CELLULAR REPAIR STUDIES OF THE AUDITORY AND VESTIBULAR SYSTEMS
RELEASE DATE: June 6, 2002
RFA: DC-02-003
National Institute on Deafness and Other Communication Disorders
(http://www.nidcd.nih.gov/)
LETTER OF INTENT RECEIPT DATE: July 10, 2002
APPLICATION RECEIPT DATE: August 15, 2002
THIS RFA CONTAINS THE FOLLOWING INFORMATION
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:
PURPOSE OF THIS RFA
The National Institute on Deafness and Other Communication Disorders is
committed to the treatment and elucidation of molecular mechanisms
involved in human deafness and balance disorders. The primary cause of
sensorineural hearing loss and impaired vestibular function results
from damage and loss of auditory and vestibular sensory hair cells of
the inner ear. Current clinical treatments are limited to the use of
devices, hearing aids and cochlear implants, not the repair of the
sensory cells.
Irreparable loss of sensory hair cells can result from numerous factors
including disease, aminoglycoside antibiotics, noise, and aging. In
lower vertebrates hair cells are capable of regeneration following
damage, but in mammals this capacity is absent. Recent advances in
stem cell biology research, especially as related to tissue and
cellular repair, hold great promise for the eventual treatment of
hearing and balance disorders. The purpose of this RFA is to support
fundamental stem cell biology research for repair, regeneration, and
cell lineage delineation, as applied to the auditory and vestibular
systems.
RESEARCH OBJECTIVES
The auditory and vestibular neuroepithelia are critical to the
functional processes of hearing and balance. The hair cells residing
in the cochlea are responsible for sound transduction, and the hair
cells of the semicircular canals and otholithic organs are responsible
for sensing rotational and linear acceleration forces of the head. The
loss of these hair cells in mammals leads to the irreparable loss of
hearing and vestibular mediated balance function.
Two contributing research avenues that could impact cellular
restoration of hearing and balance function are hair cell regeneration
and development. Regenerative studies have consisted primarily of
comparative analyses between the regenerative ability of avian systems
versus the lack of regenerative ability in mammals. Avian hair cell
regeneration involves the up-regulation of cell proliferation and
differentiation of postmitotic cells, whereas mammalian auditory and
vestibular organs show little evidence of terminal hair cell
differentiation from postmitotic cells. These renewing processes in
the avian system result in repopulation of hair cells and full
restoration of hearing and balance function. While understanding the
biological processes of avian renewal is important, there is
insufficient data to determine the clinical value to humans.
Auditory and vestibular developmental studies have revealed an
exceptionally elegant and complex system. The eventual formation of
the inner ear involves the convergence and contribution of the
epithelium, mesenchymal, mesodermal and neural crest cell layers.
Specifically, the invagination of the placodal ectoderm leads to the
formation of the otic placode, eventually giving rise to a defined base
of auditory and vestibular sensory hair cells and non-sensory support
cells. This process occurs early in embryonic development and once a
full complement of hair and support cells is established, division of
the precursor cells cease. Elucidation of the putative progenitors and
the molecular factors that impact these differentiation and
regenerative events will be crucial to defining cell lineage in the
auditory and vestibular organs.
The self-renewal and plasticity characteristics intrinsic to the stem
cell hold the promise of significant clinical application, and stem
cell research in regenerative and reparative therapy provides new
avenues of auditory and vestibular research exploration. To date, stem
cell populations have been identified from almost all normal tissues
including mesenchymal, peripheral and cord blood, neuronal and muscle,
and offer numerous possibilities for putative regenerative
capabilities. Knowledge acquired from these other systems may be
biologically relevant to the auditory and vestibular systems.
Similarly, research information acquired from the auditory and
vestibular environment may have reparative relevance for other tissue
and organ systems. At the core, many fundamental questions exist:
factors determining a cell"s multipotency that allow replenishing
capabilities, mechanisms and factors regulating de-differentiation and
trans-differentiation into a multipotent cell, factors and molecules
involved in the interaction and integration of a newly transplanted
cell and the microenvironment. Eventually, these questions should be
addressed for every tissue type and organ system to realize the full
potential of stem cell biology therapy.
Objectives and Scope
The potential translational application of stem cell biology research
to the auditory and vestibular systems is the focus of this initiative.
