OPERATION OF SENSORS IN VIVO
RELEASE DATE: October 21, 2002
RFA: EB-03-001
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
(http://www.nibib1.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD)
(http://www.nidcd.nih.gov/)
LETTER OF INTENT RECEIPT DATE: January 6, 2003
APPLICATION RECEIPT DATE: January 21, 2003
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 of Biomedical Imaging and Bioengineering (NIBIB)
and the National Institute on Deafness and Other Communication
Disorders seeks investigator-initiated applications for research grant
awards (R01) or exploratory/developmental research grant awards(R21)
for the development of innovative technologies designed to increase the
utility of a sensor in vivo. In particular, novel sensing modalities
need to be developed that operate in vivo or that alter the healing
dynamics at the sensor insertion point. A team-based approach is
strongly encouraged to capitalize upon the talents from sensor
engineers, pathologists, histologists, cell biologists, immunologists
and biomaterial scientists. Contributions from molecular and cellular
biology, implant pathology, and immunology will help advance knowledge
of the tissue reaction to sensor implantation in vivo. Materials
science, engineering design changes, pharmaceutical adaptations, and
novel transduction mechanisms are needed to improve sensor performance
in vivo. Special emphasis will be placed on the validation of the
sensor output to give a clinically relevant endpoint.
RESEARCH OBJECTIVES
The NIH's Bioengineering Consortium (BECON) held a two-day symposium
titled "Sensors for Biological Research and Medicine" on June 24-25,
2002, at the Natcher Conference Center Bethesda, Maryland. Specific
goals of the meeting were to provide a forum to showcase current
advancements in biomedical sensor technology and applications, to
identify future biomedical needs and the emerging technologies that can
meet them, and to provide advice to the NIH concerning opportunities
and needs in the field of biomedical sensors.
One concern was the utility of a sensor in vivo. The invasion of a
sensor into tissue creates a wound. The wound healing response in the
presence of a biomaterial has certain abnormal traits compared to a
sham wound healing response lacking an implant. Sensor
biocompatibility is defined by this response, beginning with the first
encounter of the sensor surface with host proteins, subsequent
encounters with immune cells, inflammatory cytokine cascades, and
fibroblasts with their fibrotic response locally around the implant.
This abrogated healing response is a continuum of dynamic histological
events influencing the sensing. The sensing surface constitutes one
component of the sensing environment in this wound site. The
surrounding tissue, responding also to the local trauma and
inflammatory sequelae, constitutes the other half of this sensing
environment. Mutual physiological influences, biochemical crosstalk,
and signaling between the two halves are poorly characterized, poorly
understood, and poorly controlled in most, if not all, sensor designs
to date. Nonetheless, it is this complex environment in which
implantable sensor performance and reliability is demanded.
Implanted sensors must not necessarily avoid the encapsulation response
to be successful. Various capsule reactions are tolerable to permit
sensing function; some can be temporally modulated, perhaps eliminated.
Yet, reliable, predictable capsule response yielding reliable,
predictable sensor response is required. Site-to-site implant
response, and species-to-species variability, must be seriously
considered as well as other design, materials, and microenvironmental
influences. These include certain performance enhancing biomaterial
features (porous texture, surface shielding from adsorbed proteins,
drug delivery, low inflammatory potential); advanced electronic signal
processing algorithms to accommodate complex in situ sensing dynamics
(and signal:noise limits); and novel designs with requisite new,
improved sensing properties in an implantable context.
To solve the long-standing challenges preventing practical realization
of a long-term implantable sensor, new innovative technical and
scientific approaches must exploit recent advances and yet-undiscovered
principles governing the behavior of materials implanted into wound
sites. The sensor implant site must be considered as a wound bed with
compromised, abnormal healing cascades that resolve acutely but persist
chronically. These healing dynamics, their physiological consequences,
and their impact on in vivo sensing must be appreciated, and to
whatever extent possible, controlled.
The next phase of research in this area must directly resolve the
problem of encapsulation by either processing sensor signals regardless
of the encapsulation, or adapting methods to alter it. To address this
problem, a team approach is strongly encouraged. The sensor and the
tissue it affects can be separated into two separate, intimately
related problems. Research addressing these problems may include, but
not be limited to:
o New knowledge of the foreign body response mechanisms, their
kinetics, dynamics, and details, including pathways leading to both
foreign body giant cell formation and fibroblast recruitment in wound
sites;
o Methods to evaluate the influence of the inflammatory reaction and
cytokine presence in a wound site with sensor response;
o Design features for new sensors that enable accurate calibration
throughout the wound healing including dynamic and complex signal
processing algorithms to adapt signals logically and reliably over
time;
o Improved sensor designs that can anticipate the wound site dynamics
and interface with tissue appropriately with multiple behaviors
depending on the environment;
o Understanding of site-to-site variability in sensing response and its
relationship to wound site-site changes;
o Understanding of species differences (histology, physiology,
accuracy, and advantage) in animal models used to evaluate sensors
intended for human application.
In addition, the NIDCD is interested in translatable in vivo sensor
systems specifically impacting the auditory, vestibular, olfaction,
taste, voice, speech and language neural and sensory systems. Research
addressing these interests may include, but not be limited to:
o Enhanced development of the neural tissue and circuitry hardware
interface(s) to improve amplification and transmission of sound and
speech;
o Development of electrosensors from biomimetic materials that will
reduce or prevent biofouling when implanted into CNS tissue;
o Development of hardware/tissue interfaces to improve the
representation of speech and sound;
o Development and enhancement of high throughput sensor technologies
for the detection of middle ear infections;
o Enhanced electrostimulatory prosthesis interfaces capable of sensing
head acceleration forces using accelerometer and gyroscope technology
for vestibular-deficient individuals;
o Development and enhancement of taste and olfaction sensor
technologies.
