BONE FORMATION AND CALCIFICATION IN CARDIOVASCULAR DISEASE

Release Date:  January 2, 2001

RFA:  RFA-HL-01-014

National Heart, Lung, and Blood Institute
 (http://www.nhlbi.nih.gov)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
 (http://www.nih.gov/niams/)

Letter of Intent Receipt Date:  February 15, 2001
Application Receipt Date:       March 19, 2001

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

The objective of this initiative is to stimulate research that addresses the
pathophysiologic and molecular mechanisms of vascular calcification, and the
possible links between vascular calcification, bone formation, and
cardiovascular disease.  Suggested research areas for this initiative include:
(a) the relationship between cardiovascular disease, osteoporosis, and related
pathologies and the delineation of potential mechanisms of vascular
calcification and bone mineralization; and (b) the determination of the
effects of statins, bisphosphonates, and other commonly used therapeutic
agents on the skeleton and the cardiovascular system.  Collaborations among
investigators from the cardiovascular and bone research communities are
strongly encouraged as are multidisciplinary approaches including molecular,
cellular and whole animal studies which can be applied to the human condition.

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 Request for Applications (RFA),
"Bone Formation and Calcification in Cardiovascular Disease", is related to
one or more of the priority areas.  Potential applicants may obtain a copy of
"Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government.  Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research project
grant (R01) award mechanism.  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the applicant.  The
total project period for an application submitted in response to this RFA may
not exceed four years.  This RFA is a one-time solicitation.  Future
unsolicited competing continuation applications will compete with all
investigator-initiated applications and be reviewed according to the customary
peer review procedures.  The anticipated award date is September 30, 2001.

Specific application instructions have been modified to reflect "MODULAR
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant
applications can be found at
https://grants.nih.gov/grants/funding/modular/modular.htm.

FUNDS AVAILABLE

The National Heart, Lung, and Blood Institute (NHLBI) intends to commit
approximately $2.0 million total costs and the National Institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS) intends to commit approximately
$1.0 million total costs in FY 2001 to fund up to 9 new grants in response to
this RFA.  An applicant may request a project period of up to four years and a
budget for total direct costs of up to 10 modules ($250,000) per year. 
Because the nature and scope of the research proposed may vary, it is
anticipated that the size of each award will also vary.  Although the
financial plans of the NHLBI and NIAMS 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.  At this time,
it is not known if this RFA will be reissued.

RESEARCH OBJECTIVES

Background

The high visibility and commercialization of a non-invasive, more sensitive
method to measure vascular calcification has focused national attention on the
role of calcification in the development and progression of cardiovascular
disease.  Calcification is a common feature of atherosclerotic plaques and may
lead to clinical complications, including myocardial infarction, impaired
vascular tone, and coronary insufficiency caused by loss of aortic recoil. 
Calcification of valves is one of the leading reasons for valve replacement in
patients with symptomatic aortic stenosis. 

Recent intriguing observations suggest that rapid advancement in our
understanding of the basic mechanisms involved in the initiation and
progression of vascular and valvular calcification is now possible. 
Historically, this ectopic calcification was considered a degenerative process
leading to passive precipitation of calcium phosphate.  New findings strongly
suggest that ectopic mineralization is part of an active ongoing process,
rather than the result of passive degeneration.  The concept of regulated
vascular calcification suggests the presence of cellular and molecular
determinants of ectopic calcification, natural inhibitors of ectopic
calcification, and regulators of resorption.

Somewhat surprisingly, preliminary studies to probe the molecular mechanisms
of vascular calcification have suggested parallels with bone formation.  Cells
with both osteoblastic (bone forming) and osteoclastic (bone resorbing)
potential have been described in vascular tissue, and bone-related proteins
have been identified in calcified arterial and valvular lesions.  The recent
progress in understanding the molecular mechanisms involved in bone formation
and resorption suggest potential new mechanisms that may be involved in
vascular calcification.  Bone-related proteins also may play some protective
role against vascular calcification since mice genetically engineered to be
deficient in specific bone-related proteins have developed extensive vascular
calcifications.  Thus, the complex mechanisms involved in vascular
calcification are not known, but if vascular calcification is regulated in a
manner similar to bone and bone is constantly being remodeled, perhaps
vascular calcification is also constantly being remodeled through similar
complex processes. 

