hm-2 product tutorial: enhancing animal welfare in high

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27-08-2012 Henrik Johansen 1

HM-2 Product Tutorial: Enhancing animal welfare in high throughput systems

Measuring Behavior 2012, UtrechtDate: Friday August 31Time: 14:00 - 15:20Location: 42


Agenda

� Presentation of MBRose and the HM-2.� Basic demonstration, functionality

� Automated animal models in a 3 R’s perspective. � Case demonstrations� Time shifted start

� Back annotation

� Your case

� And yours

� Telemetry combo, DSI embedded in HM-2

� Event based video tracking w. negative offset

� Discussion, Q&As


MBRose mission

MBRose creates value to its customers by continuous innovation and development of

systems for feed intake and activity monitoring

Group housing of animalsTurn key systems

Tailored rack system

ethical, ergonomic, hygienic, useful in large scale installations and seamlessly integrated

into the customer IT system.

New!


HM - design

� Uses standard home cages

� Online monitoring of food and water

� Online activity monitoring

� Event based video tracking with negative offset

� Control of spills and evaporation

� Hygienic and cleaning friendly

� Simple tara and diagnostic function of entire system

� Simple cabling

� Developed in cooperation with researchers and operators in the Danish Pharmaceutical industry

� 15+ years operations experience


HM-2 Idea

� Group housed animals

� Individual feed and drink monitoring

� PIR activity monitoring

� High Throughput system

RFID Chip-tag

Cage type Description Application Eurostandard

Techniplast 1354 595 x 380 x 200 mm. flat or elevated lid Multiple rats/mice Type IV

UNO Type IV S 500 x 380 x 208 mm, lid w. .hopper Multiple rats/mice Type IV S

Techniplast 1500U 480 x 375 x 210 mm, flat or hopper lid Multiple rats/mice Type IV S

Techniplast 1290D 426 x 255 x 155 mm. Flat or elevated lid Multiple mice, Type III

Techniplast 1291H 426 x 255 x 185 mm, flat or elevated lid 1-2 rats, Type IIII H

Techniplast 1284L 365 x 207 x 140 mm, flat lid w. hopper Multiple mice Type II L


HM-2 features

� Asymmetrical loadcells

� High performance electronics

� Double photo detectors

� RFID online monitoring� E-vet, Pet-ID, Datamars

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HM - Feed system

� Everything in contact with animals is:� Polycarbonate and Stainless Steel

� Easily detachable, no tools needed� All machine washable

� Modular design gives options:� Food and liquid preference.� Mice to rats change in minutes.

� Feed pills and powder

� Consumption by weight

� Mix and match your requirements


HM-2 Session Monitor

• SQL database solution• Experiment, session,

study, planning• Lab-PC cockpit chart• Online monitoring


HM-2 Results report generator


Sample study

� 12 hour sample study, group housed mice.

� Courtesy of Niels Wellner Andersen [[email protected]]

FEED Intake Start 10/3-2010 17:25

0

1

2

3

4

5 Group 1 (2,4,6,14)Group 2 (8,10,11,13)Group 3 (1,7,9,16)Group 4 (3,5,12,15)

Groups

Inta

ke (

g)

FEED Intake Start 11/3-2010 17:25

0

1

2

3

4

5 Vehicle (2,4,6,14)Drug A (8,10,11,13)Drug B (1,7,9,16)Drug C (3,5,12,15)

Dose Groups

Inta

ke (

g)

Meals Start 10/3-2010 17:25

0

4

8

12

16

20

24

28 Group 1 (2,4,6,14)Group 2 (8,10,11,13)Group 3 (1,7,9,16)

Group 4 (3,5,12,15)

Groups

No

Of

Mea

ls

Meals Start 11/3-2010 17:25

0

4

8

12

16

20

24 Vehicle(2,4,6,14)Drug A (8,10,11,13)Drug B (1,7,9,16)Drug C (3,5,12,15)

Dose Groups

No

Of

Mea

ls

Meal Duration Start 10/3-2010 17:25

0

100

200

300

400 Group 1 (2,4,6,14)Group 2 (8,10,11,13)Group 3 (1,7,9,16)Group 4 (3,5,12,15)

Groups

Mea

l Du

rati

on (

Sec

)

Meal Size Start 11/3-2010 17:25

0.0

0.1

0.2

0.3Vehicle(2,4,6,14)Drug A (8,10,11,13)Drug B (1,7,9,16)Drug C (3,5,12,15)

