ESA Announcement of Opportunity by ip00p


									 Announcement of Opportunity

Life Sciences Research in Space
  Using the Model of Bed Rest


           *     *     *        *    *

   Notification of Interest due: 12th May 2006

 Proposal information workshop: 29th May 2006

        Proposals due: 14       July 2006
           *     *     *        *    *

    Summary of New Elements in the Bed Rest
-    A roadmap for a comprehensive countermeasure evaluation strategy
     using bed rest studies has been elaborated.
-    Fundamental research and Agency objectives (evaluation of
     countermeasures) are addressed
-    A same set of standard data (Bed rest Core Data, BCD) will be collected
     in all these bed rests in order
         o To compare the efficiency of countermeasures in different bed rests
         o To compare studies performed in different locations
         o To standardise the outcomes and to have a quick turn around
              between the measurements and the data analysis
-    The standardisation will also be applied to the way bed rests are
     performed on the logistics side
-    Several short, medium and long-term bed rests are planned in advance
-    A Scientific Steering Committee will advise the Agency in the major
     decisions regarding all aspects of the bed rest programme
-    The current Announcement of Opportunity will allow to select a pool of
     experiments that will be implemented in one or several of these planned
     bed rests
-    Proposals of new and promising countermeasure ideas/concepts are not
     solicited within this research announcement. Please refer to the following
     web site where a permanently open call is available:

Table of Contents:
Summary of New Elements in the Bed Rest Programme ..................................... 2
  1.1    Introduction ............................................................................................. 4
  1.2    ESA‟s future Bed Rest Research ............................................................ 4
    1.2.1     Background ..................................................................................... 4
    1.2.2     Process ........................................................................................... 5
    1.2.3     Standardisation of Bed Rest Studies ............................................... 6
  1.3    Specific Announcement objectives ......................................................... 8
    1.3.1     Countermeasures ............................................................................ 9
    1.3.2     Fundamental and applied biomedical research ............................. 10
2 Proposal Evaluation and Selection Procedures ........................................... 11
  2.1 Scientific Merit Review .............................................................................. 11
  2.2    Evaluation of Feasibility ........................................................................ 12
  2.3    Development of a Selection Recommendation ..................................... 13
  2.4    Data Rights ........................................................................................... 14
    2.4.1     General.......................................................................................... 14
    2.4.2     Specific and Additional Data Regulations for Bed Rest Studies .... 14
  2.4    Support of Education and Outreach ..................................................... 15
3 Proposal Preparation Guide......................................................................... 16
  3.1    Contact and Submission Address ......................................................... 16
  3.2    Time Schedule ...................................................................................... 16
  3.3    Notification of Interest ........................................................................... 17
  3.4    Proposals and Funding ......................................................................... 17
  3.5    Structure & Layout ................................................................................ 17
    3.5.1     Cover Page ................................................................................... 18
    3.5.2     Proposal Abstract .......................................................................... 18
    3.5.3     Project Description ........................................................................ 18
    3.5.4     Management Approach and Personnel ......................................... 19
    3.5.5     Facilities and Equipment ............................................................... 19
    3.5.6     Ethics & Safety .............................................................................. 19
Annex 1: Roadmap for European Countermeasure Research with Bed Rest ..... 21
Annex 2: Bed Rest Core Data – Preliminary Set................................................. 22
Annex 3: Examples for Scientific Topics to be Investigated ................................ 28
Annex 4: AO-06-BR Notification of Interest ......................................................... 30
Annex 5: AO-06-BR Proposal Cover Page ......................................................... 33
Annex 6: Proposal Abstract Form AO-06-BR ...................................................... 35
Annex 7: Acronyms ............................................................................................. 37

Description of the Opportunity

1.1     Introduction
Already in the 1940s, a group of researchers studying the bone loss in polio
victims wondered whether the increased excretion of calcium was due to the
disease or the resulting immobilisation and inactivity. An experiment with healthy
young men showed that increased calcium excretion and loss of bone density
occurred with prolonged bed rest also in humans without concomitant disease.
At the beginning of the human spaceflight era in 1961, immersion in water was
used as a method to reduce the effects of gravity and thus simulate physiological
effects of weightlessness on the ground. This procedure produced the desired
effects but was too cumbersome for studies lasting longer than a few days; even
when dry immersion was used. Gradually, the model of bed rest became the
method of choice for studying the effects of prolonged musculoskeletal unloading
on the ground.
When Russian cosmonauts returned from long-duration space missions in the
early seventies, they often stated a sensation of slipping off the foot end of the
bed. For increased comfort, they raised the foot end of the bed. Each subsequent
night they lowered the foot end a little until lying horizontal felt normal again.
Russian scientists thus concluded that head-down tilt bed rest was more
appropriate for simulating physiological changes of spaceflight than horizontal
bed rest. Head-down angles of -15°, -10° and -5° were tested for comfort,
acceptability and magnitude of response. Eventually, -6° head-down tilt bed rest
(HDBR) was found to be the best compromise. Joint USA/USSR 7-day studies
performed both at the Institute for Biomedical Problems in Moscow and at the
Ames Research Center in California (1977/78), compared HDBR with horizontal
bed rest and confirmed the added value of HDBR. Since then, numerous -6°
HDBR studies have been performed. It is now generally accepted that -6° HDBR
with healthy adult volunteers is the model of choice for inducing and studying the
effects of prolonged space flight and for testing potential countermeasures. The
term „countermeasure‟ is broadly defined as „an action taken to offset another
action‟. In relation to the known deconditioning of the human body in response to
exposure to weightlessness a countermeasure (CM) can be regarded as any
method that mitigates or ideally prevents the undesirable physiological effects of
microgravity. Application of such methods can be before, during and after
exposure to simulated or real microgravity.

