I.C. Overview activities and expenditure
Budget
(01.02.2010-28.02.2013)
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Total Action Budget: 351.229,88 EUR
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Remaining Action Commitment:75.270 EUR
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Meetings
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Meeting Type
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Date
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Place
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Cost
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Total
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Management Committee Meeting & Working Group Meeting
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16.-17.02.2010
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Porto
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22,249.70
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22.249,70
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Other Cost relevant Meeting
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25.-27.05.2010
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Madrid
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795.21
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795,21
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Working Group Meeting (WG 2)
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07.-08-10-2010
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London
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9,074.25
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9.074,25
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Working Group Meeting (WG 3)
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23.-24.11.2010
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Wädenswill
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11,127.82
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11.127,82
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Other Cost relevant Meeting
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15.02.2011
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Bonn
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233.03
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233,03
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Management Committee Meeting & Working Group Meeting
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03.-05.05.2011
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Nicosia
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31,704.18
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31.704,18
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Working Group & MC Meeting
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27.-29.11.2011
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Catania
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34,173.85
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34.173,85
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Working Group Meeting
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24.-25.05.2012
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Berlin
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27.901,18
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27.901,18
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Other COST relevant Meeting
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06.-07.09.2012
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Frankfurt/ Main
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2.260,98
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2.260,98
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Management Committee Meeting & Working Group Meeting
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13.-14.09.2012
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Limassol
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34.830,80
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34.830,80
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Management Committee Meeting & Working Group Meeting
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25.-26.06.2013
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Vienna
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n/a
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n/a
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STSM
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Beneficiary
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Date
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Place
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Cost
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Total
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Agnese Lupo
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22.-29.05.2010
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Madrid
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498.00
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498.00
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Veiko Voolaid
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01.10.-30.11.2010
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Helsinki
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2,300.00
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2,300.00
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Irene Michael
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15.09.-30.09.2011
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Porto
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1,650.00
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1,650.00
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Antti Karkman
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15.09.-14.10.2011
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Tartu
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2.500,00
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2.500,00
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Mette Theilgaard
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01.01.-31.03.2012
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Cambridge
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2.500,00
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2.500,00
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Agnese Lupo
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30.01.-11.02.2012
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Verbania
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880,00
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880,00
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Carlos Rocha
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01.02.-30.04.2012
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Karlsruhe
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2.500,00
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2.500,00
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Lam Tung Nguyen
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01.03.-23.03.2012
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Dresden
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1.500,00
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1.500,00
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Patricia Reis
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01.06.-31.07.2012
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Basel
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2.500,00
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2.500,00
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Antti Karkman
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03.09.-07.09.2012
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Tartu
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750,00
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750,00
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Marko Virta
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03.09.-07.09.2012
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Tartu
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750,00
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750,00
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Serena Caucci
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02.11.-02.12.2012
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Helsinki
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2.500,00
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2.500,00
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Veljo Kisand
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03.12.-07.12.2012
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Helsinki
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750,00
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750,00
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Mailis Laht
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03.12.-07.12.2012
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Helsinki
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750,00
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750,00
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Fiorentino Antonino
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18.01.-18.02.2013
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Vandoeuvre-les-Nancy
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2.4750,00
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2.475,00
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Popi Karaolia
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15.04.-11.05.2013
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Karlsruhe
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2.500,00
(to be reimbursed)
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2.500,00
(to be reimbursed)
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Anat Bernstein
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07.04.-12.04.2013
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Nicosia
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630,00
(to be reimbursed)
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630,00
(to be reimbursed)
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Workshops
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Title
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Date
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Place
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Cost
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Total
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From
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To
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From
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To
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0
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General Support Grants
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Beneficiary
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Date
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Cost
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Total
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0
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Schools
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Title
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Date
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Place
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Cost
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Total
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Bioinformatics Winterschool 2012
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06.02.-10.02.2012
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Vienna
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12.310,00
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12.310,00
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2nd DARE Bioinformatics Winterschool
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04.02.-08.02.2013
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Vienna
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14010,00
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14.010,00
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Dissemination
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Title
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Date
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Place
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Cost
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Total
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Poster Print
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8,73
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8,73
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Webpage
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10.000,00
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10.000,00
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Poster Print
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21.91
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21,91
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Publication
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743.03
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743,03
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Flyer
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1.850,00
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1.850,00
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Others
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Cost
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Total
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Bank charges
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15.21
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15,21
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Sum Science Expenditure: 241.242,88 EUR
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Secretariat (13,26%) for Year I (expenditures: 56,308.65)
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7.468,65
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Secretariat (15,00%) for Year II (expenditures: 86.018,03)
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12.902,70
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Secretariat (14,97%) for Year III (expenditures: 95.786,20)
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14.345,65
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Action Total: 275.959,88 EUR
II. Scientific Report prepared by the Chair of the Management Committee of the Action, describing results achieved during the Action operation in this period, in no more than 3 pages (the report is “cumulative”). All items listed in Sections A, B, and C, below, must be addressed.