Paradoxically, patients with vascular calcification which has the same
composition as bone mineral hydroxyapatite, may experience osteoporotic loss
of bone mineral.  The reciprocal build up and loss of the calcium mineral in
two locations in the same patient suggests that neither process is
attributable to simple systemic calcium excess or deficiency.  The potential
for involvement of the estrogen receptors, immune system, and/or collagen in
the calcification process exists, but their roles in the calcification paradox
are not known.  Several studies have reported an association between low bone
mass and cardiovascular disease.  More recently, an association was found
between low bone mass and the risk of mortality from cardiovascular disease
later in life.  Studies to determine if patients with cardiovascular disease
have low bone mass due to osteoporosis are not available.  The association
between low bone mass and cardiovascular disease suggests that strategies to
prevent osteoporosis might prevent the development of cardiovascular disease
as well.

In some types of osteoporosis, there is an elevated number of marrow
adipocytes and a paucity of osteoblasts.  Since marrow stromal cells contain a
common progenitor cell population for both adipocytes and osteoblasts, the
observed cellular population of osteoporotic bone may be related to an
increased adipogenic differentiation at the expense of osteogenic
differentiation.  Oxidized lipids, a known factor in atherogenesis, appear to
promote adipogenesis and may stimulate osteoclasts resulting in enhanced bone
resorption.  Oxidized lipids, then, may be one potential mechanism for the
paradoxical coincidence of vascular mineralization with bone loss.  If
significant in the human disease process, lipid-lowering drugs and
antioxidants might have beneficial effects in individuals susceptible to
osteoporotic bone loss. 

Phenotypic expression of coronary calcium deposition in asymptomatic, but
high-risk adult human subjects appears to be dependent on ethnic origin.  A
lower prevalence of coronary calcification is found in black subjects as
compared with white subjects with a similar extent of atherosclerosis.  Bone
density and cardiovascular risk are known to differ by ethnicity.  The
mechanisms responsible for these ethnic differences are not known.

Preliminary results from inbred strains of mice suggest the presence of common
factors that could determine susceptibility to atherosclerosis and
osteoporosis.  Strains of mice that are very susceptible to the development of
atherosclerotic lesions have the lowest values for bone mineral density,
whereas those resistant to the development of atherosclerotic lesions have the
highest values for bone mineral density.  The basic underlying mechanisms and
the factors involved with these differences in atherosclerosis susceptibility
and bone formation/resorption have not been identified.

Several members of the statin drug family, long recognized as effective in
lowering cholesterol levels and reducing cardiovascular risk, recently have
been shown to have significant effects on bone.  Statins can directly induce
new bone formation in cell cultures and animal models, and some studies
suggest that statin use may reduce fracture risk.  Though still preliminary,
these findings suggest another possible link between cardiovascular disease
and bone remodeling.  Whether statins influence the development of vascular
calcification is not known.  The mechanism of the statin induction of bone
formation remains unclear, but may be related to complex down-stream effects
on sterol synthesis.  Since the available drugs for treating osteoporosis
generally only prevent further bone loss rather than stimulating new bone
formation, these recent findings may open up new areas of research as well as
a new era in the prevention and treatment of osteoporosis.
 
Amino-bisphosphonates are widely used to block bone resorption.  Although the
exact mechanism of action of amino-bisphosphonates is not well understood,
there is evidence to suggest that they may act, in part, by inhibiting the
lipid modification of signaling proteins.  The anti-resorptive action of
bisphosphonates, along with the observation of potentially resorptive cells in
some instances of vascular calcification, raises the possibility that
bisphosphonates could potentially exacerbate cardiovascular disease in some
patients.  Therefore, the overall health benefits of bisphosphonates,
including both bone and cardiovascular effects, needs systematic
investigation.

Although there are several lines of evidence linking vascular calcification,
bone formation and cardiovascular disease; much of the evidence is suggestive,
rather than definitive, and the mechanisms involved as well as their
regulation are unknown.  The basic cellular and molecular processes involved
in the initiation and progression of vascular calcification need to be
identified.  At present, there is no direct way to prevent or treat the
development of vascular calcification.  Given the links between bone cell
differentiation and cardiovascular disease, an entirely new approach to
treating cardiovascular disease could emerge.  Thus, this initiative should
result in insights leading to new areas for disease prevention and
intervention.

Research Scope

This RFA will support research into the pathophysiology and molecular
mechanisms of vascular calcification, and the possible links between vascular
calcification, bone formation, and cardiovascular disease.  It is expected
that progress in these areas will require the integration of insights from
both vascular biology and skeletal biology.  Thus, to be considered responsive
to this initiative, applications must demonstrate the potential to draw on
techniques, concepts, existing information, or new investigations from both
the skeletal and vascular areas of research.