1.2     ESA’s Future Bed Rest Research
1.2.1     Background
In the early 90s, ESA started performing isolation and confinement studies. As a
consequence it became clear that especially bed rest studies with strict control of
the gravitational unloading would be needed for comparison. In recent years the
European Space Agency (ESA) has led such bed rest studies resulting in a top
level and valued programme. Developed through the user-driven approach of
ESA‟s Life and Physical Sciences programme (ELIPS-1, 2000-2005), these bed

rest studies were diverse in duration, interventions, operation and site. The
following table provides a summary:

Name    Performed   Performed     Pre- bed     Bed       Post-bed              Intervention              HDT
         in year        in          rest       rest     rest period                                      angle
                                   period    duration
LTBR     2001/2     Toulouse, F     15 d      90 d         15 d           1) Flywheel exercise            -6°
01-02                                                                      2) Bisphosphonate
STBR     2001/2     Cologne, D      9d        14 d         3d         Caloric variations in nutrition,    -6°
01-02                                                                     Amino acid infusion
BBR      2003/4      Berlin, D      3d        56 d         6d              Vibration exercise             0°

WISE      2005      Toulouse, F    20 d       60 d         20 d          1) Combined resistive            -6°
                                                                       exercise, aerobic exercise,
                                                                          Lower Body Negative
                                                                        2) Nutritional supplement

New elements for the period 2006-2010:
   Over the last years exploration has become a major topic for ESA (Aurora
      programme), as it is also for international partners. Therefore, exploration
      driven objectives, especially countermeasure evaluation and the
      development of more efficient countermeasure concepts have to be
      included as one of the considerations also for bed rest activities.
   In order to adapt to these and other changes ESA decided that a 5-year
      strategy for bed rest studies would be beneficial to allow for medium term
      programmatic and budgetary planning.
   Results obtained in bed rest studies are available to the Agency only very
      late, as they primarily depend on peer-reviewed publications, which
      usually require a few years between end of study and publication. This is
      however not sufficient to take results into account in a timely manner for
      the planning of following activities.
   In order to evaluate the efficiency of different countermeasure concepts
      against each other, standardisation is needed in Europe and

1.2.2      Process

In order to define a long-term strategy for future ESA-led bed rest studies, a call
for ideas in the field of countermeasures and bed rest was published in 2005.
The response was very satisfactory; 73 ideas were received, representing 224
scientists. From those, eighteen scientists were selected to participate in a
workshop in order to analyse the received ideas and to outline the main drivers
and elements for the European strategy.
The current Announcement of Opportunity (AO) contains the major conclusions
of the workshop, which have been discussed and endorsed by ESA‟s advisory
bodies such as the Life Sciences Working Group. The major achievement was to
decide on a series of bed rests, with the same pre-defined standard
measurements.        In addition to countermeasure evaluation, fundamental,
mechanistic type of research will be implemented. This means that the current

AO will be used to select experiments that will be implemented in one or several
of these upcoming bed rests in the period 2006-2010.

1.2.3     Standardisation of Bed Rest Studies
In order to compare and draw overall conclusions from results obtained from
different bed rest campaigns conducted in different locations, it is crucial to have
standardised measures and procedures to be able to evaluate the efficiency of
various countermeasures tested.
The standards are currently being iterated with the international partners in order
to further expand the basis for comparability between bed rests.

The basic features of environmental standards consist for example of:
       Anti-orthostatic position: -6 degrees head-down tilt for the whole
          duration of the bed rest
       Controlled diet and energy intake
       Continuous monitoring of subjects (compliance with anti-orthostatic
          position, vital signs, wellbeing, etc.)
       Controlled sleep-wake cycle
       If exercise countermeasures are to be evaluated an adequate
          familiarisation must be included
       During the pre-bed rest ambulatory period adaptation to diet and
          environment should be achieved whilst maintaining physical activity

Standardisation has also been achieved by deciding on the durations of bed
rests. There will be 3 categories of bed rest in the future:

Short-term bed rest (STBR)
   Aims at countermeasure screening addressing primarily the
       cardiovascular system, using functional and surrogate measures
   Surrogate markers as outcome measures for bone and muscle systems
   Crossover design with one control- and several treatment groups (up to 3),
       with a wash out period in between. Eight to twelve subjects
   A minimum of five days ambulatory period
   Bed rest duration of five days
   Post-bed rest period can be variable and depends on the individual study.

Medium-term bed rest (MTBR)
   Countermeasure screening & confirmation of countermeasure concept;
     refining of protocols
   Functional and structural outcome parameters for cardiovascular and
     muscle systems, surrogate markers for bone
   Possibility of crossover design with one control- and a few treatment
     groups (max. 2), with a wash out period in between. Eight to twelve

      Ambulatory period pre bed rest 7-14 days
      Bed rest duration 21 days
      Post bed rest ambulatory and recovery period 7-14 days

Long-term bed rest (LTBR)
    LTBR is used for a final validation of a set of countermeasures prior to
      implementation in spaceflight
    In these settings variables that provide more functionally relevant outcome
      measures for efficiency can be evaluated i.e. structural and functional
      changes in bone and muscle.
    LTBR should be preceded by a 14 days ambulatory period, whereby five
      days are needed to adapt to diet and environment. During the ambulatory
      period, the usual individual physical activity should be maintained.
    The duration of LTBR shall be 60 days, followed by a rehabilitation period
      of 14 days
       Strict control of dietary intake (energy, macro- & micronutrients,
          minerals, vitamins) according to recommended daily dietary intakes
       Menus to be prepared ahead of selection to inform prospective
       Different dishes for 5 days (STBR), 7 days (MTBR), or 10 days
          (LTBR), then repeat. No choices
       Compliance with individual prescriptions mandatory. Leftovers need to
          be calculated and the equivalent will be given as a supplement
       Monitoring: ideally, a neutral energy balance should be maintained.
          Feasibility of this concept will be tested in one of the upcoming nutrition
          bed rests. Alternatively, a diet will be applied whereby weights will be
          kept constant using bodyweight at bed rest day 3 as reference.

Bed Rest Core Data (BCD):
Applying standardised procedures is usual practice in multi-centre clinical
research. The conclusions from completed bed rests form the basis for the
decision of design of the subsequent bed rests and this is the main reason to
have procedures that secure rapid and valid results from the conducted studies.
The standardised measurements are the main tool to evaluate the effects of bed
rest and of the applied countermeasures. In principle, the BCD will be available
on request to a Science Team Coordinator (STC) and through him/her to a
Science Team Member (STM) of a proposal selected in this solicitation. But in
case two or more teams request the same datasets in one specific study, the
Agency will set priorities regarding publication rights of such data. Factors that
influence the ranking are:
     Peer review rating
     Primary objectives of the proposed research
     Countermeasure-related issues

BCD cover basic assessment of the following research areas:
   Nutrition
   Cardiovascular system
   Bone
   Muscle
   Neuro-sensory system
   Psychology

List and schedule of BCD can be found in Annex 2.