Research efforts on the cellular, molecular and genetic mechanisms that
influence the lineage choices of stem cells relevant to the auditory
and vestibular systems are of high importance. Research areas of great
interest include, but are not limited to:
o Identification of auditory and vestibular progenitor cells. It is
unclear if stem cells exist in the auditory and vestibular systems, and
if hair cell generation involves "reserve" stem cells or
dedifferentiation of other cells. The putative replenishing involvement
of support cells in the generation of hair cells is also unknown.
Identification studies of true stem cell progenitors versus products of
trans-amplification are needed.
o Identification of auditory and vestibular cell specific markers. In
vivo and in vitro integration studies will require input cell
validation, and should assess clonality. Identification of cell
specific receptors, surface antigens etc., are needed.
o Development and validation of physiological assays. Cells delivered
to a test environment will have to demonstrate function that is
critical for experimental validation. Development of assays that
permit accurate and reliable characterization of integrated stem or
precursor cells in the auditory and vestibular systems is needed.
o Development of cell purification and expansion technologies.
Ultimate use and therapeutic efficacy will be dependent upon the
validation of cell source. The auditory and vestibular organs, due to
small size and limited accessibility, pose a difficult challenge to
cell harvest and purification. Development of novel technologies and
methodologies to isolate and expand pure lines of putative progenitors
are needed.
o Cellular and molecular commonalities. It is unknown if stem cells
from other sources can be stimulated to differentiate into auditory
and/or vestibular cells. Stem cells harvested from various sources are
currently being used successfully in other reparative systems and their
use to replenish the auditory or vestibular systems should be
investigated.
o Auditory and vestibular microenvironment. There is a need to
elucidate developmental and signaling pathways to identify
combinatorial effects between putative progenitor cell markers and the
surrounding cellular environment. There is a need to identify agents,
such as morphogens, feeder lines, and growth conditions that would
allow propagation of auditory and vestibular progenitors in vivo or in
vitro specifically for reparative assays.
o Vector and delivery systems. Synthetically fabricated or
biologically based support platforms are needed to allow propagation,
delivery and integration of cell populations within the auditory and
vestibular systems. The development of new and novel surgical
approaches to deliver these systems into auditory and vestibular target
environments is needed.
o Transplantation studies. Feasibility studies are needed to explore
cellular replacement within the auditory and vestibular systems.
Identification and characterization of putative target areas for both
hair cell regeneration and neural restoration is needed.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) R21
EXPLORATORY/DEVELOPMENTAL GRANT) and R01 (INVESTIGATOR INITIATED
RESEARCH GRANT) award mechanisms. Responsibility for the planning,
direction, and execution of the proposed project will be solely that of
the applicant. This RFA will have one submission date: August 15, 2002.
Beyond this date, 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 April, 2003. Investigators may submit more
than one application for this RFA.
Generally, applications proposing exploratory/feasibility studies with
limited preliminary data should use the R21 mechanism, while applicants
proposing more extensive projects based on significant published and
preliminary results should use the RO1 mechanism. In addition,
applicants are strongly encouraged to contact the scientific Program
Officer listed below under INQUIRIES to discuss which mechanisms (R21
or RO1) would be most suitable for the proposed research project.
This RFA uses just-in-time concepts. It also uses the modular as well
as the non-modular budgeting formats (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. Otherwise
follow the instructions for non-modular research grant applications.
FUNDS AVAILABLE
The NIDCD intends to commit approximately $1,500,000 in FY 2003 to fund
up to 3 to 5 new R21 and 3 to 5 new R01 grants in response to this RFA.
Because of the exploratory nature of the R21, applicants submitting an
R21 may only request a budget for direct costs of up to $100,000 per
year for a maximum of two (2) years. R01 applicants may request a
project period of up to five (5) years. 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 NIDCD 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.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
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.
SPECIAL REQUIREMENTS
Applications in response to this RFA with the intent to use human
embryonic stem cells (hESC) must comply with federal guidelines. A
cover letter signed by the principal investigator, appropriate
institutional official and business office, acknowledging review and
approval of the grant application proposing human embryonic stem cell
research must be included. All applications must indicate the official
identifier(s) for the appropriate hESC line(s) as found in the NIH
Registry (http://escr.nih.gov/). In addition, compliance to all of the
federal guidelines must be satisfied. These NIH guidelines are listed
at, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-049.html.
