Presentation of Activities of New Visby Hepatitis C Network 2002-2011 Anders Widell,

1. Presentation of Activities of New Visby Hepatitis C Network 2002-2011 Anders Widell, MD, PhD, Ass Prof, Network Coordinator, Department of Medicine, Lund University, Sweden Maria Isaguliants, PhD, Ass Prof Microbiology and Tumor Biology Center, Karolinska Institutet

2. Year 2002: 2879/2002 (381/M20) 6 teams; 31 researchers & students Swedish participants: Core HCV Network participants active since 2002/2003 are shadowed in yellow COORDINATOR Malmö University Hospital, Lund University Swedish Institute for Infectious Disease Control, Karolinska Institutet Participants from Baltic Region Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow Institute of Cytology, St Petersburg Biomedical Research and Study Center, Latvian University, Riga Narvac R & D Company, Moscow

3. How we started – a talk given by Network Coordinator Prof Anders Widell, Univesity of Lund, Malmö, on the 7th Annual meeting of the Network eight years later

4. 7 teams; 35 researchers & students Year 2003: NNNN Swedish participants Swedish Institute for Infectious Disease Control, Karolinska Institutet Center for Molecular Medicine, Karolinska Institutet COORDINATOR Malmö University Hospital, Lund University Participants from Baltic Region Biomedical Research and Study Center, Latvian University, Riga Moscow StateUniversity of Medicine and Dentistry, Moscow Institute of Cytology, St Petersburg Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow

5. 8 teams; 53 researchers & students Year 2005: 01789/2005 Swedish participants Swedish Institute for Infectious Disease Control, Karolinska Institutet Center for Molecular Medicine, Karolinska Institutet COORDINATOR Malmö University Hospital, Lund University Participants from Baltic Region Biomedical Research and Study Center, Latvian University, Riga, Latvia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia University of Tartu, Institute of Microbiology, Tartu, Estonia Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow Belarusian State Medical University,Minsk, Belarus

6. 8 teams; 57 researchers & students Year 2006: 01551/2006 Swedish participants Swedish Institute for Infectious Disease Control, Karolinska Institutet Center for Molecular Medicine, Karolinska Institutet COORDINATOR Malmö University Hospital, Lund University Participants from Baltic Region Biomedical Research and Study Center, Latvian University, Riga, Latvia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia University of Tartu, Institute of Microbiology, Tartu, Estonia Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow Belarusian State Medical University,Minsk, Belarus

7. 8 teams; researchers & students 57; travelling 25 Year 2007: 01420/2007 Swedish participants Center for Molecular Medicine, Karolinska Institutet COORDINATOR Malmö University Hospital, Lund University Swedish Institute for Infectious Disease Control Participants from Baltic Region Biomedical Research and Study Center, Latvian University, Riga, Latvia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia University of Tartu, Institute of Microbiology, Tartu, Estonia Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow Belarusian State Medical University,Minsk, Belarus

8. Year 2008: 01191/2008 7 teams; 46 travelling researchers & students planned Swedish participants COORDINATOR Malmö University Hospital, Lund University Swedish Institute for Infectious Disease Control Participants from Baltic Region Biomedical Research and Study Center, Latvian University, Riga, Latvia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia National Institute of Health, Tallinn, Estonia Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow Research Institute for Epidemiology and Microbiology, Minsk, Belarus

9. Year 2009: 00894/2009 7 teams; 46 travelling researchers & students planned Swedish participants (2) COORDINATOR Malmö University Hospital, Lund University, Malmö Swedish Institute for Infectious Disease Control, Stockholm Participants from Baltic Region (6) Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow, Russia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia National Institute of Health, Tallinn, Estonia Biomedical Research and Study Center, Latvian University, Riga, Latvia Department of Internal Medicine, University of Tartu, Tartu, Estonia Institute of Cytology, St Petersburg, Russia

10. Year 2010: 00747/2010 9 teams; mobility resources for 54 researchers & students Swedish participants (2) Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm COORDINATOR Malmö University Hospital, Lund University, Malmö Participants from Baltic Region (7) Biomedical Research and Study Center, Latvian University, Riga, Latvia Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow, Russia Moscow StateUniversity of Medicine and Dentistry, Moscow, Russia National Institute of Health, Tallinn, Estonia Department of Internal Medicine, University of Tartu, Tartu, Estonia Center for Communicable Diseases and AIDS, Vilnius, Lithuania Institute of Cytology, St Petersburg, Russia

