ATW April 2002 : simplebooklet.com

OFFICERS President Professor R L Gardner PhD FRS Vice Presidents G C Bantin FIAT RAnTech S W Barnett BA MSc CBiol MIBiol RAnTech J Bleby TD JP DVet Med DLAS CBiol FIBiol MRCVS J B Bridges MD MB BSc G Clough BSc PhD EurBiol CBiol MiBiol SFZSL J E Cooper BVSc Cert LAS DTVM FRCPath FIBiol FRCVS P A Flecknell MA Vet MB PhD DLAS Dip LECVA MRCVS P H M Griffiths BSc DLAS CBiol MIBiol MRCVS AnimalTechnology andWelfare Vol 1 No 1 April 2002 B M Holgate BVET MED DLAS MRCVS J MacArthur Clark BVMS DLAS CBiol FIBiol MRCVS K G Millican FIAT CBiol MIBiol D B Morton BVSc PhD MRCVS CBiol FIBiol A G Peters FIAT R I Porter BSc MSc MIBiol M W Smith MA BVSc MVSc DTVM MRCVS CBiol FIBiol J D Stewart BVMS MSc CBiol MIBiol MRCVS D Whittaker BVMS DLAS MRCVS D P Woodnott FIAT CONTENTS Foreword Editorial Life Members F Hoyland FIAT K G Millican FIAT CBiol MIBiol IE Wills FIAT Hon RAnTech D P Woodnott FIAT Honorary Members Len Bagnall MIAT RAnTech Mary Bathgate FIAT Kevin P Dolan FIAT Brian J Edmonds FIAT Roger Hussey MIAT Len Moran MIAT Jim Philips MIAT Rick W SkiIton MIAT RAnTech IAT Council Chairman R W Kemp FIAT Hon RAnTech Vice Chairman K A Applebee FIAT CBiol MIBiol RAnTech Immediate Past Chairman FIAT CBiol MIBiol RAnTech Gregory J A Honorary Secretary K A Applebee FIAT CBiol MIBiol RAnTech Honorary Treasurer C Chambers MIAT RAnTech Journal Editorial Board Chairman P H Hayes FIAT DipBA RAnTech Assessing Rodent Wellbeing Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting Penny Hawkins Secretary Johnny Roughan Alex Wilson Jill Sales Kenneth Clarke Peter Warn Peter Thornton Maggy Jennings Robert Hubrecht A Pig of a Problem Post operative care of piglets following oesophageal interposition surgery 13 L A Lawes and H Moore Assessing the Welfare of Genetically Modified Mice 19 Roger J Francis PAPER SUMMARY TRANSLATIONS 23 NEW TECHNOLOGIES 39 REPORT ON THE NACWO MEETING 41 POSTER PRESENTATION 49 Pregnancy confirmation by ultrasound scanning of the beagle Pfizer Global Research and Development Laboratories Instructions to Authors 51

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IAT INFORMATION Chairman R W Kemp FIAT Hon RAnTech Vice Chairman K A Applebee FIAT CBiol MIBiol RAnTech Immediate Past Chairman J A Gregory FIAT CBiol MIBiol RAnTech Honorary Secretary K A Applebee FIAT CBiol MIBiol RAnTech Honorary Treasurer C Chambers MIAT RAnTech Membership Secretary C Godfrey FIAT RAnTech Secretary to Examination Board S Reed FIAT RAnTech Journal Editorial Board Chairman P H Hayes FIAT DipBA RAnTech Bulletin Editor P Ruddock MIAT RAnTech Journal and Bulletin Advertising Manager E Kirkum MIAT RAnTech MIScT BRANCH SECRETARIES 2002 Aberdeen Mr Duncan Wood Department of Zoology University of Aberdeen Tillydrone Avenue Aberdeen AB24 2TZ Kent Beckenham Mr Lee Whybrow LAS 155 Pfizer Central Research Ramsgate Road Sandwich Kent CT13 9NJ Cambridge Ms Debbie Flack The Animal Health Trust Lanwades Park Kentford Newmarket CB8 7UU Cheshire Mr David B Towns Zeneca Pharmaceuticals Alderley Park Cheshire SK10 4TG Mereside Edinburgh Ms Janice Young NPU IAH Ogston Building King s Building West Mains Road Edinburgh Hertfordshire Ms Kate Burton LAS Dept GlaxoSmithKline Welwyn Herts AL6 7AR Huntingdon Mrs Diane Cooper PO Box 2 Huntingdon The Frythe Cambs PE18 6ES Irish Ms Caroline Wilson Elan Company Biochemistry Trinity College Dublin 2 Eire Welfare Officers J Barley FIAT RAnTech R J Francis FIAT RAnTech Promotions Officer s N Mortell MIAT RAnTech Council Website Coordinator Allan Thornhill FIAT RAnTech IAT OFFICERS MAY BE CONTACTED VIA THE REGISTERED OFFICE AT 5 South Parade Summertown Oxford 0X2 7JL OR VIA THE IAT WEBSITE AT www iat org uk Members of Council K Applebee J Barley C Chambers A Cunningham L Diver R Francis P J Gerson C Godfrey A J Graham J Gregory P H Hayes J Hedley A B Jackson R W Kemp E Kirkum S Lane L A Westall N Mortell S R Owen P Ruddock A Thornhill Members of Executive Committee Congress Committee Steve Owen Chairman Alan Graham Patrick Hayes Andy Jackson Allan Thornhill Co opted Nikki Stevens Board of Education Pete Gerson Chairman Cathy Godfrey John Hedley Bob Kemp Co opted David Conway Graham Crossland Glyn Fisher Dave Gregory Trish Hayes John Kelly Adele Kitching Sue McHugh Sarah Reed Pete Russell Jeremy Smith Ted Tolson Journal Editorial Board Patrick Hayes Chairman Jas Barley Roger Francis John Hedley Elaine Kirkum Norman Mortell Registration Board John Gregory Chairman Ken Applebee Charlie Chambers David Conway Gerald Clough Lynn Dorsett Paul Hecknell Cathy Godfrey Sarah Lane Judy MacArthur Clark Ron Raymond Douglas Stewart observer Jon Richmond Building London Ms Jenny Cox Biological Services Gower Street London WC1E 6BT University College London Merseyside Ms Julie Humphreys AstraZeneca Park Macclesfield SK10 4TG 19B62A Mereside Alderley Midlands Ms Sally Edwards Safepharm Derby DE1 2BT Laboratories Ltd PO Box 45 Oxford Mr Len Bagnall School of B M S Oxford Brookes University Gipsy Lane Headington Oxford 0X3 OBP Sheffield Mrs Heather Jenkins Field Laboratories University of Sheffield F Floor Alfred Denny Building Western Bank Sheffield S10 2TN Suffolk Norfolk Mr Kevin Curtis Huntingdon Life Sciences Eye Suffolk IP23 7PX Surrey Hampshire Sussex Ms Liz Diver Tecniplast UK Ltd 2240 Parkway Kettering Venture Park Kettering Northants NN15 6XR West Middlesex Mr Ted Tolson Institute of Psychiatry De Crespigny Park Denmark Hill Camberwell SE5 West of Scotland Mr Stuart Saigeman Organon Laboratories Newhouse Lanarkshire ML1 5SH Ltd PSU York Ms Tina Dunsford Central Science Laboratories York Y04 1LZ Sand Hutton

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April 2002 Animal Technology and Welfare Foreword Richard Gardner President Every organisation needs to of take regular lookandat also all its activities andandaskaspirations whether continue to meet the needs its a membership reflect its aims broader context particularly with regard to influencing policy and practice they in a Few members of the Institute can have failed to notice that the Journal has for some time lacked the excitement and appeal necessary to justify its continued existence Among possible solutions to this problem euthanasia was contemplated quite seriously as an option However it seemed imprudent for an organisation with an overriding interest in best practice regarding the care and welfare of laboratory animals to abandon such an important means of promoting it Instead therefore much collective thought was given to the matter of how the Journal could be made more effective in meeting the needs and engaging the attention of members of the Institute and others who share their interests Patrick Hayes and his colleagues on the Editorial Board have met the challenge with industry and enthusiasm and produced something in which we can all take pride whether this initiative enjoys the continuing success it deserves depends critically willingness to participate by submitting papers technical tips comments letters reviews As the Institute s Journal its fate is in your hands so please make every effort that it reflects the dynamic innovative and deeply caring commitment to education and animal technology that is the hallmark of the IAT E FAT unstinting However on your or book to ensure welfare in

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Animal Technology and Welfare April 2002 Editorial Patrick Hayes Chairman of the Editorial Board Dear Colleagues Welcome to the new look Journal Over 50 years have passed since the publication of the first Journal in June 1950 by the then Animal Technicians Association during which time it has undergone a number of changes although mainly superficial in nature On this occasion IAT Council and the Editorial Board believed it was time for a complete face lift The format size and cover design has been brought into line with most other scientific publications colour has been introduced throughout and the title has been changed to include the term Welfare As Animal Technicians we accept that the welfare of the animals in our care is intrinsic however with the increasingly public debates over the use of animals for research it is essential that our profession is recognised publicly as one that has animal welfare as its overriding interest As for content the following extract from the Editorial written by R T Charles Editor of the first Journal is worthy of note The Editorial Board will endeavour to limit the material published in the Journal to as much technical and scientific matter as possible and future numbers of the Journal will in fact largely be composed of papers written by members of the Association in this matter we hope that we shall have generous support In addition to material which we receive from members numerous extracts from other scientific publications will be included in the Journal if the Editorial Board and members of Council consider the subject matter of interest to the Animal Technician There will also be a page in the publication devoted to Letters to the Editor and correspondence will be welcomed from readers whether a complaint a criticism or it is hoped an occasional word of encouragement I feel confident that if each member tries to contribute a small measure of assistance at some time during the life of this publication it will result in a Journal that we may well be proud of The sentiments and aims expressed by R T Charles remain as valid today as they did then Any journal is dependant on the support it receives from its readership The current Editorial Board continues to believe that the Journal should largely be composed of peer reviewed papers written by members of the Institute or colleagues closely allied to our profession There is much material that could be contributed particularly from papers presented at Congress and from projects written up as part of the MSc course but unfortunately most of these are not submitted However the Board also recognises that members today often do not have the time or sufficient material to produce a formal paper To this end we are introducing a New Technology section We are seeking contributions describing any developments in animal technology whether this is in the form of new products new or refined techniques new discoveries or any other industry related progress Where new products are concerned we would welcome comments from members of their experiences with these How many of us have developed an in house technique to solve a particular problem With the exponential growth in transgenic strains what are the problems experienced by those directly involved in their care and monitoring possible adverse effects Has anybody developed a generic scoring system for assessing adverse effects in these strains The subject matter could be endless Contributions to this section can be presented as technical notes and may be submitted in any form The Board believes there is a wealth of knowledge and novel ideas at grass roots level from which the industry as a whole could benefit The Journal will continue to include sections such as book reviews and if any are received will indeed devote a page to Letters to the Editor We are all well aware of the 3Rs which quite rightly have been enshrined in the legislation and Codes of Practice to which we all adhere We also largely accept that the 4th R is Responsibility As Animal Technicians we have responsibility for the care and welfare of the animals in our charge However I believe we have a further responsibility As members of the leading organisation for the welfare of animals used in research we have a responsibility to disseminate best practice to every institution using animals for research We can do this only by communicating at meetings and by publishing our findings and experiences in mediums such as our Journal The IAT currently has over 2000 members If each were to contribute just half a page we could generate enough material to maintain the Journal for many years to come and in so doing meet the aspirations expressed by R T Charles in having a Journal we can be proud of 2

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Animal Technology and Welfare April 2002 Assessing Rodent Wellbeing Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting PENNY HAWKINS Secretary JOHNNY ROUGHAN 2ALEXWILSON 3 JILL SALES 4KENNETHCLARKE 5PETERWARN 6PETERTHORNTON MAGGYJENNINGS and ROBERTHUBRECHT8 2 3 4 5 6 7 8 Research Animals Department RSPCA Wilberforce Way Southwater West Sussex RH13 9RS Framlington Place NewcastleComparative Biology Centre University of Newcastle Upon Tyne Upon Tyne NE2 4HH 5G12 ODP Park Road Ware Hertfordshire GlaxoSmithKline Wilkins Building 150 Stamford Street Franklin College King s Division of Life Sciences London SE1 8WA Department of Biomedical Science University of Sheffield Western Bank Sheffield S10 2TN North Manchester General Hospital Delaunays Road Manchester M8 6RL of Laboratory c o University Services of Veterinary of Oxford Department University Physiology Parks Road Oxford OX1 3PT AL4 8AN Hertfordshire UFAW The Old School Brewhouse Hill Wheathampstead for all laboratory Summary to further welfare improvements The RSPCA UFAW Rodent Welfare Group holds a oneday meeting every autumn so that its members can discuss current welfare research and exchange views on rodent welfare issues rodents to bring people together for an exchange of views and opinions on rodent welfare issues to provide evidence that can be used to direct welfare research and to promote improvements in laboratory rodent welfare for on techniques meeting focused The 2001 and mice in distress and suffering pain assessing rats and monitoring the impact of procedures on their welfare Speakers described the use of video analysis of postoperative behaviour LABORAS an automated ultrasonic system classification behavioural gait analysis and non invasive body vocalisations temperature monitoring to help to assess possible discomfort pain or distress in laboratory rodents The potential for using the techniques outlined during the animals in practice was meeting for monitoring discussed following the talks Introduction The Rodent Welfare Group is organised by the Royal Society for the Prevention of Cruelty to Animals RSPCA and the Universities Federation for Animal Welfare UFAW and brings together people from a range of backgrounds with a common interest in rodent behaviour and welfare The broad objectives of the group are Rodent Welfare Group Meetings have been held annually since 1994 and provide a platform for speakers to present talks on a wide range of welfare issues The 2001 meeting held at GlaxoSmithKline was convened to address the single issue of rodent wellbeing This was laboratory assessing suggested by an RSPCA survey of UK designated that examined how pain procedure establishments and recognised were and distress suffering the covered the survey Although assessed are most rodents of all species assessment commonly used in research and testing and we thought that it would be useful and constructive for the 2001 meeting to review current research into the behavioural and physiological monitoring of rats and mice This report was compiled from material provided by the speakers and from notes taken during talks and discussion periods points raised during discussions have been included where appropriate 3