    Age 25 - 50 years (for women in LTBR max. 40 yrs)
    Healthy (determined by a standard battery of clinical questions,
      examinations and investigations)
    Non-smokers
    Used to regular moderate physical activity
    Additional selection criteria will apply depending on specific studies

   Typically, countermeasures will undergo screening in males first
   If efficient, the countermeasures should be evaluated in females as well,
     before evaluation in long-term bed rest.
   If the screening of countermeasures in males does not show efficiency,
     decisions on further screening in females will be made on a case-by-case

Scientific Steering Committee:
A Bed rest Steering Committee (BSC) will advise ESA on all matters related to
bed rest studies. It will be composed of four to six independent scientists with
expertise in clinical studies or relevant aspects thereof. The main tasks of the
BSC are to:
    Give recommendations on priorities regarding countermeasures to be
    Give recommendations on priorities regarding the implementation of
       selected experiments during bed rest
    Give recommendations on the bed rest study strategy and standardisation
    Give recommendations on any other topic related to bed rest studies
    Regularly review bed rest study results

1.3   Specific Announcement objectives
Proposals and ideas are invited from Science Team Coordinators of the scientific
communities, whose institutions are based in the states participating in the

“European Life and Physical Sciences programme“ (ELIPS-2) of ESA‟s Human
spaceflight, Microgravity and Exploration directorate (HME). STCs based in the 4
ESA member states not contributing to ELIPS-2 may also submit whereby
special conditions apply (see 3.5.4).

Such an announcement will be issued in the future approximately every 3 years.

1.3.1     Countermeasures
During the ESA-workshop held in June 2005, the following areas were
considered most promising for countermeasure applications in the upcoming bed
rests: aerobic exercise (AE), resistive exercise (RE), vibration, lower body
negative pressure (LBNP), nutrition, psychology, functional exercise, medication,
percutaneous electrical stimulation (PCES), biofeedback/ neurosensory
stimulation/ virtual reality, and artificial gravity (AG). Submission of additional
ideas is possible continuously, but not within this AO. If you are interested in
submitting such ideas, the following web site must be consulted:

Annex 1 shows a diagram of ESA‟s roadmap for bed rest research. This
roadmap is an evolutionary approach. Institutional and budgetary constraints will
influence the implementation. Results from past, current and future studies will
continuously provide inputs requiring modification of the planning. The current
concept can be described as follows: Short- and medium-term bed rests (STBR
and MTBR) will mainly be used for screening countermeasure-efficiency and
optimising protocols. Long-term bed rests (LTBR) will predominantly be used for
validation of countermeasure concepts, where probably combinations of
countermeasures will be implemented. It has been recommended to initially
focus on the countermeasures AG, vibration (with or without exercise), and to
find the optimised baseline nutritional protocol, which includes evaluating
specialised nutrition as a countermeasure. AG will initially be tested in STBR,
nutrition will be evaluated in MTBR, and vibration in MTBR or LTBR. Outcomes
from bed rest studies of previous years, like the long-term bed rest study with
male volunteers at MEDES in Toulouse (LTBR 01-02), a short-term bed rest
study at DLR Cologne (STBR 01-02), the Berlin Bed Rest study (BBR), and the
Women Space Simulation for Exploration (WISE-2005), as well as other relevant
scientific results shall be considered when the new studies are designed.
Following the next 3 studies on nutrition, AG, and vibration, respectively, it is
most likely that ESA will test AG in combination with other CM. Screening studies
for evaluation of other CM like medication, virtual reality, neurosensory feedback,
functional exercise, etc. will probably be implemented from 2009 onwards. This is
also the timeframe for the next anticipated long-term study programme. ESA
envisages testing combinations of the most efficient countermeasures with and
without AG. Finally, an operational spaceflight scenario shall be simulated. This
may include simulations of launch and landing profiles, as well as other

environmental conditions typical for spaceflight. Astronauts and cosmonauts tend
to apply certain countermeasures at different phases during a long term mission,
which will also be taken into account.

Such a sequence of complex, multidisciplinary, and international bed rest studies
require careful, coherent and logical design in order to achieve their goals.
Therefore a scientific steering committee, the BSC, will be put in place (see
1.2.3). It will advise ESA on the type(s) of countermeasures to be tested in
specific studies, whether alone or in combination. Additional experts will be
consulted when needed. In order to define the countermeasure protocols, ESA
will organise dedicated workshops.

Evaluation of countermeasure efficiency will be realised primarily by the BCD-
measurements. Scientists can apply for the use of BCD by asking for these data
in their research proposal in response to this AO (see also 1.2.3 and 2.4).
Selection of proposals will be according to ESA‟s peer-review criteria for bed rest
studies (see 2.1).

1.3.2     Fundamental and Applied Biomedical Research
Proposals should address physiological areas, which could be affected by bed
rest and countermeasure use. Any type of research field can be addressed, for
    Integrative physiology
    Bone
    Muscle
    Nutrition and metabolism
    Neurology
    Cardio-vascular system
    Psychology
    Genetics, genotype and phenotype interaction
    Rehabilitation Medicine
    Pharmacology
    Gastro-intestinal, splenic, renal, hepatic, and pancreatic function
    Immunology
    Endocrinology
    Ear/Nose/Throat
    Microbiology
    Ophthalmology
    Orodental physiology
    Ergonomics
    Others

Examples for scientific topics of interest can be found in Annex 3.
A justification for the proposed class(es) of bed rest (STBR, MTBR, LTBR) must
be included. Please bear in mind that during the bed rest phase no testing can be

performed in a sitting or standing position. Tests requiring a degree of physical
activity should be kept to an absolute minimum or be avoided during the bed rest
phase. Instead, such testing should be scheduled before and after bed rest. In
this way countermeasure effects caused by testing procedures are minimised.
However, if compelling scientific reasons exist, a trade-off will be made
assessing the value of the procedure from a selected proposal in the context of a
specific study.

2      Proposal Evaluation and Selection Procedures
2.1 Scientific Merit Review

Programme-compliant proposals submitted in response to this AO will undergo a
scientific merit (peer) review. Only those proposals most highly rated in the merit
review process will undergo the additional review for feasibility.
A merit review of proposals, which are submitted in response to this AO will be
conducted by independent scientific peers appointed by ESA. The number and
diversity of experts required will be determined by the response to this AO. The
reviewers will be encouraged to include comments concerning the feasibility of
integration into the overall study protocols.

All of the following criteria will be used in determining the merit score:

Significance: Does the study address an important problem? If the aims of the
application are achieved, how will scientific knowledge or technology be
advanced? What will be the effect of these studies on the concepts, methods, or
products that drive this field?

Approach: Are the theoretical framework, experimental design, data analysis and
interpretation methods adequately developed, well integrated, and appropriate to
the aims of the project? Is the proposal hypothesis-driven? Is the proposed
approach likely to yield the desired results? Does the applicant acknowledge
potential problem areas?

Innovation: Does the project employ novel concepts, approaches, or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

Personnel: Are the scientific personnel appropriately trained and well suited to
carry out this work? Is the evidence of the personnel‟s productivity satisfactory?
Are the functions and responsibilities of the team members adequately described
and appropriate? Does the project employ useful collaborative arrangements?

Environment: Does the institutional environment, in which the work will be
performed, contribute to the probability of success?

