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CamTechCare Newsletter

July | 2018

Keeping you informed In this Newsletter Directors Blog NC3Rs 3Rs Prize Event Report Bronze Green Impact awards Mouse Handling Webinar Upcoming Events 2018 Plus much more‌..


Directors Blog Welcome to another edition of Camtech Care. Thanks once again to Debs Flack and everyone who has contributed to another great edition of our quarterly departmental magazine. Last month we held the 2nd UBS Tech Forum which is proving to be a good opportunity for the Directors to hear about some of the queries, concerns and ideas that you all have. Watch out for the notes from the last meeting, they should be out shortly. This coming month we have the next round of UBS Open Meetings, with a focus this time on Dignity at Work. This is of course a subject that is receiving more and more attention in the press and social media and whilst, pleasingly, we don’t have the same levels of concern around the department, dignity at work is something we all need to be aware of, both in terms of how we are treated and how we treat others. We have received feedback about how difficult it is having everyone out of the unit to attend these meetings but as a large department we need to make the most of these opportunities to better our working environment and also get together. Also, these meetings give you the chance to ask more questions! We still hear that some of you find it hard to find the opportunity to ask the questions you really want to ask, not just to Directors but sometimes to your own manager. With very few exceptions, none of us bite! As an alternative please do make use of the comments box etc‌ Also if you have any good ideas about anything please let us know. Looking forward to seeing you all at the BBQ on the 3rd, otherwise until next time! Have a good Summer.

Cover photo: Rue Jones-Green, Xenopus laevis Anti-clockwiseTop Left: Frog lays Bottom Left: Eggs are collected (bi-coloured) Bottom Right: Eggs rotate so animal pole (dark side) faces up Top Right: Eggs divided.

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Congress feedback! http://www.iat.org.uk/congress

Having the opportunity to expand my knowledge of the industry, connect with new people and gain an insight into other facilities and the operations that support them.

IAT Congress 2018 was interesting, informative, educational and fun! I learnt about what Home Office inspectors look for in Animal Technologists, biosecurity and how to build an animal facility. Hearing about the evolution of language and what chimpanzees have to say was fascinating and amusing. The Trade Exhibition was great for seeing the diversity of suppliers and products used within the field of Animal Technology. All the company representatives were welcoming and provided lots of freebies. The social programme was enjoyable and entertaining too. I recommend IAT Congress to everyone!

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Responsible animal testing: Centro 3R set up in Italy Interuniversitary Center for the Promotion of the Principles of the 3Rs in Teaching and Research https://www.researchitaly.it/en/projects/responsible-animal-testingcentro-3r-set-up-in-italy/ “The Universities of Genoa and Pisa have recently set up in Italy Centro 3R-Interuniversitary Center for the Promotion of the Principles of the 3Rs in Teaching and Research, a new initiative on the Italian academic scenario which aims at starting a process for raising awareness of students, researchers and teachers of responsible experimentation and alternative methods to animal testing.�

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NC3Rs 3Rs Prize Event Report By Emma Filby and Lucy Mulderrig Surgery Technicians from West Cambridge were invited to attend the annual 3Rs Prize event, hosted by the NC3Rs and sponsored by GSK, who, due to their ongoing commitment to animal care are encouraging the replacement, reduction and refinement of animals in research by funding work in line with those principles since 2005. The International 3Rs prize is an annual award given to highlight an outstanding contribution to scientific and technological advances in the 3Rs across the world. The award itself is a £28k research grant and £2k personal reward. The event we attended was a showcase of past winners of the prize and how their work has evolved, which is summarised below:

where real smoke goes into an air interface inside the chip and can be shown moving across membranes. • The research from these chips is described as better than human studies as each chip is essentially the ‘same patient’ and therefore has less variability in results. • They have also cultured the following on chips: human gut epithelium, human bone marrow chip and a blood-brain barrier. • In the future they hope to be able to model the whole human body by interconnecting the chips, which can be kept alive for up to 8 weeks. • Potential impacts include a decrease in costs associated with drug development as it would reduce the numbers of failures at clinical trials and also the potential to personally tailor medicine to individuals. • There is variation in founding cells due to human phenotypes but the results are still reproducible and more comparable than animal models.

Human organs-on-chips Professor Don Ingber, Wyss Institute, Harvard University (2012 Prize winner) • Biological Inspired engineering has led to the creation of a device able to accurately replicate lungs proving a viable alternative to animals • This was important as often there was not found to be a relationship between animals and human models in drug development and cultures do not function like a body so they are not a complete viable alternative.

Summary: Using biology to inspire engineered cell cultures, coupled with the progression in design there are exciting new non-animal methods emerging. Visit their website: https://wyss.harvard.edu/ Reducing anxiety in mice and their handlers Professor Jane Hurst, University of Liverpool (2009 winner) • Jane identified a problem with the reproducibility of research performed using mice. • The mice were the same strain, sex, from the same source but showed differing results due to the laboratory in which the mice were housed

• Instead the group uses Microchips containing human cells that mimic organs.