This interdisciplinary character may be achieved in a number of different
ways.  For example, the efforts of investigators with complementary expertise
may be integrated within a single application, using sub-contracts if
necessary to extend support to scientists at different institutions. 
Alternatively, if a substantial body of work already exists in one tissue or
disease area, a team specializing in the other area may be able to meet the
standard of responsiveness without proposing overtly interdisciplinary
studies.  For example, proposed studies of cardiovascular physiology or
atherosclerosis that would take place in an existing clinical cohort that was
originally developed for studies of the skeletal system would be responsive if
results can be correlated with the skeletal parameters that have already been
determined.  Similarly, it may be valuable to study the skeletal system of a
genetically modified animal model developed for studies of atherosclerosis
that is already well characterized with respect to its cardiovascular
phenotype. 

The following areas are of interest.  This list is illustrative and is not
intended to exclude other investigations that are consistent with the overall
purpose of this initiative.

o  Differences and similarities between the mechanisms of vascular
mineralization and bone formation (e.g., cell types involved, gene expression
patterns, regulatory factors).  Variation of this comparison with different
types of vascular mineralization (e.g. atherosclerotic lesions, valve
implants).

o  Influence of lipid metabolism on bone, and parallels with its influence on
calcification in vascular tissue.  Role of oxidized lipids in bone metabolism
and vascular calcification.

o  Possible parallels and interactions between bone remodeling and vascular
maintenance and repair.  Possible presence of osteoclast-like resorptive
function in vascular tissue. 

o  Comparison of bone and vascular responses to pharmacological agents with
beneficial effects in one of these diseases such as statins and
bisphosphonates with emphasis on mechanistic studies and early responses as
well as pathophysiology.  Determine whether bisphosphonates exacerbate or
reduce vascular calcification.

o  Studies to determine whether osteoporosis (bone loss) and vascular
calcification or atherosclerosis progress in parallel.  Correlations between
cardiovascular disease and osteoporosis with respect to incidence,
progression, or outcomes.  Dependence of correlation on gender, race, or
ethnicity; common and distinguishing genetic and environmental risk factors.

EXCLUSIONS

This RFA is intended to support R01 programs that draw on techniques,
concepts, existing information, or new investigations from both the skeletal
and vascular areas of research.  Therefore, proposed research examining only
vascular calcification or only bone development will not be considered
responsive to this RFA.  New epidemiological studies or large clinical trials
are beyond the scope of this initiative.  Ancillary studies to ongoing
clinical trials or epidemiologic studies would be considered.  Proposed
research examining lipids or lipid oxidation and atherosclerosis or
calcification without including a connection to osteoporosis or bone
development will not be considered responsive to this RFA.
 
SPECIAL REQUIREMENTS

Upon initiation of the program, annual meetings will be held in Bethesda, MD,
to encourage exchange of information among investigators who participate in
this program.  A major goal of these meetings is to facilitate progress by
providing a forum that will lead to sharing ideas, technology, data, skills,
and biological materials.  Applicants must budget for travel funds that will
allow Principal Investigators and other key research scientists as appropriate
to participate in these meetings.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their sub-populations must be included in all NIH-supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification are 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 research involving human subjects should read the
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for Grants and Contracts on
August 2, 2000
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a
complete copy of the updated Guidelines are available at 
https://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.  The
revisions relate to NIH defined Phase III clinical trials and require: a) all
applications or proposals and/or protocols to 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) all
investigators to report accrual, and to conduct and report analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH 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 was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: https://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

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.  Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a
descriptive title of the proposed research, the name, address, and telephone
number of the Principal Investigator, the identities of other key personnel
and participating institutions, and the number and title of the RFA in
response to which the application may be submitted.  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 NHLBI and
NIAMS staff to estimate the potential review workload and plan the review.

The letter of intent is to be faxed, E-mailed, or mailed to Dr. Deborah Beebe
at the address listed under INQUIRIES by February 15, 2001. 

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants.  These forms are available at most institutional
offices of sponsored research and from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge Drive,
MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email:
GrantsInfo@nih.gov.