In the review, each proposal will receive a scientific merit score between 0 and
100 points. As a result of the scoring the proposals will receive one of the
following marks:

      Outstanding 100 - 91 points
      Excellent 90 - 81 points
      Very Good 80 - 71 points
      Good to Fair 70 - 46 points
      Unacceptable 45 - 0 points

The scoring will be weighted according to the 5 sub-criteria:

      Significance 30%
      Approach 25%
      Innovation 20%
      Personnel 15%
      Environment 10%

The peer board will also evaluate the proposal‟s relevance to space- and/or
space simulation medicine/physiology. Again, scores between 0 – 100 will be
given, resulting in a second mark.

2.2       Evaluation of Feasibility

For the selected proposals following the peer review (the most highly rated
proposals), a second review level will determine the feasibility of the proposed
protocols. This review will also determine in which bed rest studies the proposed
experiments best fit. Thereafter an integrated protocol with the BCD
measurements and the protocols from the selected experiments will have to be
integrated in a common overall protocol before being submitted to the
institutional review board for final acceptance. This process is typically done by
Investigator Working Group meetings. The overall efficiency of any
multidisciplinary bed rest study does depend on how many different highly scored
proposals can be accommodated in this final integrated study protocol.
The assessment of feasibility refers to the extent as well as the adaptability of the
proposed work, and how well it can be integrated into an overall study scheme. It
will be in favour of the research proposal, which is being evaluated, if it utilises
the measurements of BCD instead of proposing similar redundant protocols.
Indeed, BCD will be performed in any case independent of any specific
experiment selected (see Annex 2). Proposed measurements should not
interfere with or disturb the foreseen BCD. Flexibility in scheduling the
additionally required measurements will also be of advantage. The tests required
in addition to the BCD should ideally have a high “value for effort ratio”, i.e. yield
a maximum amount of valuable scientific data with as little technical effort and
time constraints as possible.

The marking on technical feasibility shall cover the following sub-criteria:
    Functional requirements
    Resource requirements
    Safety
    Preparation for the experiment

The following scoring scheme will be applied:
              Can be           Feasible with      Some issues        Major        Not
           implemented            minor               to be        concerns     feasible
            immediately         adaptations         resolved
 Score           A                   B                  C              D            E

Those proposals receiving one or more „E‟s or three or more „D‟s in any of the
above sub-criteria shall be deemed to be not feasible and will therefore be
proposed to be not approved.

2.3    Development of a Selection Recommendation

A selection recommendation will be developed based on the merit review, space
relevance and feasibility as described above. The most important element in the
evaluation process is the merit review, which carries the highest weight in final
evaluation and selection. The other factors are approximately equal in weight to
each other. Deficiencies in any one of these factors may prevent selection
of a proposal.       The development of selection recommendations is the
responsibility of ESA supported by its advisory bodies.

ESA reserves the right to select only a part of a Science Team Coordinator‟s
project if this portion is still of high scientific merit. The applicant will be given the
choice to accept or decline such a partial opportunity. If two or more proposals
address similar problems and/or adopt similar approaches, ESA may request that
the STCs consolidate specific parts of their projects into a single project and work
as one team.

The selected experiments will enter a pool of experiments and will be
accommodated as soon as possible in the upcoming bed rests of the next 3
years. An experiment may therefore be implemented in more than one bed rest
campaign if needed, depending for example on the type of countermeasure, the
duration of a bed rest or the number of subjects required.

2.4     Data Rights
2.4.1         General
Data resulting from the experiments in the context of this AO will be analysed
and exploited in line with applicable general data policies of the Agency.
Final results of the study shall be made available by the scientific teams to the
scientific community through publication in appropriate journals or other
established channels as soon as practicable and consistent with good scientific
practice. In the event such reports or publications are copyrighted, ESA shall have
a royalty-free right under the copyright to reproduce, distribute, and use such
copyrighted work for their purposes.

2.4.2         Specific and Additional Data Regulations for Bed Rest

Data Classification: Three types of experiment data are identified:

1.      Category 1 data will be obtained and processed under the responsibility of
a Science Team Coordinator for the experiment protocol. Data not requested by
any other STC may be used exclusively by the STC for scientific purposes. For
data requested by more than one STC, each STC must agree before the study
starts as to the conditions for the data usage for scientific purposes. This
category of data shall be referred to as “STC proprietary data.” The STC
proprietary data may be used by the sponsoring agencies for internal purposes.
The sponsoring agencies agree that this data will not be made public for 1 year
after the completion of the study‟s clinical phase (last point of data collection in
the ambulatory recovery period following the bed rest).

2. Category 2 data comprise BCD, as defined and owned by ESA. STCs can
apply, and are even encouraged to use BCD. ESA, in consultation with the BSC,
will decide on the first publication rights for BCD. Scientific merit of the respective
proposal and thematic relevance will be the key factors influencing the ranking.

3. There will also be common clinical data (Category 3) for usage by all
STCs/STMs. This will be distributed to STCs.

Category 2 and 3 data will be stored in the European Microgravity Database for
Clinical Research (EMD-CR). It is compulsory that the respective STC will make
Category 1 data available to ESA for any use 12 months after completion of the
study‟s clinical phase.

In case follow-up points are required, long after the bed rest per se, for
publication, a STC can apply for extension of the one-year exclusive publication
period by submitting a scientific report in the format of a manuscript 1 year after
the completion of the study‟s clinical phase.

Data Access:

A STC can access proprietary data from other STCs participating in the study
through a written data sharing agreement (signed by involved STCs). ESA will
ensure that a data-sharing plan among the participating STCs is established prior
to the beginning of the respective bed rest study.

All STC proprietary data and BCD will be treated as medical confidential
information by the participants and ESA.


Any publication on the results generated during bed rest studies solicited in this
AO must acknowledge ESA‟s sponsorship of the study.

2.5       Support of Education and Outreach

The activities covered in this AO provide an opportunity for ESA to enhance and
broaden the public‟s understanding and appreciation of research facilitated by
ESA. Therefore the investigators of selected experiments are expected to
promote and communicate their experiments to a wide audience (general public,
colleagues, involvement of students) and to support ESA in the event of
organised press conferences, educational events, publications etc.

3      Proposal Preparation Guide

3.1    Contact and Submission Address

For questions related to this research announcement please contact


                                    Peter Jost

                               Tel. +31 71 565 6612

                Announcement-specific email:

Proposals should be submitted in electronic format AS ONE SINGLE FILE to
the above email address. Notifications of intent, questions, and other files
concerning the AO can also be emailed to this address.

Possible formats for the electronic files are:

-      Microsoft Word (.doc)
-      Adobe Acrobat (.pdf)

To facilitate transmission of file the total file size should be no more than 5 MB
(incl. pictures). Whenever signatures are required on a form, the completed,
signed form should be scanned and inserted into the proposal file.