• This could be attributed to the stress of mice responding to different researchers.

• The microchips are a functional unit rather than whole organ, the same size as memory stick! What we mean by a functional unit, instead of growing a whole lung, they replicate the alveoli, capillary which can be used for imaging instead of in-vivo work.

• She measured anxiety response to traditional tail handling and alternative non aversive methods.

• The work is applied for disease modelling.

• They have found brief handling during cleaning out was as effective as the initially proposed 60 second handling session. The minimum handling required to get the positive results was four sessions.

• When the lung on a chip was compared to whole lung in mouse, results were comparable. • They have even made a cigarette smoking machine,

• They have produced online tutorials along with other material such as posters and looked into barriers to adoption.

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• Mice which were handled using non-aversive methods showed an increase in voluntary interaction with handlers and, when tested using an elevated T maze, showed reduced anxiety compared to mice handled using traditional methods. • Following tunnel handling with an injection did not affect the animals interaction or response to behavioural tests, whereas following tail handling with an injection does; this suggests that tail handling is actually a greater stress to the mouse than a procedure Summary: Tunnel handling produces the most reliable behaviour. Removing the animal from the cage by the tail is the stressor, subsequent restraint/ manipulation by the tail, including procedures, does not produce negative effects. Using hepatic organoids to model human liver tissue in healthy and disease Dr Meritxell Huch, University of Cambridge • Dr Meritxell Huch from the Gurdon institute here in Cambridge won the 2013 3Rs Prize for her work in hepatic organoids. • The liver is a special organ due to its ability to regrow after injury - a similar ability to limb regrowth in the axolotl. • The research group identified the specific stem cells that are activated after injury to provide regrowth. • By developing a culture which provides the right nutrients and conditions they were able to isolate these stem cells from an adult mouse liver and grow them in vitro, creating multiple “organoids” which are essentially fully functioning mini-livers which are able to survive for over a year in the lab environment. • They are able to mimic liver diseases so many drugs and treatments can be trialled. • This breakthrough in hepatocyte research will allow huge reductions in the numbers of animals used; previously a typical study to test one drug would need up to 50 mice whereas using organoids 1000 drugs can be tested using cells from one single mouse. • Organoids can be implanted back into mice where they have been shown to continue to grow and develop. In mice with liver disease this reduced the effects of the condition and allowed them to live longer.

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• Since winning the award Dr Huch has expanded this research using other animals, including the use of human cells which has the benefit of being more relevant to human diseases. This has enabled Dr Huch to model several human liver diseases in vitro including liver cancer, hence providing first proofof-concept for personalised medicine (in which the patient’s own cells can be tested for the best compound in a patient-specific manner to find the best treatment for them individually). Summary: Taking stem cells from an adult mouse liver and growing them under the correct conditions in vitro can produce multiple mini-livers which can mimic diseases and greatly reduce the number of animals needed in drug development. Refining dog care: Improving welfare in the laboratoryhoused dog Dr Laura Hall, University of Stirling (2015 prize winner) • Dr Hall’s aim was to improve training techniques in laboratory dogs to reduce negative welfare impacts of common procedures such as oral gavage. • Previously oral gavage had little standardisation with regard to best practise. • Dr Hall discovered that the use of habituation training (“sham dosing”) was often producing a “freezing” fear response which could be mistaken for the calm compliance they were aiming for. • She and her colleagues set out to produce a refined protocol in which desensitisation and positive reinforcement methods were used instead. • There were three groups: o Group 1: control group receiving no training and no sham dosing o Group 2: receiving no training and two sessions of sham dosing o Group 3: receiving four training sessions using treats as positive reinforcement followed by two sham dosing sessions under the refined protocol. • This refined protocol included modifications to handling techniques, and a predictive signal (turning over a card in front of their pen) to the dog to inform them that the procedure was about to happen. • During the dosing the tube used was coated in a palatable substance rather than the standard method of warm water, and the dogs were given rewards afterwards.


• The welfare of the dogs under the refined protocol was most positively impacted; they spent the most time interacting with their environment and handlers/ technicians and spent less time exhibiting freezing behaviour. It also increased the quality of the data collected at the end of the study. • It was concluded that desensitisation was more effective than habituation, and positive reinforcement training was more effective than either. • In the future, they would like to refine other procedures, measuring other parameters such as cardiovascular output which is collected by getting the dogs to wear telemetry jackets. • The design of the telemetry jackets will need to be modified to prevent single housing while wearing them as currently the novelty of them causes too much excitement in their companions! Summary: Desensitisation to a stimulus was more effective in reducing anxiety than simply habituating the dogs to it. Small refinements to traditional methods can have large impacts on animal welfare. A dedicated website to report these and future findings has been set up at www.refiningdogcare.com with the aim of engaging the industry to develop and implement best practise for laboratory dogs to improve their welfare.

