideology.

A corpse will begin to decompose almost immediately following death and this creates an unpleasant odour. The odour is mainly caused by putrescine and cadaverine, two pungent organic compounds that result from the breakdown of decaying tissue in living organisms (Hussain et al., 2013 ₃). Animal research has established both compounds function as important chemosensory signals, prompting threat-mediated behavioural responses (e.g. heightened alertness, fight or flight responses) in multiple species, including rats and mice (Yao et al., 2009 ₁₀ ;Prounis and Shields, 2013 ⁷).

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The scientific evidence indicates, the presence of these compounds can be perceived as threatening due to the risk of predation and disease that are associated with cadavers in communal species (Prounis and Shields, 2013 ⁷ ; Boissy et al., 1998 ₂ ). Misslin (2003) ⁴ described the compounds as essential alarm cues for prey species since a large proportion of deaths in the wild are the result of predation, thus eliciting escape and avoidance responses would be beneficial to the survival of rodents.

This has been demonstrated by Prounis and Shields ⁷ (2013) in wild rodents and laboratory mice. In the wild, experimental food trays containing Mus Musculus cadavers were avoided in favour of trays containing novel objects or no objects, suggesting that animals visiting the experimental tray perceived the Mus cadaver as a threat to their wellbeing. In addition, mice in Y maze studies took significantly longer to pass Mus cadavers than in trials with a toy mouse. Both studies indicate domesticated Mus Musculus displays necrophobic behaviour towards intraspecific cadavers.

Pinel’s ⁵ ⁶ (1981) lab experiments involving rats burying dead or anaesthetised conspecifics coated in putrescine & cadaverine in their home cages, indicates rats also perceive intraspecific cadavers as dangerous and will mobilize the protective response of cadaver burying to deal with the perceived threat. Mice are also known to display the same cadaver burying behaviour in laboratory environments.

It can be seen from the above evidence that mice and rats are necrophobic in nature and consideration should be made to what impact

this has on their welfare in the lab environment.

Receiving a new cage if an occupant is discovered dead should be just as much as important as removing the dead animal. In doing so, however, careful thought should be taken to minimise cage-change induced anxiety and stress (Bind et al., 2013 ₁ ). By transferring across nesting material from the dirty cage, the stress and anxiety instigated from the loss of scent markers can be mitigated (Ramussen et al., 2011 ⁸ ). Of course nesting material should only be deemed suitable

for transfer if its proximity from the cadaver is of a sufficient distance, otherwise putrescine & cadaverine coated bedding may continue to have negative effects on the remaining animals in the cage.

References (1) Bind, H.R., Minney, S.M., Rosenfeld, S. and Hallock, R.M. (2013) ‘The Rolfe of Pheromonal Responses in Rodent Behavior: Future Directions for the Development of Laboratory Protocols’, Journal of the American Association for Laboratory Animal Science, 52(2), pp. 124-129.

(2) Boissy, A., Terlouw, C., and Le Neindre, P. (1998) ‘Presence of Cues from Stressed Conspecifics Increases Reactivity to Aversive Events in Cattle: Evidence for the Existence of Alarm Substances in Urine ‘, Physiology.

Behaviour. , 63(1), pp. 489-495.

(3) Hussain, A., Saraiva, F.R., Ferrero, D.M. and Ahuja G. (2013) ‘High-Affinity Olfactory Receptor for the Death-Associated Odor Cadaverine’, Proc Natl Acad Sci U S A., 48(1), pp. 19579-19584.

(4) Misslin, R. (2003) ‘The Defense System of Fear: Behavior and Neurocircuitry. ‘, Clin.

Neurophysiol., 33(2), pp. 55-66.

(6) Pinel, J.P.J., Hoyer, E. and Terlecki L.J. (1980) ‘Defensive Burying and ApproachAvoidance Behavior in the Rat’, Bulletin of the Psychonomic Society, 16(5), pp. 349–352.

(7) Prounis, G.S. and Shields, W.M. (2013) ‘Necrophobic Behavior in Small Mammals.’

Behav Processes., 94(1), pp. 41-44.