Applications not including this information will be returned
without further consideration. Answers to frequently asked questions
about hESC may be found at:
https://grants.nih.gov/grants/stem_cell_faqs.htm
This announcement highly encourages collaboration between stem cell
biologists and auditory/vestibular investigators.
WHERE TO SEND INQUIRIES
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:
Dr. Nancy L. Freeman
Scientific Program Director
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
nancy_freeman@nih.gov
Tel: (301) 402-3458
Fax: (301) 402-6251
o Direct your questions about peer REVIEW issues to:
Dr. Craig Jordan
Chief, Scientific Review Branch
Division of Extramural Research
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Telephone: 301-402-8683
Fax: 301-402-6250
Email: jordanc@nih.gov
o Direct inquires of FINANCIAL or grants management matters to:
Ms. Sara Stone
Chief, Grants Management Branch
Division of Extramural Research
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 402-0909
Fax: (301) 402-1758
Email: stones@nidcd.nih.gov
LETTER OF INTENT
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 institute staff to estimate the potential
review workload and plan the review.
The letter of intent is to be sent by July 10, 2002. The letter of
intent should be sent to:
Dr. Nancy L. Freeman
Scientific Program Director
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
nancy_freeman@nih.gov
Tel: (301) 402-3458
Fax: (301) 402-6251
SUBMITTING AN APPLICATION
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: GrantsInfo@nih.gov.
ADDITIONAL R21 APPLICATION PROCEDURES
All application instructions in the PHS 398 research grant application
instructions and forms (rev. 5/2001) apply to the R21 with the exception
of the following modifications:
1. R21 applications may request up to four (4) $25,000 modules for a
maximum direct cost of $100,000 per year for up to a maximum of two (2)
years.
2. The Research Plan for the R21 application may not exceed 10 pages.
Tables and Figures (color and black and white) must be included within
the 10-page limit. However, to aid reviewers, additional original color
figures should be included in the appendices if the data cannot be
adequately evaluated when copied in black and white (see APPLICATION
SUBMISSION.)
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:
Applications requesting up to $250,000 per year in direct costs must be
submitted in a modular grant format. The modular 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:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
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 and
appendix material must be sent to:
CHIEF, SCIENTIFIC REVIEW BRANCH
DIVISION OF EXTRAMURAL RESEARCH
NATIONAL INSTITUTE ON DEAFNESS AND
OTHER COMMUNICATION DISORDERS
6120 EXECUTIVE BOULEVARD, ROOM 400-C, MSC 7180
BETHESDA, MD 20892-7180
ROCKVILLE, MD 20852 (for express/courier service)
APPLICATION PROCESSING: 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.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIDCD. Incomplete and non-responsive
applications will be returned 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 NIDCD 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 NDCD 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 the written comments, reviewers will be asked to discuss the
following aspects of your 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 your application"s overall score, weighting them
as appropriate for each application. Your 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,
you 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 your study address an important problem? If the
aims of your application are achieved, how do they advance scientific
knowledge? 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? Do you acknowledge potential problem areas and
consider alternative tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project
challenge existing paradigms or develop new methodologies or
technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to your
experience level as the principal investigator and to that of other
researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your 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, your
application will also be reviewed with respect to the following:
o PROTECTIONS: 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.
o INCLUSION: The adequacy of plans to include subjects from both
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 included in the section on Federal Citations, below)
o DATA SHARING: The adequacy of the proposed plan to share data.
o OTHER REVIEW CRITERIA: RO1/R21 applications proposing the use of
human embryonic stem cells will not be required to contain the same
amount of pilot data as judged for a typical RO1/R21. It is
appreciated that this area of investigation is in the early stages of
research development and assessment of pilot data will be reviewed
accordingly, however, the application still must demonstrate the
feasibility of the approach.
o BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: July 10, 2002
Application Receipt Date: August 15, 2002
Peer Review Date: November, 2002
Council Review: January 2003
Earliest Anticipated Start Date: April 1, 2003
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.
REQUIRED FEDERAL CITATIONS
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 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 AMENDMENT
"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
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
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.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The 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
https://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy 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
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at
https://grants.nih.gov/grants/stem_cells.htm 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 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.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The 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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
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.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.173 and is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. 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 described
at https://grants.nih.gov/grants/policy/policy.htm and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
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 people.