In addition to the digital version one printed copy of the proposal shall be
submitted to:

Peter Jost
Keplerlaan 1
NL-2201 AZ Noordwijk
The Netherlands

Your submission will be acknowledged within 10 working days of receipt.

3.2    Time Schedule

    Notification of Interest due     12th May 2006

    Proposal Workshop                29th May, 2006 (at ESA/ESTEC, NL)

    Proposals due                    14th July, 2006

3.3    Notification of Interest

To facilitate timely proposal processing (e.g. organisation of peer review),
potential investigators are requested to confirm their plans to submit a
proposal in response to this announcement. The notification of interest is not
binding. It should contain:

     the names, addresses, affiliations and telephone numbers of a single
STC and all STMs.
     a title descriptive of the proposed research.
     a brief summary (10 lines maximum) describing the proposed research.
     up to 6 keywords that best describe the research area of the pending

A template can be found in Annex 4.

3.4       Proposals and Funding
Costs related to access to the bed rest facility and subjects are covered by
ESA. However, ESA does not financially support the work of selected
experimenters. Any additional expenses related to the proposed work of an
experimenter, including costs for travel and subsistence, are considered
investigator-related costs, which are not sponsored by ESA. Co-funding from
national agencies / organisations, universities, or other institutions is required
to cover investigator-related costs. ESA strongly advises STC/STMs to submit
their proposal to their national bodies in parallel with their application in
response to this AO, in order to commence applying for national funding as
early as possible. If the proposed experiment is selected a proof of
appropriate funding is mandatory in order to commence the feasibility phase
and especially the integrated protocol phase.

The proposal should be written in the format described below. This format is
not intended to increase the “paper work” but should be considered as a
useful guideline, which will permit a fair and standardized evaluation of the

Please state the status of co-funding availability and/or application in
“Supporting Budgetary Information”

3.5       Structure & Layout

The proposal should include the following material in this order:

      Cover Page with signatures (template: Annex 5)
      Proposal Abstract (template: Annex 6)
      Project Description
      Management Approach and Personnel
      Facilities and Equipment

       Supporting Budgetary Information
       Ethics & Safety

3.5.1         Cover Page

Please find in Annex 5 an example of the standard cover page form. All
information asked for must be filled in.

3.5.2         Proposal Abstract

Prepare a brief description of the application stating the broad, long-term
objectives and specific aims of the proposed work. Describe concisely the
research design and methods for achieving these objectives and aims. This
abstract is meant to serve as a succinct and accurate description of the
proposed work when separated from this application. Limit abstract to 300
words or less. Find in Annex 6 the standard form for the proposal abstract.

3.5.3         Project Description

The project description section of the proposal should be 15 pages maximum
(excluding references and CVs). The proposal should contain sufficient detail
to enable a reviewer to make informed judgements about the overall merit of
the proposed research and about the probability that the investigators will be
able to accomplish their stated objectives with the resources requested and
with their own resources. In addition, the proposal should indicate clearly the
relationship between the proposed work and the research emphasis defined
in this announcement.
The STCs are encouraged to describe any preparatory research from their
laboratory relevant to the proposal.
If possible, provide the following information:

-      Type of countermeasure targeted, length of bed rest (5 and/or 21
and/or 60 days)

-      Are there any specific environmental conditions requested for your
experiment such as air composition, humidity, temperature control or

-       Estimate the total set of operations required to carry out the experiment
(e.g. the number of session and the time required for each session).

-      Estimate the amount of time for the participation of the test subjects
before, during and after the experiment (e.g. data collection, training of test
subjects, etc.).

3.5.4         Management Approach and Personnel

Each proposal must specify a single Scientific Team Coordinator, who is
responsible for carrying out the proposed project and coordinating the work of
other personnel involved in the project. The scientific institution for which the
coordinator of a proposal is working must be located in one of the ESA
member or associated member states that financially contribute to the ELIPS-
2 programme: Austria, Belgium, Canada, Denmark, France, Germany,
Greece, Ireland, Italy, The Netherlands, Norway, Spain, Sweden,
Switzerland. Proposals from coordinators who work for scientific institutions,
which are located in ESA member states that do not share the costs of the
ELIPS-2 programme, i.e. Finland, Luxembourg, Portugal, and United
Kingdom, will be evaluated on an individual basis. If selected, ESA may
request funding in addition to the experimenter-related costs from these
countries, in order to cover an appropriate share of the operational expenses.
In proposals that designate several senior professionals as key participants in
the research project, the management approach section should define the
roles and responsibilities of each participant, and note the proportion of each
individual‟s time to be devoted to the proposed research activity. The proposal
should state clearly and unambiguously whether the key personnel have
reviewed the proposal and endorsed their participation.
Despite the fact that cooperative research proposals are favoured, big
clusters of research proposals are not welcome because of the difficulty for
the peer reviewers to make their judgement and later on the difficulty of
implementation with the other selected protocols.
The STC is the main ESA point of contact for a team and must participate in
the conduct of the research. He/she is responsible for direct supervision of the
work and efficient communication among STMs. A short curriculum vitae (not
exceeding 3 pages) of the STC, which includes her or his current position, title
and educational background, list of principal publications (up to 20), and any
exceptional qualifications should be included. Give similar biographical
information on other senior professional personnel who will be directly
associated with the project (STM). Universities should list students or other
assistance involved, together with information as to their level of academic
achievements. Any special industry-university cooperative arrangements
should be described.

3.5.5         Facilities and Equipment

Describe the facility requirements and the major items of equipment especially
adapted or suited to the proposed project, including size, weight, power and
consumables requirements.

3.5.6         Ethics & Safety

A statement from the proposal‟s institution is required which states that the
proposed work will meet all local human subjects requirements if applicable. A

letter signed by the chairperson of the local Institutional Review Board (IRB)
regarding approval of the experimental protocol and using human subjects,
should be included with the proposal. In addition, the proposal must be
compliant with applicable European laws and guidelines for human biomedical

Safety hazards and assessments, including a description of possible
hazardous situations for the test subjects and the foreseen countermeasures,
must be provided. This refers especially to any proposed exercise regimes,
and devices, whether the applications are intended for
prevention/therapy/rehabilitation, or clinical tests.