(8) Rasmussen, S., Miller, M.M., Filipski, S.B. and Tolwani, R.J. (2011) ‘Cage Change Influences Serum Corticosterone and Anxiety-Like Behaviors in the Mouse.’ J Am Assoc Lab Anim Sci., 50(4), pp. 479-483.

(9) Wisman, A. and Shrira, I. (2015) ‘The Smell of Death: Evidence that Putrescine Elicits Threat Management’, Frontiers in Psychology, 6(1), pp. 1274.

(10) Yao, M., Rosenfeld, J., Attridge, S and Sidhu, S. (2009) ‘The Ancient Chemistry of Avoiding Risks of Predation and Disease’, Evolutionary Biology, 36(3), pp. 267-281.

(5) Pinel, J.P, Gorzalka, B.B and Ladak F. (1981) ‘Cadaverine and Putrescine Initiate the Burial of Dead Conspecifics by Rats’, Physiology & Behavior, 27(5), pp. 819-824.

CamTechCare Newsletter | February 2018 | 13

UBS Directors Feedback Suggestions

Complaints

Compliments

Hi All. Sadly just a trickle of queries this time and a few jokes but here we go!

Q1) Following the (open forum) meeting last week and the talk about the importance of biosecurity, would it be possible to have a document showing the health status of the different animal units and maybe the barriers they have in place, also what is the recommended period between visiting each unit?

Apologies if this is already in existence and I just haven’t found it!

A1) Yes…. ;-) We’ll chase someone to find it and circulate.

Having said that you everyone should abide by the local facility procedures and if unsure contact the local manager by phone before entering a facility.

Q2) Fairer parking for colleagues A2) This one is a bit tricky to answer anonymously….the parking policy is set by the University in general and we thought most were happy with this year’s allocation but if someone feels they weren’t allocated a space and feel they should have been, please let us know...

If you don’t let us know who you feel should have a parking space we cannot look into the possibility of reallocating any space that becomes available.

Q3) Appraisals should be done every three years and not every year, this would be better as this would give more time for training and developing.

A3) There are strong arguments for and against annual appraisals and how we structure our review programmes for instance a 3 yearly SRD would not help those staff that are new to their careers as annual appraisals make it easier to track progress and identify areas of development, improvement, consolidation etc. However we are constantly looking for ways to improve our staff development process and will feed this suggestion back into discussions

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Q4) I would like to say how disappointed I am reading the comment in the last issue of CamTechCare - about someone asking to move their start and finish times so as to avoid 10-15 min hold ups in the changing rooms.

It is disappointing that the focus of that individual’s job is the minute by minute start and finish time of the clock, and not the care and welfare of the animals.

They are complaining that a 10-15 min queue in the changing room makes them late leaving the unit. What if an animal’s needs required more time? Would they not continue to care for it because it would make them late?

Culture of Care.

A4) We don’t want to start a debate here and as its anonymous we shan’t publish a reply but as a general principle I think we’ll always assume that any suggestions come with the caveat “unless animal welfare needs to be prioritised”. It might be 10-15 extra in the unit in the morning rather than the changing room.

Q5) Who is our departments IT support?

A5) Depends which building you are in…. we are still bringing all the units under 1 structure. Ultimately (although we don’t have a timeframe for this) the UIS will support all of UBS. Bonus Joke Box: Q: What’s Forest Gump’s Wifi password?

A: 1FOREST1 That’s it for this time. – Please keep your comments coming, questions and anything else coming in and we’ll see you in the next edition.

Ongoing Funding Opportunities Laboratory Animals Limited provides funding for a range of education and training initiatives in the field of laboratory animal science.

Deadlines for applications are 31st of March and 30th of September annually Individual scientists, who wish to attend training (courses) in laboratory animal science and welfare, can apply for bursaries from Laboratory Animals Limited. In the application a clear and concise statement outlining why attending the course is necessary and relevant for the work of the applicant should be provided. http://www.lal.org.uk/funding-and-opportunities LASA Bursaries LASA bursaries can be applied for at any time of the year and for any event considered relevant to LASAâ&#x20AC;&#x2122;s mission statement.