MECHANISM OF SUPPORT
This RFA will use the NIH investigator-initiated research grant award
mechanism (R01) and the development/exploratory grant award mechanism
(R21). 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 R01
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,
2003.
The R01 mechanism is recommended for applications that emphasize basic
discovery or cross-cutting research that addresses specific aspects of
sensors operating in vivo. Research periods associated with the R01
proposals are limited to five years with no cap on budget amount.
The R21 Exploratory/Developmental Award supports exploratory or
developmental research aimed at proof-of-principle for high-risk
projects where very little or no preliminary data is available. An R21
application can be for up to two years with a maximum budget request of
$150,000 direct costs per year and a maximum page limit of 10 pages.
R21 applications are not renewable. Investigators are encouraged to
use data generated from the R21 application to apply for further
funding through the R01 mechanism (or other appropriate mechanisms).
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
(including total costs of consortium arrangements) 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 participating Institutes intend to commit approximately $4.6M in FY
2003 to fund 10 to 16 new and/or competitive continuation grants in
response to this RFA. An applicant may request a project period of up
to 5 years for an R01 and a project period of up to 2 years for an R21.
Budgets for direct costs of up to $150,000 per year will be accepted
for an R21. There is no budget limitation for R01 applications.
Applications requesting up to $250,000 per year in direct costs must be
submitted in a modular grant format. Since the total costs for a
subcontract or consortium are included in the direct cost request, one
additional module of $25,000 may be requested for the facilities and
administrative costs associated with third party agreements. Under
these guidelines, applications requesting $250,000 may request $275,000
to cover the facilities and administrative costs described above. A
module requested for this purpose must be clearly identified in the
budget justification section of the application, and will be restricted
for this purpose only at the time of award.
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 NIBIB and 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
General Clinical Research Centers: Applicants from institutions that
have a General Clinical Research Center (GCRC) funded by the NIH
National Center for Research Resources 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 principal
investigator should be included with the application.
Grantee Meetings: Principal Investigators will be required to attend
an annual meeting in the Bethesda, MD region organized by NIBIB.
Investigators must include travel to this meeting as part of the budget
request and state a willingness to participate in this meeting.
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:
Christine A. Kelley, Ph.D.
Acting Director
Division of Bioengineering
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
Suite 200
6707 Democracy Blvd.
Bethesda, MD 20892-5469
Telephone: (301) 451-4778
Fax: (301) 480-4973
Email: kelleyc@mail.nih.gov
Nancy L. Freeman, Ph.D.
Scientific Program Director
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
NIH/DHHS
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 402-3458
Fax: (301) 402-6251
Email: nancy_freeman@NIH.gov
o Direct your questions about peer review issues to:
David T. George, Ph.D.
Chief, Office of Scientific Review
Division of Extramural Activities
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
Suite 920
6707 Democracy Blvd.
Bethesda, MD 20892-5469
Telephone: (301) 496-8633
FAX: (301) 480-0675
Email: georged@nih.gov
o Direct your questions about financial or grants management matters
to:
Ms. Nancy Curling
Division of Extramural Activities
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
Suite 900
6707 Democracy Blvd.
Bethesda, MD 20892
Telephone: (301) 451-4786
Fax: 301-480-4974
Email: curlingn@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 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 David T.
George, Ph.D. at the address listed under WHERE TO SEND INQUIRIES.
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.
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.
SUBMITTING AN APPLICATION: 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
all five collated sets of Appendix material must be sent to Dr. David
T. George at the address listed under WHERE TO SEND INQUIRIES.
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.
Principal investigators should not send supplementary material without
first contacting the Scientific Review Administrator (SRA). The SRA
will be identified in the letter sent to you indicating that your
application has been received. If you have not received such a letter
within three weeks after submitting the application, contact Dr. David
George at the address listed under WHERE TO SEND INQUIRIES.
Please Note: As of November 27, 2001, all applications and other
deliveries to the Center for Scientific Review must come via courier
delivery or the USPS. Applications delivered by individuals to the
Center for Scientific Review will no longer be accepted. For
additional information, see the NIH Guide Notice
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIBIB. Incomplete applications will be
returned to the applicant without further consideration. And, if the
application is not responsive to the RFA, CSR staff may contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next appropriate NIH review cycle.
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 NIBIB 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 appropriate National Advisory
Council or Board.
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
For both the R01 and R21 grant applications, 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 be reviewed with respect to the following:
o TEAM APPROACH: The inclusion of researchers with divergent
backgrounds, for example, the partnering of an engineer, a physiologist
and/or a clinician.
o R21 MECHANISM ONLY: Since the R21 mechanism is intended to
encourage exploratory/developmental research, proposals submitted as an
R21 will also be reviewed based on their high risk/high impact
potential and whether or not the proposal is significantly distinct
from those traditionally submitted through the R01 mechanism. For
example, R21 projects designed to produce incremental advances in
knowledge will not be considered.
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 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: January 6, 2003
Application Receipt Date: January 21, 2003
Peer Review Date: May/June, 2003
Council Review: September, 2003
Earliest Anticipated Start Date: September 30, 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. 93.286 (NIBIB), 93.287 (NIBIB), and No.
93.173 (NIDCD) 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.