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting RSPCA Survey on Assessing and Monitoring Adverse Effects PENNY HAWKINS Research Animals Department RSPCA The Research Animals Department has conducted a study to evaluate how animal wellbeing and departures from wellbeing i e pain suffering or distress are currently recognised and assessed in UK designated research and testing establishments The objective was to explore a range of issues relating to monitoring and recording adverse effects training people to observe animals alleviating pain and distress the role of the UK Ethical Review Process ERP and ways of disseminating good practice A total of 28 designated procedure establishments were visited between June 1999 and April 2001 and 137 people were interviewed including animal technicians scientists and veterinarians The survey found that the clinical signs most routinely used to assess animals included changes in body mass and food consumption changes in interaction with conspecifics tremors lethargy starey coat laboured gait hunching not grooming and soggy skin due to dehydration All establishments used clinical observation sheets for noting these mainly in the form of free text Some also used score sheets 2 3 4 5which differ from clinical observation sheets in that a list of potential clinical signs is assigned numerical scores or in the case of binary score sheets marked with a when present The numerical score or distribution of marks is then interpreted and acted on as appropriate Despite a broad awareness of score sheets these were used at nine establishments but not universally within each one Computerised data management systems these include lexicons with lists of terms for clinical signs and boxes for free text were used at seven establishments all of which were contract research organisations or toxicology departments of pharmaceutical companies The project addressed all species but people frequently raised issues relating to observing and monitoring adverse effects in rodents in particular There were a number of practical problems with implementing effective pain management and humane endpoints for rodents which were mostly associated with the relatively large numbers of mice and rats to be cared for their small size and the inherent uncertainties in interpreting their behaviour It was generally recognised that rodents are adapted to conceal signs of suffering but this was sometimes misinterpreted such that rats were regarded as tough These problems with 4 interpreting rodent behaviour meant that in practice people were generally relying on subjective measures to assess wellbeing that have not been validated In addition to the potential negative welfare consequences for rodents associated with the lack of objective techniques commonly used clinical signs such as piloerection may indicate more than mild discomfort or suffering 6J Furthermore the time available to assess individual rodents is relatively limited in comparison with larger animals used in smaller numbers such as dogs or primates Despite the practical difficulties associated with monitoring mice and rats most people were concerned about rodents and their welfare and very much wanted to minimise any pain suffering or distress that animals may experience Researchers at some of the participating establishments were also conducting studies that aimed to evaluate objective and or noninvasive ways of assessing rodents The RSPCA and UFAW therefore decided to convene these and other researchers representing a range of different approaches to monitoring mice and rats to speak at the 2001 Rodent Meeting The aim of the day was to raise awareness and interest further and to encourage multidisciplinary approaches to assessing welfare and the presence of adverse effects This was very well received and there was a great deal of interest in the subject to the extent that over 80 delegates attended the meeting and it was oversubscribed for the first time The report of the RSPCA survey is currently in press please contact the Research Animals Department for further information Behavioural Assessment of Post Operative Pain in Laboratory Rats JOHNNY ROUGHAN University of Newcastle Upon Tyne Pain is an unavoidable consequence of experimental surgical procedures and should always be prevented or alleviated At present there is a considerable shortfall in the level of analgesic use in small animals in veterinary clinical practice and this problem may also exist to some extent in research establishments This represents a significant welfare concern which needs to be addressed by developing appropriate methods of assessing animal pain in an appropriate manner Objective approaches to assessing post operative pain in rats include monitoring food and water consumption

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting body mass changes in locomotor activities such as walking and rearing and grooming behaviour e g licking or guarding wounds There are still problems with these approaches in that the basis for selecting these commonly measured activities is a subjective one i e they are traditionally used and monitoring them effectively can be very time consuming Ideally behaviours used for pain scoring would be easily recognised so that minimal training to observe them would be required and they would be unaffected by the administration of drugs such as Buprenorphine or by the influence of procedures such as injections or anaesthesia Very importantly the selected behaviours should occur at an either greatly increased or reduced frequency or duration in the presence of discomfort or pain At Newcastle we have developed a behaviour based technique for assessing post laparotomy pain in rats using objective behavioural analyses to evaluate which behaviours fit the above criteria and are most useful for detecting discomfort or pain in practice Video analysis of rat behaviour using the Observer Version 3 0 Noldus Information Technology enabled us to code 150 behaviours and calculate their frequency and duration Behaviours were analysed continuously for 1 hour prior to darkness and then one 15 minute sample was taken during each of 4 subsequent hours Complex analyses have identified some previously unstudied in of behaviour that are increased components frequency following surgery from 10 200 h1 but are by pre operative reduced dependently dose administration of ketoprofen or carprofen 5 10 or 15 mg kg They were a twitching of the back and flank a momentary loss of or compromised balance fall a cat like arching of the back and a squirming of the flank As the occurrence of these activities was unaltered in pain free drug treated control animals were a indicated that these behaviours results behavioural response to pain The behaviours were easily identifiable and occurred at measurable frequencies within a short space of time 5 10 mins following recovery from anaesthesia After could naive observers of training 10 minutes distinguish rats who had undergone laparotomy and the ability of trained animal technicians to detect painThese was also improved behaviours related characteristics add to the potential for back arching twitching staggering and wound licking to be developed into a useful means for assessing postlaparotomy pain and for the first time a very simple rapid and sufficiently objective technique for reliably assessing the analgesic requirements of individual rats subjected to abdominal surgery 8 The advantages and limitations of the method are set out in Table 1 While these behaviours are extremely useful for assessing rats post laparotomy it is not clear whether they would occur in other species e g the mouse hamster guinea pig and rabbit So far we have studied midline and lower abdominal laparotomy in Fisher and Wistar rats of differing ages and the data obtained suggest that the technique is at least not limited to a particular strain or age of rat and is also still applicable when the laparotomy procedure is modified Future work should evaluate which behaviours indicate which species pain in different post operative behavioural changes are associated with pain following different surgical procedures and whether there are differences in behaviours with different anaesthetics e g to see whether sedation affects the occurrence of behaviours Table 1 Behavioural assessment advantages and limitations Advantages Limitations Behaviours can be identified that are diagnostic of pain so that analgesia can be provided Initial development of similar scoring systems for other may be species procedures time consuming and require specialist equipment and expertise Technique is simple and quick to use Behaviours may be species and or procedure specific Na ve observers can be trained to detect signs of discomfort or pain with a short period of training e g 10 minutes Technique can be used to improve skills of trained animal technicians LABORAS An Automated Behavioural Classification System for Rats and Mice ALEX WILSON GlaxoSmithKline An effective method for monitoring animal behaviour is essential if subtle behaviours that could indicate compromised welfare are to be detected in good time Behavioural monitoring for scientific purposes can be used to help to reduce animal numbers and refine humane endpoints e g by providing better quality data on drug effects and pharmacodynamics in the whole animal The types of behaviours that can contribute to of a the understanding of the pharmacodynamics shakes wet dog include grooming compound 5

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting and rearing activity eating sedation locomotor changes in these behaviours can also indicate that animals are experiencing discomfort pain or distress Monitoring behaviour by eye can be very labour subjective making and may involve intensive of the classification so automating judgements behaviours can help to refine animal monitoring and assessment Note that automation can help to improve welfare provided that it is used as an adjunct to more traditional methods of monitoring animals welfare assessment by trained observers using appropriate aids remains essential LABORAS Laboratory Animal Behaviour Observation Registration and Analysis System is a behavioural registration system that can detect the behaviour of individual rodents over a fixed period of time 9 1 The LABORAS project was an initiative of Utrecht University Solvay Duphar and Metris System Engineering and is currently marketed through Metris One LABORAS system comprises up to eight platforms and consists of i weight displacement sensing platforms ii signal conditioning and acquisition hardware and iii analysis and classification software Fig 1 It is capable of position and including locomotion distinguishing distance covered climbing eating immobility drinking and grooming of eight singly housed animals over a period of up to 48 hours age support Base plate Conan Cage upper half Calibration spot Measurement plate carbon fibre Cage lower half displacement of the animal into electrical signals The enables orthogonal placement of the transducers of the approximate position of the determination animal in the lateral plane The transducer signals from eight platforms are filtered and amplified and stored on software one PC The analysis and classification using unique signals the vibrational translates algorithms one per behaviour in accord with amplitude and frequency giving a read out of behavioural events over time Validation studies have been carried out comparing behavioural classification data from LABORAS with that of human observers via CCTV video equipment both at the University of Utrecht and at GlaxoSmithKline The results of these studies demonstrated approximately 90 95 correlation of LABORAS scores with those of studies In initial human observers numerous LABORAS consistently detected grooming at a higher rate than the observers which was believed to be due to the greater accuracy and sensitivity of the automated has now been system The grooming algorithm enhanced to improve the correlation between the LABORAS is and human observers automated therefore a reliable system for registering behaviours that are important for assessing welfare and improving science It should be noted that as a consequence of the way in which LABORAS detects vibrations animals have to be housed singly Using LABORAS therefore needs to be considered very carefully and the potential of the system to reduce animal numbers and study durations has to be weighed against the welfare consequences of singly housing social animals These factors are set out in Table 2 and should be considered in full within the research for individual assessment cost benefit projects and by the relevant animal care and use committee e g the local ERP in the UK Table 2 LABORAS advantages and limitations Height adjustment Cage fixabon points Advantages Limitations Fig 1 The LABORAS system Copyright Metris b v Saturnusstraat 12 2132 HB Hoofddorp The Netherlands E mail info metris n1 or more information at www metris n1 Increased accuracy and reproducibility better quality data reduces animal numbers Requires single housing Can reduce study times Can only detect behaviours for which algorithms are available The ability of LABORAS to detect distinct behaviours is a function of the weight displacement and vibrations induced by the movement of the laboratory animal under test when performing particular behaviours The platform is attached to two weight displacement weight the applied that transform transducers Uses standard caging allows recording over extended periods of time Algorithms currently available for rats and mice only 6 Can use with telemetry Can use to monitor overnight

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting Ultrasound in Rats A Means of Assessing Pain and Stress JILL SALES King s College Rats emit several different types of ultrasonic call The with different calls can generally be associated situations such as isolation in infants deprivation of her litter in mothers or aggressive interactions Perhaps the most well known of the various calls are the relatively short 50 kHz call often only a few ms in duration and the so called long or 22 kHz call of up to 3s in duration The 22 kHz is emitted by adult rats in a number of situations e g when submissive after ejaculation by lone animals separated from the colony and when colony members are exposed to a predator It is also produced during apparently stressful or painful experimental situations such as avoidable and unavoidable aversion conditioning following tail shock and during certain drug withdrawal tests J 1 4 3 It has therefore been suggested that ultrasound emission may be a useful measure of pain and stress in rats and this knowledge has also contributed to current opinion that audible vocalisations in rodents should be taken extremely seriously and are not acceptable as endpoints can be made audible to Ultrasonic vocalisations humans using a bat detector but are unfortunately very difficult to interpret as rats do not simply cry out whenever they are in pain or distress Studies have shown that the presence of a familiar cage mate or an unfamiliar intruder can affect the number of 22 kHz calls made by rats following experimental procedures These effects are not consistent between procedures and controls and there are large differences between individuals however so it is unfortunately difficult to correlate call frequency with the presence or degree of pain and or stress Nevertheless some studies have found broad trends for call rates to change in a Predictable way e g call rates increased with body of injections intracranial following temperature intruder an of presence the in and lipopolysaccharide Ultrasonic vocalisations may therefore provide useful insights into wellbeing provided that all relevant factors are taken into consideration but it is not clear which factors are important in modulating communication between rats and the presence of any minimum frequencies discernible patterns Ongoing studies are collating vocalisations and attempting to interpret them but the lack of knowledge about calls made in natural situations makes this difficult The current advantages and limitations associated with the use of ultrasound as a measure of pain or stress are set out in Table 3 Table 3 Ultrasound in rats advantages and limitations Advantages Limitations Objective quantifiable response Very difficult to interpret Easily detected at relatively low cost Individual difference patterns Can be monitored remotely Can be a subjective measure in calling objective Can reflect abnormal behaviour Lack of information on function of natural calls Allows monitoring of nonvisible behaviour It is not clear which properties are most useful to analyse Recordings can be made over long periods Could be time consuming to apply Helps scientists empathise more with their subjects could be a In conclusion ultrasonic vocalisations powerful tool for measuring pain or stress but are currently best used as part of a battery of observation techniques More research is needed to evaluate how social situations and pain suffering or distress interact to shape vocalisations in the rat Meanwhile the major current benefit is in adding another sensory dimension to human observations of rats This is important because it may encourage those responsible for monitoring rats to pick up welfare problems that would otherwise have been missed this is also likely to contribute to greater empathy for laboratory rodents For example it was not known that mother rats called for their missing pups until people had the facility to listen in to them in ultrasound Bat detectors also help humans to realise how much ultrasonic noise they are making and think about the potential impact of this on animals who can hear it It is also not clear which components of vocalisations or how these should be should be measured it is possible to note the example interpreted For number of calls rate of vocalisation bouts and duration of each call most common pitch maximum and 7

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting Gait Analysis in Rats and Mice KENNETH CLARKE University of Sheffield My primary research interest is in the neurophysiology of motor control Initially I started to develop and use techniques of gait analysis in rodents as a behavioural method of monitoring normal and pathological neural function 14 5 However it rapidly became apparent that had potential for the study of these techniques pathologies in many other systems 16 The rationale for using gait analysis for identifying the presence of pathology is as follows Since locomotion consumes large amounts of energy an animal will always move in way available This is the most energy efficient achieved by exerting tight semi automatic control of the relationships underpinning locomotion such as forces exerted velocity stride stance and swing times The presence of pathology results in quantifiable disturbances to these relationships The presence of pain e g pain due to osteoarthritis or vascular insufficiency therefore often affects the way for methods moves Objective that an animal quantifying these movement changes may help in the study of the disease itself possible therapeutic interventions and in estimation of the severity of the pain Analysis of gait the way the animal moves to produce locomotion is one such approach and has the added advantage of being non invasive In our laboratory rodents are videoed from below locomotion in a glass floored during spontaneous chamber Fig 2 The chamber is tunnel shaped so that it is attractive to the mice and they want to explore it but it does not allow them to rear up or deviate from a relatively straight course A simple optical technique is used to highlight points of paw contact with the floor which can also compute the pressure being applied at those points This allows identification of the extent to which the animal is prepared to allow mechanical stimulation of particular paw parts In addition the forces Pa which the animal applies via its limbs are A number of variables are analysed measured including velocity stride stance and swing times and P for each limb to maximise energy Under normal circumstances efficient movement the relationships between these Thus anything are highly predictable variables disturb these will affecting an animal s movement in a rat model of For example relationships osteoarthritis of the knee the severity of the lesion relates to a degree of gait impairment as measured by the relationship between the Pz of the affected and unaffected limb Putative therapeutic agents can then be tested against this model Objective gait analysis is thus a useful non invasive technique for demonstrating the presence of a wide therapeutic and possible variety of pathologies interventions It is more sensitive than the human eye and can detect levels of limb favouring earlier and or with milder versions of arthritic changes This high sensitivity allows an earlier endpoint to many types of protocol However the extent to which it separates the pain associated with the pathology has yet to be established i e causes of altered gait can sometimes be purely mechanical such that the animal may not be in pain would seem to be Several areas of application of general promising These include assessment welfare in identifying lameness or accidental injury lesions to the skin of the paws e g models of adjuvant induced inflammation or hyperalgesia lesions to the Table 4 Gait analysis advantages and limitations Advantages Fig 2 Composite diagram of the two pieces of apparatus used to collect video and pressure data T plexiglass tunnel G glass walkway Li lights along edge of walkway C video cameras Lo load cells M Monitors Note detailed print of forepaw track on M3 8 Limitations Provides a truly objective measure of gait Requires specialised equipment Is far more sensitive than a human observer Gait changes may not always involve discomfort or pain Can be applied to a range of pathologies Could be used in other studies e g toxicology tumour studies

