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RELEASE DATE:  August 5, 2003

RFA Number:  RFA-HL-04-005 
National Heart, Lung, and Blood Institute (NHLBI)
Institute of Circulatory and Respiratory Health (ICRH),
Canadian Institutes of Health Research (CIHR)


o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
The processes of inflammation and thrombosis interact at multiple points and 
there is abundant evidence to suggest that there are mechanisms common to both 
these processes. The possibility exists that anti-inflammatory agents could be 
utilized to manage thrombotic processes underlying disease.  The goal of this 
initiative is to identify molecular targets and develop novel therapeutic agents 
towards better management of thrombotic disorders. Thus, NHLBI and the Institute 
of Circulatory and Respiratory Health (ICRH) invite applications that utilize 
innovative research approaches to the molecular and cellular interactions 
between the hemostatic and inflammatory systems to identify novel therapeutic 
agents and that translate this knowledge to preclinical research. 

Formation of a blood clot resulting in ischemia may precipitate cardiovascular 
diseases and stroke, which are the leading causes of morbidity and mortality in 
the United States and Canada.  Rapid response and early intervention with 
thrombolytic, antiplatelet, and anticoagulant drugs have contributed to reduce 
the mortality of these patients. However, the anticoagulants in use are decades 
old and there is a need to apply new scientific knowledge and improve therapy 
of thrombotic disorders.
The proteins of the coagulation cascade and the inflammatory molecules work in 
concert to mediate the adhesion of leukocytes, platelets, and the endothelium 
that occurs during thrombotic and inflammatory complications. In addition to 
their well established role in hemostasis and thrombosis, it is now recognized 
that platelets play a pivotal role in orchestrating the process of inflammation.  
Activated platelets shed CD40 ligand (CD40L) that directly activates the 
inflammatory process on the endothelium.  The concentration of soluble CD40L in 
serum increases in acute coronary thrombosis and induces tissue factor 
expression on monocytes. Not only do platelets contain about 90 percent of the 
CD40L in the body, they also produce key inflammatory mediators such as 
platelet-derived growth factors, thrombospondin, P selectin and interleukins.  
CD40L can also activate platelets through the integrin, GP IIb/IIIa, and 
appears to be necessary for stabilizing the arterial thrombi.  Similarly, 
activated protein C (APC), traditionally considered to be an anticoagulant 
protein, has now been shown to have antiinflammatory and antiapoptotic 
properties and was demonstrated to be neuroprotective in an animal model of 
stroke. Thus platelets and clotting proteins which are essential in hemostasis/ 
thrombosis have indeed a dual role as initiators and modulators of the 
inflammatory process. 
The selectin family of receptors is now known to mediate the critical cell-cell 
interactions involved in leukocyte trafficking, thrombosis, and inflammation.  
The rolling of leukocytes is thought to be mediated by P-selectin and its 
ligand, P-selectin glycoprotein ligand 1 (PSGL-1), but extravasation probably 
involves the integrins.  This is a complex process that seems to be regulated 
by internalization of the ligand - receptor molecules and signaling events in 
leukocytes.  Monocytes also rapidly bind activated platelets that display 
P-selectin on their surface.  An emerging area of critical importance is the 
role of blood tissue factor (TF) in thrombosis.  An alternatively spliced 
soluble TF in humans has recently been reported. Monocyte tissue factor in the 
form of microparticles may be transferred to activated platelets at the site of 
injury and P-selectin has been proposed as the TF binding protein or receptor.  
Thus, P-selectin plays an important role in coagulation as well as in 
inflammation.  Over expression of soluble P-selectin in an animal model creates 
a hypercoagulable state.  Infusion of PSGL-Ig, an inhibitor of P-selectin, 
reversed this procoagulant state.  Moreover, PSGL-1 mimetics, in the absence of 
anticoagulants, showed therapeutic benefits in reducing hypercoagulation and
vein wall inflammation in animal models in thromboembolic disorders.  A role 
for E-selectin in thrombosis has been suggested but not confirmed. These 
observations show that thrombosis and inflammation are biologically inseparable 
processes.  P-selectin may no longer be considered only as a marker of platelet 
activation or inflammation, but also a direct inducer of procoagulant activity 
related to vascular and thrombotic diseases.  
It is known that TF – Factor VIIa complex can activate Factor X which is an 
important step in the initiation of blood coagulation.  Recent observations 
suggest that the complex, TF – FVIIa or TF-FVIIa - FXa, can also initiate the 
inflammatory pathway by cleaving the protease activated receptors, PAR -1 and 
PAR-2, thereby activating endothelial cells.  Thus, the initiation of 
coagulation and the initiation of inflammation are kinetically coupled events. 
This is further supported by the observation that tissue factor pathway 
inhibitor (TFPI) reduces inflammatory responses as well as antithrombotic 
effects.   PARs are known to mediate the biological actions of thrombin and 
other proteases released during tissue injury.  PARs coordinate the hemostatic 
and inflammatory responses in endothelial and other cells.
Activation of the coagulation cascade in Gram-negative septicemia is known to 
trigger thrombotic and inflammatory events.  Recently, recombinant APC, a major 
regulator of the anticoagulant pathway, has been observed to be effective in the 
treatment of sepsis. Sepsis is also the major risk factor for acute lung injury 
(ALI) / acute respiratory distress syndrome (ARDS) and this finding needs to be 
extended to non-septic ARDS.  Like tissue factor, APC also has cell receptor 
mediated anti-inflammatory properties.  It is now reported that APC also 
directly prevents cell death and improves cell survival that involves p53 and 
PAR on the endothelial cells.  APC has been shown to be beneficial in 
experimental stroke in animal models and provides a potential treatment option 
in any ischemic injury.  