11. SUGGESTED INCOMMING PROJECT: New Visby Network on Hepatitis C 2011-2012 (two years): Identification, Control and Prevention of Hepatitis C Utilizing Novel Biomedical Technologies

12. Network Structure Applied for in 2011: Sweden Karolinska Institutet, MTC (Coordinator) Lund Universitet Estonia Tartu University, Tartu National Institute for Health Development, Tallinn Latvia Biomedical Research and Study Center, Riga; Lithuania Center for Communicable Diseases and AIDS, Vilnius Russia Academy of Medical Sciences, Moscow; State University of Dentistry and Medicine, Moscow; St Petersburg University, Biomedical Center, St Petersburg Institute of Cytology, St Petersburg New partner: Biomedical Center, St Petersburg University, St Petersburg, Russia

13. Selected joint publications of the teams 2002-2010

14. Selected joint publications of the teams 2004

15. Selected joint publications of the teams 2005

16. Selected joint publications of the teams 2006 Euro Surveill. 2006 Jan 26;11(1):E060126.3. Tefanova V, Tallo T, Kutsar K, Priimgi L. Urgent action needed to stop spread of hepatitis B and C in Estonian drug users. National Institute for Health Development, Estonia.

17. Selected joint publications of the teams 2006

18. Selected joint publications of the teams 2006

19. Selected joint publications of the teams 2007

20. Selected joint publications of the teams 2008

21. Selected joint publications of the teams 2009

22. Selected joint publications of the teams 2009

23. Selected joint publications of the teams 2010

24. Selected posters from research meetings 2002-2010

25. DNA Vaccine Conference, Monaco, 2006 IMMUNIZATION WITH HEPATITIS C VIRUS CORE GENE RESULTS IN THE LOSS OF T-CELLS M Isaguliants1, 2, N Petrakova1, Yu Suzdaltzeva1, V Makhonov1, A Krivonos3, B Wahren2, and E Nordenfelt2 1Ivanovsky Institute of Virology, Russia; 2Swedish Institute for Infectious Disease Control, Sweden; 3Narvac R&D Company, Moscow; Russia BACKGROUND: Highly conserved core protein of HCV presents an attractive target for anti-HCV vaccine design. Numerous attempts to induce immunity against HCV core by genetic immunization met serious difficulties in optimizing core-specific T-helper cell and antibody responses (Vidalin et al., 1999). Immunomodulatory properties of HCV core could be blamed, since in mice it was shown to interfere with vaccinia-specific CTL responses (Large et al., 1999). No demonstrable effects of HCV core were, however, observed for adenovirus-specific immune responses (Liu et al., 2002). A C B • Fig. 1 Mouse fibroblasts NIH3T3 transiently transformed with pCMVcore191. Field A, nuclei and immunofluoresent staining (rabbit anti-HCV core rabbit polyclonal antibodies and FITC-conjugated anti-rabbit antibodies); field B, immunofluoresent staining; field C, phase contrast. • EXPERIMENTAL • cDNA encoding full-length core of HCV 1b isolate 274933RU was cloned under the control of CMVIE-promoter and HPV16 polyA signal. Eukaryotic expression was verified by Western blotting and IF staining (Fig. 1). Groups of 10 to 12 C57BL/6 (H-2b) mice were immunized by intramuscular injections of 50 mg of HCV core gene, or empty vector, or water, four times at 2 week intervals. Mice (3 to 5) were sacrificed every 3rd week, tissue samples and spleens were withdrawn. Splenocytes were isolated by gradient centrifugation. Percent of CD19+, CD3+, CD4+, and CD8+ splenocytes was evaluated by flow cytometry. Proliferative responses of spenocytes were assayed by [3H]-incorporation test using recombinant core and core-derived