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting musculo skeletal system e g osteoarthritis lesions to the cardiovascular system e g models of peripheral vascular disease and lesions to any tissues or organs where locomotion produces mechanical disturbance As the technique can be used to detect very subtle changes in gait it may also be of use in setting humane endpoints in studies involving tumour growth where movement is impeded and in toxicology studies or safety tests A number of causes of gait disturbance in rats and mice are currently being investigated Non Invasive Body Temperature Monitoring in Mice PETERWARN North Manchester General Hospital Laboratory mice are currently used to develop and test the efficacy of novel antifungal drugs It has previously been demonstrated that the core body temperature of mice is reduced during sepsis and after treatment with endotoxin Temperature cut offs can be established below which mice are unlikely to survive for example 34CC after a bacterial infection Mouse temperatures have traditionally been measured by invasive probes or implanted microchip telemetry These techniques can cause distress to laboratory animals because they require handling which also increases body temperature e g by a couple of degrees C after 2 to 3 seconds and or the implantation of relatively large chips There is an ongoing demand for treatments for invasive fungal infections because they still carry a high mortality partly due to the relatively poor efficacy of drugs For example the mortality of candidaemia is 40 in US hospitals even with treatment which compares with 25 maximum of bacterial sepsis Invasive aspergillosis carries a mortality rate averaging 50 depending on the patient group despite therapy with either amphotericin B or itraconazole New problems are the increasing amount of antifungal resistance especially due to Candida and the increasing diversity of infection by rare moulds and yeasts All of these factors contribute to the demand for the development of broader spectrum antifungal agents which currently involves animal studies We measured temperatures of mice using an infrared high performance non contact thermometer Raynger MX4 Raytek Portable Products Ltd that had been microchips against implantable initially calibrated Mice were transponders temperature containing into the implanted with temperature transponders subcutaneous tissue of the neck region and infected with three species of Candida isolates 5 days later Temperature was measured using the chips in parallel with the infra red gun at least four times daily more frequently if the mice were in distress Any mice with significantly reduced mobility who were in continuing distress or could not reach their food or water were humanely killed immediately There was good correlation between temperatures obtained using implanted chips and the infrared gun such that mouse temperatures could be reliably and rapidly measured using the infrared device The device caused little distress to the mice and prevented problems with infection around implantation sites to increased which is likely to have contributed in the group with implants observed mortality Adoption of a hypothermia endpoint is a difficult decision as the exact temperature at which animals effect on the are killed can have a significant experimental outcome and we do not want to risk having to repeat these procedures In this case we were able to demonstrate that mice rarely recover if their body temperature drops below 33 3 C Adoption of a 33 3 C endpoint in fungal sepsis experiments measured by infrared non contact thermometer would enable mortality to be predicted in 80 of mice before This can significantly their condition deteriorated reduce the suffering in the terminal stages of this type of infection model and could be used to refine endpoints in many other types of study Table 5 Non contact thermometry advantages and limitations Advantages No contact required at all minimises stress and improves data Limitations Can be time consuming if there are large numbers of animals to monitor or measurements need to be taken at night Equipment relatively cheap and easy to obtain Can be used to significantly refine endpoints Calibration can be quickly conducted using recently culled mice with an electronic or conventional thermometer inserted into the anus Accurate over temperature range 30 38 C 9

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting Assessing Housing and Husbandry What Can We Learn From the Farm Animal Experience PETERTHORNTON University of Oxford Welfare assessment exercises in laboratory animals with the period following are largely concerned procedures rather than the whole lifetime experience of animals including those held in stock or kept for breeding In most cases the time spent undergoing procedures is often a short period of the animal s life in comparison with the time spent in the holding cage or pen and so welfare problems can arise at any time between birth and death Can laboratory animal welfare assessment be extended beyond procedures to include normal husbandry and housing is usually assessment welfare animal Farm set systems scoring the that in differently approached out in farm assurance schemes e g the RSPCA Freedom Food scheme are provisions based This means that they score what is provided for the animals in terms of housing husbandry and care and reduction of painful procedures rather than focusing solely on the animals themselves following procedures The University of Bristol has been developing an outcomes based system for evaluating the welfare of farm animals that uses parameters such as in cattle the number of lame cows in a herd assisted calving cases dirty flanks interaction with stockpersons bedding type and presence of rising restrictions this signifies poor pen design so that cows cannot get up This approach is useful because it comfortably identifies areas where individual farms are either performing better than others or not as well this encourages farmers to maintain good practice and improve weaker areas In practice no farm has been found to be consistently good or bad in all areas and the same is very likely to be true of designated establishments Using these provisions based systems is time consuming requires training and is resource dependent and so it is important that they provide a demonstrable benefit For example it has been shown that farmers under perceive the levels of lameness in their own dairy cattle 6 versus actual prevalence of 22 The true level of 22 is exactly the same as 10 years ago despite publicity from organisations such as the Farm Animal Welfare Council describing this as unacceptably high There are two reasons for this lack of progress one farmers are not monitoring lameness 10 levels effectively and two there is no national system farms are not able to results of publishing benchmark themselves in comparison with others Can we learn anything from this that could be applied to designated establishments We already know that different research testing and vary in the standard of breeding establishments resources that they provide including both physical environmental provisions e g housing macro and enrichment etc and environmental microclimates stockmanship e g training attitude quality of humananimal interaction The first step in addressing this should be to provide a reference point by evaluating the current situation and attempting to determine the extent of the variation This process would identify risk areas for example single for particular establishments housing of social species lack of environmental enrichment and provide a tool to manage any problem areas It would also represent a motivating force to performance about current personnel educate encourage staff to improve poor areas and aid enforcement of good practice Note that these elements are compatible with the terms of reference of the ERP If we want to be able to provide an assurance that the priority given to animal wellbeing is being raised in biomedical research then we must be able to assess and monitor animal welfare at all times To this end we really need to consider the viability of extending welfare assessment scoring systems beyond the immediate post procedural period and look at the entirety of the animal s life as in the farm animal sector Discussion The techniques and approaches described by the promising speakers were all very useful and or but were also in rodent monitoring innovations procedure specific or required specialised equipment There is no single objective system that is suitable for all procedures strains and husbandry protocols and it is unlikely that there ever will be Nevertheless the Rodent Group felt that any means of inferring animal wellbeing more effectively was to be welcomed and that it would be useful to think about their potential applications Three breakout groups discussed the by the described of the techniques implications speakers for i monitoring animals in practice ii pilot studies and iii training technicians and scientists The breakout groups conclusions are summarised below Monitoring The group was asked to consider what changes members would make to their current monitoring protocols as a result of the meeting a given the time and resources that they currently had and b with With the current time and resources limitless

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting resources at their disposal members said that they would like to increase the frequency and duration of daily monitoring and to train their staff to recognise and record a broader spectrum of behaviours The methods that people were most interested in and felt could most monitoring into existing easily be incorporated protocols were gait analysis e g for tumour studies non contact thermography new behavioural indicators such as muscle twitch post laparotomy and postsurgery ultrasound vocalisations in rats suffering and distress in species relevant to the trainee The group believed that it is essential for trainees to first be able to recognise normal animals This can be taught by observation but it is very difficult for both practical and ethical reasons to show animals experiencing suffering to trainees on modular courses It was also felt that there was a general lack of time and resources effectively to teach the recognition of adverse effects on modular training courses which is why good in house training is so important Problems that would have a bearing on the ability to implement all of these measures and techniques were principally related to a lack of resources For example it was felt that animals were used in such large that it would be numbers at some establishments difficult to extend monitoring times and that night time monitoring would always be a problem as this required resources that were frequently not available Given unlimited resources members said that they would like to try using software to observe and recognise behaviours as an adjunct to monitoring by eye and a approach using a broad range of multi disciplinary techniques They would also hire many more staff to monitor animals It is very important to challenge any false expectations that people may have about behavioural indicators of discomfort pain or distress and how easy they are to detect More effective monitoring and greater empathy with animals could be encouraged by demonstrating to trainees that subjective impressions of animal wellbeing are very useful but not necessarily always correct The group felt that demonstrations e g by video of objective monitoring techniques would be very useful in achieving this Pilot Studies The group was asked to consider how the techniques could be used to define endpoints and set out pain management protocols in pilot studies It proved to be or recomto make specific statements difficult mendations but the most important factors identified were the relevance of each method to both the study and the species in question and the feasibility of applying it down into validated simple Is in practice Practical issues were broken five key factors Has the method been Is it foolproof What does it cost Is it it sufficiently robust It was felt that a clear understanding of the benefits to animal welfare and to the study of using new monitoring techniques in particular their specificity and sensitivity was extremely important It was also essential to recognise that there would be resource issues associated with using new monitoring techniques and it might be necessary to persuade several different groups that animals and science would benefit These included study sponsors funding bodies scientists for which peer pressure would be useful and project licence holders noting that changes to project licences may be necessary Training The training breakout group considered the techniques in relation to module 2 of the training course required under the Animals Scientific Procedures Act 1986 because this includes the recognition of signs of pain More general issues discussed by the training group included ways of disseminating new information and ideas on training syllabuses materials and outcomes Members used meetings for Named Animal Care and dialogue Welfare Officers talks at establishments within the ERP pre study meetings and posting meeting reports on websites for disseminating information on training More training resources are urgently needed such as videos slides and better facilities for trainer networking such as a central training database In addition sufficient financial and staff resources should be made available to allow for effective modular training continuous professional development and regular retraining Conclusion Predicting how rodents are feeling can be very difficult and there are currently no accurate reliable objective methods for assessing discomfort pain or distress in mice and rats These problems are recognised and taken seriously by many technicians scientists and and the Rodent Group hopes that veterinarians type of objective measures covered in the research into the 2001 meeting continues to make progress and to be applied in practice It is also essential that developments in these fields are regularly reviewed and for responsible people and that consolidated monitoring animals and training those who will do so are open minded and always prepared to consider new techniques and approaches We encourage members of the ERP at all UK establishments and its equivalent outside the UK to explore the questions considered by the breakout groups for themselves and think seriously about how these techniques might be put to immediate use in reducing suffering and improving welfare at their establishments 11

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Report of the 2001 RSPCA UFAW Rodent Welfare Group Meeting D B Biomedical Research C F M Hendriksen Medicine of Society Morton eds London Royal Press pp 40 47 Acknowledgements The Group would like to thank GlaxoSmithKline for providing the venue and lunch especially Martin Heath it all Thanks also to Lillico for who organised contributing towards the cost of the day We are very grateful to all the speakers and everyone who attended and joined in the discussions 8 9 References 1 Hawkins P in press Recognising and assessing a survey of UK pain suffering and distress Laboratory designated procedure establishments Animals 2 3 4 5 6 Lloyd M H and Wolfensohn S E 1999 Practical Use of Distress Scoring Systems in the Application of Humane Endpoints In Humane Endpoints in Research for Biomedical Animal Experiments C F M Hendriksen D B Morton eds London Royal Society of Medicine Press pp 48 53 Morton D B 1998 Implementing Assessment Techniques for Pain Management and Humane Endpoints In Proceedings for Pain Management and Humane Endpoints http altweb jhsph edu science meetings pain morton htm D B and Griffiths P H M 1985 Morton Guidelines on the Recognition of Pain Distress and and an Animals in Experimental Discomfort Hypothesis for Assessment Veterinary Record 116 431 436 van der Meer M Rolls A Baumans V Olivier B and van Zutphen L F M 2001 Use of Score Sheets for Welfare Assessment of Transgenic Mice Laboratory Animals 35 379 389 van de Weerd H A Bulthuis R J A Bergman A F Schlingmann F Tolboom J van Loo P L P Remie R Baumans V and van Zutphen L F M 2001 Validation of a New System for Automatic of Behaviour in Mice and Rats Registration Behavioural Processes 53 11 20 11 Kaltwasser M T 1991 Acoustic Startle Induced Ultrasonic Vocalisation in the Rat A Novel Animal Model of Anxiety Behav Brain Res 43 133 137 12 Miczek K A Tornatsky W and Vivian J 1992 Rodent UltraEthology and Neuropharmacology sounds In Animal Models in Psychopharmacology B Olivier J Mos and J L Slangen eds Basel Birkhauser Verlag 13 Calvino B Besson J M Boehrer A and Depaulis A 1996 Ultrasonic Vocalisation 22 28 kHz in a Model of Chronic Pain the Arthritic Rat Effects of Analgesic Drugs Neuroreprot 7 581584 14 Clarke K A and Still J 1999 Gait Analysis in the Mouse Physiology and Behaviour 66 723 729 15 Clarke K A and Still J 2001 Development and Consistency of Gait in the Mouse Physiology and Behaviour 73 159 164 16 12 Schlingmann F van de Weerd H A and Baumans V 1998 A Balance Device for the Analysis of Behavioural Patterns in the Mouse Animal Welfare 7 177 188 10 FELASA Working Group on Pain and Distress 1994 Pain and Distress in Laboratory Rodents and Lagomorphs Laboratory Animals 28 97 112 Jones H R P Oates J and Trussell B A 1999 An Applied Approach to the Assessment of Severity In Humane Endpoints in Animal Experiments for Roughan J V and Flecknell P A 2001 Behavioural Effects of Laparotomy and Analgesic Effects of Ketoprofen and Carprofen in Rats Pain 90 65 74 Clarke K A Heitmeyer S A Smith A G and Taiwo Y O 1997 Gait Analysis in a Rat Model of Osteoarthrosis Physiology and Behaviour 62 951954

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Animal Technology and Welfare April 2002 A Pig of a Problem Post operative care of piglets following oesophageal interposition surgery L A LAWESand H MOORE Biomedical Research Facility Mail Point 828 University of Southampton S016 6YD General Hospital Tremona Road Southampton Southampton A Young Technicians presentation given at IAT Congress 98 Summary Oesophageal long gap atresia is a life threatening condition of children This presentation outlines the pre and post operative care of piglets used in a study the and highlights interposition of oesophageal care problems and misconceptions encountered in the of these animals Key words Atresia piglets post operative care oesophageal surgery Introduction Infants born with long gap oesophageal atresia require surgical oesophageal interposition with either have stomach or bowel All existing techniques complications that result in long term growth failure or constriction of the oesophagus due to scar tissue formation which prevents normal passage of food some of which are probably related to bypassing the oesophageal sphincter and the obliteration of the angle of His An initial non recovery pilot study in pigs allowed surgeons at Southampton General Hospital SGH to assess the feasibility of a new repair technique of this condition This technique would preserve the sphincter and use part of the stomach as a conduit rather than the entire stomach or bowel This surgical technique of the redundancy the also minimise would interpositioned tube prevent mechanical compression of thoracic structures by the stomach in the chest Prevent the use of the entire stomach as a conduit etc However it was essential for surgeons to a confirm the suitability of the new tecl inique for the growing child of the new and b to compare the effectiveness technique to that of existing methods of repair The study would also allow surgeons to study oesophageal healing stricture and stenosis mucosal change in the oesophagus adjacent to the interposed tissue and maturation of live animals following surgery The study was performed under the authority of a project licence issued according to the Animals Scientific Procedures Act 1986 To mimic the human situation newly weaned piglets were required to remain on the study for a minimum of sixty days but in some cases until 120 days For the technique to be deemed a success it was essential for piglets to grow and develop as normally as possible and for the interposed tissue to remain healthy The surgeons involved had no experience of working with animals and their initial ideas had to be adapted to what would be feasible in pigs especially as they thought that pigs would behave like human infants and stay in bed Materials and Methods The new technique involves the fashioning of a pedicle tube from the greater curvature of the stomach based on the gatroepiploic circulation which is then used to replace a segment of the thoracic oesophagus A fundoplication and pyloroplasty to the stomach was also involved as was the siting of a feeding tube The existing techniques for human oesophageal interposition used for comparison involved either segments of the large or small intestine being used as a conduit to replace the thoracic oesophagus segment or pulling the stomach up into the chest and anastomosing the stomach to the thoracic oesophagus Pre operative care and considerations In addition to the extensive wounds to both the stomach or bowel there were to be external wounds one following the line of the ribs one over the ribs and one in the neck To enable the piglets to lie comfortably on one side surgeons were asked to make all incisions on the same side of the animal However it transpired 13