Dose Groups

Mea

l Siz

e (g

)

Meal Size Start 10/3-2010 17:25

0.0

0.1

0.2

0.3 Group 1 (2,4,6,14)Group 2 (8,10,11,13)Group 3 (1,7,9,16)Group 4 (3,5,12,15)

Groups

Mea

l Siz

e (g

)

Meal Duration Start 11/3-2010 17:25

0

100

200

300

400 Vehicle(2,4,6,14)

Drug A (8,10,11,13)Drug B (1,7,9,16)Drug C (3,5,12,15)

Dose Groups

Mea

l Du

rati

on (S

ec)

Habituation Study


Office-PCw. HM-View

OFFICE

LABORATORY

Office-PCw. HM-View

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

EMB-RDMBSFIREBIRD

CorporateDBMS

IT-DEPT.SERVER ROOM

HM-RDMBSFIREBIRD

Office-PCw. HM-View

Lab-PCw. HM02Lab

HM-2 Network Setup


Stations in cabinet 100% drawers

� Separate drawers

� Integrated cabling

� Washable rack

� Daylight control

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HM-2 in test


HM-2, Best in class

� Event-based data acquisition� 20 mg accuracy

� Group housing of animals� Cockpit chart view with built in alarms� Robust system, immune to network failures

� Hygienic, easy to clean� Results available during experiment� Flexible data mining tool


Agenda



� Back annotation

� Your case

� And yours




Discussion, Q&A

� Feed and water intake, measures of animal welfare� Electronic identification, RFID

� Group housing advantages� Work flow, Animal Caretaker, Lab Technician,

Researcher



Agenda



� Back annotation

� Your case

� And yours




Automated animal models in a 3 Rs perspective.

� The 3R principle (replace, reduce, refine) has its origins with William M. S. Russell & Rex L. Burch, who published their “Principles of Humane Experimental Technique” in 1959. These principles are regarded internationally as the guideline for avoiding or reducing animal experiments and the suffering of laboratory animals:

� Replacement: replacement of animal experiments by methods that do not involve animals

� Reduction: reduction in the number of animals in unavoidable animal experiments

� Refinement: improvement in experimental procedures, in unavoidable animal experiments

� http://en.wikipedia.org/wiki/Basel_Declaration


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The Basel Declaration


� “The Basel Declaration was issued on 30 November 2010 by over 60 scientists from Switzerland, Germany, the United Kingdom, France and Sweden. The signatories commit to accepting greater responsibility in animal experiments and to intensive cooperation with the public in the form of a dialogue with prejudice. At the same time, they demand that essential animal experiments for obtaining research results remain permitted both now and in the future. With their Basel Declaration, researchers are seeking to achieve a more impartial approach to scientific issues by the public and a more trusting and reliable cooperation with national and international decision makers.”

� Basel Declaration | Münchhaldenstrasse 10 | PF 876 | 8034 Zurich |www.basel‐declaration.ch | contact@basel‐declaration.org

EU Directive on social housing


� DIRECTIVE 2010/63/EU of 22 September 2010 onthe protection of animals used for scientific purposes– section 3.3. Housing and enrichment, (a) Housing.

� “Animals, except those which are naturally solitary,shall be socially housed in stable groups ofcompatible individuals. In cases where single housingis allowed in accordance with article 33(3) theduration shall be limited to the minimum periodnecessary…”

Wireless electronic identification, RFID


The use of databases in data acquisition


Structured Query Language

Combining RFID and SQL in automated systems


Keeping your data alive and in good health


“What’s it really like to be a SQL Server DBA and ho w do I know if it is the right career for me?” .

� Retrievable data in new environments� SQL keeps your data alive

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On line monitoring of feed and water intake, a practical example.