• Rats were housed in semi-naturalistic caging, monitoring the type and frequency of natural behaviours that were displayed with the aim of proving how important these behaviours are to them. • Rats at 3, 8, and 13 months old were used because as with many animals their amount of active time each day decreases with age. • It is therefore thought that the more important an activity is, the more motivated they will be to continue to perform it as they age. • Rats in this environment were recorded burrowing around 30 times per day no matter what age which suggested that this is a very important activity to them. • Creating their own tunnels and being able to modify their housing was seen to be very exciting for the rats as it gave them some form of their own agency and ability to use different areas for different purposes: sleeping, defecating etc. • Climbing was shown to reduce with age • Upright standing decreased with age but was still performed frequently to explore and stretch.

The expression of natural behaviour in laboratory rats Dr Joanna Makowska, University of British Columbia (2016 winner) Our final talk of the evening was from Dr Joanna Makowska who presented her work on the expression of natural behaviour in laboratory rats. She was inspired by a video of laboratory rats being released into an outdoor environment where they almost immediately began displaying natural behaviours such as climbing, burrowing and standing upright, which they were often unable to express in standard laboratory housing. These behaviours are very important for wild rats as they use them to escape predation and when for foraging for food. As people are generally accustomed to the current situation with rat housing she hoped to find out what natural behaviours are being inhibited, how important these behaviours are and therefore what effect standard laboratory housing is having on rat welfare. The study was designed with two aims: to record the frequency of burrowing, climbing and standing upright in rats of different ages housed in seminaturalistic environments and to compare lateral stretching behaviours between rats housed in standard laboratory caging to those in the semi-naturalistic environments.

Figure 1: Semi-naturalistic caging used in Dr Makowska's experiment; large wire bar cage with many different levels, enrichment items, opportunities for climbing and a large depth of soil in the bottom level.

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• When stood upright it was noted that they were often standing taller than the 18-20cm allowed by a standard cage. • Lateral stretching was found to be 8 times more frequent in standard housing than the seminaturalistic housing in rats of the same age, suggesting restricted movement in standard housing was causing stiffness which is why Dr Makowska has since proposed solutions to alleviate lateral stretching. • A practical way to implement this idea in a laboratory setting is allowing rats into an enriched “playpen” for an hour a day, which has been shown to have positive effects; rats will display increased anticipatory behaviour, have a greater engagement with their environment, show less aggression towards each other and it was easier to pick up on smaller health issues which may have been overlooked when in the home cage. • Importantly, preliminary results showed that when placed back into the home cage the amount of lateral stretching performed was greatly reduced for up to 2 hours. Speaking to her in the evening networking event we discussed the issues of implementing this with IVC housed animals. Evidently, semi-naturalistic caging would be impossible to implement in a working IVC unit, and while the idea of a playpen is great it would need to be selfcontained and sterilised between animals or risk breaking bio containment barriers. She suggested that, knowing the importance of expressing natural behaviours to rats, any novelty we can add to their environment would have a positive effect. For example at Mira we are going to look at rotating the disposable enrichment items available to the animals on a weekly basis during cage cleaning in addition to their minimum cage furniture (substrate, nesting material, shelf, chew block) such as wood wool, play ball, tunnel, edible enrichment, tissue above their grid, cable ties and by measuring the time spent interacting with each item quantify why this is an important consideration. Also, given that the rats in semi-naturalistic caging used their space and ability to burrow to control their environment (simplified, this could be just the ability to defecate in a different area to where they choose to nest) this reiterates the importance of cage design, such as the shelves and lofts available in new IVC housing.

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This Year’s Winner: Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical ProArrhythmic Cardiotoxicity Dr Elisa Passini, Oxford University (2017 Winner) At the end of the evening, Dr Elisa Passini and her colleagues at Oxford University were presented with the 2017 International 3Rs prize for their work on an in silico model of human cardiac cells. In their winning paper they tested 62 different drugs with the aim of predicting the risk of drug-induced cardiac arrhythmia in the human heart. The computer simulations they ran were able to predict this risk with 89% accuracy whereas previously conducted comparable animal models were only able to reach up to 75% accuracy. Thousands of animals of a wide range of species are used every year in the early stages of drug development with the aim of predicting side effects and preventing potential cardiovascular safety issues in humans, however due to interspecies differences these drugs often fail at human trials. Over the course of the evening it was very exciting to learn that in the near future the use of biological inspired engineering, organoids and in silico testing could vastly reduce the number of animals used in experimentation. Two further entries were also granted Highly Commended awards for their input; Dr Christian Teide for the development of an ‘alternative binding protein’ which can be used to replace animal-generated antibodies in many common practises, and Dr Michael Walker for his work on improving the statistical power of animal models via the use of novel experimental designs and inter-strain housing of mice. More information about these and all previous winners can be found on the NC3Rs website, www.nc3rs.org.uk


Applying for a level 2 or 3 IAT course Once you know which level you will be applying for, there are 3 application forms to complete: 1. Your PPD funding application 2. Your UBS candidate information form 3. Your IAT registration form

PPD funding Funding should be applied for using a PD5 form (see below), and sent directly to the PPD department.