Animal technicians, post-graduate students and others for whom funds may be limited are especially encouraged to apply http://www.lasa.co.uk/bursaries/ Universities Federation for Animal Welfare Small Projects and Travel Awards Awards up to ÂŁ3,500 for research and other projects, and awards to support travel.

Research and Project Awards Awards over ÂŁ3,500 for research or other animal welfare projects. https://www.ufaw.org.uk/grants-and-awards/ufaw-grants-andawards

CamTechCare Newsletter | February 2018 | 15

Mira Dosing Refinements MiraDosing DosingRefinements Refinements Mira

Author: Emma Filby & Lewis Whatley Dosing refinements refinements 1.1: Aim 1.1: Aim We aimed to refine our dosing procedure as we identified potential downsides. This was

Weaimed aimed to to refine refine our as we identified potential downsides.

This was We ourdosing dosingprocedure procedure as we identified potential downsides.

This achieved by the with highly palatable substances. achieved by mixing mixing thedrugs drugs highly substances. was achieved by mixing the with drugs withpalatable highly palatable substances.

Downsides: Downsides: × × Oral Oral gavage gavage requires requiresskilled skilled technicians technicians × × Requires Requires restraint restraint × × Administration Administrationof ofsubstance substanceinin water or diet requires water or diet requiressingle singlehousing housing (temporary/permanent) (temporary/permanent)

Benefits Benefitsofofrefined refinedmethods: methods:  Doesn’t Doesn’trequire requirerestraint restraint forfor the  Positive Positivereinforcement reinforcement the animal who receive highly palatable animal who receive highly palatable Nutella Nutellaororgelatine. gelatine.  Although is is needed toto Althoughsupervision supervision needed ensure rats eat their jelly portions, ensure rats eat their jelly portions, this method is still an improvement this method is still an improvement from adding analgesia to drinking from adding analgesia to drinking water as allows more control of the water as allows more control of the dose rate (Liles et al. 1998). dose rate (Liles et al. 1998).

Whatwe we mix mix the depends on its What thedrug drugwith with depends onproperties: its properties:

What we mix the drug with depends on its properties: Hydrophilic Hydrophobic Hydrophilic Hydrophobic Ribena is given orally with a syringe Condensed milk to be orally dosed with Ribena is given orally with a syringe Condensed milk to be orally dosed with syringe syringe Concentrated jelly is eaten from a spatula, Mixed with hazelnut spread fed with a Concentrated jelly is eaten from a spatula, Mixed or with split or in a tub then re-consolidated. spatula tubhazelnut spread fed with a split or in a tub then re-consolidated. spatula or Nutella was suitable for our drug and we chose it because oftub the reference in literature to it Nutella was suitable our drug we chose it because of the reference in literature to it being highly palatablefor (Abelson et and al.,and 2012 Hawkins et al., 2015) Nutella was suitable for our drug weand chose it because of the reference in being highly palatable (Abelson et al., 2012 and Hawkins et al., 2015) literature to it being highly palatable (Abelson et al., 2012 and Hawkins et al., 2015) 1.2: Habituation to substance: 1.2: Habituation to substance: 1.2: Habituation toun-dosed substance: The animals are given an portion of hazelnut spread a week before the procedure, Thethat animals are given anit un-dosed portion of hazelnut a week procedure, so post-operatively will be readily eaten (Flecknell,spread Roughan, and before Stewartthe 1999; Liles The animals are given an un-dosed portion hazelnut spreadand a week before the so al. that post-operatively it will be readily eaten of (Flecknell, Roughan, Stewart 1999; Liles et 1998). procedure, et al. 1998).so that post-operatively it will be readily eaten (Flecknell, Roughan, and

Stewart 1999; Liles et al. 1998).

1.3: Preparation of hazelnut chocolate spread: Preparation procedure:

Figure 1: Rats consuming Nutella from cage wall

1. Break pills into a powder making sure there are no large pieces that would block the syringe.

Figure 1: Rats consuming Nutella from cage wall

2. Weigh the appropriate amount of Nutella needed

Figure 1: Rats consuming Nutella from cage wall

a. 1ml Nutella = 1.1 gr Nutella (For example 10ml of Nutella is needed, 11gr

Author: Emma Filby be & Lewis Whatley Nutella must weighed).