3 Rs improvement, conclusion

� The 3 Rs of improvements using RFID and SQL are

� Social housing, individual monitoring

� Data extraction interactive� Event based approach and open SQL interface

� Pointing to the future


• Replace• Reduce• Refine

• Reliable• Reproducible• Retrievable


Agenda



� Back annotation

� Your case

� And yours




Time-shifted start

Case demonstration


Back annotation,viewing old data with new filters

Case demonstration


Your Case

Case demonstration


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HM-2 – DSI ComboPilot study on sibutramine

27-08-2012 H. Johansen 31

Work made with the integrated DSI telemetry system in an existing HM-2 system at Neurosearch A/S, Ballerup Denmark, involving researchers Henrik Hansen and Bo Hjort Bentzen, February – October 2011

Confidential

DSI – HM-2 Combo



From DSI Tutorial, Tuesday, afternoon August 28th

DSI Configuration, 2 x pair, 4 x single


[20-07-2012 15:49:28]

Display Connected Devices HM-02 position

PCI Card: CQ2240 SN 4168

Matrix: MCC-1 SN 2366

A MCC-1 SN 2366

A1 MCC-1 SN 6492

A2 APR-1 SN 1826

B MMX-1 SN 3154

B1 RPC-1 SN 6757 Station 1, front, 450 kHz

B2 RPC-1 SN 6787 Station 1, rear, 450 kHz

B3 RPC-3 F0 SN 42 Station 3, front, 450 kHz

B4 RPC-3 F0 SN 41 Station 3, rear, 450 kHz

B5 RPC-3 F2 SN 42 Station 3, front, 18 MHz

B6 RPC-3 F2 SN 41 Station 3, rear , 18 MHz



C MMX-1 SN 3185

Matrix: MCC-1 SN 6492

A MCC-1 SN 6492

B MMX-1 SN 11276





B5 9010 SN 9998 Station 4, front, 18 MHz

B6 9010 SN 9999 Station 4, rear , 18 MHz



C MMX-1 SN 11277

OK

MCC-1

RPC-1

Conclusions from pilot study (n=2)

27 August 2012 H. Hansen, B. H. Bentzen 35

� The effect of acute sibutramine treatment of telemetrized rats reflects findingsin human subjects with respect to:- appetite suppression- increased blood pressure and heart rate

� In this acute setting, sibutramine did not affect diastolic blood pressure,suggesting that subchronic or chronic dose settings may be required to detectsignificant effects on this parameter

� The integration of HM-2 and DSI telemetry system provides data with extremelyhigh data and temporal resolution

� The integrated HM-2:DSI telemetry system can detect even minor changes inphysiological endpoint parameters

� The pilot study was conducted in normal-weight rats, hence, the physiologicaleffects monitored in the HM-2:DSI telemetry system may be more pronouncedin obese rats

Confidential

Findings, pilot study (n=2)

� Dose level of sibutramine (7.5 mg/kg, p.o.) is reported being a typical dose usedin a series of research papers

� The parent compound sibutramine is a dual SNRI

� Sibutramine (racemate of R- and S-form) is metabolized in the liver to producemetabolites being potent triple MRIs, with the R-enantiomers being most potent,i.e. R-desmethylsibutramine (Tmax 2.3h, T½ 4.2h) and R-didesmethylsibutramine(Tmax 2.7h, T½ 7.9h) (Noh et al., Arch Pharm Res 33(2):267-273, 2010).

� Sibutramine produces a strong anorectic response in telemetrized rats, lastingfor up to 48 hrs (PPP slides 3-5), likely reflecting the DMPK proporties ofsibutramine

� Sibutramine increases systolic (peak effect of +9 mm Hg) and mean (peak effectof +6 mm Hg), but not diastolic, blood pressure over at least 48 hrs

� Sibutramine increases heart rate (peak effect of +48 bpm) over 24 hrs

� Sibutramine slightly affects core body temperature

� No significant effect on motility

August 27, 2012 H. Hansen, B. H. Bentzen 36Confidential

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Cumulated food intake (15 min intervals, first 24h)


Sibutramine stronglyreduces food intake over at least 24h

Confidential

Food intake over several light-dark periods


Normalization offeeding activity

Confidential

Food & water intake (12h intervals)

27 August 2012 39Header and footer

Food intake

Water intake

Confidential27 August 2012

Systolic blood pres. (15 min intervals, first 24h)

27 August 2012 H. Hansen, B. H. Bentzen40 Confidential

Systolic and diastolic blood pressure

27 August 2012 Header and footer41 Confidential27 August 2012

Mean blood pressure (15 min intervals, first 24h)


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Mean blood pressure


Heart rate (15 min intervals, first 24h)


Heart rate


Activity/Motility


Core body temperature

27 August 2012 H. Hansen, B. H. Bentzen47

Event-based video tracking w. negative offset

Case demonstration


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THANK YOU FOR YOUR TIME!

This is the end!


hm-2 product tutorial: enhancing animal welfare in high

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