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A Pig of a Problem that the piglets appeared not to experience any discomfort through lying on their wounds and in fact did so at almost every opportunity In addition a vascular cannula for fluid administration was inserted into the jugular of each animal and exteriorised to the piglets back A winged Malecot gastric cannula was inserted into the stomach and tunnelled subcutaneously to emerge on the animals back All cannulae were contained within pouches made from elastic adhesive bandage the method of attachment varying as the study progressed The pens used were constructed from galvanised tubular steel 4 62 square metres in area and had originally been constructed to house sheep and goats many years previously In order to make them suitable for housing pigs the bottom half of the pen wall was covered in a plastic coated strong metal mesh that prevents escape but still allows visual and olfactory contact Water was supplied via an automatic drinker and because of the piglets small size a concrete block was provided for piglets to stand on to drink These also provided considerable piglet entertainment as they were chewed from the start and as the piglets grew shoved around with their noses a good indication of the strength of these animals as the blocks weighed 20 kilos All pens were equipped with a bed and an infrared heat lamp Piglets were given artificial sheep skin to lie on rather than sawdust or similar material as due to the need to fast animals for long periods post operatively there was concern that it may lead them to eat their bedding materials and that any change post operatively may cause additional stress Pens were also provided with environmental enrichment such as footballs and old wellington boots suspended within the pens Despite toys being provided piglets quickly lost interest in them much preferring to play with the humans especially attacking the hosepipe sucking shoes and trouser bottoms and untying shoe laces The piglets were obtained through a local farming contact and were a Landrace hybrid The specification for the supply of animals was that they were to have been weaned for at least one week and to be between seven and nine kilograms Animals were delivered to the Biomedical Research Facility BRF at SGH at least seven days prior to surgery in order to allow for an acclimatisation period for both piglets and staff involved in the study These young animals had been exposed to considerable stress in a very short period of time i e weaning from the dam regrouping in nonsibling groups transportation and arrival in a facility that smelt and sounded very different from the environment that they were familiar with It was therefore considered essential to attempt to reduce any further stress to a minimum consequently a minimum of two piglets was to be supplied at each time 14 so that they would always have companions On arrival at SGH each piglet was identified weighed and subjected to a thorough health assessment including treatment for ectoparasites Any signs giving cause for concern were noted together with the resulting treatments All routine treatments had previously been agreed following consultation with our Named Veterinary Surgeon NVS and additional treatments were first authorised by him before being applied to the piglets Initially piglets were grouped housed until surgery as it was felt that separation on arrival would cause additional stress However it was found that stress increased at the most crucial stage of the proceedings if piglets were separated for the first time during the recovery period i e immediately after surgery This led us to abandon group housing with all piglets being housed singly on arrival although always within sight and smell of each other As soon as the piglets arrived the most important task for technicians was to attempt to overcome their fears In addition to the piglets becoming used to close human contact our aim was for technicians to know and as far as possible understand each piglet individually becoming aware of each one s mannerisms and character This we believed would provide us with vital clues as to each animal s wellbeing during the post operative period Familiarisation was achieved by technicians involved spending large amounts of time with the piglets at first just sitting in the pen with them and quietly talking to them and letting the piglet take the initiative Understandably apprehensive at first the piglets gradually approached the technicians sniffing and generally exploring these strange additions to their environment Once this first approach was made the staff would first touch and then stroke them until their confidence was gained Staff soon realised that a pig s soft spot is its belly and that piglets would collapse on their sides if the belly area was stroked or tickled They will endure this for as long as someone is prepared to stay there a habit that continued into adulthood This behaviour enables simple procedures such as flushing of cannulae and injections to be performed whilst these active animals are relatively immobile without the need for restraint The pig human relationship was found to be absolutely vital as this highly intelligent animal requires contact with a familiar face to provide comfort and reassurance after surgery and we required a calm trained animal that would permit us close contact During the pre operative period the piglets became used to regular husbandry routines that in addition to being part of our basic care of the animals provided us with indicators as to their health status eating

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A Pig of a Problem and habits This gave an accurate requirements recovery post operative monitoring for database routines husbandry that fact the was important Equally time quality with animal and provided both technician confident thoroughly together Once the piglets were around us the opportunity was taken to train the piglets to being moderately restrained as this would be necessary in order to feed the piglets post operatively etc As these animals and for drug administration would require at least seven days of intensive postoperative care it was essential that the surgeon involved in the study was also familiar with the animals and they with him and these piglets were his first real contact with any animal let alone such a potentially difficult one as a pig Due to the need to assess the passage of food through the intestine and graft viability post operatively it was and records of urination to maintain essential defecation both pre and post operatively The volume of urine and faeces were not measured but assessed on a scoring system The presence or absence quantity and consistency of urine and faeces are a very indication of the piglets post operative important must be recorded at every inspection and condition Post operative care Due to the Landrace genes present in our piglets and the consequent potential malignant hyperthermia from given the considerable anaesthesia Halothane investment in terms of time given to these piglets it use Alphaxalone alphadolone to decided was injectable anaesthetic with Buprenorphine given as an analgesic during the pre medication process Surgery time varied according to technique but was never less than 2 hours Full recovery from anaesthesia varied considerably between piglets but did not seem linked to the length of surgical time Continuous observation of respiratory rate temperature and skin colour were maintained until consciousness was regained As consciousness began to return it was essential to establish if the piglet was in pain or stressed Stress could be relieved to a certain extent by sitting in the pen with the piglet reassuring it both vocally and by touch Although and maintained analgesia levels were monitored throughout surgery they needed to be reviewed and adjusted according to demand as consciousness returned Analgesia was given routinely three times daily for forty eight hours post operatively at a dose of 0 1mg per kilogram of bodyweight The understanding technicians had gained of the animals normal preoperative behaviour proved invaluable in assessing animals for signs of pain As the risk of infection was high due to the extensive external and internal surgical sites prophylactic antibiotics in the form of Ampicillin were given at the rate of 250milligrams per day for a minimum of five days the period to be extended if signs of infection were seen Mobility was encouraged as soon as possible after surgery which allowed us to observe any postural abnormality which is a good indicator of abdominal Early mobility also helps post operative discomfort recovery as it aids normal respiration an important factor in this model as one lung is retracted for long periods during surgery with a consequent risk of pneumonia In the early stages of the study we attempted to restrict the pen area for the first 24 hours as we were concerned that the piglet may wander away from the bed area with its additional heat source and be too weak to return however the piglets soon showed us that these precautions were unnecessary from as often within two hours of recovering anaesthesia they were attempting to climb over the 2 foot high temporary barrier Feeding Due to the surgical sites in both oesophagus and the stomach or bowel access to food and water were withdrawn this proved to be extremely stressful to both staff and more importantly to the piglets which often upon regaining consciousness appeared thirsty despite intravenous fluid replacement during surgery and post operatively This denial of water seemed cruel but was very necessary as leaks from the internal wounds would cause pneumonia or peritonitis In an attempt to ease the stress the piglets were allowed to suck on damp cloths which provided some moisture to the lips and mouth Obviously fluid therapy is continued via the intravenous cannula but this does not satisfy the animals instinct to search for water Gastric feeding was introduced at varying times depending on which surgical technique had been used In order to re establish the intestinal flora after the long fast feeding commenced with 5 ml of organic natural yoghurt followed an hour later by a feed of gruel of a commercial weaner pellet liquidised in water Yoghurt was included in further feeds for at least three days and in order to increase palatability and calorific content CompIan meal replacement was added to the was gruel This recipe provided good nutrition palatable when oral feeding commenced and produced soft but well formed faeces which was considered to be important in maintaining gut motility and piglet recovery The consistency of the gruel had to be sufficiently liquid for it to pass easily through a 6mm diameter Malecot tube whilst being thick enough to give the maximum calories in the minimum volume Feeding was carried out at four hourly intervals with the amount of fluid and feed administered gradually being increased from a starting point of 10m1 Due to the consistency of the gruel it was important to flush the gastric tube after feeding 4 Dextrose saline being 15

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A Pig of a Problem used for this Any reactions from the piglets were recorded in order to determine whether adjustments to the next feed were necessary Gruel must be introduced in small quantities and at regular intervals Adverse reactions included uncomfortable stretching tooth grinding and retching Experience taught us that these problems could be overcome by giving the gastric feeds very slowly and by being careful not to introduce any air into the tube It was felt that the reactions noted were more due to the unusual sensation the feeds caused rather than being due to pain although this is a purely subjective observation and cannot be proven Intravenous feeding was continued and consisted of warmed 4 Glucose Saline and Hartmans fluid given as a bolus the amount given being calculated according to the weight of the piglet and the quantity of urine being produced This feeding regime allowed us to maintain a relatively normal growth pattern whilst avoiding any of the complications resulting from the surgery The practicalities of supplying fluids and of feeding were quite difficult as the piglets were very excited and active therefore it was essential for the technician to follow the piglets around the pen whilst at the same time trying not to put any tension on the gastric tube or cannula It was found that the longer the gastric tube and cannula were the easier it was to follow the piglets without causing problems although care had to be taken not to kink the intravenous cannula Continuous infusions were attempted but we had great difficulty in overcoming the problem of giving the piglets sufficient freedom for natural behaviour without the lines becoming entangled consequently this was discontinued in favour of bolus fluids and feed There was a gradual increase in the gastric feed volume until oral feeding could be resumed If the piglets appeared to be coping with the amounts of saliva produced i e no signs of drooling then small amounts of water were given orally from Day 3 and water in a bowl from Day 5 If the animals temperature remained normal and there were no signs of pneumonia the drinker was re instated 24 hours later and oral feeding commenced The feed offered was the same gruel mix as for gastric feeds but was given at a thicker consistency As the piglets were generally very excited at being offered oral food very small amounts were given literally a teaspoonful at a time so that the whole meal could not be gulped down in one go Another way to overcome the tendency to gulp the food was to spread a thin layer around a bowl forcing the piglet to lick it up thus slowing down intake If liquid feed or water was given in a bowl in their enthusiasm the piglets had a tendency to inhale fluid into their lungs thereby causing pneumonia Once piglets were seen to be coping with more normal volumes of feed orally and that they were once again using an automatic drinker although this element often required re 16 training the water volume of feeds was gradually decreased until the piglets were once again eating dry weaner pellets The most worrying aspect of feeding particularly with the first piglets undergoing the new procedure was that they would regularly vomit saliva after meals Initially this was thought to indicate stricture at the site of anastomosis however after some time this was found to be part of normal recovery due to the presence of transplanted mucus producing tissue being present higher in the alimentary canal than normal Reflux associated with allowing the piglet to become hungry was also observed This appeared to cause no problems with the piglets re ingesting the regurgitated food This was overcome by ensuring that once feeding normally they were truly fed ad libitum Problems encountered Gastric Tube Removal technicians were initially worried when following normal piglet growth the gastric tubes became detached not realising that the Malecot cannula is designed to simply be tugged out and that fistula layers would close immediately preventing any leakage The lesson from this was that better communication between surgeons and technicians was needed Pneumonia due to compression of the lung during surgery leakage from the anastomosis into the thorax or following inspiration of food due to overeager feeding Any signs of pneumonia resulted in immediate antibiotic therapy and withdrawal of oral feeds until the disease appeared under control Feeding was then recommenced in the controlled manner described above Persistent regurgitation of food at an advanced stage of growth was due to stricture at the site of anastomosis Unfortunately in animals it would not be deemed to be humane to attempt to cure this problem and once animals were observed to be losing body condition or showed signs of distress they were euthanased Fortunately this was observed in only one technique and in two piglets Inappetance usually occurred at the transition to oral feeding and appeared to be due to the piglet s unfamiliarity with the food offered and to once again having to feed itself The only solution to this problem was persistence and providing the piglet did not become distressed not to back down However it is important to differentiate between force feeding and enticing the piglet to feed If an animal showed complete lack of interest in feeding but was still drinking and showing no signs of pain or distress we found that a period of fasting for up to 24 hours in some cases followed by a return to normal feeding stimulated the piglet s interest in

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A Pig of a Problem food again In our experience we found that gastric feeds may need to be maintained for up to a week before normal eating was restored 5 Behavioural normal piglet behaviour has previously been cited some of the abnormal behaviour observed during this study was toothgrinding an unwillingness to rise lying in a wet place change in skin colour unusual vocalisation and even something as subjective as vague as facial expression techniques we applied to maintaining the health and wellbeing of these delightful animals has in the long run proved beneficial both to the piglets and to human medicine The new technique of oesophageal interposition is now being used both in infants with long gap atresia and also in adult patients where injury or disease has necessitated removal of a large part of the oesophagus We understand from our medical colleague that the new technique has helped to both restore quality of life and to aid recovery from life threatening conditions Conclusion Acknowledgements Although at many times caring for these young animals was very stressful and time consuming the positive results gained at the end far outweighed some of the setbacks we incurred along the way The various Our thanks go to Mr Kerry Taylor Mrs J B Barley and Mr C M Gould MRCVS for their advice and support in both the care of the animals and assistance in preparation of this presentation 17

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Animal Technology and Welfare April 2002 Assessing the Welfare of Genetically Modified Mice ROGERJ FRANCIS University of Bristol School of Medical Sciences Summary In the United Kingdom research that uses genetically modified animals requires a project license granted under The Animals Scientific Procedures Act 1986 ASPA All project license applicants are required to make a cost benefit analysis of the work that is to be carried out on the animals in addition to predicting the adverse effects on the animals that are likely to result from the procedures During the creation of genetically modified animals the uncertainty of the effect of the DNA modification can lead to unexpected adverse effects that could have major welfare consequences for the animals involved The effect can be negligible or in other cases extreme Extreme effects can include embryonic lethality deformity sterility major organ malfunction and epileptic seizure The present study addresses how the welfare of genetically modified mice can be assessed Key words Genetic modification behavioural tests University Walk Bristol BS8 1TD England were the strains of choice for comparison since these are the strains that our unit currently uses for genetic construction Material and Methods Sixty animals ten of each line of mixed sex were tested The operator performing the test did not know the genetic background of each mouse tested An accurate date of birth was known for each litter Age of pups used for each test varied but all were born on the same day between 0900 1600 3 5 hours The three genetically modified lines of mice were H 2Kb tsA58 3 genotype tested mGluR1 4 genotype tested and mGluR7 4 genotype tested Each line was produced under ASPA project licenses and was classified with a severity band of moderate The three lines of unmodified mice were CBA Ca Harlan UK Ltd and Ola Hsd C57BL 6 0Ia Hsd B6CBAF1 F1 hybrid between the CBA and the C57 adverse effect animal welfare Introduction The aim of the study was to assess the welfare of three genetically modified lines of mice A behavioural of pre weaning animals was used to assessment compare the welfare of mice from three genetically modified lines to that of two unmodified inbred strains and the Fl hybrid from the inbred strains The three genetically modified lines of mice were chosen because they have defects that could have welfare implications if humane endpoints were not applied in their use The H 2Kb tsA58 transgenic line of conditionally which are bred as a source cells have problems with premature immortalised The ageing and reduced breeding performance mGluR1 line which are deficient for the metabotropic glutamate receptor 1 show ataxia in the homozygote knockout population 4 The mGluR7 line which are deficient for the metabotropic glutamate receptor 7 have seizures similar to epileptic seizures if stressed during later life The inbred strains and their Fl hybrid Behavioural testing Several behavioural described below tests labyrinth Statokinetic righting response were used and these are response accelerated The pup is held perpendicular with its head pointing downwards and its back against the panel C shown in Figure 1 approximately twenty centimetres above a padded landing pad D in Figure 1 It is then dropped onto the pad and the way in which it lands is scored as Landing on all four feet in a righted position or Failing to land in a righted position Pups used for this test were eleven days of age Locomotion This is a test to establish if the pup has developed the ability to walk in a mature manner i e with controlled co ordinated movement of all four limbs with its belly raised above the ground Pups used for this test were eight days of age 19