Author: Emma Filby & Lewis Whatley

3. Mix the hazelnut spread portion with the drug powder in a small beaker.

4. Use 1ml syringes to fill in with 0.5ml of the mixture. Each syringe is the daily dose for one animal.

TIP: Supermarket branded spread is easier to use than the branded Nutella because it is more liquid based which makes it easier to suck up with the syringe.

Recommended to use 1ml syringes than 2ml or bigger.

16 | CamTechCare Newsletter | February 2018

1.4: Habituation to handling: The rat is handled by restraining the front legs and supporting their backs. We encouraged the rat to eat from the syringe by allowing the rat to hold the syringe.

Once the rats have are acclimatised to taking the drug from the syringe we were able to give it at cage level using their tail marks to identify the individuals.

Figure 2: Technician orally dosing a rat

2.1: Other applications 2.2: Pain relief Analgesia can also be administered orally, this is a refined method (Flecknell, Roughan, and Stewart 1999) and has been proven to have the same effects using subcutaneous route for dosing (Flecknell, Roughan, and Stewart 1999)(Liles et al.

1998).

2.3: Comfort food Figure 3: Rat given a drug dose from cage

Much like human behaviour, the rat’s analogy can be drawn to comfort food.

Insulin pathways mean that the intake of sugary substance reduces the pain the rat feels post operatively (Liles et al. 1998) so un-dosed jelly is offered to all animals post operatively.

Gelatine preparation procedure: 1. 12 cubes of jelly will be melted by 140ml of boiling water and stirred until dissolved.

2. 140ml of cold water is added.

3. Buprenorphine is administered at 0.3mg/kg, 10% buprenorphine into the jelly.

4. 1ml buprenorphine + 9ml Jelly will be put into ice cube trays.

5. Allow to cool then set in the fridge.

• 1g fed per 100g body weight.

• The cost is less than £1 per rat.

Figure 4:(left) Rats eating buprenorphine orally, (right) premixed ice cubes provide convenient portions TIP: seems to be more palatable making it less dilute than recommended and to mask the drug we found it necessary to use the stronger flavoured Hartley’s branded jelly opposed to a supermarket own brands.

CamTechCare Newsletter | February 2018 | 17

3.1: 3Rs impact 3.2: Reducing stress These refined methods of administrating drugs orally will benefit the welfare of these animals because it promotes good work practices within a laboratory. It reduces the animal’s stress levels as these methods promote positive associations with the drugs. In addition to this, it requires minimum restraint compared to other methods such as intraperitoneal injection which you need to restrain the animal every time.

3.3: Surgical recovery Some surgeries require the animal to have analgesia. Our method of using pain relief jelly (Figure 4) allows us to replace the more common administration route via subcutaneous injection. The benefits of using this method is that the animals don’t have to be handled resulting in minimum disturbance but still allows the technician to perform post-operative checks effectively. As jelly is used, it gives the animal a glucose boast which is good for repair and at the same time creates a positive association to the analgesia agents. Additionally, being predominately water based the jelly is highly hydrating for the recovering animal. There still needs to be further investigation as to whether this can be applied to other agents as well as buprenorphine.

3.4: Animal model: Overall these refined oral methods of dosing an animal for experimental or surgical practices are having a good impact to the welfare and reduce stress of laboratory animals. This also increases the clinical and scientific relevance as an animal model and prevents any adverse effects occurring.

Refinement is an ongoing practice, and it is still important to consider the 3R’s in day to day practices of dosing methods and allows good animal welfare to be shared.

4: Reference Abelson, K., Jacobsen, K., Sundbom, R., Kalliokoski, O. and Hau, J. (2012). Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice.

Laboratory Animals, 46(4), pp.349-351.

Hawkins, P., Armstrong, R., Boden, T., Garside, P., Knight, K., Lilley, E., Seed, M., Wilkinson, M. and Williams, R. (2015). Applying refinement to the use of mice and rats in rheumatoid arthritis research. Inflammopharmacology, 23(4), pp.131-150.