Previous qualifications that would allow exemption from these units include GCSEs at grade C or above in single sciences, double science, science + additional science, maths, English and IT / ICT. Key skills at level 2 in numeracy, communication and / or ICT / IT can also give you exemption from the numeracy, communication & ICT units. Other level 2 qualifications, such as First Certificates / Diplomas in animal based subjects (such as Animal Care or Animal Management) MAY get you exemption, but it depends on the subjects studied and passed. At level 3, the background subjects are: • Animal Physiology • Cell Biology Previous qualifications that would allow exemption from these units include A level biology and National Certificates / Diplomas in Animal Management (again, depending on the units studied as above).

Currently, the person to contact in PPD is Sue Pandey (765654 or at sue.pandey@admin.cam.ac.uk). The funding form (and process) does not need to involve UBS as, when funding is granted, we are informed by PPD. One thing that can affect how much funding you apply for is whether or not you will be claiming exemptions from any of the units that make up your course. It is highly unusual for anyone to gain exemption from the ‘animal technology’ subjects, but not uncommon to gain exemption from the ‘background’ subjects.

Higher level qualifications can be used to exempt you from background subjects also, but it is easier to compare the same level qualifications. Exemptions are granted where it is possible to show that similar learning outcomes to those in the IAT qualifications have been met elsewhere. To be granted exemption, I need to complete a claim form (see below).

At level 2, the background subjects are: • Laboratory Animal Biology • Animal Facility Physical Science • Numeracy for Animal Technologists • Communication for Animal Technologists • ICT for Animal Technologists

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Regardless of the qualification, exemption can only be applied for when I see the original certificates.

This will take you to the following page:

The other stages of the process involve completing the UBS candidate form and the IAT online registration. The UBS form (see below) just provides myself and the office with information that is not provided by the IAT registration form:

As you scroll down the page, you will see the link indicated above – ‘Enrol for an IAT course’. If you click on this, the online enrolment form will appear.

This form should be completed by you and your line manager and returned to UBS via ubsenquiries@admin. cam.ac.uk . This information allows us to enter you onto our database and to set you up on Moodle (our Virtual Learning Environment). The IAT registration form can be found on their website (www.iat.org.uk). You do not need to be a member of the IAT to access this. When you first enter the website, this is what you will see. You need to click on the ‘education’ tab (see below).

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Complete your personal details, including your Unique Learning Number (ULN) if known. If you are applying for level 2, you will probably not have a ULN yet. If you are applying for level 3, you will find your ULN on your level 2 certificate.


Moving on to the next page, you will be asked for various information regarding your employer, but importantly a purchase order number should be obtained prior to completing the IAT registration form from your line manager / NACWO.

When you move on to the next page – registration details – you are required to confirm which course you are applying for and which centre you want to study through. You are also asked for your candidate name as this is what will appear on your certificate. Make sure you get it right!

The IAT administrator will send me a notification of your enrolment, and then you are all set to go!

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3Rs Science Prize 2018 Call for submissions The European Partnership for Alternative Approaches to Animal Testing (EPAA) is proud to announce that a call for submissions is now open for its 2018 3Rs Science Prize.

Application deadline: 3 September 2018 at 12:00 (noon) Brussels time The EPAA aims to promote the development, validation and acceptance of 3Rs alternative approaches (replacement, reduction and refinement of testing on animals). The 3Rs science prize is granted every other year to a scientist with an outstanding contribution to 3Rs. This way, positive contributions from industry or academia are promoted and more scientists are encouraged to focus their research on the 3Rs goals. Scientists working on methods for regulatory testing (e.g. safety, efficacy, batch testing) and applying the 3Rs to those methods may apply for the prize. An EPAA jury (made up from 2 industry, 2 European Commission and 2 EPAA mirror group representatives) evaluates the submissions and provides the EPAA steering committee with the results of the evaluation and a recommendation on the ranking of the submissions. Based on this recommendation, the steering committee should then endorse the winner, and grant a €10,000 prize. The prize will be granted to the institution of the winner to be announced at the EPAA annual conference, on 20 November 2018. The awardee will have the opportunity to present his/her work in front of the annual conference participants, gathering regulators, industry stakeholders, academia and civil society. Applicants should, therefore, confirm that they are available on 20 November 2018 (to present their work at the annual conference if they win).

Who should apply?

  

Scientists working on alternative methods for regulatory testing purposes. Applicants should be based in Europe and have no more than 10 years of postgraduate experience (i.e. after obtaining their Bachelor’s or Master’s degree). Applicants should submit a written case study based on actual research (not a project on future research and no older than 5 years) where their role and involvement are shown. The application should make clear: how the above criteria are met (e.g. how the method or approach relates to regulatory testing) for which regulatory requirements the applicant's approach can be used what the applicant's postgraduate experience, role and involvement in the research are. The EPAA Secretariat will screen applications for eligibility criteria and inform the jury of their findings. The jury may exclude applications that do not comply with at least one of the eligibility criteria and deem them 'not eligible'.