II.A. Innovative networking
The Action has formulated a strategy for a first data assembly and a strategy to obtain necessary epidemiological data. The strategy has been formulated in two proposals and a review on antibiotics and WWTPs has been published. Furthermore, the Action identified appropriate test systems for the test of resistance evolution or gene transfer these test systems have been jointly published – however this topic still needs further development. Based on this the Action has published a strategy for the detection of antibiotic resistance detection. Especially during this work did the Action realize again that many of the experts miss some the bioinformatics key competences in order to evaluate and develop some of these new test systems. Accordingly in the last year another training school was conducted on the sequence assembly and alignment database search and functional Annotation and resistance gene identification. Many (early stage) researchers (ca. 35) have now valuable competences for their future research in antibiotic resistance gene identification in the environment.
Furthermore, the Action has improved the development of a first concept for a risk assessment of antibiotics. Also to include other contaminants of emerging concern. The Action has formulated that a new unified approach of analysis and risk assessment involving the scientific disciplines assembled in the fields of public health and environmental sciences is mandatory to address the human and environmental risk posed by emerging pollutants. The Water Framework Directive (WFD) (EC 2000) requires achieving a good status for water bodies in regard to ecological and chemical criteria. In order to determine the chemical quality of a water body, Environmental Quality Standards (EQSs) for priority substances and other significant pollutants are applied (Annex X and Annex VIII substances). The guidance document No. 27 “Technical Guidance For Deriving Environmental Quality Standards” (TGD 27) (EC 2011) is the central basis for deriving EQSs irrespective of the compartment or receptor at risk. Although for environmental EQSs there is special focus on long-term effects from chemicals on aquatic organisms and even protection of predators from secondary poisoning or protection of humans from consuming fishery products, the procedure for EQS derivation generally is linked to the predicted no-effect concentration (PNEC) approach. Furthermore the nature of the substance (e.g. chemical properties and environmental fate) is a central criterion within the EQS derivation procedure. With few exceptions (e.g. endocrine disruptors) for most of the relevant pollutants, no substance specific mode of action and, therefore, no specific toxicological endpoint can be defined. As a consequence, lethal effects and, at the best life cycle studies (that involve a high effort and usually do not consider environmental substance mixtures), are frequently used as a basis for EQS derivation together with assessment factors. Yet, more and more emerging pollutants are shown to exert an effect at sublethal levels, suggesting a possible impact at concentrations possibly encountered in the environment.
According to this the Action has written a proposal for the call “Call: FP7-ENV-2013 Toxicants, environmental pollutants and land and water resource management” with the title Emerging Pollutants As Drivers of Antibiotic Resistance in the Environment (EPADARE). Unfortunately the proposal was not funded, but that was mainly because the reviewing board did not think that this was the appropriate call for such a project or concept.
Furthermore, the Action compiled different methodologies to monitor antibiotic resistance and horizontal gene transfer (cultivation methods, quantitative PCR, horizontal gene transfer markers, etc) – usefulness, bias and limitations and produced an overview of the occurrence of antibiotic residues in wastewaters in different world regions – methodological bias, implications, mitigation and control measures. As well as an overview of advanced processes available on the removal of antibiotics and antibiotic resistant bacteria from wastewaters. Furthermore the Action made a Statement about the inadequacy of the Environmental Risk Assessment guidelines to assess the impacts of the environmental contamination with antibiotics and the consequent emergence and spread of antibiotic resistance. Accordingly, the Action currently develops an appropriate risk assessment, which is already since the last year on its way. However, it needs to be noted that the Action aims to formulate a risk assessment, which is effect based and will be accepted by medical, environmental, and chemical engineering stakeholders and is consequently very complex.