Flecknell, P., Roughan, J. and Stewart, R. (1999). Use of oral buprenorphine (‘buprenorphine jello’) for postoperative analgesia in rats-a clinical trial. Laboratory Animals, 33(2), pp.169-174.

Liles, J., Flecknell, P., Roughan, J. and Cruz-Madorran, I. (1998). Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat.

Laboratory Animals, 32(2), pp.149-161.

18 | CamTechCare Newsletter | February 2018

The Universityâ&#x20AC;&#x2122;s sustainability newsletter.

Issue 84, January 2018. https://mailchi.mp/admin.cam.ac.uk/your-greenlines-newsletter-april-924893?e=[UNIQID]

CamTechCare Newsletter | February 2018 | 19

University of Cambridge News Feeds

Shoals of sticklebacks differ in their collective personalities

Sheep are able to recognise human faces from photographs

07 Feb 2018 Research from the University of Cambridge has revealed that, among schooling fish, groups can have different collective personalities, with some shoals sticking closer together, being better coordinated, and showing clearer leadership than others

08 Nov 2017 Sheep can be trained to recognise human faces from photographic portraits â&#x20AC;&#x201C; and can even identify the picture of their handler without prior training â&#x20AC;&#x201C; according to new research from scientists at the University of Cambridge.

Read More

Handling Slides The slides from this meeting are available from UBS

Handling method alters the hedonic value of reward in laboratory mice Jasmine Clarkson Candy Rowe, Matt Leach & Paul Flecknell

20 | CamTechCare Newsletter | February 2018

Read More

Events Diary March 1 Biosecurity Workshop Red Kite: Training@redkitevets.co.uk March 13 Course “Organizing and Operating Activities in a Rodent Animal Facility” http://www.fondazioneguidobernardini.org/en/training_initiatives/event_detail.aspx?IDEvent=106&IDEventType=3&IDEventSection=1&year=2018 March 20-23 IAT Congress http://www.iat.org.uk/calendar March 23 NC3Rs Cardiovascular Showcase event Central London https://www.nc3rs.org.uk/events/nc3rs-cardiovascular-sho wcase-event March 27 AALAS Webinar “How to improve rat welfare” https://www.aalas.org/calendar/2018/03/27/aalas-webinarhow-to-improve-rat-welfare April 15-19 JAX Workshop on Colony Management https://www.jax.org/education-and-learning/ course-and-conferences/workshop-on-colony-management April 24 AALAS Webinar: Rat Tickling: A Technique for Eliciting Positive Affect https://www.aalas.org/store/meeting?productId=8269066 April 26-28 Scand-LAS Symposium, Kristiansand http://www.scandlas.org/wp-content/uploads/2017/06/ SCAND-LAS-2018-flyer-A4.pdf May 21 Advances in Cell and Tissue Culture Cardiff, UK http://actc2018.com/ May 24-25 Course “The Management of Genetically Altered Rodent Colonies” http://www.fondazioneguidobernardini.org/en/train ing_initiatives/event_detail.aspx?IDEvent=108&IDEvent Type=3&IDEventSection=1&year=2018

June 5-7 Workshop “Pathology of Fish” Leiden University Medical Centre, the Netherlands http://www.fondazioneguidobernardini.org/repository/pub lic//materiale_corsi/fondazione/Pathology2018/Pathology Programme.pdf June 28 Symposium, Italy “The three Rs in research project design: a prerequisite for good science” http://www.fondazioneguidobernardini.org/repository/pub lic//Events2018/3Rs/3RsProgramme.pdf June 28 UFAW conference: Recent Advances in Animal Welfare Science VI, Newcastle https://www.ufaw.org.uk/ufaw-events/recent-advances -in-animal-welfare-science-vi September 23-26 European Congress on Alternatives to Animal testing / 18th Annual EUSAAT Congress, Linz http://www.eusaat-congress.eu/ October 15-16 ESLAV-ECLAM-AAALAC SECAL Conference, Barcelona http://www.barcelonacongress2018.com/modules. php?name=webstructure&idwebstructure=16 October 28 AALAS Baltimore, Maryland, USA National Meeting of the American Association for Laboratory Animal Science https://www.aalas.org/national-meeting