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Assessing the Welfare of Genetically Modified Mice Results Initially it was very easy to influence the results especially in the Statokinetic Labyrinth Response where the position that the pup was released from has significant bearing on its ability to right itself To allow the behaviour tests to be conducted with reduced operator error testing apparatus was constructed that could be used in all of the procedures Figure 1 Somato sensory Vibrissae placing This test was found to be extremely difficult to use because the pups were so agitated when suspended by their tails that responses could not be scored The use of this test was consequently abandoned Fig 1 A Behavioural Testing Box Locomotion The statokinetic and locomotion tests were scored as all or nothing responses with a positive score awarded two points and a negative score one point Each animal was tested on two occasions Only three animals two ataxic mGluR1 mice and one of the CBA Ca line failed in this test Somato sensory function Vibrissae placing The two ataxic mGluR1 This test is carried out with the pup lifted by its tail the vibrissae are then lightly stimulated and the response should be for the head and fore limbs to turn in the direction of the stimulus Pups used for this test were six days of age two non ataxic mice of the mGluR1 group The H 2KbtsA58 mice were the quickest to move away from the cliff edge Somato sensory Cliff drop aversion Somato sensory function Cliff drop aversion In this test the animal is placed overhanging the of a surface with its head and front paws over the B in Figure 1 The normal response is to move from the edge to safety Pups used for this test eight days of age edge edge away were Labyrinth postural response Righting reflex The pup is placed onto its back on a clear unobstructed surface with its limbs pointing upward The normal response is to turn over immediately Pups used for this test were eight days of age Geotaxic response 45 slope test The pup is placed head pointing downwards onto a surface that is angled at 45 the normal response is to turn 1800 and to climb up the slope A in Figure 1 Pups used for this test were eight days of age The latter three tests were scored by the number of seconds taken to complete the normal response Scores were recorded and given values as follows 1 second 1 point 1 3 seconds 2 points 3 5 seconds 3 points 5 7 seconds 4 points 7 9 seconds 5 points 10 seconds 6 points Failure was also recorded as 6 points The scores for all tests were then statistically analysed using single factor ANOVA 20 mice failed this test as did Geotaxic response 45 The ataxic animals failed this test The H 2Hb tsA58 mice were the quickest to complete the test with a mean time of 1 8 seconds The mean time for completion for the C57BI6 mice was 2 2 seconds Statokinetic labyrinth response In this test the H 2Hb tsA58 line and the Fl hybrid performed equally well followed by the mGluR7 mice The C57BI6 mice performed as badly as the mGluR1 mice Labyrinth postural response Righting reflex The two strains that performed best in the statokinetic test were the fastest to respond in the labyrinth postural response test with mean times of 1 4 seconds and 1 6 seconds The groups with the worst response rate were the CBA Ca mice with a mean time of 2 8 seconds and the mGluR1 mice with a time of 3 1 seconds Statistical analysis Statokinetic labyrinth response P value 0 16 Locomotion P value 0 11 Somato Sensory cliff drop P value 1 40 Labyrinth Postural Response P value 0 39 Geotaxic Response 45 P value 0 09

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Assessing the Welfare of Genetically Modified Mice Conclusions Considerable care has to be taken when carrying out these tests to reduce operator error especially in the statokinetic test where positioning of the pup can influence the result The genetically modified lines used in this study were chosen because welfare problems had been obviously identified However the behavioural tests used in this study suggested that no problems exist The H 2Kb tsA58 shows premature ageing and fails to breed after approximately 16 weeks old If the results of the behaviour tests were used they would show this mouse to be the super mouse because it out performed all the other mice The mGluR1 Homozygote displays ataxia which is visually obvious Two of the ten animals from this line were ataxic homozygotes and these animals failed many of the tests instance of abnormal response or welfare problems no matter how small Assessment needs to be made not only throughout the entire life of the animal but from conception This assessment is necessary to ascertain whether the genotypes are being produced according to normal Mendelian expectations or is there a possibility of embryonic lethality Acknowledgements The author wishes to thank the project licence holders who gave permission to use their animals in this welfare assessment References 1 The mGluR7 can have epileptic type seizures in old age None of the tests used would have shown any problem with this mouse In previous tests growth curves breeding production and breeding frequency of this mouse compared favourably with the Fl hybrid unpublished data In conclusion there applied to genetically welfare each new observed over many is no one simple test that can be modified animals to assess their construct needs to be carefully generations Each new construct should be subjected to rigorous assessment before its creation The care and welfare of genetically modified animals should only be entrusted to trained animal care staff with instruction to observe the animal very closely and record any Tomizuka K Yoshida H Uejima H Kugoh H Sato K Ohguma A Hayasaka M Hanaoka K Oshimira M and Ishida I 1997 Function Expression and Germline Transmission of a Human Chromosome Fragment in Chimaeric Mice Nature Genetics 16 133 143 Costa P 1997 Welfare Aspects of Transgenic Animals Proceedings EC Workshop October 1995 68 77 3 4 Jat P S Noble M D Ataliotis P Tanaka Y Yannoutsos N Larsen L and Kioussis D 1991 Direct Derivation of Conditionally Immortal Cell Lines from an H 2Kb tsA58 Transgenic Mouse Proc Natl Acad Sci USA 88 5096 5100 Conquet F Bashir Z Davies C H Daniel H Ferraguti F Bordi F Franz Bacon K Reggiani A Matarese V and Cond e F 1994 Motor Deficit and Impairment of Synaptic Plasticity in Mice Lacking mGluRl Nature 372 237 242 21

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April 2002 Animal Technology and Welfare PAPER SUMMARY TRANSLATIONS INHALTVERZEICHNIS von Beurteilung des Gesundheitszustands Nagetieren Bericht des Treffens 2001 der RSPCA UFAW Rodent Welfare Group PENNY HAWKINS Secretary JOHNNY ROUGHAN 2ALEX WILSON 3JILL SALES 4 KENNETHCLARKE 5PETERWARN 6PETERTHORNTON MAGGYJENNINGS und ROBERTHUBRECHT8 2 3 4 5 6 7 8 RSPCA Royal Society for the Abteilung f r Forschungstiere Research Animals Department Wilberforce Way Southwater West Sussex Protection of Animals britischer Tierschutzverein RH13 9RS Comparative Biology Centre Zentrum f r komparative Biologie University of Newcastle UponNE2 4HH Tyne Framlington Place Newcastle Upon Tyne SG12 ODP Park Road Ware Hertfordshire GlaxoSmithKline King s College Franklin Wilkins Biowissenschaften Division of Life Sciences Fachbereich Building 150 Stamford Street London SE1 8WA Studien University of of Biomedical Science Fachbereich f r biomedizinische Department Sheffield Western Bank Sheffield S10 2TN North Manchester General Hospital Delaunays Road Manchester M8 6RL c o University of Oxford Department of Veterinary Services Fachbereich f r Veterinardienste University Laboratory of Physiology Parks Road Oxford OX1 3PT The der Universitaten Federation of Animal Welfare Tierschutzverband UFAW Universities AL4 8AN Hertfordshire Old School Brewhouse Hill Wheathampstead Zusammenfassung Alljahrlich im Herbst organisiert die RSPCA UFAW Rodent Welfare Group RSPCA UFAW Gruppe zum Schutz von Nagetieren ein eintagiges Treffen bei dem die Mitglieder den aktuellen Stand der Tierschutzforschung er rtern und ihre Meinungen Ober Fragen des Schutzes von Nagetieren austauschen k nnen Das Treffen 2001 konzentrierte sich auf Techniken zur Beurteilung von Schmerzen Qualen und Leiden bei Mausen und Ratten und untersuchte die Wirkung von Magnahmen zum Schutz dieser Tiere Sprecher beschrieben den Einsatz von Videoanalysen des Postoperativen Verhaltens LABORAS ein automatisiertes System zur Verhaltensklassifizierung Ultraschallaufnahmen Ganganalysen und nicht invasive Messungen der K rpertemperatur die bei der Beurteilung moglicher Beschwerden Schmerzen oder Leiden bei Labor Nagetieren helfen k nnen Nach den Pr sentationen wurde diskutiert welchen Potenziellen Nutzen die wahrend des Treffens skizzierten Techniken f r die Uberwachung von Tieren in der Praxis bieten k nnten 23

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Inhaltverzeichnis Ein Problem bei Schweinen Postoperative Betreuung von Ferkeln nach chirurgischer Osophagusinterposition L A LAWES und H MOORE University of Southampton Biomedical Research Facility Biomedizinische Forschungseinrichtung Mail Point 828 Southampton General Hospital Tremona Road Southampton S016 6YD Zusammenfassung Erkrankung bei Kindern Diese long gap ist eine lebensgefahrliche Die langstreckige bsophagusatresie Prasentation skizziert die pr und post operative Betreuung von Ferkeln die in einer Osophagusinterpositionsstudie eingesetzt wurden Es werden auch die Probleme und Irrt mer hervorgehoben die bei der Versorgung dieser Tiere anzutreffen sind Schhisselbegriffe Atresie Ferkel postoperative Betreuung 6sophagusoperation Einfiihrung long gap m ssen einer chirurgischen bsophagusatresie langstreckiger Sauglinge mit angeborener unterzogen werden Bei alien derzeit mit entweder Magen oder Darminterponaten Osophagusinterposition eingesetzten Verfahren k nnen Komplikationen auftreten die langfristig das Osophaguswachstum stoppen oder zu einer Verengung des Osophagus aufgrund des sich bildenden Narbengewebes mit Behinderung der normalen Nahrungspassage f hren Einige dieser Komplikationen hangen vermutlich mit der Umgehung des osophagealen Sphinkters und der Blockierung des His Winkels zusammen In einer ersten Pilotstudie an Schweinen ohne Genesung konnten Chirurgen des Southampton General Hospital SGH f r diese Erkrankung bewerten Bei diesem Verfahren die Durchf hrbarkeit einer neuen Wiederherstellungstechnik anstatt des gesamten Magens oder Darms als Magens des Teil ein nur wird es und erhalten bleibt der Sphinkter die Uberlange der interponierten R hre auf ein auch w rde Verfahren chirurgischen diesem Bei Conduit verwendet durch den Magen im Brustkorb verhindert Thoraxstrukturen von Minimum beschrankt die mechanische Kompression mussten jedoch a die Eignung des Chirurgen Die vermieden und der Einsatz des gesamten Magens als Conduit des neuen Verfahrens mit Wirksamkeit neuen Verfahrens f r das wachsende Kind bestatigen und b die Chirurgen ferner den konnten Studie vergleichen Anhand der Wiederherstellungstechniken herk mmlichen im Osophagus Schleimhautveranderung asophagealen Heilungsprozess die osophageale Striktur und Stenose die neben dem interponierten Gewebe sowie den Aufwuchs lebender Tiere nach dem Eingriff beobachten Die Studie wurde auf der Basis einer Projektlizenz durchgef hrt die im Rahmen des Animals Scientific Procedures Act 1986 britisches Tierschutzgesetz von 1986 wissenschaftliche Verfahren erteilt wurde 24

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lnhaltverzeichnis Beurteilung Ver nderter des Gesundheitszustands M use Gentechnisch ROGERJ FRANCIS University of Bristol School of Medical Sciences Medizinische Fakultat University Walk Bristol BS8 1TD England Zusammenfassung In GroSbritannien d rfen Forschungsarbeiten bei denen gentechnisch veranderte Tiere verwendet werden nur mit einer Projektlizenz durchgefUhrt werden die irn Rahrnen des Animals Scientific Procedures Act 1986 ASPA britisches Tierschutzgesetz von 1986 wissenschaftliche Verfahren erteilt wird Alle Antragsteller f r eine Projektlizenz m ssen eine Kosten Nutzen Analyse der Arbeiten vorlegen die an den Tieren vorgenommen werden sollen und sie mOssen die unerwOnschten Wirkungen angeben die aufgrund der Verfahren vermutlich an den Tieren zu beobachten sein werden Bei der Zuchtung gentechnisch veranderter Tiere kann die Ungewissheit wie sich eine Veranderung der DNA auswirken wird unerwartete unerw nschte Wirkungen zur Folge haben die den Gesundheitszustand der betroffenen Tiere erheblich beeinflussen k nnten Die Wirkung kann geringfugig sein mitunter aber auch extrem Die folgenden extrernen Wirkungen sind denkbar Embryoletalitat Missbildungen Sterilitat Funktionsstarungen bei wichtigen Organen sowie epileptische Anfalle Die vorliegende Untersuchung pr ft wie die Gesundheit gentechnisch veranderter Mause beurteilt werden kann Schlfisselbegriffe Gentechnische Veranderung unerwOnschte Wirkung Tierschutz Verhaltenstests 25

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April 2002 Animal Technology and Welfare INDICE DE LA REVISTA Evaluaciim del Bienestar de los Roedores Informe de la junta de 2001 del Grupo para el Bienestar de los Roedores RSPCA UFAW PENNY HAWKINS Secretaria JOHNNY ROUGHAN 2ALEX WILSON 3JILL SALES 4 KENNETHCLARKE PETERWARN 6PETERTHORNTON MAGGYJENNINGS y ROBERTHUBRECHT8 1 2 3 4 5 6 7 8 Way Southwater RSPCA Wilberforce para Investigaciones de Animales Departamento West Sussex RH13 9RS Place Framlington de Newcastle Upon Tyne Universidad Centro de Biologia Comparativa NE2 4HH Newcastle Upon Tyne SG12 ODP Park Road Ware Hertfordshire GlaxoSmithKline de Ciencias BiolOgicas King s College Franklin Wilkins Building 150 Stamford Departamento Street Londres SE1 8WA Western Bank Sheffield de Sheffield Universidad de Ciencia Biom dica Departamento S10 2TN North Manchester General Hospital Delaunays Road Manchester M8 6RL de Servicios de Veterinaria para entregar a Laboratorio Universidad de Oxford Departamento de Fisiologia de la Universidad Parks Road Oxford OX1 3PT AL4 8AN Hertfordshire UFAW The Old School Brewhouse Hill Wheathampstead Sumario El Grupo para el Bienestar de los Roedores RSPCA UFAW celebra una reuniOn de un dia todos los otohos para que los socios puedan tratar acerca de las investigaciones en materia de bienestar e intercambiar opiniones sobre los temas de bienestar de los roedores La reuniOn de 2001 se centre en las t cnicas para evaluar el dolor el sufrimiento y la angustia de los ratones y las ratas asi como en el control del impacto de los procedimientos en su bienestar Los ponentes describieron el uso de analisis por video del comportamiento postoperatorio LABORAS un sistema de clasificaciOn de comportamiento automatizado vocalizaciones ultrastmicas anblisis del andar y control no invasivo de la temperatura corporal para ayudar a evaluar las molestias dolores y angustias posibles de los roedores de laboratorio Tras las ponencias se tratO del potencial de utilizar en la practica las t cnicas bosquejadas durante la reuniOn para el control de los animales 27