There is evidence linking inflammation, atherosclerosis, and thrombosis.  
Circulatory inflammatory mediators, in particular, C-reactive protein, has 
emerged as a marker of coronary risk and seems to be associated with increased 
cardiovascular events.  The interaction between inflammation and thrombosis may 
involve a series of biochemical and cellular events, and the severity of the 
clinical outcome may depend on other risk factors and genetic predisposition.  
Thus, anti-inflammatory therapy may limit thrombosis and antithrombotic therapy 
may reduce vascular inflammation. 
The recent scientific developments described above have important therapeutic 
implications. Thrombotic diseases such as myocardial infarction, stroke, and 
thromboembolism are major public health problems with significant mortality and 
morbidity.  It has been considered to be primarily a disorder of the coagulation 
and platelet function.  Accordingly, the mainstay of its therapy has been the 
anticoagulant and platelet aggregation inhibitors. The carbohydrate specificity 
of PSGL-1 in its interaction with P-selectin has been defined and several 
mimetics have been developed.  In experimental models of venous thrombosis, 
these inhibitors of P-selectin produced encouraging results without the use of 
anticoagulants.  Another pertinent example is the possible early use of aspirin 
after bypass surgery.  The beneficial effects in averting some of the ischemic 
complications by early aspirin use are likely to relate to its antiinflammatory 
properties. Recognition of the basic molecular processes involved and the 
interplay between inflammation and thrombosis provide opportunities to develop 
novel therapeutics to combat thrombotic and thromboembolic diseases.
Examples of Research Areas
The goal of this RFA is to identify new targets and develop novel therapy for 
thrombotic disorders such as heart attack, stroke, deep vein thrombosis (DVT), 
and pulmonary embolism in preclinical studies.  These are examples of thrombotic 
disorders to study but applicants are encouraged to develop their own ideas.

This RFA will use NIH Research Project Grant (R01) award mechanism. Applications 
submitted in response to this RFA may have a project period of up to four years. 
As an applicant you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project will 
compete with all investigator-initiated applications and will be reviewed 
according to the customary peer review procedures. The anticipated award date 
is September 30, 2004. Applications that are not funded in the competition 
described in this RFA may be resubmitted as NEW investigator-initiated 
applications using the standard receipt dates for NEW applications described in 
the instructions to the PHS 398 application.  
This RFA uses just-in-time concepts.  It also uses the modular budgeting format. 
(see https://grants.nih.gov/grants/funding/modular/modular.htm).   Specifically, if 
you are submitting an application with direct costs in each year of $250,000 or 
less, use the modular format.  This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at 

Applications submitted by foreign institutions can request facilities and 
administrative (F&A) costs up to a maximum of eight percent.  Please see the web 
site https://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html for more 
information on allowable F&A costs for foreign grants and domestic grants with 
foreign components.

The NHLBI intends to commit approximately $3,000,000 in FY 2004 to fund about 10 
to 12 new grants in response to this RFA. The ICRH intends to commit 
approximately $1,200,000 to fund meritorious applications, relevant to their 
mission, involving Canadian institutions.  ICRH will make the award of grants 
for meritorious applications of interest to them.  Applicants who wish to have 
their projects considered for funding by ICRH should include with their 
application a letter stating that their application and summary statement may be 
shared with ICRH.  An applicant may request a project period of up to four years 
and a budget for direct costs of up to $200,000 per year. Because the nature and 
scope of the proposed research will vary from application to application, it is 
anticipated that the size and duration of each award will also vary. Although 
the financial plans of the NHLBI and ICRH provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications.
You may submit (an) application(s) if your institution has any of the following 
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, and 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based or community-based organizations 

