1. 2004 All Hands Meeting Welcome to the BIRN All Hands Meeting

2. Welcome  Thanks to BIRN-CC, Local organizers from MGH The Crossover Working Group

3. Welcome  NCRR Mike Marron Anthony Hayward  BIRN-CC Mark Ellisman  Testbed PI introductions

4. Why are we here?  BIRN-CC: Central infrastructure  Mouse BIRN: Animal models of human disease  BIRN-CC and Mouse BIRN reports this morning  Function and Morphometry BIRN: Human diseases Alzheimer’s Disease Schizophrenia

5. Alzheimer’s Disease  Affects a third of those over age 75  Progressive degenerative illness  Loss of memory, ability to plan and think  Loss of activities of daily living and develop troublesome behavior leading to institutionalization  Third most expensive illness  A family illness with enormous economic and social costs

6. AP = amyloid plaques; NFT = neurofibrillary tangles; Slide courtesy of: George Grossberg, M.D.; St. Louis University Neuropathological Changes Characteristic of AD Normal AP AD NFT

7. Impact of delaying onset of Alzheimer’s disease in USA Adapted from: Brookmeyer R et al. Am J Public Health. 1998; 88: 1337–42 16 Delay (years) 12 8 4 0 2052 2042 2032 2022 2012 2002 015015 Prevalence AD (millions) AD = Alzheimer’s disease

8. Course of aging: MCI & AD AAMI MCI Clinical AD Time (years) Cognitive decline ‘Brain’ AD Brain ageing Mild Moderate Moderately severe Severe AAMI = age-associated memory impairment; MCI = mild cognitive impairment Distinguish other diagnoses

9. 30 Nondemented Subjects with ApoE4 or E3 Allele ApoE4 Genotype and Brain Activation Change in Signal Intensity (%) Trial Number 1.6 -0.4 6 -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 54321 ApoE4 ApoE3 Bookheimer SY,, et al. N Engl J Med. 2000(Aug 17);343(7):450-456

10. The Development of Schizophrenia Sheitman BB, Lieberman JA. J Psychiatr Res. 1998(May-Aug);32(3-4):143-150 Age (Years) Good Function Poor 15203040506070 Premorbid Progression Stable Relapsing Prodrome ? Improving First Episode

11. Working Memory in Schizophrenia Sternberg task: Sternberg task: Five Two 5 6 2 8 1 + 8 + 3 Five items compared to Two 0 9 + 6 + 9

12. Genomics and Human Brain Function Genomics and Human Brain Function Clinical and cognitive measures Neuroimaging Inherited genotype DNA -48 A 3’ 5’ - 3’ 5’ - -48 G DRD1

13. Why are we here?  A concerted effort is required  To achieve more in synergy than as multiple uninvolved efforts  This is a new way to do science Is it a useful one? Is the whole greater than the sum of its parts?

14. Infrastructure development  Data sharing is essential and requires infrastructure  Terabytes of data are not amenable to ftp or mail  Data has to be meaningfully combined to generate new findings that would not otherwise be possible Clinical Measures Genotype Data Local Storage DUP Human Data Protection INSTITUTION A BIRN Rack SRB MCAT HID Portal Mediator Calibration & Analysis Tools Grid Federation: distributed DB, autonomous, access integrated resources Mediator: translates heterogeneous data sources to consistent representation Imaging Data

15. Infrastructure development  We need resources to support this scientific strategy The Shared Resource Broker (SRB) A federated database system Intelligent queries of nonlocal, integrated data,etc  The resources we develop are applicable beyond the original testbed intentions U54s, etc., MIND, TURNS, CATIE, NTROI, industry GCRC interactions

16. A new way of studying diseases  Cooperation among top competitors How to share, work, glory and $ Who makes and keeps the rules  Integrative and synergistic

17. A new way of studying diseases  Multidisciplinary research: Researchers working in parallel, in sequence, or jointly on a common problem maintaining a discipline-specific basis.  Transdisciplinary: Bridging several fields Develop a shared conceptual framework formed by integrating and synthesizing discipline-specific theories, and perspectives to address a common problem Such that the whole is more than the sum of its parts (Rosenfield, 1992).

18. A new way of studying diseases  This meeting is an invaluable opportunity to enrich your own research Collaborating with top researchers around the country and Developing novel methods across disciplines  What can the other test bed tools, methods, and findings offer you?  What of your methods and findings might enhance their research?

19. Challenges: Creating a New Culture  How to communicate across fields efficiently: Clinician scientistsComputer scientists Experimental psychologistsMRI physicists StatisticiansDatabase engineers Semantic WEB  How to show a clear scientific benefit from cooperation Efficiency of multiple studies in parallel; quick revisions Different perspectives create new ideas or achieve the lowest common denominator “designed by committee” Unique opportunity to do science differently & more richly and more productively

20. Today: Testbed Discussions BIRN-CC (9:30 am) Mouse BIRN (10:45 am) Morph BIRN (1:45 pm) Function BIRN (2:45 pm)

21. Today: BIRN Development  New initiatives involving BIRN (4:15 -5:00) Four NCRR U54 funded and two directly involve BIRN Roadmap Exploratory Center for Imaging Genetics ADNI, etc…  Cross-testbed interactions & coordination (5:00- 6:00) Information sharing, exploration of cross-test beds syngery Eg. Can Mouse use Morphometry’s Slicer? Eg. How FBIRN use Mouse registration tools?

22. Tomorrow: Steering the BIRN Future  Genetics: Its promise and challenge (8:30-10:00)  Task Force discussions: (10:30-3:30) Other institutions, investigators want access to the data and resources  This challenges current data sharing methods and policies  This requires clear IP and human subjects’ protections  This has IT resource implications and demands Given our experiences so far: How do we enable this access? This is an All-BIRN issue: these decisions affect YOU

23. Tomorrow: Where do we go now?  Providing BIRN toolkit and data, aka: Do you know where your portal is? (3:30 – 4:30 pm) What are the resources and tools currently available, developed by BIRN-CC and all the test beds How do you use these tools now? What are the current plans for future developments  Milestones for the next year (4:45 – 6:00 pm) How is the whole greater than the sum of the parts Does this infrastructure being created allow discovery of new, integrated findings based on the collaborative synergy of BIRN?

24. Also not to be missed  Executive Committee meetings Noon-2 pm each day  FBIRN Image Processing Pipeline Working Group meeting Noon Today in the Nantucket Room  Mediator hands-on demos Noon Tomorrow in the Nantucket Room  FBIRN Statistics Discussion Noon-3 pm Tomorrow in the Quincy Room