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Indica de la revista Un Gran Problema Cuidado postoperatorio de cochinillos tras cirugia de interposicitm esof gica L A LAWESy H MOORE Universidad de Southampton Unidad de InvestigaciOn Biom dica General Hospital Tremona Road Southampton S016 6YD Mail Point 828 Southampton Sumario La atresia de esOfago con cabos distantes es una condiciOn infantil potencialmente letal Esta ponencia bosqueja el cuidado pre post operatorio de los cochinillos utilizado en un estudio de la interposiciOn esofagica y resalta los problemas y conceptos equivocados encontrados en el cuidado de estos animales Palabras clave atresia cochinillos cuidados postoperatorios cirugia esofagica Introducci n Los ninos nacidos con atresia de esofago con cabos distantes precisan interposici6n esofagica quir rgica en el estOmago o en el intestino Todas las t cnicas existentes tienen complicaciones que degeneran en fallos de crecimiento a largo plazo o encogimiento del esofago debido a formaciOn de tejido cicatrizal que previene el paso normal de la comida Probablemente algunas de estas complicaciones se relacionan con la anastomosis del esfinter esofagico y la obliteraciOn del Angulo de His Un estudio piloto inicial de no recuperaci6n realizado con cerdos permitiO a los cirujanos del Southampton General Hospital SGH evaluar la factibilidad de una nueva tecnica reparadora de esta condiciOn Esta t cnica conservaria el esfinter y utilizaria parte del estOmago a modo de conducto en vez de la totalidad del estOmago o del intestino Esta t cnica quirOrgica tambi n reduciria al minimo la redundancia del tubo interposicionado evitaria la compresiOn mecAnica de las estructuras torAcicas ocasionada por el est6mago en el pecho evitaria el uso de la totalidad del estOmago como conducto etc No obstante resulta esencial que los cirujanos a confirmen la apropiabilidad de la nueva t cnica para el nirio en crecimiento y b comparen la eficacia de la nueva t cnica con la de los m todos reparadores existentes El estudio tambi n permitiria a los cirujanos estudiar la curaci6n del es6fago la estrictura y estenosis el cambio mucoso del esOfago adyacente al tejido interpuesto y la maduraci6n de los animales vivos despu s de la cirugia El estudio se realizO bajo la autorizaci6n de una licencia de proyecto emitida de acuerdo a la Ley de Animales Procedimientos Cientificos de 1986 28

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Indice de la revista Evaluaci n del Bienestar de los Ratones Manipulados Gen ticamente ROGERJ FRANCIS Universiclad de Bristol Facultacl de Ciencias M dicas University Walk Bristol BS8 1TD Inglaterra Sumario En el Reino Unido la investigaciOn que usa animales manipulados geneticamente requiere una licencia de proyecto concedida de acuerdo a la Ley de Animales Procedimientos Cientificos de 1986 ASPA Todos los que soliciten licencias de proyectos tienen que realizar un anAlisis de coste beneficio de la labor que se va a realizar con los animales adem s de predecir los efectos adversos potenciales en los animales a causa de estos procedimientos Durante la creaciOn de los animales manipulados gen ticamente la incertidumbre del efecto de la modificaciOn del ADN puede conducir a efectos adversos inesperados que podrian tener consecuencias importantes en cuanto al bienestar de los animales involucrados El efecto puede ser insignificante o en algunos casos extremo Los efectos extremos pueden incluir letalidad embriOnica deformidad esterilidad disfunciOn importante de Organos ataque epil ptico El estudio actual se enfoca en c rno se puede evaluar el bienestar de los ratones manipulados geneticamente Palabras clave ManipulaciOn genetica efecto adverso bienestar de los animales pruebas de cornportamiento 29

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April 2002 Animal Technology and Welfare CONTENU DE LA REVUE Evaluation du Bien etre des Rongeurs Rapport de la Reunion 2001 du RSPCA UFAW Rodent Welfare Group PENNY HAWKINS Secr taire JOHNNY ROUGHAN 2ALEX WILSON 3JILL SALES 4 KENNETHCLARKE 5PETERWARN 6PETERTHORNTON MAGGYJENNINGS et ROBERTHUBRECHT8 2 3 4 5 6 7 8 RSPCA Wilberforce Way Southwater West Sussex RH13 9RS Research Animals Department Framlington Place NewcastleComparative Biology Centre University of Newcastle Upon Tyne Upon Tyne NE2 4HN SG12 ODP Park Road Ware Hertfordshire GlaxoSmithKline Wilkins Building 150 Stamford Street Franklin College Division of Life Sciences King s London SE1 8WA Department of Biomedical Science University of Sheffield Western Bank Sheffield S10 2TN North Manchester General Hospital Delaunays Road Manchester M8 6RL of Laboratory c o University Services of Veterinary of Oxford Department University Physiology Parks Road Oxford OX1 3PT UFAW The Old School Brewhouse Hill Wheathampstead Hertfordshire AL4 8AN R sum Les membres du RSPCA UFAW Rodent Welfare Group se r unissent chaque ann e en automne pendant une journ e de fawn a discuter des recherches actuelles sur le bien tre des rongeurs et a echanger leurs points de yue sur les questions aff rentes a ce sujet La reunion d automne 2001 s est ax e sur les techniques d evaluation de la douleur de la souffrance et de rangoisse chez les souris et les rats et sur le contrOle des consequences des procedures sur leur bien tre Les intervenants ont d crit l utilisation de l analyse video du comportement postop ratoire du systame LABORAS syst me de classification automatisbe du comportement des vocalisations ultrasoniques de l analyse de la d marche et du contrdle par m thode non invasive de la temperature corporelle pour aider a avaluer le malaise la douleur ou l angoisse aventuels chez les rongeurs de laboratoire Le potentiel d utilisation des techniques mises en avant lors de la reunion sur la surveillance pratique des animaux a fait l objet de d bats apr s les exposes 31

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Contenu de la revue Question sur les Cochons Soins post op ratoires pour les porcelets ayant subit une chirurgie de rcesophage avec interposition L A LAWESet H MOORE University of Southampton Biomedical Research Facility Mail Point 828 Southampton General Hospital Tremona Road Southampton S016 6YD R sum L atr sie de rcesophage est une affection qui met en danger la vie des enfants qui en sont atteints Cette presentation touche aux soins pr et post op ratoires apport s aux porcelets lors d une etude de la chirurgie sur l cesophage avec interposition et souligne les problemes et les id es fausses qui ont t soulev s a propos des soins apport s a ces animaux Mots des Atr sie porcelets soins post op ratoires chirurgie de rcesophage Introduction Les nourrissons souffrant d atr sie congenitale de l cesophage doivent subir une intervention chirurgicale de l cesophage avec interposition avec l estomac ou l intestin Toutes les techniques existantes pr sentent des complications qui emp chent a long terme la croissance de l cesophage ou en provoque le r tr cissement du fait de la formation de tissu cicatriciel g nant le passage normal de la nourriture certains de ces tissus tant probablement lies au pontage du sphincter oesophagien et a robliteration de l angle de His Une etude pilote sans r tablissement portant sur les cochons a permis aux chirurgiens du Southampton General Hospital SGH d valuer la faisabilit d une nouvelle technique de reparation de ces conditions Cette technique permettrait de preserver le sphincter et de n utiliser qu une partie de l estomac comme conduit et non l estomac ou l intestin entier Cette technique chirurgicale permettrait egalement de r duire la redondance des tubes interpositionn s d emp cher la compression mecanique des structures thoraciques par l estomac dans la poitrine d viter l utilisation de l estomac tout entier comme conduit etc Cependant il est essentiel pour les chirurgiens de a confirmer l ad quation de la nouvelle technique pour les enfants en pleine croissance et b de comparer l efficacit de cette nouvelle technique a celle des m thodes de reparation existantes L tude devrait egalement permettre aux chirurgiens d tudier la cicatrisation le r tr cissement et la st nose de l cesophage et les modifications muqueuses de rcesophage dans le voisinage du tissu interpose ainsi que la maturation des animaux vivants apres l intervention L tude a t r alis e dans le cadre d une licence de projet mise selon la loi Animals Scientific Procedures Act de 1986 Loi sur les animaux Procedures scientifiques 32

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Contenu de la revue Evaluation du Bien Etre des Souris G n tiquement Modifi es ROGERJ FRANCIS University of Bristol School of Medical Sciences University Walk Bristol B58 1TD Angleterre R sum Au Royaume Uni les recherches qui utilisent des animaux genetiquement modifies doivent disposer d une licence de projet mise dans le cadre de la loi Animals Scientific Procedures Act de 1986 Loi sur les animaux Procedures scientifiques Tous les candidats a une licence de projet doivent proceder a une analyse des coOts b n fices des travaux effectu s sur les animaux et pr voir les effets ind sirables possibles pour les animaux utilises lors de ces procedures Au cours de la creation d animaux genetiquement modifies l incertitude li e aux effets de la modification de l ADN peut conduire a des effets ind sirables pouvant avoir des consequences majeures sur le bien tre des animaux concernes L effet peut tre negligeable ou dans d autres cas extreme Parmi les effets extremes on notera l talit embryonnaire difformit st rilit dysfonctionnement d un organe majeur crise epileptique La pr sente tude a pour objet la maniere d valuer le bien tre des souris genetiquement modifi es Mots des modification genetique effet ind sirable bien etre animal tests de comporternent 33

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April 2002 Animal Technology and Welfare INDICE DELLA REVISTE Valutazione del Benessere dei Roditori Relazione del convegno RSPCA UFAW Rodent Welfare Group 2001 PENNY HAWKINS Segretario JOHNNY ROUGHAN 2ALEX WILSON 3JILL SALES 4 KENNETHCLARKE 5PETERWARN 6PETERTHORNTON MAGGYJENNINGS e ROBERTHUBRECHT8 1 Research Animals Department RSPCA Wilberforce Way Southwater West Sussex RH13 9RS GB 2 Comparative Biology Centre University of Newcastle Upon Tyne Framlington Place NewcastleUpon Tyne NE2 4HH GB 3 GlaxoSmithKline Park Road Ware Hertfordshire SG12 ODP GB 4 Division of Life Sciences King s College Franklin Wilkins Buildings 150 Stamford Street London SE1 8WA GB 5 Department of Biomedical Science University of Sheffield Western Bank Sheffield S10 2TN GB 6 North Manchester General Hospital Delaunays Road Manchester M8 6RL GB 7 University of Oxford Department of Veterinary Services c o University Laboratory of Physiology Parks Road Oxford OX1 3PT GB 8 UFAW The Old School Brewhouse Hill Wheathampstead Hertfordshire AL4 8AN GB Sommario II convegno dell RSPCA UFAW Rodent Welfare Group si tiene per la durata di un giorno ogni anno in autunno per consentire ai soci di esaminare la ricerca attuale e scambiare punti di vista sugli aspetti concernenti il benessere dei roditori Il convegno del 2001 era focalizzato sulle tecniche di valutazione del dolore della sofferenza e dell angoscia nei topi e ratti e di monitoraggio dell impatto dei procedimenti sul loro benessere Gli oratori hanno descritto l uso della videoanalisi del comportamento postoperatorio del LABORAS un sistema automatico di classificazione comportamentale delle vocalizzazioni ecografiche dell analisi dell andatura e del monitoraggio non invasivo della temperatura corporea per valutare il possibile disagio dolore o la sofferenza nei roditori di laboratorio Durante il convegno e stato discusso l uso potenziale delle tecniche delineate per monitorare gli animali in pratica 35

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lndice della reviste Un Problema Considerevole La cura postoperatoria dei maialini dopo la chirurgia esofagea con interposizione L A LAWESe H MOORE University of Southampton Biomedical Research Facility Mail Point 828 Southampton General Hospital Tremona Road Southampton S016 6YD GB Sommario L atresia esofagea con long gap una malattia pericolosa per la vita nei bambini Questa presentazione delinea la cura in fase pre e postoperatoria dei maialini utilizzati in uno studio sulla chirurgia esofagea con interposizione ed evidenzia i problemi e gli equivoci riscontrati nella cura di questi animali Parole chiave atresia maialini cura postoperatoria chirurgia esofagea Introduzione I bambini nati con atresia esofagea con long gap richiedono l interposizione esofagea chirurgica con lo stomaco o l intestino Tutte le tecniche attuali comportano complicazioni con conseguente mancata crescita o costrizione a lungo termine dell esofago a causa della formazione del tessuto cicatriziale che previene II normale passaggio del cibo in parte probabilmente correlato al bypass dello sfintere esofageo e all obliterazione dell angolo di His Uno studio pilota iniziale sulla mancata guarigione nei maiali ha consentito ai medici presso il Southampton General Hospital SHG di valutare la fattibilita di una nuova tecnica di riparazione di questa patologia Questa tecnica preserverebbe lo sfintere e utilizzerebbe parte dello stomaco come condotto piuttosto che tutto lo stomaco o l intestino Questa tecnica chirurgica sfrutterebbe inoltre al massimo la ridondanza del tubo inserito con interposizione prevenendo la compressione meccanica delle strutture toraciche da parte dello stomaco nel torace prevenendo l uso di tutto lo stomaco come un condotto ecc Era tuttavia essenziale che i chirurghi a confermassero l idoneita della nuova tecnica per i bambini in fase di crescita e b paragonassero l efficacia della nuova tecnica a quella dei metodi di riparazione attuali Lo studio consentirebbe inoltre ai chirurghi di studiare la guarigione ii restringimento e la stenosi dell esofago il cambiamento mucosale nell esofago adiacente al tessuto interposto e la maturazione degli animali vivi dopo l intervento chirurgico Lo studio stato condotto con l autorizzazione di una licenza di progetto emessa in conformita alla legge britannica ASPA The Animals Scientific Procedures Act 1986 36

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Indice della reviste Valutazione del Benessere Geneticamente Modificati dei Topi ROGERJ FRANCIS University of Bristol School of Medical Sciences University Walk Bristol BS8 1TD GB Sommario Nel Regno Unito la conduzione di ricerche che impiegano animali geneticamente modificati richiede la concessione di una licenza di progetto ai sensi della legge britannica ASPA The Animals Scientific Procedures Act 1986 Tutti i richiedenti della licenza di progetto devono effettuare un analisi dei costi e dei benefici dello studio che sera condotto sugli animali nonch prevedere gli effetti avversi sugli animali che potranno risultare dai procedimenti Durante la creazione degli animali geneticamente modificati l incertezza dell effetto della modifica del DNA pub causare effetti awersi imprevisti che potrebbero avere conseguenze importanti sul benessere degli animali interessati L effetto pub essere trascurabile o in altri casi estremo Gli effetti estremi possono includere letalita embrionale deformita sterilit malfunzionamento organico importante accesso epilettico Lo studio attuale considera come pub essere valutato il benessere dei topi geneticamente modificati Parole chlave modifica genetica effetto avverso benessere degli animali test comportamentali 37