Selection criteria

The jury, applying 6 selection criteria as shown below, will assess the eligible applications. Each member of the jury will evaluate the submissions and assess each criterion individually with a rating from 1 (very poor) to 5 (very good). The most important criteria will be double-weighted and therefore, ratings for those are very important. Every single jury member may rate applications 0-40, thus the total ranking of an application will be 0-240 points. 1. Impact on the 3Rs (reduction of animal numbers etc.) *Weighted 2* 2. Innovativeness/Contribution to meeting an urgent unmet scientific need 3. Possible applicability of the method/approach for regulatory testing (including for safety or potency) *Weighted 2* 4. Impact on predictive safety science (better data/science is obtained thanks to the work of the applicant compared to the current animal method) 5. Work potentially applicable widely e.g. to other methods and endpoints and across sectors 6. International remit (already published work, number of publications, rankings in peer-reviewed journals etc.) Should no application get at least 160 points, the EPAA steering committee may decide not to grant the prize.

Application process

To submit an application, send an email to grow‐epaa@ec.europa.eu by Monday 3 September at 12:00 (noon), Brussels time with the following documents: 1. CV with a list of publications. 2. Cover letter where the applicant explains why his/her work is relevant and how it contributes to the 3Rs. 3. A max. 2500 words case study where the applicant introduces his/her work or project selected for the application and its achievements/results. Pictures, illustrations and videos may also be attached to the case study if relevant. The case study should clearly define the regulatory endpoint targeted, the method implemented and the results obtained. 4. Letter of support/endorsement from their current organisation/employer. Enquiries should be directed to grow‐epaa@ec.europa.eu

Timeline -

3 April: Launch of the call for submissions 3 September at noon: Deadline for submissions by 9 November: Winner is notified and invited to attend the EPAA conference in Brussels (sponsored by EPAA) 20 November: EPAA annual conference in Brussels.

More information Find out more about previous 3Rs Science prize winners

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LASA 3Rs Section Annual Conference 2018 Call For Speakers The LASA 3Rs section conveners are inviting submissions for spoken presentations on any aspect of the 3Rs (Replacement, Reduction and Refinement) to be given at the 2018 LASA annual conference, which will be held in Birmingham on the 27th November to 29th November 2018. We are particularly interested in hearing from recently qualified research scientists of new advances that are supported by scientific data but will consider other submissions. If you wish to contribute, please submit a title and abstract to Patricia Pimlott for consideration no later than 30th June 2018 at patricia.pimlott@fera.co.uk Abstracts should be written in English and not exceed 400 words, excluding the title and the authors’ names and addresses. Please use Microsoft Word for Windows when submitting an abstract. Text should be in Times New Roman 12 pt font. The title should be centered and in bold capital letters (as below). TITLE OF PAPER AB Authorone1 and CD Authortwo2 Department of Research and Development, Institution, UK Department of Applied Animal Welfare, University of Brewhouse Hill, UK ab.authorone@institution.ac.uk 1

2

A blank line should precede the text. The text should clearly and concisely outline the main findings or premise without reference(s) to other text or paper or to future findings. It can include graphs or tables but must fit on one side of A4. Speakers selected to give a presentation will be given free registration. Travelling expenses (standard air/rail fare or reasonable alternative) and one overnight stay at the venue will be provided, if required by LASA.

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UBS Bronze Winners! Green Impact Awards A Bronze Green Impact award is typically the first step for many participants. With 12 teams taking part in Green Impact for the first time in 2016-17, there were a number of teams taking this first step to embed good environmental practices, and to communicate to colleagues and students on a range of sustainability issues. The winners of a Bronze award were: • • • • • • • • • •

17 Mill Lane Department of Zoology Faculty of Law Faculty of Asian and Middle Eastern Studies Fitzwilliam College Isaac Newton Institute Meet Cambridge The Old Schools University Biomedical Services Cambridge University Botanic Garden

1. Ensure any computers are shut down when not in use, particularly at the end of the day. Check that printers, copiers and PC monitors are all off too 2. Check the temperature control on any fridges to check that they are set between 3-5°C 3. Wash laundry at 30°C or below to avoid unnecessary energy use 4. Switch mobile/laptop chargers off when not in usethey still use power even when your device isn’t connected 5. Place energy awareness stickers next to plugs and switches to remind people or to tell them what can be switched off when no longer needed 6. Use the highest efficiency lighting possible and where possible, make use of natural lighting

The Green Team submitted their workbook for the year, to have all of their efforts audited. Our final push is on energy saving and we thought we might share some of our favourite energy saving ideas for the home and workplace. As we’ve seen in the news, energy bills continue to rise, so it’s not just energy but money that we can save by following a few simple tips! We also need your help! Do you have any ideas of energy saving ideas that could be implemented within the Department? However big or small, submit your ideas to ubs-greenteam@lists.cam.ac.uk

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7. Switch lights off when not needed 8. Consider energy efficiency ratings when purchasing new items 9. Dress for the weather rather than turning up the heating or air conditioning 10. Carry out an audit of your home and workspace- are you using any energy needlessly? Could anything be improved or made more efficient? We look forward to hearing your ideas! Lisa Wright, Sarah Stone and Andrea Franklin


Mouse handling webinar https://www.nc3rs.org.uk/mouse-handling-webinar In this webinar, which originally took place on 27 April 2018 at 11am (BST), Professor Jane Hurst of the University of Liverpool shares the evidence base supporting refined mouse handling techniques as well as practical advice and tips for implementing them in your institution.