Any individual with the skills, knowledge, and resources necessary to carry out 
the proposed research is invited to work with their institution to develop an 
application for support.  Individuals from underrepresented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply 
for NIH programs.   
The goal of this initiative is to develop new targets for therapy of thrombosis 
by focusing on translational research at the interface of thrombosis and 
inflammation.  In order to be responsive to the RFA, studies must propose 
specific approaches to identify novel therapeutic agents in preclinical studies. 
Studies purely on either inflammation or thrombosis will not be considered 
responsive to this RFA.  In addition studies on currently established agents 
such as aspirin will not be considered responsive.  The expectation is that the 
results from studies supported under this RFA will contribute to the development 
of novel therapeutic agents for thrombotic disorders.
General Clinical Research Centers
Applications from institutions that have a General Clinical Research Center 
(GCRC) funded by the NIH National Center for Research Resources (NCRR) may wish 
to identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement from either the GCRC program director or the principal 
investigator should be included with the application.
Principal investigators will be required to attend an annual meeting organized 
by the NHLBI/ICRH.  Please include travel to Bethesda, MD area as part of the 
budget request.
We encourage inquiries concerning this RFA and welcome the opportunity to answer 
questions from potential applicants.  Inquiries may fall into three areas:  
scientific/research, peer review, and financial or grants management issues:
o Direct your questions about scientific/research issues to:
Ahmed A.K. Hasan, M.D., Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
Building RKL II, Room 10180
Bethesda, MD  20892
Telephone:  (301) 435-0070
Email:  hasana@nhlbi.nih.gov
Stephen Goldman, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Diseases
Building RKL II, Room 10192
Bethesda, MD 20892
Telephone: 301-435-0565
E-mail:  goldmanS@nhlbi.nih.gov
Andrea Harabin, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Disease
Building RKL II, Room 10120
Bethesda, MD 20892
Telephone: 301-435-0233
E-mail: vreimC@nhlbi.nih.gov
Teri Manolio, M.D.
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Building RKL II, Room 8160
Bethesda, MD 20892
Telephone 301-435-0708
E-mail: manolioT@nhlbi.nih.gov
o Direct your questions about peer review issues to:
Anne P. Clark, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Building RKL II, Room 7214
Bethesda, MD  20892
Bethesda, MD 20817 (for express/courier service)
Telephone:  (301) 435-0270
FAX:  301-480-0730
Email: ClarkA@nhlbi.nih.gov
o Direct your questions about financial or grants management matters to:
Robert Vinson
Division of Extramural Affairs
National Heart, Lung, and Blood Institute 
Building RKL II, Room 7156
Bethesda, MD  20892 - 7926
Telephone:  (301) 435-0166
FAX:  301-480-0166
Email: VinsonR@nhlbi.nih.gov

Direct any questions directed to ICRH, please contact:
Elissa Hines Reimer
Senior Associate
Institute of Circulatory and Respiratory Health
Telephone: (613) 954-0544
Email: ehinesreimer@cihr.gc.ca
Prospective applicants are asked to submit a letter of intent that includes the 
following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 
Although a letter of intent is not required, is not binding, and does not enter 
into the review of a subsequent application, the information that it contains 
allows IC staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to Dr. Anne Clark at the address 