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April 2002 Animal Technology and Welfare NEW TECHNOLOGY This section is designed to bring to the attention of readers advances in technology whether it is new products new or refined techniques new discoveries or any other industry related developments Where this involves new products a factual account is given based on information supplied by the manufacturer but the Editorial Board makes no recommendation or warranty as to its accuracy or fitness for purpose We would welcome comments from members of their experiences with these Contributions to this section can be presented as technical notes and may be submitted in any form THE LAMINAR AIR FLOW CABIN ensures that the containment area cabin works efficiently as a New to the UK from Scanbur is a system for the safe and protected manipulation of animals and caging within the animal room Suitably PPE attired staff working inside a LAF Cabin are free to move around and perform a whole range of tasks previously only done with difficulty or restriction in mobile change stations However like all new equipment own working SOPs should be developed and simple no touch techniques devised The Laminar Air Flow Cabin can be compared best to an up scaled Class II bench The difference is that you walk into the cabin where you are ensured and protected by HEPA filtered down flow air It should perhaps be remembered that particle contamination increases with activity A motionless person generates some 500 000 particles A person walking at 2 mph generates 10 times this amount The LAF Cabin offers simultaneous optimal protection of animals staff and the working environment The cabin offers a new approach to working in an animal room The ventilated rack or cabinet is taken to the safe area and aligned to the front of the cabin Mobile cage racks ventilated cabinets or IVC systems are offered up to the edge of the LAF Cabin allowing access to the cages be it an open top filter top or an IVC type cage The cage and its contents can be handled quickly without risk of cross contamination The LAF Cabins work by ensuring that the air is laminar over the whole of the working area A specially designed laminator is used that ensures against the creation of dead areas or turbulence The down flow air has a velocity of 0 40 0 50 m s 0 03 rn s all measured points are within 20 of this average in the entire working area This is essential to achieve sterile working conditions Dust particles allergens and pathogens all downwards and away to the pre filters at floor Allergen and pathogen particle spread to the environment is effectively minimized LAA risk to is vastly reduced move level room staff Perforated benching or mobile trolleys can act as competent down flow benches to provide safe working conditions for shaving tail snips bleeds and minor surgery Made of polyester coated steel the robust structure has easy wipe clean surfaces The pre filters are easily accessible at floor level Air is pulled through the prefilters and forced into the pressure plenum by the ventilator fan at 1620 m3 hour per m2 It is then pushed through the HEPA filters The HEPA laminated down flow air pushes through the bench perforations and prevents upward contamination Cages can now be stacked stored within the LAF Cabin area in complete safety until the end of the task The LAF Cabin is a stand alone unit 80 of the air is re circulated within the cabin 20 is exhausted to the roorn The 20 roorn exhaust HEPA air effectively This equipment offers a new method of providing safe work areas for the protection of animals staff and the environment 39

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Animal Technology and Welfare April 2002 NACWO Continuing Professional Development Annual Meeting The following extracts are from papers presented at the NACWO Advanced Course held at Staverton Park Daventry from 23rd 25th January 2002 relatively cheap easy to install only system suitable for germ free animals Wednesday 23rd 19 00 Taking the Barrier to the Cage the pros and cons of Filter Top Caging IVCs and Isolators Dr Gianpaulo Milite Tecniplast Disadvantages floor space density poor increased use of disinfectants risk of canopy glove puncture low number of air changes hour sometimes noisy evidence of reduced breeding performance A potted history of the development of cage materials was given from the 1950s to modern day In the early years no specific health status of the animals cages were just a container with food and water Stainless steel was one of the first materials used offering an easy clean autoclavable unit but expensive The mirror effect with rats affected their behaviour Development of filter top cages Filters from reduced when 5 20 micron but efficiency autoclaved Offered increased microbiological between but marked difference protection Very low air macro and microenvironment changes hour and measurements of the cage environment produced results of Rh 70 Ammonia 200ppm CO2 2 900ppm Filtertop cages housed in cabinets offered a better barrier but reduced cage density and not suitable for large breeding colonies In these could create a positive or negative flow but not pressure Next came polypropylene but problems with light intensity and non visualisation of animals autoclavable developed Finally Makrolon animals and of visualisation cheap lightweight polypropylene over light intensity reduced Advances in science initiated re derivation of animals into SPF units but all animals at risk if a disease breakdown However SPF was a of successful answer to the requirements biological research It offered Development of the IVC clean and dirty animals in the same area positive or negative pressure racks limited protective clothing required by staff good allergy protection for staff efficiency dependant on learning correct procedures homogenous health status of rodents used in research limited number of strains from few sources between of colonies limited movement centres but there was poor allergy protection alternatives and no Next came the isolator age The first of these was stainless steel offering good protection but difficult to maintain followed by the Trexler flexible film isolator Advantages good protection for animals and staff no special environment required Thursday 24th 09 00 What s new at the Home Office Jon Richmond Chief HO Inspector Topics covered Review Ethical Local NACWO training Processes Licensing Freedom of Information Act House of Lords European issues The Inspectorate 41

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NACWO Continuing Professional Development Annual Meeting NACWO training mandatory NACWO training accepted in principle combined IAT Home Office syllabus APC to add more on ethics IAT likely accrediting body but can be more than one cannot be both accrediting body and course provider offers parallels to NVS training part of Continued Professional Development not mandatory for current NACW0s but will be encouraged to attend scope ASPA and beyond combination of written evidence hearings site visits likely to concede there is no alternative report due summer 2002 but likely to be late outcome is advisory European issues proposed revision of Directive 86 609 by European Commission Commission ratified ETS 123 and must now implement science groups generally not well represented at meetings but opponents are revision of Appendix A aims to set standards for cage sizes for next 10 years UK wants to see real improvements likely transition period for implementation of changes Local Ethical Review Processes review of ERP by the Home Office on its web site concludes that it s made a difference but still evolving ERP to continue as it underpins the legislation process not going to change instances of best practice in the report not all NACW0s given institution support early consult with NVS NACWO is proven worth Licensing measures to smooth out license application processes recommendations from Expert Group being taken on board average license issue time is 40 days performance measured by time application actually with the Home Office applicants should look to improve quality of applications avoid necessity for repeat amendments certificate holders not in favour of information being electronic Freedom of Information applies to all public bodies and all recorded information anybody can ask and if recorded information must be disclosed exemptions where disclosure compromises health safety involves publishable material or have intellectual commercial value FOI will be retrospective statutory bar will apply to ASPA section 24 full implementation by 2005 public bodies must publish a charter anybody in an organisation can be asked and must reply within 20 working days House of Lords Enquiry enquiry into continued research 42 use of animals for The Inspectorate measures introduced to expand the structure aim to have 33 inspectors by 2003 2004 not a measure designed to increase visits inspectors expected to become more proactive 09 45 Where are we now and challenges for the future Simon Research Festing Association what of are the Medical Charities Animal rights extremism continues to be of great concern General concern over lack of engagement with extremists NAVS BUAV and Animal Aid main organisations Future loss of political influence following HLS extremism potentially subject to backlash media giving more in depth coverage dwindling membership but increase in income due to legacies a good expos would revitalise the organisations tendency to concentrate on peripheral issues e g cat food EU chemicals policy SHAC groups extreme end of animal movement highly organised fast moving creative claim to be non violent operate at the margins of the law indulge in secondary targeting SHAC future low morale as losing media argument rights

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NACWO Continuing Professional Development Annual Meeting by owned facility animal Traditional department often small inflexible design low staff numbers difficult to arrange cover poorly equipped little accountability loss of middle class support faced with choice of becoming more violent or less effective police new powers to crack down HLS survived the campaign HLS may become new Greenham Common Centralised facilities becoming more common Advantages larger staff improved weekend sickness cover pool of expertise and sharing of skills more opportunities for career development shared equipment controlled access Scientific community enjoying greater Government support fairer media public support favourable shifts in policy research community more united some concern over extremists next move becoming more proactive in communications media activity and policy lobbying increasing dialogue with the public recognising importance of co ordination and exchange of information Perceived disadvantages animal area not not next to facilities animal owned shared facilities with other laboratory office departments To instigate change in Academia have to seek high level backing from central administration senior academics and usually very slow Future challenges FOI outcome of House of Lords enquiry continuing communication In Commerce based on costs and benefits and change usually very quick FOI applies to all recorded information including draft and annotated documents Organisations expected to proactively produce information including ERP minutes May have to include Project Licence titles and job descriptions of staff Management of ASPA ERP Commerce few project licences but broad scope Academia many project licences narrow scope Lay members often more vocal Conclusion industry must be more open and transparent members should engage in policy process whenever possible Full cost recovery Commerce unquestioned approach Academia why We have no money 11 30 11 00 Academia working vs Industry a comparison between practices training compliance Alan Peters Oxford University Marked differences in management structures Commercial Managing Director Board of Directors Managers Staff everybody employed in producing marketing a product work centres around team organisation Academia diverse collective of governing bodies Vice Chancellor Chief Executive chairs Council but only elected for 4 years and may change Proctors elected annually and represent silent majority Ensure customs practices and traditions of University upheld Registrar Chief Official of University and Secretary to Council work concerned with individual projects Different approaches to the provision of a NACWO David Key MRC Mill Hill Terry Priest Manchester University Cathy Godfrey Sheffield University Nigel Plummer HLS At Mill Hill combination of Animal Technicians and non Animal Technicians fulfil this role Animal Technician NACW0s responsible for all animal holding units non Animal Technician NACW05 cover 33 registered laboratories sited in the main building Procedures in labs include egg inoculation non schedule 1 killing and short term holding of transgenics Rationale for non animal Technician NACWO accessing the labs regularly know the scientific staff work when scientists work have authority within the division 43

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NACWO Continuing Professional Development Annual Meeting Qualified by PhD and attendance on a NACWO training course more than 1 NACWO per species depending on the work involved Limitations potential conflict of interest untrained in animal husbandry often other responsibilities so science may suffer difficulty of arranging cover in their absence NACW0s appointed at Animal Facility Manager level control training to ensure compliance and standards are met liaise with PPL holders and NVS to make decisions on welfare not revenue grounds Empowered to turn away work if resources not available Support from NVS PPL ERP Certificate Holder and Managing Director Ideally labs would be part of the animal facility and monitored by trained staff but site layout proscribes cover by Animal Technician NACW0s Current system works but appointment right person essential HLS have 47 NACWO qualified staff Rationale excess numbers provide back up and replacement when staff leave allows company to plan ahead allows assessment of NACWO attributes at an early stage of the At Manchester University NACWO duties are the responsibility of facility manager who reports directly to the academic director and certificate holder Facility includes 2 deputy managers and 7 area supervisors reporting back to the manager All NACW0s undergo theory and practical training to ensure highest welfare standards Provided by IAT qualifications and 10B accredited courses Level of experience NACWO courses Rationale is that NACWO should have senior academic status which is easier for a single NACWO to achieve Advantage of single NACWO over multiple NACW0s offers consistent advice to ERP and users Disadvantage single NACWO more remote from shop floor but views of staff can be recorded via a veterinary request form plus involvement in discussions with scientists At Sheffield University considered whether to have 1 or multiple NACW0s Initially there was 1 but has been increased to 5 to cover large and expanding areas and multiple sites Rationale was that 1 NACWO could not ensure every animal checked once daily owing to the number of animals diversity of species and different sites Additionally NACWO must be familiar with project licences in every area of work Multiple NACW0s can share the load of advising on project licence applications and attendance on the ERP Regular meetings NACW0s are held between all At HLS 15 separate animal units with 20 NACWO positions owing to range of species diversity of work and site location May have 44 achieved by hosting IAT Belief that benefit of external opinions broadens knowledge and prevents internal politics and practise being the only source of experience 13 30 Dealing with suppliers and the procurement of capital equipment Andy Williams CPM Training Purchasing divided into The Sellers World The Buyers World the selling process ethics unique selling points terms conditions buying signals musts and wants key points closing The selling process involves the development of USPs building a rapport recognition of buying signals and closing the deal Salesperson uses USPs buyers should look for points not being mentioned USPs reasons why customers buy a product salesmen perceive these as strengths used as sales pitch used to differentiate product and maintain price can be genuine benefits or just features countered by sticking to buying benefits and defining needs and wants

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NACWO Continuing Professional Development Annual Meeting Buying signals include indication of working together talk of competitors failings revealing deadlines and budgets body language and chasing supplier Buyer should avoid before agreeing a deal Closing techniques involve 4 main types panic bounce back gradual and reverse selling Buyers should be aware of add ons Involves low initial price but profit coming from delivery spares and maintenance Study of incidence in 342 workers 24 had eye nose symptoms 17 had skin symptoms 10 had chest symptoms Some cases presented with symptoms immediately others after work or at night The buying process involves a standard of ethics not accepting inducements Buyers must determine terms and conditions of the contract Business contracts not covered by Sales of Goods Act Buyers should prepare a list of features equipment must have and would ideally have Order of risk by species small animals insects and birds Buyers checklists include Prices are they affected by volume what discounts available is VAT included can there be price variation under what terms situations Known risk factors susceptibility and Initial costs Delivery installation commissioning included in the price or extra what payment terms apply at what point are goods accepted what happens if goods fail to perform Through life costs what is the design life how long is the warranty and what s covered cost of maintenance and frequency Key points on purchasing be a professional demanding and ethical customer work with suppliers to allow them to offer best value for money ensure people who have contact with suppliers know what they are doing do business under own terms and conditions Friday 25th 09 30 10 of these may develop asthmatic symptoms Once sensitised lasts for lifetime 80 develop within 2 years of exposure Laboratory Animal Allergy Meinir Jones Imperial College Investigation into LAA has revealed 30 of people working with animals become sensitised Current trend of cases is downward Risk of contracting LAA working with animals is 10x general population exposure atopic genetic Exposure low levels of LAA can increase risk 3x reducing LAA reduces number of cases approx 10 reduced levels of LAA do not necessarily reduce sensitisation Atopy associated with LAA 4x greater risk of developing LAA if atopic test not sensitive enough to use as pre employment check Genetic susceptibility case study done to determine HLA 16 of 741 workers susceptible HLA those with DR7 or DR11 HLA molecules more at risk DR3 HLA a protective factor not sensitive enough for pre employment check Currently measures to reduce exposure levels occupational health measures should include pre employment lung function test with follow up questionnaire at 6 weeks 6 months and 1 year requirement for employers to provide a safe environment but there may not be a safe threshold level for those genetically susceptible work ongoing to produce a vaccine to switch off allergic response 45