peptides. Production of IFN-g, IL-2 and IL-4 in response to T-cell stimulation was assessed by sandwich ELISA. Mouse tissue samples were fixed in 10% neutral-buffered formalin. Fixed tissue sections embedded in paraffin were cut into 4-6 mm sections, mounted on glass slides and stained by the routine hematoxyline and eosin techniqu. Immunization and follow-up experiments were repeated three times. RESULTS No pathological changes were found in muscle, skin, spleen, liver, lungs, heart, brain, or lymph nodes of pCMVcore191-recipients. Immune response was induced in the majority (24/32, 75%) of mice. Strong T-helper cell response to HCV core and core-derived peptides (SI 2.5 to 80) was induced after three pCMVcore191 injections (Fig. 2). Immunodominant T-helper epitope mapped to aa 76-90 was recognized by 70% of pCMVcore191-recipients (Fig. 2). HCV-core and core peptide-stimulated splenocytes of immunized mice responded by strong sustained production of IFN-g, moderate levels of IL-2 and infrequent low-level production of IL4 (Fig. 3). Antibody response against core and/or its linear epitopes was weak (titer ≤100) and infrequent (6/22, 27%). Fig. 2 Proliferation of splenocytes of pCMVcore191-immunized mice in response to HCV core and core-derived peptides Fig. 3 Cytokine secretion in proliferating splenocytes of pCMVcore191-immunized mice RESULTS Surprisingly, after one month, CD3-positive-cell population in pCMVcore191-recipients started to decrease. One month after the last gene injection, the decrease amounted to 7-9% of CD3+-cells, more CD4+ than CD8+ (p<0.05; day 80,Fig. 4). • CONCLUSIONS • Transient expression of HCV core in the gene recipients did not exert any histopathological changes, despite multiple effects of HCV core on cell function (Zhuet al.,1998; Ray & Ray, 2001; Sogueroet al.,2002) including the oncogenicity (Rayet al.,1996). • HCV core gene immunization induced potent T-cell, but only weak B-cell reactivity. • Repetitive injections of HCV core gene induce a significant (p<0.05) decrease in CD3-positive cell population. Depletion might be linked to the increased apoptosis sensitivity of core-expressing T-lymphocytes , while B-lymphocytes were shown to be unaffected (Giannini et al., 2002). T-cell deficit resulting from the immunomodulatory properties of HCV core can explain its specific immunogenic performance. Fig. 4 Dynamical changes in % of CD4+ and CD8+ T-cell populations in pCMVcore191- versus empty vector-immunized mice (each time-point is represented by five mice) Acknowledgements: This work was financed by European Commision grants ERB IC CT98-0313, INTAS 96-1565.

26. Immune imprints of hepatitis C identified in clinical cases of hepatitis of unknown origin Elena Tsyganova1,2* ; Olga Znoiko1,2; Natalia Petrakova2; Tatjana Petrova3,4; Igor Maljkov4; Maxim Vonsky5; Alexander Ivanov6,10; Birke Bartosch7; Mikhail Mikhailov8, Nikolai Yushchuk1; Anders Widell9; and Maria Isaguliants2,10 1 Moscow State University of Dentistry and Medicine, Moscow; 2. DI Ivanovsky Institute of Virology, Moscow; 3 Russian State Institute of Immunology, Moscow; 4. DNA Technology R&D Company, Moscow; 5. Institute of Cytology, St Petersburg; 6 WA Engelhardt Institute of Molecular Biology, Moscow; 7 INSERM U758, Lyon, France; 8. Institute of polyomyelitis, Moscow; 9. Malmö University hospital, University of Lund, Malmo, Sweden 10 Swedish Institute for Infectious Disease Control, Stockholm, Sweden 24th IUSTI-Europe Conference on sexually transmitted infections and HIV/AIDS, Milano September 4-6, 2008, p 79-80, P41