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3Rs Relevant Publications Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data Viola André et al Abstract Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse husbandry without creating a divide between past and future experimental results. Previous small-scale studies have been inconsistent throughout the literature, and it is not yet completely understood whether and how enrichment might endanger comparability of results of scientific experiments. Here, we measured the effect on means and variability of 164 physiological parameters in 3 conditions: with nesting material with or without a shelter, comparing these 2 conditions to a “barren” regime without any enrichments. We studied a total of 360 mice from each of 2 mouse strains (C57BL/6NTac and DBA/2NCrl) and both sexes for each of the 3 conditions. Our study indicates that enrichment affects the mean values of some of the 164 parameters with no consistent effects on variability. However, the influence of enrichment appears negligible compared to the effects of other influencing factors. Therefore, nesting material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions. What exactly is ‘N’ in cell culture and animal experiments? Stanley E. Lazic , Marcus R. Munafò Abstract Biologists determine experimental effects by perturbing biological entities or units. When done appropriately, independent replication of the entity– intervention pair contributes to the sample size (N) and forms the basis of statistical inference. If the wrong entity–intervention pair is chosen, an experiment cannot address the question of interest. We surveyed a random sample of published animal experiments from 2011 to 2016 where interventions were applied 16 | CamTechCare Newsletter | July 2018

to parents and effects examined in the offspring, as regulatory authorities provide clear guidelines on replication with such designs. We found that only 22% of studies (95% CI = 17%–29%) replicated the correct entity–intervention pair and thus made valid statistical inferences. Nearly half of the studies (46%, 95% CI = 38%–53%) had pseudoreplication while 32% (95% CI = 26%–39%) provided insufficient information to make a judgement. Pseudoreplication artificially inflates the sample size, and thus the evidence for a scientific claim, resulting in false positives. We argue that distinguishing between biological units, experimental units, and observational units clarifies where replication should occur, describe the criteria for genuine replication, and provide concrete examples of in vitro, ex vivo, and in vivo experimental designs. Squeaky clean mice could be ruining research Nature NEWS FEATURE • 04 April 2018 http://www.nature.com/articles/d41586-018-03916-9 Cassandra Willyard Abstract Most lab mice are kept in pristine conditions, but a few immunologists think a dose of dirt On an unseasonably warm February morning, Mark Pierson takes a 20-minute drive to one of Minneapolis’s larger pet shops. Pierson, a researcher in an immunology laboratory at the University of Minnesota, often comes here to buy mice, so most of the staff know him. Today he asks for ten, and an employee fishes them out of a glass box. Pierson requests the smaller mice because they’re typically younger, but he isn’t too picky. They probably all have what he wants: germs. These mice are about to enter one of the most tightly controlled labs in the country, a facility normally reserved for studying dangerous pathogens such as tuberculosis and chikungunya virus. The rodents probably don’t carry serious human infections, but they do harbour diseases that pose a grave threat to the hundreds of other research mice in the building.


Tickling, a Technique for Inducing Positive Affect When Handling Rats. Cloutier S1, LaFollette MR2, Gaskill BN2, Panksepp J3, Newberry RC4. Abstract Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk for both the animals and the hands of their handlers, decreased animal welfare, and less valid research data. To minimize negative effects on experimental results and human-animal relationships, research animals are often habituated to being handled. However, the methods of habituation are highly variable and often of limited effectiveness. More potently, it is possible for humans to mimic aspects of the animals' playful roughand-tumble behavior during handling. When applied to laboratory rats in a systematic manner, this playful handling, referred to as tickling, consistently gives rise to positive behavioral responses. This article provides a detailed description of a standardized rat tickling technique. This method can contribute to future investigations into positive affective states in animals, make it easier to handle rats for common husbandry activities such as cage changing or medical/research procedures such as injection, and be implemented as a source of social enrichment. It is concluded that this method can be used to efficiently and practicably reduce rats' fearfulness of humans and improve their welfare, as well as reliably model positive affective states. Behavioral Training as Part of the Health Care Program. Drug Discov Today. 2018 May 4. pii: S13596446(18)30038-2. doi: 10.1016/j.drudis.2018.05.002. [Epub ahead of print] Authors: Schapiro SJ, Magden ER, Reamer LA, Mareno MC, Lambeth SP. Management of Animal Care and Use Programs in Research, Education, and Testing. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2018. Chapter 32.