Annex 1: Roadmap for European Countermeasure Research with Bed Rest

Annex 2: Bed Rest Core Data – Preliminary Set
    BCD Procedure                    Timing                                    Comments                                  Outcome measures
                        Pre BR:-1 and -6
                        during BR: weekly
Resting ECG in HDT                                                                                           Standard 12 lead recording
                        post BR: R+0 + weekly until
                        Pre-BR: -4
Holter ECG monitoring   During BR ¼, ½, and ¾ of                                                             24-hour holter ECG recording, activity
(no exercise)           duration of BR (adjust for short                                                     monitoring.
                        BR), R+0
                                                                                                             Standard echocardiographical parameters
Echocardiography        Once BR -3
                                                            Cardiac volume/flow Arterial and venous          of cardiac size and function. Doppler
Echo Doppler at rest    during BR: every 2 weeks
                                                            vessels: cerebral, upper & lower limbs           recordings of arterial and venous vessels in
                        R+0, R+2
                                                                                                             upper and lower limbs, cerebral vessels

                                                            10-min tilt. > 10 min: continuing tilt +
                                                            increasing LBNP
Tilt Test+ LBNP         Pre BR -2, R+0                                                                       BP, ECG, cardiac output, doppler
Orthostatic Tolerance   LBNP only during HDT (towards                                                        recordings of peripheral arteries (cerebral,
                                                            Test is discontinued once stop criteria are
reference test          the end of BR)                                                                       leg) & veins (calf)
                                                            reached (very low BP, extreme tachycardia,
                                                            clinical symptoms)

Exercise                Mainly MTBR and LTBR
                                                                                                             O2, CO2, ventilation, gas exchange ratio
                                                            7 min at rest, 7 min at 50 W, 5 min recovery,
                        Pre BR -7 or -5                                                                      (CO2/O2), HR, BP, stroke volume
                                                            7 min at 100 W, 5 min recovery, 7 min 150 W,
VO2max                  R+2                                                                                  arterial O2 saturation, haemoglobin, lactate
                                                            5 min recovery… increasing workload (50 W
                        (All categories of BR)                                                               blood gas composition at rest and at end of
                                                            each step) up to exhaustion
                                                                                                             maximal workload
Maximal Isometric       Twice before BR                     Unilateral knee extension, plantar flexion and
Voluntary Contraction   R+0, R+7, and R+15                  elbow flexion. Three positions/joint
                        Performed together with isometric   Knee extension
Voluntary activation                                                                                          Voluntary / max. electro-muscular
                        strength                            Plantar flexion
                                                                                                             stimulation (expressed in %)
                        Performed together with isometric   Knee extension 60 sec maximum voluntary
Fatigue                                                                                                      % torque reduction
                        strength                            contraction

      BCD Procedure                      Timing                                    Comments                                    Outcome measures
                           Performed together with isometric
Max Grip Force                                                                                                     Hand grip in Newton
                           BR-14, last day(s) of BR,
MRI                                                              Continuous axial MRI of thigh, calf and arm       Muscle cross sectional area, volume
                           and R=15
Bodyweight                 Daily in the morning                  Weight after first void before breakfast on       Weight in kg
                                                                 same scale for each subject/bed + subject
                                                                 with same type of clothing
Temperature                Daily in the morning                                                                    Body temperature in degrees C
Body height                Admission, R+0 (after tilt-test)                                                        Height in cm
                           R+3, R+15 (only LTBR)
DEXA                       STBR and MTBR: shortly before                                                           Body composition
                           and 2 days after BR. LTBR:
                           Every 2 weeks.
Bio-impedance              STBR: daily in the morning after      Multi-frequency impedance.                        Extra-, and intracellular water, total body
measurements               first void before breakfast                                                             water
                           MTBR and LTBR: every third day
Deuterium dilution         Pre- & post BR (possibly outside                                                        Total body water, body composition
method                     ambulatory period)
Nitrogen balance           Only STBR: daily (Pre-, during-,      From 24 hr urines.                                Nitrogen in grams per day
                           post BR)
Doubly labelled water in   1-3 months prior to admission for                                                       Total energy expenditure
free-living conditions     BR if possible. Alternatively after
Clinical blood tests       Pre- and post BR, for LTBR also                                                         See separate list at end of annex
                           twice during BR
Vitamin, mineral and       Prior to STBR; before and after                                                         Standard clinical parameters
iron status                MTBR and LTBR
Skin fold thickness        MTBR and LTBR only: once at           Monitoring of fat mass. Sites: biceps, triceps,   Thickness of the double layer of skin and
                           the beginning + once at end of        subscapular, suprailiac. Device: Harpenden        subcutaneous tissue
                           pre-BR period supine in the           Skinfold caliper, model HSK-BI.
                           morning. Weekly during bed rest.

    BCD Procedure                        Timing                                  Comments                                   Outcome measures
Total urinary              8:00 AM                              Resorption marker. Measurement in spot          pmol DPD/μmol creatinine
deoxypyridinoline (DPD)                                         urine. Use 2 fasting morning sample.
                                                                Waking up volunteer at 6am, first void.
                           STBR: daily
                                                                Only low-calcium water (i.e. Volvic) to drink
                                                                between 6 and 8am, no food.
                                                                Second void at 8am under UV-shielding,
                                                                breakfast allowed thereafter.
                           MTBR and LTBR: as for pQCT           Mild physical activity (upright during
                                                                ambulatory phases, HDT during BR) in
                                                                between the 2 voids is allowed, but no
                                                                10ml samples will be collected in plain
                                                                container and frozen at –80 degrees for
                                                                storage. Shipping/transport on dry ice.
                                                                Analysis by HPLC.
Urinary N-terminal         As above                             Resorption marker                               NTX
cross-linked telopeptide
of type I collagen (NTX)
Urinary C-terminal         As above                             Resorption marker                               CTX
cross-linked telopeptide
of type I collagen (CTX)
Bone alkaline              As above                             Formation markers: from blood serum             BAP, PINP
phosphatase (BAP) and                                           freeze at –80 degrees for storage,
N-terminal propeptide of                                        ship/transport on dry ice
type I procollagen
DEXA                       At selection for all BR              Device: HOLOGIC 4500 W or upgraded              Bone mineral density at proximal femur,
                                                                model                                           lumbar spine (L 1-4) according to the 2005
                                                                                                                official position of the International Society
                                                                                                                of Clinical Densitometry (
                                                                                                                BMD will also be calculated from
                                                                                                                measurements performed for body
DEXA                       Only LTBR: post BR (ambulatory       Device: HOLOGIC 4500 W or upgraded              Bone mineral density at proximal femur,
                           recovery period), post 1 and 2 yrs   model                                           lumbar spine (L 1-4) according to the 2005
                                                                                                                official position of the International Society
                                                                                                                of Clinical Densitometry (