27. 16th Conference on hepatitis C, Nice, 2009 Personalnytt Personalhandboken Lediga tjänster Fackliga frågor Personalsektionen Alkohol- och drogproblem Anställningens upphörande Arbetsskador Arbetstid Arbetstidslängd schema 2006 Arvode Avtal (lokala) Bisyssla och jäv Blanketter Egenrapportering Egenrapportering av resor, Lathund Ersättning för sjukvårds- och läkemedelskostnader Etik och moral Flextid Friskis & Svettis, Friskvård Föredrag, externa Företagshälsovård Försäkringar Föräldrarledighet Introduktion Jämställdhet Kommunikation Kompetensutveckling Kostnadsersättning / Kontantutlägg Lathund för forskarstuderande Ledarrollen Ledigheter (övriga) Lön Medarbetarrollen Mobbning och/eller etnisk diskriminering Mångfaldsplan Nit och redlighet i rikets tjänst Pensioner Pensioner (lathund uträkning) Personalgåvor Personalredogörare vid SMI Post.doc./doktorandtjänster Rehabilitering Rekrytering Representation Samverkansavtal Semester Sjukfrånvaro Skatter och sociala avgifter Stipendier och utbildningsbidrag Terminalglasögon Tidomat/lathund Tjänsteresor policy Tystnadsplikt och sekretess Uppföljningssamtal/ utvecklingssamtal Lediga tjänster Tillsatta tjänster Fackliga organisationer vid SMI Samverkansavtal för SMI Huvudskyddsombud och skyddsombud-förteckning Skyddsombud E-post FAQ IT-support IT-säkerhet Kontakt Regler - Frånvaromeddelanden i Notes Ekonomihandboken Elektronisk fakturahantering Verksamhetsplan 2006 Inköpsavtal och regler Centraliserade inköp Kontakt Konferenser och SMI-dagar Kontakt Logotyp Mallar och instruktioner Mediekontakter Nyhetsbrev PowerPoint-presentation av SMI Riktlinjer för intern och extern information Skrivregler Tidningen Smittskydd Trycksaksproduktion Webb: Bildhantering på webben Webb: Hemsidan Webb: Intranätet Webb: Lokala redaktörer Checklista - att ordna konferens SMI-dagar Brev och fax med SMI:s logotyp Postermallar Korrespondens- och visitkort OH-bilder/PowerPoint Rapportserien Riktlinjer för massmediekontakter Vem ska uttala sig i media? Att tänka på när du blir intervjuad Rapportera mediekontakt Rapporterade mediekontakter Lagar och etiska regler EPI-aktuellt EPI-aktuellt - grafisk form Influensarapporter Norovirusrapporter RSV-rapporter Allmänna skrivregler Specifika skrivregler för SMI Råd för webbskrivande Riktlinjer för trycksaker Layout Struktur och innehåll Färger Typografi Tabeller Bokmärkeslänkar Att infoga dokument på webben Bildhantering på webben Regler för länksamlingen Att publicera nyheter på startsidan Redaktörshandbok för EPiServer Instruktion för vetenskaplig publicering Struktur och innehåll Färger Typografi Tabeller Bokmärkeslänkar Att infoga dokument på intranätet Att publicera nyheter på startsidan Redaktörshandbok för EPiServer Lathund för ekonomihandboken Lathund för publicering av protokoll på intranätet Utbildning i EPiServer Ansvar och roller Styr- och stöddokument för redaktörer Biosäkerhet och kvalitet Centralförrådet Corefaciliteter Königs Restaurang Posthantering internt Reception och växel Statistikerna Turbilar och bud Biosäkerhet och Kvalitet Kontakt FACS Genomik - Senaste Nytt ELEKTRONMIKROSKOPI Presentation av SMI:s corefaciliteter MICROARRAY GENOMIK Sekvenskemi Guidelines/sekvensering FAQ-extraktion FAQ-realtids-PCR FAQ-sekvensering PROTEOMIK Prislista för corefaciliteterna Veckans matsedel Restaurang Königs SMI:s matråd Andra restauranger vid/kring KI Besöksbokning (esSDe Reception) Dokumenthantering (SmiDok) Egenrapportering (Palasso) Ekonomisystem (Agresso) Lokalbokning Avdelningsvisa dokument Krispärm Protokoll Styrdokument Personalklubben Annonser Aktiviteter Köpes Säljes Uthyres Önskas hyra The presence of neutralizing activity against genotype-matched HCV pseudoparticles in acute phase sera correlates with resolution of HCV infection 1Swedish Institute for Infectious Disease Control, Stockholm; 2Ivanovsky Institute of Virology, Moscow; 3Malmö University hospital, Malmö; 4St Petersburg Institute of Cytology, St Petersburg; 5Moscow State University of Dentistry and Medicine, Moscow; 6INSERM, U871, 7Université Lyon 1, IFR62 Lyon-Est, and 8Hospices Civils de Lyon, Lyon, France. Isaguliants M1,2, Petrakova N2,3, Jansons J3, Vonsky M3,4, Dudina K2,5, Gutman E3, Znoiko O5, Bartosch B6,7,8, Widell A3 Serum neutralizing activity can be assessed usingpseuo-typed retroviral particles displaying HCV envelope proteins E1and E2.We investigated at the time of jaundice and during follow up the neutralizing capacity in sera of patients clearing HCV infection and patientswho developed chronic HCV infection Generation of HCV pseudoparticles HCVpps were generated by co-transfection of HEK293 cells with MLV expressing vector mediating formation of retroviral pseudoparticles, and HCV E1/E2 and GFP expression vectors that provided for incorporation of HCV E1 and E2 onto particle surface and GFP into the particles, respectively (Fig 1). The