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The Future of Lab Animal Pathology. Mouse 2007: We need more mouse pathologists !!!! Cardiff RD.Cardiff RD. Pathologists needed to cope with mutant mice.

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Presentation on theme: "The Future of Lab Animal Pathology. Mouse 2007: We need more mouse pathologists !!!! Cardiff RD.Cardiff RD. Pathologists needed to cope with mutant mice."— Presentation transcript:

1 The Future of Lab Animal Pathology

2 Mouse

3 2007: We need more mouse pathologists !!!! Cardiff RD.Cardiff RD. Pathologists needed to cope with mutant mice. Nature May 31;447(7144):528. Barthold SW, Borowsky AD, Brayton C, Bronson R, Cardiff RD, Griffey SM, Ince TA, Nikitin AY, Sundberg J, Valli VE, Ward JM.Barthold SW, Borowsky AD, Brayton C, Bronson R, Cardiff RD, Griffey SM, Ince TA, Nikitin AY, Sundberg J, Valli VE, Ward JM. From whence will they come? - A perspective on the acute shortage of pathologists in biomedical research. J Vet Diagn Invest Jul;19(4):455-6.

4 Schofield PN, Brown SD, Sundberg JP, Arends M, Warren MV, Dubus P, Ellender M, Fiette L, Rozell B, Quintanilla-Martinez L, Raspa M, Song JY, van der Valk M, McKerlie C. PRIME importance of pathology expertise. Nat Biotechnol Jan;27(1):24-5. Warren MV, Studley ML, Dubus P, Fiette L, Rozell B, Quintanilla-Martinez L, Raspa M, Breuer M, Song JY, Gates H, Brown SD, Schofield PN.Warren MV, Studley ML, Dubus P, Fiette L, Rozell B, Quintanilla-Martinez L, Raspa M, Breuer M, Song JY, Gates H, Brown SD, Schofield PN. An impending crisis in the provision of histopathology expertise for mouse functional genomics. J Pathol Jan;217(1): “…lack of trained pathologists and a lack of trainees entering the field” “…a significant proportion of vacant posts across Europe remain unfilled for 6 months or more, due to lack of qualified applicants, lack of funding” 2009: Really, you do need us….

5 Nature May 27;465(7297):410. Mouse project to find each gene's role. Abbott A. International Mouse Phenotyping Consortium (IMPC) The knockout strains will then be put through rigorous, systematic phenotypic screens, which will check for physical and behavioural differences. The information will be stored in a purpose-built, open-access database Knockout science: massive mouse project to provide window into human diseases. Hampton T. JAMA Nov 9;306(18): : The role of pathology in high throughput phenotyping Dis Model Mech Jan;5(1): doi: /dmm Epub 2011 Oct 25. Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice. Schofield PN, Vogel P, Gkoutos GV, Sundberg JP.

6 “….not only the authors but also the reviewers and editors often have neglected to consult a comparative pathologist during the evaluation of such manuscripts. “ Ince TA, Ward JM, Valli VE, Sgroi D, Nikitin AY, Loda M, Griffey SM, Crum CP, Crawford JM, Bronson RT, Cardiff RD.Ince TA, Ward JM, Valli VE, Sgroi D, Nikitin AY, Loda M, Griffey SM, Crum CP, Crawford JM, Bronson RT, Cardiff RD. Do-it-yourself (DIY) pathology. Nat Biotechnol Sep;26(9):978-9; 2008: Ummmm….don’t do this at home….

7 Lamborghini Macaque

8 Giles J. Animal experiments under fire for poor design. Nature Dec 21;444(7122): : Hmmm…there seems to be a problem of translation…

9 Unreliable research Trouble at the lab Oct 19th scientists-think-science-self-correcting- alarming-degree-it-not-trouble December 2, 2011 Scientists’ Elusive Goal: Reproducing Study Results reproducing-study-results 2011: WALL STREET JOURNAL 2013: THE ECONOMIST

10 2013 Couzin-Frankel J. When mice mislead. Science Nov 22;342(6161):922-3 Baker D, Lidster K, Sottomayor A, Amor S. Reproducibility: Research-reporting standards fall short. Nature Dec 6;492(7427):4 Nat Rev Neurosci May;14(5): Power failure: why small sample size undermines the reliability of neuroscience. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafò MR. Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. Sena ES, van der Worp HB, Bath PM, Howells DW, Macleod MR. PLoS Biol Mar 30;8(3)Sena ES, van der Worp HB, Bath PM, Howells DW, Macleod MR.

11 2005: Ioannidis JP. Why most published research findings are false. PLoS Med Aug;2(8):e : the CONSORT guidelines. Adopted by many clinical journals: the requirements to report whether and how the studies were blinded and randomized, how sample size was determined, how data were handled, and other important determinants of quality clinical science Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Plos Med 2010;7:e : Improved design and reporting for human clinical trials 2010: ARRIVE guidelines. Br J Pharmacol Aug;160(7) For animal studies

12 Howells DW, Sena ES, Macleod MR. Bringing rigour to translational medicine. Nat Rev Neurol Nov 19 Landis SC et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature Oct 11;490(7419): Announcement: Reducing our irreproducibility. Nature 496, 398 (25 April 2013) CHECKLIST FOR REVIEWERS: INCL ARRIVE GUIDELINES 2013: Improved design and reporting for animal trials

13 Mice are not small humans A mouse is not a mouse is not a mouse Academic environment favors positive results prolific publication tight budgets promote small sample sizes Journals: do not enforce consistent design/interpretation standards Vet pathologists: need genetics/cell bio/research training


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