   BCD Procedure                     Timing                                  Comments                                  Outcome measures
Conventional pQCT      MTBR: pre BR, HDT 20. Post BR:         Double measurements for baseline pre-bed      Mineral content (g/cm) of tibia (4% and
                       2 weeks, 4 weeks, also during        rest, single measurements for follow-up data.   66%) and distal radius
                       long-term follow-up
                       LTBR: pre BR, HDT 20, 40, 60.         Device: Stratec XCT 2000 or upgraded           Volumetric density in mg/ cm
                       Post BR: 2 weeks, 4 weeks, 2         model                                           Apparent trabecular density in tibia and
                       months, 3 months, 6 months, 12
                                                                                                            distal radius,
                       months, 24 months
                                                                                                            Bending stiffness of radius and tibia (SSI)
                                                                                                            Geometry of radius and tibia, periosteal
                                                                                                            Cross sectional area (CSA) of forearm and
                                                                                                            tibial muscles, also in relation to bone CSA
                                                                                                            in mm
Additional blood and   All BR: at selection, just before                                                    Blood: 25-OHD, PTH, calcium (total and
urine parameters of    BR starts, at the end of BR, and                                                     ionized), phosphate, testosterone (male
interest               during follow-up until                                                               volunteer), oestrogen (female volunteer),
                       normalisation                                                                        cortisol, creatinine
                                                                                                            Spot urine: creatinine, phosphate
                                                                                                            24 hr urine: calcium
Neuro-vestibular       Mainly MTBR and LTBR
Computerised Dynamic   Pre BR-10                            Use sensory organisation test (SOT) to          Equilibrium score
Posturography (CDP)                                         determine effect of BR on vestibular,
Equitest (e.g.         R+0, R+3, week 2 (if needed)         somatosensory and visual inputs to balance
Neurocom)                                                   control
Treadmill Locomotion   Pre BR-10                            Subject walks on treadmill and fixates visual   Head stabilization (head pitch vs
                                                            targets at 4 m                                  translation)
                       R+0, R+3, week 2 (if needed)                                                         Stride length and cadence (m, Hz)
                                                                                                            Gait width (m)
                                                                                                            Dynamic Visual acuity
Motion Sickness        Motion History Questionnaire                                                         History
Questionnaire          (MHQ) Pre BR-1
                       After centrifugation session a bed                                                   Scores
                       rest adapted version of the
                       Readaptation Symptoms
                       Questionnaire (RSQ)

    BCD Procedure                       Timing                                 Comments                                   Outcome measures
Vestibular Bedside          Pre BR-1                                                                          Otoneurologic clinical evaluation
Screening                   During BR (if AG is used as CM                                                    Clinical assessment of vestibular
                            in the study): every other week                                                   disturbances
Psychology                  Mainly MTBR and LTBR
Log of critical incidents   Anytime when applicable           Log                                             Description of event
POMS                        Pre BR-10, BR-4                   Profile of Mood State (questionnaire)
                            During BR: every 2 weeks                                                          Qualitative and quantitative psychological
                            R+2, R+10
PANAS                       Pre BR-10, BR-4                   Positive and Negative Affect Schedule
                            During BR: every week             (questionnaire)
                            R+2, R+10
BDI                         During BR: day 40                 Beck‟s Depression Inventory (without the item
                                                              on suicide)
Individual support          Pre BR-10, -4                      Interview
conversation                During BR: every 2 weeks
                            R+2, R+10
Sleep assessment            Pre BR-10, -4                     Questionnaire
                            During BR: every week
                            R+2, R+10
GHQ                         Pre BR-10, -4                     General health questionnaire
                            During BR: every week
                            R+2, R+10
Device specific             During BR: every week             Assessment of the acceptability of the
questions                                                     applied countermeasure

BCD clinical blood tests:

                                      Parameter          Unit
                            Haemoglobin                g/100ml
                            RBC volume                    µ3
                            TGMH                          pg
                            Haematocrit                   %
                            RBC                           /µl
                            Mean corp hemoglob conc.      %
                            Platelets                     /µl
                            WBC                           /µl
                            Neutrophils                   /µl
                            Eosinophils                   /µl
                            Basophils                     /µl
                            Lymphocytes                   /µl
                            Monocytes                     /µl
                            Reticulocytes                 /µl
                            Sodium                      mmol/l
                            Potassium                   mmol/l
                            Chloride                    mmol/l
                            Proteins                      g/l
                            Urea                        mmol/l
                            Creatinine                  µmol/l
                            Glucose                     mmol/l
                            Calcium                     mmol/l
                            Phophorus                   mmol/l
                            Alkaline phosphatase         UI/l
                            AST                          UI/l
                            ALT                          UI/l
                            LDH                          UI/l
                            CK                           UI/l
                            TP                            %
                            TCA                            s
                            Fibrinogen                    g/l

Annex 3: Examples for Scientific Topics to be Investigated
Without being exhaustive, topics of particular interest are those which
    - Investigate mechanisms explaining the effects of bed rest alone or countermeasure
        application on target systems
    - Aim at defining valid outcome measures to assess countermeasure effectiveness in
        addition to or in the context of BCD: what are acceptable limits of loss of tissue or
        function? Are these based on average or relative loss from previous studies or space
        missions? Is it relative to the required ability to perform/recover/rate of recovery and/or a
        subjective feel of wellbeing?
    - Will result in comparative analyses of changes induced by bed rest versus space flight
    - Determine if the bed-rest induced bone loss is fully reversible in terms of mass, ultra-
        and microstructural organisation
    - Compare mechanisms and time course leading to loss of bone mass, structure, and
        function caused by bed rest with those underlying age-related osteoporosis
    - Investigate the ability to sustain muscle performance levels to meet demands of
        performing activities of varying intensities
    - Investigate the impact of deficits in skeletal muscle structure and function on other
    - Determine the factors influencing the regulation of muscle metabolism during normal
        activity and exercise, in acute and chronic gravitationally unloaded states, and during
        recovery from unloading
    - Identify bone and muscle metabolism markers convenient for monitoring the bed rest
        induced muscle and bone impairments
    - Determine the endocrine, nutritional and mechanical mechanisms relevant for the
        degenerative changes in bone, muscle and connective tissue
    - Determine sensory inputs and coordination processes of neuromuscular function before,
        during, and after bed rest
    - Determine whether decreases in afferent inputs (vestibular, proprioceptive,
        somatosensory) that are associated with bed rest, result in any temporary or permanent
        deficits (i.e. reflexes, vertigo, perception). According to anecdotal evidence about 10%
        of bed rest subjects experience vertigo. Some volunteers report changed spatial
        perception on rising following long-term bed rest.
    - Determine to what extent the cardiovascular adaptation to bed rest affects the post bed
        rest orthostatic intolerance
    - Determine whether bed rest could trigger the manifestation of previously asymptomatic
        cardiovascular disease
    - Monitor cardiac excitation with the view to determine whether bed rest influences the
        occurrence of dysrhythmias
    - Investigate whether the cardiovascular response to exercise stress is altered
    - Assess to which degree blood components are altered causing changes in
        cardiovascular haemodynamics
    - Assess the underlying causes for diminished cardiac function
    - Determine whether vestibular factors contribute to cardioregulatory dysfunction following
        bed rest
    - Determine alterations in blood pressure and blood flows, and the functional
        consequences in tissues and organs
    - Describe the effects of combined countermeasures (i.e. nutrition and mechanical stress)
        to maintain muscle mass, endurance capacity, cardiovascular function and bone density