nature of HCVpps was confirmed by PAGE and Western blotting using anti-E2 monoclonal antibody (Fig 2). HCVpp neutralization At early time points sera of patients clearing HCV had a significantly stronger capacity to inhibit HCVpp infection.Already at day 3 to 10 from jaundice, sera of patients clearing HCV inhibited infection with HCVpp at dilution 300±150, and by month 6, at 400±200. Early sera of patients developing chronic hepatitis C did not inhibit HCVpp infection. Inhibition titers of 450±250 were reached with a delay of 3 to 6 month. Statistically, early sera of clearing patients were different from sera of healthy controls, as they have the capacity to inhibit infection, while early sera of chronizing patients behaved as that of the healthy controls (no inhibition over the background levels; Fig. 3AB). Inhibition was severely diminished by the removal of serum IgG (Fig. 4). Results Materials and Methods • Patients and controls: • One patient infected with HCV 1b (St Petersburg, Russia) and one with HCV 3a (Malmö, Sweden) with high viral load. Their sera was used as a source of HCV RNA to create HCV pseudoparticles (HCVpp´s). • Patients (n=19) with acute hepatitis C were followed from onset of symptoms, at month 1, 3, 6, and 12 to either clearance confirmed by repetitive PCR analysis of sera and PBMC (RE; n=7;) or chronicity (CHR; n=12). Of clearing patients, 4 were infected with HCV 1b, 1 with HCV 1a; of chronizing, 6 had HCV 1b, and 4 - HCV 3a. In totally four, HCV could not be typed. These sera and sera of healthy individuals (n=9) were used to inhibit HCVpp infection. • Assays & Methods: • HCV RNA was amplified by RT-PCR from sera of chronic patients infected with HCV 1b (Gene Bank FJ411253) and HCV 3a (Malmö, Sweden). • Fragments encoding the last 60 aa of core, E1 and E2 were cloned into eukaryotic expression vector phCMV-7a (Bartosch B et al, 2003) in exchange for the respective HCV 1a sequence. • HEK293T/17 cells were co-transfected with HCV E1/E2 encoding plasmids, CMV-Gag-Pol murine leukemia virus (MLV) packaging construct encoding MLV gag and pol genes, and the MLV-GFP plasmid expressing GFP. Supernatents containing pseudoparticles were collected 40 h later. Control particles carried feline endogenous virus RD114 glycoproteins (RD114pp). • HCVpp based on HCV 1b FJ411253 (HCV1bRU) and on HCV3a (HCVpp3aSE) were purified by ultracentrifugation in sucrose gradient, precipitated with TCA and analysed by Western blotting. • HCVpp1bRU, HCVpp3aSE and control RD114pp were used to infect Huh7 cells in the presence/absence of sera of healthy and HCV-infected individuals. Sera were supplemented in dilutions 60, 240 and 960. All assays were run in triplicates. Efficacy of infection was monitored by FACS using GFP as a reporter. Read outs were % inhibition by test sera compared to uninhibited infection, and the inhibition titer. • The levels of serum antibodies against E1, E2 of HCV 1b and the consensus sequence of the hypervariable loop of E2 (HVR1) represented by synthetic degenerate peptides (Isaguliants M et al, 2002) were assessed by in-house ELISA. Fig. 2 Fig. 1 Fig. 3a Fig. 3b Inhibition of HCVpp infection by sera of chronizing patients (n=12) correlated with the presence of antibodies against N-terminus of hypervariable loop of E2 (HVR1; R=0.446, p<0.05). Inhibition of HCVpp infection by sera of clearing patients did not depend on either the total level of anti-env, or antibodies against N-terminus of HVR1, while anti-HVR1 C-terminus antibodies were not detected. Fig. 4 Percent inhibition of infection with HCVpp 1b (Fig. 3a) and HCVpp 3a (Fig. 3b). RecE, sera of patients clearing HCV collected at month 0-1 (n=7); RecL, sera of patients clearing HCV collected >6 month (n=7); ChrE, sera of patients developing chronic hepatitis C collected at month 0-1 (n=12); ChrL, sera of patients developing chronic hepatitis C collected > 6 month (n=12); HCV negative, sera of healthy individuals (n=9); HCV positive, control sera of chronic hepatitis C patients with strong neutralizing capacity (positive control, n=2; 6 independent assays). All inhibition assays were performed in triplicates. Acknowledgements: New Visby program of the Swedish Institute, INTAS and Lund University ALF grants are gratefully acknowledged for financial support. Mabtech (Sweden) is acknowledged for the gift of kits for antibody quantification, and Imtek Ltd.(Russia), for the columns for selective removal of IgG and lipoproteins. ConclusionsAlready at early time points, sera of patients clearing HCV infection contain the components (suggestively antibodies) that inhibit HCVpp infection of target cells. No protective components are contained in the sera of patients developing chronic hepatitis C. The nature of inhibition, specifically the role of immunoglobulins, low and high density lipoproteins, is currently under study.