In addition, for this RFA, principal investigators located in Canada are 
requested to notify ICRH of their intent to apply by sending an email to by 
Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  
For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: 
to $250,000 per year in direct costs must be submitted in a modular budget grant 
format.  The modular budget grant format simplifies the preparation of the 
budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the research 
grant application instructions for the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular grants 
is available at https://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label could 
result in delayed processing of the application such that it may not reach the 
review committee in time for review.  In addition, the RFA title and number must 
be typed on line 2 of the face page of the application form and the YES box must 
be marked. The RFA label is also available at: 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the Checklist, and three signed, photocopies, in one 
package to:
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
At the time of submission, two additional copies of the application plus all 
five collated sets of appendix material must be sent to Dr. Anne Clark at the 
address listed under WHERE TO SEND INQUIRIES.
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an application 
is received after that date, it will be returned to the applicant without 
Although there is no immediate acknowledgement of the receipt of an application, 
applicants are generally notified of the review and funding assignment within 8 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is the application for the RFA 
must not include an Introduction describing the changes and improvements made, 
and the text must not be marked to indicate the changes.  While the investigator 
may still benefit from the previous review, the RFA application is not to state 
explicitly how.
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI and ICRH.  Incomplete applications will be returned 
to the applicant without further consideration.  
Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NHLBI, in consultation with ICRH, and in accordance with the review criteria 
stated below. As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, will 
be discussed and assigned a priority score
o Receive a second level review by the NHLBI National Advisory Council. 
The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In the 
written comments, reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research will 
have a substantial impact on the pursuit of these goals: 
o Significance 
o Approach 
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these criteria in 
assigning the application's overall score, weighting them as appropriate for 
each application.  The application does not need to be strong in all categories 
to be judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, an investigator may propose to carry out important 
work that by its nature is not innovative but is essential to move a field 
SIGNIFICANCE: Does this study address an important problem? If the aims of the 
application are achieved, how will scientific knowledge be advanced? What will 
be the effect of these studies on the concepts or methods that drive this field?
APPROACH: Are the conceptual framework, design, methods, and analyses adequately 
developed, well-integrated, and appropriate to the aims of the project? Does the 
applicant acknowledge potential problem areas and consider alternative tactics?
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?
INVESTIGATOR: Is the investigator appropriately trained and well suited to carry 
out this work? Is the work proposed appropriate to the experience level of the 
principal investigator and other researchers (if any)?
ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:
subjects and protections from research risk relating to their participation in 
the proposed research will be assessed. (See criteria included in the section 
on Federal Citations, below).
to include subjects from genders, all racial and ethnic groups (and subgroups), 
and children as appropriate for the scientific goals of the research.  Plans 
for the recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria in the sections on Federal Citations, below).
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be 
used in the project, the five items described under Section f of the PHS 398 
research grant application instructions (rev. 5/2001) will be assessed.  
BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.
Letter of Intent Receipt Date:  December 22, 2003 
Application Receipt Date:  January 22, 2004 
Peer Review Date:  June, 2004 
Council Review:  September, 2004
Earliest Anticipated Start Date:  September 30, 2004
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against these 
risks, the potential benefits of the research to the subjects and others, and 
the importance of the knowledge gained or to be gained.
involving Phase I and II clinical trials must include provisions for assessment 
of patient eligibility and status, rigorous data management, quality assurance, 
and auditing procedures.  In addition, it is NIH policy that all clinical trials 
require data and safety monitoring, with the method and degree of monitoring 
being commensurate with the risks (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
NIH that women and members of minority groups and their sub-populations must be 
included in all NIH-supported clinical research projects unless a clear and 
compelling justification is provided indicating that inclusion is inappropriate 
with respect to the health of the subjects or the purpose of the research. This 
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public 
Law 103-43).
All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts on 
October 9, 2001 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) all 
applications or proposals and/or protocols must provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender and/or 
racial/ethnic groups, including subgroups if applicable; and b) investigators 
must report annual accrual and progress in conducting analyses, as appropriate, 
by sex/gender and/or racial/ethnic group differences.
NIH maintains a policy that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them. This 
policy applies to all initial (Type 1) applications submitted for receipt dates 
after October 1, 1998.
All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research 
using hESC lines that are registered in the NIH Human Embryonic Stem Cell 
Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide, in the project description 
and elsewhere in the application as appropriate, the official NIH identifier(s) 
for the hESC line(s) to be used in the proposed research.  Applications that do 
not provide this information will be returned without review.
Office of Management and Budget (OMB) Circular A-110 has been revised to provide 
public access to research data through the Freedom of Information Act (FOIA) 
under some circumstances.  Data that are (1) first produced in a project that is 
supported in whole or in part with Federal funds and (2) cited publicly and 
officially by a Federal agency in support of an action that has the force and 
effect of law (i.e., a regulation) may be accessed through FOIA.  It is 
important for applicants to understand the basic scope of this amendment.  NIH 
has provided guidance at 

Applicants may wish to place data collected under this PA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description 
of the archiving plan in the study design and include information about this in 
the budget justification section of the application. In addition, applicants 
should think about how to structure informed consent statements and other human 
subjects procedures given the potential for wider use of data collected under 
this award.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for 
NIH funding must be self-contained within specified page limitations. Unless 
otherwise specified in an NIH solicitation, Internet addresses (URLs) should not 
be used to provide information necessary to the review because reviewers are 
under no obligation to view the Internet sites.   Furthermore, we caution 
reviewers that their anonymity may be compromised when they directly access an 
Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 2010," 
a PHS-led national activity for setting priority areas. This RFA is related to 
one or more of the priority areas. Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.healthypeople.gov/Default.htm. 

ICRH WEBSITE: Applicants are encouraged to visit the ICRH website, accessible 
through the Canadian Institutes of Health Research homepage () for information 
concerning the ICRH mandate, current research initiatives and publications such 
as the ICRH Strategic Plan (available in English and French).
AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are 
subject to the terms and conditions, cost principles, and other considerations 
described in the NIH Grants Policy Statement. The NIH Grants Policy Statement 
can be found at https://grants.nih.gov/grants/policy/policy.htm
The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the PHS 
mission to protect and advance the physical and mental health of the American 

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