The Action established guidelines for environmental risk assessment of antibiotics, regard
ing the effects as selectors/stressors for resistance dissemination and the improvement of wastewater treatment technology aiming at antibiotics and antibiotic resistance removal to safe levels as well as standardization of protocols and interpretative criteria to assess antibiotic resistance in the environment.
II.B. Inter-disciplinary networking
On the 13th and 14th of September 2012, a workshop was held jointly by the NORMAN Network, COST Action TD0803 (DARE) and the NIREAS- International Water Research Center. Approximately 80 scientists gathered in Limassol, Cyprus, to discuss the challenges of wastewater reuse practices with regard to contaminants of emerging concern, with a focus on antibiotics and antibiotic resistance evolution and technologies that are able to remove such contaminants from wastewater. The workshop aimed at addressing the following themes:
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Which are the contaminants of emerging concern that are relevant to wastewater reuse applications? (e.g. antibiotics and other licit and illicit drugs, transformation products, disinfection by-products)
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What are the new concerns related to reuse applications? (direct and/or indirect effects)
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What technologies can enhance the ‘conventional’ treatment by removing such contaminants?
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Is the current risk assessment appropriate for contaminants of emerging concern ?
The workshop consisted of three Sessions combined with a panel discussion in each session as follows:
Session 1: Applied practices and current challenges
Session 2: WWTPs and Antibiotic resistance
Session 3: Uptake of contaminants, Treatment technologies
The entire event managed to keep the interest of the participants alive until its completion, and through the panel discussions held, various important issues were raised concerning a number of open questions with regard to wastewater reuse applications and antibiotics/antibiotic resistance evolution and other related challenges. Therefore a suggestion was made to formulate a relevant working group within the framework of Norman Network that will be able to deal with these issues and promote further the corresponding field of research and policy development.
The Added value / Link with other NORMAN activities and / or other projects will be to link to all other already ongoing NORMAN activities as they are all considered relevant (e.g. contaminants, sampling, bioassays, etc), to ongoing projects (national, European, etc) in which the WG members are participating, to link to Joint Programming Initiative on Water challenges for a changing world (http://www.waterjpi.eu). The efforts will be directed towards The development of protocols for assessing uptake, the most relevant bioassays and development of criteria to assess the efficiency of technologies that will be able to produce safe wastewater for reuse, define costs for technologies and p erform case studies and collect geographical data on antibiotic resistant bacteria, genes and in parallel data on micropollutants (enhance databases)
As a further outcome of the above mentioned workshop was a joint special issue published in the journal: “Environmental science and pollution research.”
II.C. New networking
At the moment 123 persons (inclusive MC members, working group members, experts, STSM candidates, others, trainers, trainees etc.) are involved in the Action. This is a further increase to last year´s participation of 84 members.
Since the establishment of an STSM coordinator in 2011 the numbers of research stays are five times as high as before. Until June 2010 only two STSM were implemented, in 2011 it were already 5 and 2012 up to February 2013 in total 10 STSMS were implemented. For the last budget period (until September 2013) two STSM applications have been submitted already. Almost 45% out of the 123 persons involved in the Action are females. The vice chair is a female, two of the working group leaders are females and the PhD representative as well.
One of the unexpected outcome of the last activities of the Action is the intense exchange with the veterinary scientists. Together with other veterinarians the Action has proposed key actions to reduce antimicrobial resistance levels in the food chain while maintaining good animal health and welfare. The Action believes that this will increase food safety and further improve consumer trust.
The Action has determined that a holistic evaluation of antimicrobial resistance hazards, evaluating the molecular and microbiological processes of resistance evolution and transmission, constructing a scenario representative of the antibiotic use in farming throughout Europe and assessing the economic impacts of antimicrobial resistance in the food chain is necessary for combating antibiotic resistance in the food chain. This holistic perspective will provide science-based tools to tackle antimicrobial resistance spread and assure adequate animal health and animal welfare, contributing to environmental and human health protection. However, while combating antimicrobial resistance, it is also necessary to assess the impacts for individual stakeholders. The relationship cost-benefits must be determined in order to improve the safety of European food and enhance consumer trust.
The Action took a substantial part in formulating a proposal of the call: FP7-KBBE-2013-7 single-stage Ecology of drug resistant bacteria and transfer of antimicrobial resistance throughout the food chain. The title of the proposal was “Solutions for antimicrobial resistance control in the food chain (STRICT)”. Although the proposal was not funded it assisted in exchanging very different views between veterinarians and environmental biologists on the ecology and environment concerning the evaluation of antibiotic resistance evolution in the environment.