28. Photogallery from annual meetings and individual researcher exchange

29. PhD students Andreas Boberg (SMI, Stockholm) and Liza Starodubova (IVM, Moscow) working in Ivanovsky Institute, Moscow, December 2006

30. Andreas Boberg and Maria Isaguliants (SMI, Stockholm) presentation in Ivanovsky Institute, Moscow, December 2006

31. Natalia Petrakova (PhD, researcher), Liza Starodubova (PhD student, now Postdoc), Alexey Morozov (student), mouse experiments in Ivanovsky Institute, Moscow 2006-2007

32. 20080204_Helmut Diepolder (Munich University, Germany) speaking on Moscow meeting 2008

33. 20080204_Anders Widell (Lund University, Sweden) speaking on Moscow meeting 2008

34. 20080204 Moscow meeting 2008 at Ivanovsky Institute of Virology

35. 20080204 Matti Sällberg (Karolinska Institutet, Stockholm) speaking on HCV DNA vaccine, Moscow meeting 2008

36. Prof Kochetkov and Dr Znoyko (Moscow, University of Dentistry and Medicine), discussions on Moscow meeting 2008

37. Network members on sight-seeing tour in Kremlin, 5th Moscow meeting 2008

38. Network members on sight-seeing tour in Kremlin, 5th Moscow meeting 2008

39. Dr Heléne Norder (Swedish Institute for Infectious Disease Control, Stockholm), Moscow meeting 2008

40. Prof Lars Magnius and Dr Heléne Norder (Swedish Institute for Infectious Disease Control, Stockholm), discussions on Tallinn meeting 2009

41. Group photo at closing of the 7th Annual Network meeting in Tartu February 20-23, 2010

42. Group photo at closing of the 7th Annual Network meeting in Tartu February 20-23, 2010

43. One of the group photos on 8th Network meeting, Vilnius, February 13-16, 2011

44. On the lecture course ”Hepatitis ABC” held by the Network members at the Lithuanian Academy of Sciences, February 17, 2011

45. Heading for the meeting on the very cold Vilnius streets (-24 C)

46. We hold fingers for our Network application being granted. If the decision is positive, we will meet for our 9th meeting in St Petersburg, April 2012! All are very welcome to join, look for meeting announcements on the Network web page!