applies to health care programs for laboratory animals. Training laboratory animals to voluntarily participate in necessary veterinary, husbandry, and research procedures is an important refinement (refinement is one of the 3Rs [Russell and Burch 1959]) that can substantially improve the well-being, welfare, and wellness of captive animals, enhancing the quality and utility of the animals as research models, and therefore the reliability and validity of many types of research (Graham et al. 2012). Applying the 3Rs to neuroscience research involving nonhuman primates. Lemon RN1. Abstract This Feature focuses on UK neuroscience research using nonhuman primates (NHPs), and the application of the 3Rs, in the light of the recent EU SCHEER report and subsequent article by Prescott et al. (2017). The challenge of understanding the human brain and its disorders means that NHP research is still very much needed, although it is essential that this research is complemented by studies using other approaches, such as human volunteers and patients, and other alternatives to NHP use. Analysis of recent publications shows that these complementary approaches are already being actively exploited by NHP researchers in the UK. Application of the 3Rs has been led by the UK National Centre for the 3Rs (NC3Rs), with active participation of UK NHP researchers, who are constantly refining research methodology. However, not all refinements work, and those that do succeed need to be fully validated before they can be introduced more widely into current practice. More generally, the 3Rs have helped to ameliorate harm experienced by NHPs in procedures, although there is still more to do. Accumulating evidence from recent UK Home Office statistics suggests that most monkeys used in scientific procedures experience a moderate rather than a severe level of harm.

Abstract This chapter focuses on behavioral training, specifically positive reinforcement training (PRT) techniques, as it CamTechCare Newsletter | July 2018 | 17


New platform to maximise the 3Rs impact of NC3Rs-funded research

The NC3Rs Gateway is a new publication portal on the F1000Research publication platform dedicated to the 3Rs, featuring methodology articles, reviews and source data that describe in detail how the use of animals in research can be replaced, reduced or refined. All articles will be published almost immediately and then undergo invited open peer review

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Events Diary September 19 The LASA/UFAW 3Rs Section Meeting - Applying the 3Rs to the breeding of animals for research purposes, Stevenage UK. To find out more about this meeting, email info@lasa.co.uk. September 21 RSPCA Lay Members’ Forum in Scotland. You can register to attend this event here. September 23-26 European Congress on Alternatives to Animal testing / 18th Annual EUSAAT Congress, Linz http://www.eusaat-congress.eu/ October 30 RSPCA/UFAW Rodent and Rabbit Welfare meeting, Central London

October 30 RSPCA/UFAW Rodent and Rabbit Welfare Group’s 25th Annual Meeting You can register to attend this event here. November 15 NC3Rs Primate Welfare meeting. London https://www.nc3rs.org.uk/events/2018-primate-welfare-meeting November 27-29 LASA Annual Conference 2018 Birmingham, To find out more about this meeting, visit the LASA website or email info@lasa.co.uk.

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

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University of Cambridge News Feeds

The body in miniature 20 Mar 2018 The past few years has seen an explosion in the number of studies using organoids – so-called ‘mini organs’. While they can help scientists understand human biology and disease, some in the field have questioned their usefulness. But as the field matures, we could see their increasing use in personalised and regenerative medicine. Read More

Study in mice suggests personalised stem cell treatment may offer relief for progressive MS 22 Feb 2018 Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis (MS). Read More

RSPCA/UFAW Rodent and Rabbit Welfare Meeting The 25th edition of our popular rodent and rabbit welfare meetings will be held in central London on 30 October 2018. Presentations will cover refinements in housing; nest building behaviour in rats; welfare implications of identification methods in mice; classifying the severity of repeated anaesthesia; and the contribution of modern imaging techniques to the 3Rs. There will also be an update on relevant issues from the Home Office Animals in Science Regulation Unit. You can register to attend this event here.

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Scientists discover the secrets behind the cuttlefish’s 3D ‘invisibility cloak’ 15 Feb 2018 An international team of scientists has identified the neural circuits that enable cuttlefish to change their appearance in just the blink to eye – and discovered that this is similar to the neural circuit that controls iridescence in squids.

Read More


UBS BBQ 12.30 to 17.00 Friday 3rd August 2018. Erasmus Lawn, Queen’s College, Silver Street, CB3 9ET. RSVP (with any dietary requirements) to your NACWO or andrea.franklin@admin.cam.ac.uk by Friday 6th July 2018.

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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

http://www.lasa.co.uk/bursaries/ LASA bursaries can be applied for at any time of the year and for any event considered relevant to LASA’s mission statement. Animal technicians, post-graduate students and others for whom funds may be limited are especially encouraged to apply. Download bursary rules and form.

Universities Federation for Animal Welfare

https://www.ufaw.org.uk/grants-and-awards/ufaw-grants-and-awards 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.

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Two Cambridge highlights from Pint of Science 2018 The NC3Rs sponsored three events as part of the worldwide Pint of Science festival, which brings researchers into local pubs every May to talk about their work. This year NC3Rs grant holders had the chance to speak about their research and the 3Rs in pubs in Leeds, Cambridge and Cardiff. Here are highlights from our two Cambridge Scientists Chris and Maja. The excerpts below are reproduced from NC3Rs June news.