Activities and projects with COST network colleagues.
See Annex 2
II.D. Self evaluation
The biggest indicator of the currently successful running of the Action is for sure the high number of STMS (10) and that the Action was able to perform two training schools in the last two years. Furthermore, several first and well published joined articles are now available. Although the last proposals have not been successful for funding, they have assisted in identifying important gaps of knowledge and increased the understanding between the very diverse disciplines in this Action. One of the major reasons that the proposals have not been successful is that none of the calls were really at the hard of the expertise of the Action. It therefore remains a necessary aim of the Action to convince stakeholders of the necessity of more research in order to understand the evolution of new antibiotic resistances in the environment. One of the biggest gaps of knowledge is certainly that currently Europe has not the smallest dataset on the current geographic distribution of antibiotic resistant bacteria in the environment. However such a database should be the first start in order to develop measures to curb the spread of new resistances within Europe.
It is therefore at least very promising that parts of the Action will continue within NORMAN network in order to assess the risk of antibiotic resistances for the imminent problem of water reuse. A problem which is certainly not only of a European, but surely also of a global scale.
The Action is now coming in its last year and we are confident that the Action will have a lasting impact not least because many publications originating from the last STMS will emerge in the near future. A problem which remains to be solved in the last year is a better involvement of the relevant stakeholders, which has been difficult in the past mainly as it was not possible to attract them to the meetings or workshops of the Action. The Action hopes that this will at least be possible for the final meeting of the Action as it was possible to extend the Action beyond its original ending date. The original end would have been in September and therefore the last meeting would have been at a time where many scientist had already other obligations (September is traditionally a month with many scientific meetings – due to the semester break). The plan for the final workshop would therefore to have a workshop next to the European Public Health Association 13-16 Νovember 2013 meeting in Brussels or alternatively at the BioMicroWorld 2013, 2-4 October 2013 in Madrid.
III. Previous scientific report(s)
II. Scientific Report prepared by the Chair of the Management Committee of the Action, describing results achieved during the Action operation in this period, in no more than 3 pages (the report is “cumulative”). All items listed in Sections A, B, and C, below, must be addressed.
Additional documentation such as extended scientific reports, proceedings of workshops, seminars or conferences may be provided separately as an annex to this report, and should be referenced in the report.
II.A. Innovative networking
The risk assessment for antibiotics has been re-evaluated and common eco-toxicological concept values have been integrated. The necessity of a risk assessment for antibiotics, which act at a sub lethal level has been underlined by recent scientific publications which have documented for the first time that antibiotics will act as selective forces also at very low concentration levels. However, it should be noted that these findings are all based on laboratory scale experiments.
The integrated eco-toxicological values are for example the predicted no effect concentration (PNEC). Furthermore, the graphical presentation has been modified such that the concentration of antibiotics is the measure variable and evolution of antibiotic resistance is the response variable. Currently, the action discusses which process of antibiotic resistance evolution should be investigated or if all processes should be investigated. As significant processes have been identified mutation rate, selection coefficient, gene transfer rate.
Furthermore the action has re-evaluated the minimum inhibitory concentration of the EUCAST clinical database. The action has identified the urgent need for a similar database of environmental resistant bacteria. It has been agreed that for environmental bacteria the epidemiological cut off value should be used as threshold for the definition of antibiotic resistance and not the clinical breakpoint which is used for clinical bacteria. Furthermore a minimum selection concentration would be the more appropriate measure as suggested by Gullenberg et. al.
The Action group further prioritized the organisms of interest:
Phenotypic screening of AR will focus of the following species:
1. Escherichia coli (WWTP & AH) (general Enterobacteriacae), 2. Enterococcus (WWTP & AH)
3. Aeromonas (WWTP & AH environments)
If additional resources are available we will also assess AR in these species:
1. Acinetobacter (WWTP), 2.Pseudomonas (WWTP), 3. Vibrio (AH), 4.Staphylococcus MRSA (AH), 5.Salmonella (WWTP & AH)
And reformulated the hot spots for urban, rural and receiving environments:
hotspots urban: wastewater treatment plants, sewer systems
hotspots rural: farms, manure receiving soils
receiving environments: rivers and groundwater
FOR WATER- SEDIMENT and SOIL SAMPLING SITE. The following information could be considered “metadata”. A common excel file or sampling scheme can be arranged to uniform data and sample collection
- Coordinates
- description of the site (for example, previous recorded contamination, heavy metal presence)
- transect: “point of contamination”, impacted and not-impacted area, annotate distance from the contamination source(depending on the environment in which samples are taken)
- Meteorological data during(and previously to) sampling
RECEIVING WATERS:
Depending on the typology: collect samples from a)water column; b)sediment-water interface
- Physical-chemical data: pH, temperature, oxygen concentration
- water depth, water regime (e.g. river), water shed characteristics
RECEIVING SOILS:
Depending on the typology: collect samples from a)soil; b)bulk soils and rhyzosphere where important c) include where possible a “reference” site. Likely no transect is definable in soils.