IAT Events Calendar http://www.iat.org.uk/calendar NC3Rs Events Calendar www.nc3rs.org.uk/event.asp?id=33 FGB Events Calendar https://www.fondazioneguidobernardini.org/en/ training_initiatives/events.aspx?IDEventType=3 AALAS Events Calendar https://www.aalas.org/calendar

CamTechCare Newsletter | February 2018 | 21

ASRU Operational Newsletter 5 February 2018 Contents • Publication of Compliance Policy • Publication of updated annotated Project Licence Application Form • Retrospective Assessments • Website Improvements • Non-technical summaries 2016

Compliance policy You can read the Compliance policy (PDF, 280KB, 17 pages) which explains how ASRU identifies and investigates potential incidents of non-compliance and decides on appropriate and proportionate measures and remedies aimed to minimise the risk of recurrence. This document is primarily aimed at those who work within the life science research community under ASPA, but will also be of interest to those wishing to know more about how ASRU regulates.

and the updated version is now available on our website. It explains what is required in each box of the form. Failure to adhere to this guidance could significantly increase the time taken to grant a licence and could result in a rejection of the application Practical guidance on how to apply for project licences. https://www.gov.uk/government/publications/ animal-testing-and-research-improve-yourproject-licence-application

https://www.ubs.admin.cam.ac.uk/home-officelicensing/asru-operational-newsletter Animal testing and research: improve your project licence application

Updated annotated Project Licence Application Form Last year we published an annotated project licence application form to assist all those applying for a licence. Following feedback from several groups of stakeholders this has been improved 22 | CamTechCare Newsletter | February 2018

Retrospective Assessments Since 1st January 2013, retrospective assessment requirements have been applied to project licences which entail the use of non-human primates, dogs, cats and equidae, the use of procedures classified as severe, endangered animals or for the purpose of education and training.

ASRU has developed a preliminary process which it intends to use from January 1st 2018. An additional communication that outlines the process and

some key points to help establishments undertake their part in gathering the information required for the Secretary of State to complete the Assessment will be circulated early in the New Year.

Website Improvements Our last newsletter provided an update on steps being taken to improve the layout and content of ASRUâ&#x20AC;&#x2122;s website making it easier for users to find what they are looking for.

The aim is to remove large blocks of text/ documents from the main page and replace with clear headings. Under each heading there will be links to sub pages where further guidance and documents can be found. The main changes are a separate page for technical advice aimed at licence holders and separate pages for the annual returns.

have a preference for how they are published.

Please can you reply to this email and answer the following: 1. Does categorising by primary purpose assist the reader? Please give your reasons.

2. Would you prefer it if they were published in date order (not by scientific purpose) so that they can be published quicker during the year?

3. If, instead of categorising into 30+ purposes, they were just categorised by the nine overall purposes that the project licence holder is required to specify in their application would this be sufficient to assist the reader e.g. basic research, translational or applied research, preservation of species etc.

The responses to this survey will inform how we publish the non-technical summaries for projects granted in 2017 onwards.

Non-technical summaries The non-technical summaries for project licences granted in 2016 are now on our website: https:// www.gov.uk/government/collections/nontechnical-summaries-granted-in-2016 Since 2014 we have been publishing them in volumes according to the primary purpose of the project. The aim of this was to make them more user-friendly for anyone interested in reading them, including the public and those working in the area e.g. research scientists. The â&#x20AC;&#x2DC;searchâ&#x20AC;&#x2122; facility on gov.uk does not always make it easy for people to find what they want.

Publishing them by scientific purpose is a very time consuming process as each project must be categorised before compiling all the different volumes and this does delay publication. Therefore we would like to do a survey to ask all potential readers of non-technical summaries whether they CamTechCare Newsletter | February 2018 | 23

CamTechCare

Keeping you informed

Contact Information UBS Enquiries: ubsenquiries@admin.cam.ac.uk UBS Training enquiries: ubssts@admin.cam.ac.uk UBS Website: www.ubs.admin.cam.ac.uk/user UBS Home Office Licensing: ubsHOLicencing@admin.cam.ac.uk