-   Investigate effects on mood and cognition in general and more specifically in the context
    of countermeasure application, which should include assessments of the interventions‟
-   Monitor psychosocial adaptation and assess how this influences human performance
-   Determine whether the bed rest study environment can trigger neurobehavioral
    dysfunction in previously healthy volunteers, and how this influences human
-   Investigate influences on sleep-wake cycles, sleep quality, and biological rhythms in
    general. If altered, does it result in behavioural changes?
-   Investigate which roles genetics play in inter-individually different responses to
    gravitational unloading by bed rest
-   Investigate genotype and phenotype interactions
-   Develop efficient rehabilitation protocols/procedures and/or determine the kinetics of
-   Aim at optimising the bed rest environment ergonomically
-   Assess the risk to develop muscle injury, connective tissue dysfunction, joint cartilage
    changes, intervertebral disk rupture and bone fractures due to deficiencies in motor skill,
    muscle strength and muscular fatigue
-   Assess the ability to adequately perform tasks due to changed motor performance,
    muscle endurance, and disruptions in structural and functional properties of soft and
    hard connective tissues of the axial skeleton
-   Determine the factors causing bed-rest induced discomfort: facial congestion,
    headache, gastro-intestinal complaints, musculoskeletal complaints on rising after bed
    rest (sore feet, joints, tendons, muscles)
-   Assess whether and to what degree there is an increased susceptibility to injury after
    bed rest and which role inflammation plays in the repair and regeneration of muscle and
    connective tissue
-   Determine whether and to what degree absorption, pharmacodynamics/-kinetics,
    bioavailability and adverse drug reactions of common pharmaceuticals are altered
-   Assess whether and to which degree a placebo-effect may contribute or be responsible
    for partial protection by a countermeasure. In most cases it is difficult to design truly
    blinded studies, for example when testing a mechanical countermeasure
-   Assess potential changes in functions of inner organs
-   Investigate to which degree bed rest results in an increased risk of renal stone formation
    and what the underlying causes are
-   Assess immunological function such as susceptibility to infection, allergies, and
    hypersensitivity reactions
-   Explore wound healing functions
-   Investigate potential changes in host-microbial interactions
-   Systematically investigate the influence of countermeasures on other systems than the
    target, positive as well as negative (determining side-effect profiles)
-   Are likely to result in applications for both space- and clinical medicine. Credit will be
    given for more detailed plans where partners, applications, and procedures for transfer
    of knowledge and/or technology have already been identified.

Annex 4: AO-06-BR Notification of Interest

                              ESA ANNOUNCEMENT OF OPPORTUNITY

                             USING THE MODEL OF BED REST

I intend to submit the following type of proposal in response to the AO-06-BR:

   Scientific Proposal           Scientific Proposal with industrial participation

The proposed project is aimed to be implemented in (more than one choice possible):

   Short-term bed rest (5d)      Medium-term bed rest (21d)

   Long-term bed rest (60d)

I will participate in the AO-06-BR Information Workshop at ESTEC on 29th May, 2006

   YES                   NO

The information in this Notification of Interest can be distributed to the participants at the AO-06-BR
Information Workshop

   YES                   NO

1. Submitted by:

Please insert data of the Science Team Coordinator (STC)
Title, name and function:
University/Research Centre:


Please insert data for each Science Team Member (STM). Copy/paste box for inclusion of more than 3
Name and function:


Name and function:


Name and function:


2. Descriptive title of intended proposal

3. Six (6) keywords of your proposal/research focus

4. Area of Research

Please indicate the area of research of your experiment/project

5. Brief summary

Please provide a brief summary of the experiment/project you intend to perform giving a clear
understanding of the objectives of the project and how these objectives will be achieved.

Annex 5: AO-06-BR Proposal Cover Page

                              ESA ANNOUNCEMENT OF OPPORTUNITY

                             USING THE MODEL OF BED REST


   Scientific proposal        Scientific proposal with industrial participation

2. I WAS INFORMED OF THIS                      (For ESA use only)

   LETTER ANNOUNCEMENT FROM ESA                Proposal Registered Number



4. REQUIRED LENGTH OF BED REST (more than one choice possible)

   Short-term bed rest (5d)       Medium-term bed rest (21d)

   Long-term bed rest (60d)


Name and function:
University/Research Centre:



Name and function:

Name and function:

Name and function:



    YES         NO





  YES      NO


11. COMMENTS                             SIGNATURE OF PERSON NAMED IN POINT 4

                                         SIGNATURE ……………………..…………..

                                         Place, date

Annex 6: Proposal Abstract Form AO-06-BR

                           ESA ANNOUNCEMENT OF OPPORTUNITY

                             USING THE MODEL OF BED REST

I hereby submit the following type of proposal in response to the AO-06-BR:

   Scientific proposal                  Scientific proposal with industrial participation

1. Submitted by:
Please insert data of the Science Team Coordinator
Name and function:
University/Research Centre:


Please insert data for each Science Team Member (no limit to number):
Name and function:


Name and function:


Name and function:



Proposal Title:

Required length of bed rest (more than one choice possible):

   Short-term bed rest (5d)      Medium-term bed rest (21d)

   Long-term bed rest (60d)

Abstract of proposal:

Prepare a brief description of the proposal, stating hypothesis/hypotheses and specific aim(s) of the
proposed work including the broad and long-term objectives,. Describe briefly the research design and
methods for achieving these objectives and aims. This abstract is meant to serve as a succinct but accurate
description of the proposed work when separated from the main text of the proposal. The abstract should
be no more than about 300 words.

Annex 7: Acronyms
AG                  Artificial gravity

BCD                 Bed rest core data

BP                  Blood pressure

BR                  Bed rest

CM                  Countermeasure

DEXA                Dual energy X-ray absorptiometry

ECG                 Electrocardiogram

ELIPS               European programme for Life and Physical sciences and
                    applications utilising the International Space Station
HDT                 Minus 6° head-down tilt bed rest position

HME                 ESA‟s Human spaceflight, Microgravity and Exploration
LBNP                Lower body negative pressure

LTBR                Long-term bed rest (60 days)

MRI                 Magnetic resonance imaging

MTBR                Medium-term bed rest (21 days)

R                   Recovery day after BR (+0, +1, +2, …)

STBR                Short-term bed rest (5 days)


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