The modular grant concept establishes specific modules in which direct costs
may be requested as well as a maximum level for requested budgets. Only
limited budgetary information is required under this approach.  The
just-in-time concept allows applicants to submit certain information only when
there is a possibility for an award. It is anticipated that these changes will
reduce the administrative burden for the applicants, reviewers and Institute
staff.  The research grant application form PHS 398 (rev. 4/98) is to be used
in applying for these grants, with the modifications noted below.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to
a total direct cost request of 10 modules ($250,000) per year.  The total
direct costs must be requested in accordance with the  program guidelines and
the modifications made to the standard PHS 398 application instructions
described below:

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total
Direct plus Facilities and Administrative (F&A) costs] for the initial budget
period Items 8a and 8b should be completed indicating the Direct and Total
Costs for the entire proposed period of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4
of the PHS 398. It is not required and will not be accepted with the
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398.  It is not required
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative
page. (See https://grants.nih.gov/grants/funding/modular/modular.htm for sample
pages.)  At the top of the page, enter the total direct costs requested for
each year.  This is not a Form page.

o Under Personnel, list all project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should
be provided.  However, the applicant should use the NIH appropriation language
salary cap and the NIH policy for graduate student compensation in developing
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the nearest
$1,000.  List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of all personnel,
and the role on the project. Indicate whether the collaborating institution is
foreign or domestic.  The total cost for a consortium/contractual arrangement
is included in the overall requested modular direct cost amount.  Include the
Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the
number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a specific
role in the proposed project, as well as to evaluate the overall
qualifications of the research team.  A biographical sketch is required for
all key personnel, following the instructions below.  No more than three pages
may be used for each person.  A sample biographical sketch may be viewed at: 
https://grants.nih.gov/grants/funding/modular/modular.htm.

- Complete the educational block at the top of the form page.
- List position(s) and any honors.
- Provide information, including overall goals and responsibilities, on
research projects     ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations.

o CHECKLIST - This page should be completed and submitted with the
application.  If the F&A rate agreement has been established, indicate the
type of agreement and the date.  All appropriate exclusions must be applied in
the calculation of the F&A costs for the initial budget period and all future
budget years.

o The applicant should provide the name and phone number of the individual to
contact concerning fiscal and administrative issues if additional information
is necessary following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) 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 sample RFA label available at:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change.  Please note this is in pdf format.

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 must be
sent to Dr. Deborah Beebe at the listing under INQUIRIES.

Applications must be received by 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 review.
  
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.  The
CSR will not accept any application that is essentially the same as one
already reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must include
an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NHLBI and NIAMS.  Incomplete and/or non-responsive
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 accordance with the review criteria stated below.  As part of the
initial merit review, all applications will receive a written critique and
undergo a process in which only those applications deemed to have the highest
scientific merit will be discussed, assigned a priority score, and receive a
second level review by the National Heart, Lung, and Blood National Advisory
Council and/or the National Institute of Arthritis and Musculoskeletal and
Skin Diseases Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In
their 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.  Each
of these criteria will be addressed and considered in assigning the overall
score, weighting them as appropriate for each application.  Note that 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 forward.

(1) 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?

(2) 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?

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

(4) 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)?

(5) 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?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research.  Plans for the recruitment and retention of subjects will also be
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the
proposed research.

o  The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project 
proposed in the application.

Schedule

Letter of Intent Receipt Date:    February 15, 2001 
Application Receipt Date:         March 19, 2001
Peer Review Date:                 June/July, 2001
Council Review:                   September 6-7, 2001
Earliest Anticipated Start Date:  September 30, 2001

AWARD CRITERIA

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.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding NHLBI programmatic issues to:

Deborah Applebaum-Bowden, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10184, MSC 7956
Bethesda, MD  20892-7956
Telephone:  (301) 435-0550
FAX: (301) 480-2858
Email: applebad@nhlbi.nih.gov

Direct inquiries regarding NIAMS programmatic issues to:

William J. Sharrock, Ph.D.
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Natcher Building, Room 5AS-37A, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX: (301) 480-4543
Email: ws19h@nih.gov                                             

Direct inquiries regarding review matters, letters of intent, and two copies
of the application to:

Deborah Beebe, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7178, MSC 7924
Bethesda, Maryland 20892-7924 (20817 for express mail)
Telephone: (301) 435-0270
FAX: (301) 480-3541
E-mail: beebed@nhlbi.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Michelle Gosha
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7136, MSC 7926
Bethesda, MD 20892-7926
Telephone:  (301) 435-0177
FAX:  (301) 480-0422
E-mail: gosham@nhlbi.nih.gov

Ms. Melinda Nelson
Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Natcher Bldg. Rm. 5A49, MSC 6500
Bethesda Md 20892-6500
Telephone: (301) 594-3535
FAX (301) 480-5450
Email: mn23z@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.837 and No. 93.846.  Awards are made under authorization of Sections 301
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
administered under NIH grants policies and Federal Regulations 42 CFR 52 and
45 CFR Parts 74 and 92.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and promote the non-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 people.

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