1. Touchscreens aren’t just for humans Dr Chris Heath began his presentation in Cambridge on 15 May by comparing doctors asking patients about their wellbeing with researchers trying to establish the emotional state of laboratory animals. To bridge the ‘translational gap’ between the lab and the clinic, he uses a touchscreen testing system analogous to those designed for human patients to assess the motivation, behaviour and cognition of laboratory mice. Through this system, using strawberry milkshake as a reward for performing cognitive tasks, Chris can identify changes that could be linked to the development of depression or schizophrenia. Also in attendance at Chris’s talk was artist Susan Abbs, who encapsulated the talk in a work of art to be exhibited at the Creative Reactions art-science exhibition in Cambridge.

2. You can find out a lot about mice by looking at their ears The idea behind Dr Maja Wållberg’s project might sound like an old proverb, but it has very practical implications. Maja uses mice to study type 1 diabetes, but rather than using invasive procedures, she looks at pancreatic islets transplanted in the pinna of the mouse ear. This is possible thanks to multi-photon microscopy, which allows the imaging of living tissue up to about one millimetre in depth. Using this non-invasive technique, Maja can observe immunological events in the islets of the same mouse over a long course of time, reducing the number of mice needed for her research. During her talk in Cambridge, the audience were treated to some remarkable live imaging videos.

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Dear Colleagues, Welcome to our Summer Newsletter. This quarterly newsletter contains information about our research, resources, training and more. It is available to any researchers interested in using our facilities and hearing about our latest news and events, for example our expanding archive of publicly available mouse lines. Please share with your collaborators, they can sign-up by clicking here. You can opt out at any time. This month, we are excited to announce that nominations are open again for Genome Editing Mice for Medicine. This time applications are for point mutations and deletions. This service has been very successful with delivering a number of new and innovative lines to researchers throughout the UK. Best wishes, Sara Wells, Director of the Mary Lyon Centre

Genome Editing Mice for Medicine Could genome editing advance your research? Do you need a genetically altered mouse line with a point or deletion mutation? Applications are now open for Genome Editing Mice for Medicine (GEMM) – a bespoke service delivered by MRC Harwell to advance biomedical science.

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Novel mouse lines will be made for successful applicants. These are at no cost to the nominating scientist (apart from delivery costs). Get in touch with us at gemm@har.mrc.ac.uk Start your application now

Freeze your mouse strains for FREE Want to archive a mouse strain? MRC Harwell offers a free archiving service to researchers who want to make their strains available to the wider scientific community. We will also take care of distribution to anywhere in the world. All you need to do is submit the strain details to the European Mutant Mouse Archive (EMMA: www.infrafrontier.eu), provide five mature males and we will do the rest. Click here for more info and to register

Community call for IMPC gene nominations Researching a novel gene? Need a knockout to investigate further? We have a new call open to nominate genes to enter the IMPC programme. We will generate a null allele, fully available to the academic community, which will be comprehensively phenotyped by our Harwell team. Get in touch with us by emailing impc@har.mrc.ac.uk.

Latest research in type 2 diabetes An exciting international collaborative project between MRC Harwell, Kings College London and others has identified a gene that in females is linked to the creation and location of new fat cells and therefore is thought to contribute to the risk of type 2 diabetes. The study integrated human, mouse, and cellular data to show how regulatory variants near KLF14 influence

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diabetes risk in a sex, parent of origin and fat distribution specific way. Find out more

CRACK IT Challenge 24: EASE (Ending Surgical Embryo Transfer) We have been working hard over the last year to refine our Non-Surgical Embryo Transfer (NSET) procedure to improve the welfare of the embryo transfer recipients we use. Click below to find out more about the challenges and what we're doing to overcome these. Click here to find out more

Training and events Mouse Embryo and Spermatozoa Cryopreservation Training Course MRC Harwell Institute, Oxford, 3–6 September 2018 This course is running again in September to give animal technologists practical, hands-on experience of the murine embryo and spermatozoa freezing techniques routinely used at MRC Harwell, as well as a simple, robust in vitro fertilization procedure. Click here for more info and to register

Autumn Training Courses MRC Harwell Institute, Oxfordshire, 8–19 October 2018 This Autumn we are running training courses across a wide range of disciplines: Genetics training week: 8–12 October

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Courses include Introduction to inheritance, Conditional transgenics and Genome editing in the mouse (CRISPR/Cas9). Technical training week: 15–19 October Courses include Necropsy, tissue cut-in and processing and Introduction proteomics.

to

histology,

microscopy

and

Click here to find out more

A Practical Training Course in Transgenic Technology MRC Harwell Institute, Oxford, 16–18 October 2018 This course is aimed at newcomers to the transgenic field or those looking to brush up their skills. Participants will have practical hands on experience in a technique that will enable them to generate their own mutant mouse models using CRISPR-Cas9 reagents. Click here for more info and to register

Modelling the Mammalian-Microbiota Host Superorganism Institut Pasteur, Paris, 15–16 October 2018 Infrafrontier and Institut Pasteur are jointly organising a conference to bring together specialists in the field to discuss novel insights into microbiota-host mutualist and parasitism. Click here for more info and to register

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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

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