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NACWO Continuing Professional Development Annual Meeting 11 45 statistical advice to be sought on a study by study basis any animal with an obvious procedure related welfare problem will be promptly and humanely killed all the above must be auditable The Pitfalls in a Project Licence Application Jon Richmond Chief Home Office Inspector Why NACW0s involved may be project licence holder or deputy may be personal licence holder may have to interpret authorities for users may have responsibilities relating to compliance within ERP provide must be consulted guidance to PPL applicants HO perspective limits of what may be done must be clear and justified must be clear what will typically be done assurances that on every occasion only the most refined protocols and endpoints will be applied Must be auditable Material on the application considered within the ERP forms basis for licensing decisions defines authorities granted with to those be accessible must responsibilities under ASPA must be current and allow for progress and change Main pitfalls failure to use Notes to Applicants basic ASPA requirements not met detail not enough too much technical information prescriptive text and lack of flexibility duplication and inconsistency use of primates must state why other species not suitable top ten faults listed on HO website as annexe to ERP Application preparation allow plenty of time seek information advice from sources other than NVS NACWO early consultation with ASPI present to ERP at an early stage e g of authorities remember continuity maintaining transgenic strains acknowledge focus on the immediate uncertainties and stage work build in reflection time aim for low maintenance licence describe optional procedures rather than fixed flexibility of procedures within institutional e g routes and endpoints standards frequency describe GM HM animals by phenotype not strain allows use of newly developed strains exhibiting same phenotype Useful phrases include GA and analgesic regimens determined by to the nature of NVS and appropriate duration of the procedure and the clinical condition of the animal 46 NACWO input should be able to understand what is to happen and why and be involved when outcomes reviewed animal supply housing and care dosing sampling methods schedules observation schedules fate of animals 12 15 An HO Licence Tracking System Julian Braidwood Triveritas Requirement under ASPA for annual project licence return Consists of 12 page paper form 15 rows 26 columns Computerised record system developed using Microsoft user friendly application Access runs on PC with Windows system simple to use with very clear screens user instructions included on screen all codes and classifications built in few options entries can be made throughout the year not just year end entries made directly on screen drop down lists allow easy selection of codes integral error traps decision tree for rows A B codes i e cannot mix codes easy to check entries accepted by HO as separate printed form providing returned with green form audit trail of all entries provision for updating annually with latest guidelines monitors progress of completions by staff limitation controls available

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NACWO Continuing Professional Development Annual Meeting 14 00 Function Future Direction scrutiny outside independent facilitate co operation and co ordination 3Rs of the APC John Gregory Imperial College History of the APC envisaged Commission Royal 1875 Secretary of State would be guided by and knowledge of competent advisors experience 1876 Cruelty to Animals Act 1912 Royal Commission recommended non to advise Body of Experts statutory Secretary of State on animal committee Advisory 1980 experiments 1986 Animals Scientific Procedures Bill White Paper led to APC Terms of Reference of State on matters advise Secretary concerned with ASPA matters referred by Secretary of State or as Committee may determine balancing act of science and industry vs of animals against avoidable protection suffering and unnecessary use Membership all appointed by Secretary of State Chairman at least 12 others must be one barrister solicitor or advocate must have medical of members 2 3 qualification registration veterinary experience in a biological subject 50 must not have held any licence under ASPA for 6 years includes philosopher ethicist traditionally certificate holder NI representative 4 year term with option of one reappointment 14 30 of NACWO Training have we got it right Bob Kemp AstraZeneca The story so far Jan 1987 Named Animal Care person introduced 1996 name changed to NACWO May 1996 introductory course for NACW05 April 1998 issue of NACWO guidelines Feb 1999 syllabus to HO call for mandatory training Jan 2000 1st NACWO weekend Nov 2000 revised NACWO guidelines Jan 2001 APC letter to Secretary of State recommending mandatory training APC sub committee training not retrospective training should follow other established models one or more accrediting bodies no longer than 1 year between appointment and completion Function 6 full committee meetings year reactive to licence applications infringements scientific developments expos s proactive with advice on policy and practice sub committees for primate use education and training and research and alternatives plus ad hoc working groups visits to establishments for awareness and education Course objectives develop an appreciation of the importance of the NACWO role develop an understanding of the scope regulation administration spirit of ASPA and other legislation and guidelines develop an appreciation of the responsibilities and interactions of those within the Act develop an awareness of ERP and NACWO role in it provide a forum to discuss the 3Rs and contribution a NACWO can make develop a process for assessing pain and suffering promote exchange of ideas and experiences keep abreast of scientific developments promote the develop an awareness concept of CPD and life time learning Future sub committee alternatives research monitoring existing projects and identifying new ones primate sub committee monitoring supply of primates and xenotransplantation education training committee monitoring ethics training and module 5 overworking groups on cost benefit breeding endangered wild caught species schedule 1 Syllabus ASPA and other relevant legislation NACWO role Project licensing system 3Rs ERP recognise and quantify pain suffering distress general introduction to ethics training welfare observations and 47

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Animal Technology and Welfare April 2002 POSTER PRESENTATION The Institute of Animal Technology Annual Congress Jersey 28 30 March 2001 The following poster is reprinted in full from the December 2001 Journal with apologies to the authors Pregnancy confirmation of the beagle by ultrasound scanning Pfizer Global Research and Development Laboratories Introduction At Pfizer Global Research Development we are constantly seeking new methods to provide the highest possible welfare standards for the animals in our care Ultrasound scanning of bitches for pregnancy confirof mation has allowed more accurate estimation parturition dates This has enabled better management of pregnant bitches within the colony The time Pregnant bitches are singly housed prior to whelping has been reduced This has positive benefits for animal welfare and also assists in maximising resources Within the dog breeding colony at Pfizer a harem system is used for breeding Bitches are observed three times per week for signs of pro oestrus signalling the onset of their mating season Pro oestrus lasts for approximately 9 days in the dog and is followed by oestrus We know that in the bitch sexual receptiveness is generally between day 1 and day 4 of oestrus 472 so expected mating dates for reference purposes are recorded as day 1 of oestrus If an observed mating has not been seen assumption is made that mating has occurred Prior to the purchase of an ultrasound scanner manual palpation for gestational sacs were performed as routine at approximately 28 days post expected mating date to confirm pregnancy If the bitch was too fat manual palpation proved unreliable and was recorded as TFTF too fat to feel It was assumed that the bitch was pregnant due to it being housed with a male and observed in oestrus Estimated parturition dates were then calculated accordingly At a minimum of 12 days prior to whelping the bitch was moved and housed in the whelping area Single housing for longer than necessary is recognised to be less desirable than group housing in animal welfare terms In addition the e g daily observation documentation associated record temperature and mastitis record is increased Pregnancy confirmation by ultrasound scanning Gestational sac 72 ors RAM FRZ 14 4 49

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Poster Presentations At 5 days prior to the estimated parturition date the bitches had their temperatures recorded twice daily A drop in body temperature in the bitch from normal between 101 5 F to 98 F usually indicates whelping within 48 hours Whelping occurred from day 1 in some bitches and up to day 10 in others because of approximations in estimating due date Any bitch that reached day 10 and had not whelped was returned to the harem area as non pregnant unless obvious signs were shown to the contrary As a result valuable time and resource were consumed for approximately one month on any bitches that were assumed to have been mated but not confirmed pregnant What has ultrasound scanning done for us Enables us to accurately predict whelping The programme itself has given us a whelping date that is 95 accurate The other 5 could be operator error It prevents non pregnant bitches coming into the whelping area Contributing to welfare and also saving time space and resources on the single housing of bitches In the past bitches that were confirmed pregnant by manual palpations and at the end of their gestation period did not give a litter were presumed to have reabsorbed the foetuses Taking a picture of the gestation sac allows us to check for this phenomena Each picture is put into the bitch s own record folder Since the purchase of the ultrasound scanner this waste of resource has been almost eliminated It is not however 100 accurate and on occasions we still perform manual palpations The scanner itself Allows us to pair house pregnant bitches as soon as we diagnose them as pregnant We remove them from their harem avoiding possible injuries from fighting and then house them individually from 12 days before whelping so reducing single housing to the minimum The scanner Dynamic Imaging with a 6 5MHZ oscillating wand has an in built programme which works out the estimated delivery date EDD by measuring the gestation sac If the sac is more than 35mm in diameter it will be too large for the programme to compute and means that the foetus is over 40 days old Alternative measurements can be used instead such as head diameters crown to rump length and also body diameter With these combined figures the scanner can predict an EDD based on a gestational period of 65 days Whelping dystocia The scanner has also proved to be an invaluable tool when a bitch is having problems during whelping Because of the ease with which we are able to see if pups are alive in the uterus we are able to arrange for additional staff to revive pups when a caesarean is performed It also provides a more reliable way for us to check if a bitch has finished whelping if she is too fat to palpate Head diameter Acknowledgements Animal Resources PGRD Tim Davies MIAT RAnTec Additional scanner programmes Other hjild 0 g I4e t Vitra Menu Animal Menu t LeFt A E Rat EMILT p Trace Ellipse Area Area g g CLL Irt Z Time Velpcity _ Cenine Animal NW Speciel Dynamic 50 Canine MEMO Other 1121 ge Pmly Japer Oiam Mode grAL 11 11 isa5Fe rime Velocity Fi Y Canine leasing 1 Menu V ttyh d Time Valecite reqoency IIIIIIIIIII Special Dynamic Imagine Animal Other Special Dynamic Imaging

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April 2002 Animal Technology and Welfare Instructions Subjects considered for publication may include original short articles technical notes and reviews pertaining to all aspects of animal science and technology management and education The Editorial Board wishes to offer particular encouragement to papers leading to improvements in environmental enrichment the general care and welfare of the animals used in particular those species and strains exhibiting harmful genetic defects and papers describing refinements in techniques a reduction in the number of animals that need to be used or alternatives to animal use Papers describing experimental procedures will only be accepted for publication if authors clearly state that the procedures conform to the prevailing principles and Codes of Practice of the Animals Scientific Procedures Act 1986 Papers submitted from outside the U K should state what legislation and or ethical approval the work has been carried out under In addition authors who describe surgical techniques with recovery should include details of post operative care and any analgesic therapy provided The Editorial Board reserves the right to seek independent advice on any aspect of the content of an article but the final decision on acceptance or rejection remains with the Board Submission Material submitted for publication will be considered provided that it is contributed exclusively to Animal Technology and becomes the property of the Institute of Animal Technology The original and two copies of the manuscript are required All sheets should be typewritten on one side in double spacing with 4 cm margins and serially numbered Additionally a copy on disk should be provided Articles for submission should be sent to Patrick Hayes Journal Editorial Board Chairman 5 South Parade Summertown Oxford OX2 7JL No responsibility will be accepted for loss or damage to such articles Format 1 The first sheet of the article should contain the following the full title of the paper the initials and last name of the author s to Authors the full address of the department s and institution s where the work was carried out the address for correspondence if different to above 2 For the remainder of the paper the text should be clear and concise and where appropriate sub divided under the following headings Summary Introduction Methods Results Discussion Acknowledgements References 3 Measurements should be given in metric units see The use of S I Units 1969 British Standards Institution publication and spelling should follow that of the Oxford English Dictionary Abbreviations must be defined in full at their first appearance in the text The 24 hour clock should be used for times Words to appear in italic type should be underlined Designation of inbred strains should be in accordance with the International Index of Laboratory Animals 6th edition compiled edited and published by M W Festing 1993 4 Illustrations should be clearly drawn in indian ink on stiff white card Lettering should be plain block capitals Photographs should have clear and well contrasted tone values and preferably be colour All illustrations and photographs should bear on the reverse side the author s name a number corresponding to the order in which it appears in the text e g Figure 1 and an arrow pointing to the top Illustrations supplied on disk should be in JPEG TIFF or EPS formats and have a resolution of no less than 300dpi The captions for illustrations should be typed in double spacing in numerical order on a separate sheet of paper 5 References to other literature should be indicated in the text by superior figures12 and should be typed in numerical order in the order in which they appear in the text on a separate sheet of paper References should be set out as follows Journals Surname and initials of author s date title of article Name of journal in full volume number first and last page numbers e g Saigeman S 1998 Environmental enhancement 51

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Instructions to Authors of cats what why how Animal Technology Vol 49 No 3 145 154 Books Surname and initials of author s date title of book Name of publisher Town of publisher e g Flecknell P A 1987 Laboratory Anaesthesia Academic Press London Animal Chapter from a multi author book Surname and initials of chapter author s date title of chapter In title of book surname and initials of book editors Name of publisher Town of publisher first and last page numbers of chapter e g Gregory J A 1985 Principles of Animal Husbandry In Laboratory Animals An Introduction for Experimenters Second Edition Tuffrey A A John Wiley Sons Ltd Chichester 87 105 Content Papers describing procedures involving the use of animals should always include full details of the animals and husbandry conditions used These would be as follows Animals Species Breed or strain Sex Age and weight at start of procedure Genetic status inbred outbred hybrid mutant Source Microbiological status conventional specified pathogen free define which pathogens animals are 52 free from gnotobiotic define which organisms are present Quarantine or acclimatisation period micro Husbandry during procedure Type of housing material size cage type if relevant Number of animals per cage or unit Bedding type quality any pretreatment Type of system conventional barrier ventilated rack isolator Environmental temperature C range Relative Humidity range Lighting natural artificial state hours of light and dark Ventilation number of air changes per hour Period of acclimatisation before start of procedure Feed type composition any pretreatment amount frequency Water type quality any pretreatment amount frequency Scientific procedure Number of animals and any pretreatment Time of day of procedure s Quantity and frequency of any samples Statistics Tests used should be named Reprints The number of copies the Chairman of the author s that the publication The first charge required should be ordered when Editorial Board has informed the paper has been accepted for 50 copies are provided free of

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NE MI 1111 11111111 international Joining forces to bring you a service that is better than ever hytwational Product Supplies IPS is the new name for fittiotech and PMI in the UK The new name brings together the expertise the experience and the brands of these two successful companies into a larger and more responsive customer focused organisation As the sole European distributor of PNI 1products IPS will supply the complete range of LabDier animal nutrition products The new company also inherits a diverse and growing portfolio of biotechnology fines from Unisorb paper products and Lignocel Contact Bedding to environmental enrichment products and protective clothing Now virtually all of your biotechnology needs are available from a single source And our range and service are set to go from strength to strength Shouldn t you be working with the new force in biotechnology For more details about IPS and our full range of products call us today on 01933 680133 IPS International Product Supplies Limited P O Box 6655 Wellingborough NN9 5YH Tel 01933 680133 Fax 01933 680155 E mai info ipsltd biz

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e4 4T 442e AUTOMATED WATERING SYSTEMS Eliminate bottles They are costly time consuming and lead to ergonomic injuries By using Edstrom Automated Watering Systems you can recoup your cost in as little as 2 years Besides Edstrom watering systems are reliable and VERY easy to maintain U1STANDING WATER QUALITY Using Reverse Osmosis water purification clean system design principles and automated flushing you can achieve outstanding water quality bacteria counts measuring consistently below 10cfu mL iletAtte A160 SHIELDED DRINKING VALVE The Edstrom A160 shielded Drinking Valve is precisely manufactured and calibrated Designed for use in IVCs the A160 features a bedding proof shield and low actuation force even weanling mice can use it 4heti ArmAt44 EDS IROM WATCHDOG SYSTEM Watchdog s access control lighting control and monitoring and environmental monitoring are all integrated into a common user interface This means your staff can easily learn the system The alarms are also integrated notifying the RIGHT people at the RIGHT time Watchdog Web provides site wide access to information and the whole system is compliant with electronic signatures rules le 44 to DUTIES OBSERVATIONS AND MESSAGING ViewPort is a digital clipboard for your animal facility By accessing ViewPort on web enabled devices like our VLP touchscreen or wireless handheld devices staff can view tasks that need to be done in animal rooms make observations and view room information When a task is complete the tech simply checks it off in ViewPort It becomes a permanent part of the record Imagine generating reports that show what tasks have been done and what tasks have not Edstrom Watchdog Contact our European Office V5 James Wilson B Eng Hons P O Box 13 HEREFORD HR4 8YP UK Tel Fax 44 0 1432 830 026 europe edstrom com INDUSTRIES INC Edstrom Industries Inc Waterford WI 53185 4299 USA Tel 1 262 534 5181 Fax 1 262 534 5184 IsNsNs ecktroin coni xiv

ATW April 2002

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