- physical-chemical data: pH, temperature, salinity, soil moisture
- soil texture
- description of type of manure- or sludge- treatment with waste-water- use of fertilizer
RECEIVING ANIMALS:
Basically the choice fell on wild birds, and in particular fowls, as water-associated birds that can be considered as “integrating agents”. Obviously there will be no “reference” birds, that is no “not-impacted” birds, but a strong enough comparison could be done within the network of sampling sites (e.g. South- North)
Feces of wild birds will be sampled
- Identify local and common species, establish more or less how many species there are in the place.
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Tangible medium term socio-economic impacts achieved or expected. (Specific examples)
See Annex 2
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Spin off of new National Programme proposals/projects. (List)
See Annex 2
II.B. Inter-disciplinary networking
The Action has conducted a training school for all members of the action the participation was very successful many young scientists of all the different disciplines have participated and work together on the following topics:
High Throughput DNA Sequencing, Principles in Short Read assembly, Sequence alignments and
Database searches, Systematic Classification of Proteins, Ortholog Prediction, Primer in phylogenetic tree reconstruction, Functional Characterization of Proteins, Functional Annotation and Ontologies.
The Action has agreed on the following summarizing concept on how to achieve first data on a comprehensive risk assessment.
II.C. New networking
Currently there are 84 members involved in the Action. This is a significant increase in comparison to last year, were only 58 members took part, this demonstrates the high interest in the Action. The Action has now established the new website were lots of data and documents can be deposited and downloaded. Furthermore young scientist can gain an overview on the different expertise of the varying scientists after action. In consequence, the conducted STSMs have increased to 6. during the last year of the action.
Action group has presented itself at the last meeting of the European society for evolutionary biology (ESEB) and has also been involved in organising a special session on antibiotic resistances, during the world SETAC (Society of environmental toxicology and chemistry). During this meeting, the results of the action have been presented as well as individual projects several oral presentations as well as posters were presented. A lively discussion with other scientists and stakeholders took place.
Within the action group two consortia have been formed which will endeavour to write grant proposals during the last funding period of the FP7. One consortium will focus on the question how emergent pollutants interact with classical contaminants and will catalyse the evolution of harmful organisms. The second consortium focuses on the role of antibiotics and antibiotic resistances along the food chain in farming environments.
It has already been agreed and the planning is already at a highly developed level, that this year for the next funding period a joint meeting with the NORMAN (network of reference laboratories) , NIREAS (International Water Research Center) and and the Action group will take place on the topic of WASTEWATER REUSE APPLICATIONS AND CONTAMINANTS OF EMERGING CONCERN
Activities and projects with COST network colleagues.
See Annex 2
II.D. Self evaluation
The Action has made great progress in synthesising the different approaches of the different disciplines and is on a good way to harmonize future assessments on the risks of antibiotics and on the evolution of antibiotic resistances in the environment. The webpage has been already a great success not only for the internal communication, but also concerning the dissemination. The STSM have increased and the action expects that they will increase again in the coming the funding period. The training school has been a great success and was discussed intensely again during the last action group meeting. Generally, the action still receives a lot of applications of scientists who would like to join the action (currently 113 members). Especially after the last presence of the action at the SETAC meeting the Echo was quite overwhelming. We made some first contacts to scientists which follow a very different modelling approach and we look forward to future joint discussions. Since the last report more than 40 (selected) new manuscripts, all in international journals, have been published. This does not include several review publications in the journal: Frontiers in Antimicrobials, Resistance and Chemotherapy. Therefore the Action is very active in disseminating results on a scientific, but also on an interdisciplinary level. Last but not least the forming of two consortia focussing on two funding possibilities will speed up the process of focussing on the most important gaps of knowledge.
III. Previous scientific report(s)
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