PHENOTYPIC CHARACTERIZATION OF SLEEP IN MICE Release Date: December 18, 1998 RFA: HL-99-001 P.T. National Heart, Lung, and Blood Institute National Institute of Mental Health National Institute on Aging National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Date: January 26, 1999 Application Receipt Date: February 26, 1999 THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. THIS RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS RFA. PURPOSE The primary goal of this initiative is to advance our understanding of sleep and wakefulness by developing improved molecular, cellular, and systems approaches to investigate sleep and circadian phenotypes in mice. Better and more extensively-characterized mouse models will help determine the genetic underpinnings of sleep and wakefulness, elucidate the physiological role of sleep, and develop new directions for the treatment of sleep disorders. Establishing inbred mice strains as a platform for sleep studies will advance our understanding of normal sleep phenotypes; facilitate the use of targeted and transgenic gene modification approaches; and lead to a refinement in the definition of sleep state in molecular and genomic terms. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of Health People 2000, a PHS-led national activity for setting priority areas. This RFA, Phenotypic Characterization of Sleep in Mice, is related to the priority areas of heart disease and stroke, chronic disabling conditions, mental health and disorders, maternal and infant health, immunization and infectious diseases, and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic 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. Foreign institutions may not apply. However, foreign components that are critical to the proposed research may be included as subcontracts. Ethnic minority individuals, women, and persons with disabilities are especially encouraged to apply as principal investigators. Multiple applications from the same institution will not be considered unless each application is submitted by a different principal investigator, and is self-contained and independent of others from that institution. Overlap in the scientific scope of applications from the same institution will not be accepted. This does not preclude cooperation among participants after awards are made. If more than one application is envisioned from an institution, the investigators are encouraged to discuss their plans with the program administrator listed under INQUIRIES. Applications submitted in response to this RFA will only be considered as new applications. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research project grant (R01) mechanism of support. Awards will be made and managed by the sponsoring Institutes of this RFA. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. However, specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts currently being examined by the NIH. 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 in the application 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, applicant institutions, reviewers, and Institute staff. Funds must be requested in $25,000 direct cost modules and a maximum of nine modules ($225,000 direct costs) per year may be requested for four years. The cost of equipment is included in the budget limitation. Any necessary escalation must be included within the number of modules being requested. Only limited budget information will be required and any budget adjustments made by the Initial Review Group will be in modules of $25,000. Instructions for completing the Biographical Sketch have also been modified. In addition, Other Support information and the application Checklist page are not required as part of the initial application. If there is a possibility for an award, necessary budget, Other Support and Checklist information will be requested by staff of the awarding Institute following the initial review. The APPLICATION PROCEDURES section of this RFA provides specific details of modifications to standard PHS 398 application kit instructions. This RFA is a one time solicitation. Applications for continuation beyond this initial award period will compete with all investigator-initiated applications in the regular grant program and according to customary peer review procedures. FUNDS AVAILABLE It is anticipated that for fiscal year 1999, total costs of $3,500,000 will be available for this initiative. Award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. Approximately eight to eleven new grants requesting direct costs of up to $225,000 per year for four years are expected to be awarded under this program. The specific number of grants to be funded, however, depend on the merit and scope of the applications received and on the availability of funds. Direct costs will be awarded in modules of $25,000, less any overlap and other administrative adjustments. The earliest anticipated award date for successful grant applications is September 30, 1999. RESEARCH OBJECTIVES Background Sleep is a fundamental and essential biological process. An estimated 40 million individuals in the United States experience chronic or intermittent sleep-related problems and disorders, such as sleep apnea, behavioral and cognitive dysfunction, narcolepsy, insomnia, restless legs syndrome, fibromyalgia, and Sudden Infant Death Syndrome. Sleep disorders are associated with increased morbidity and mortality, as well as the loss of life due to accidents caused by excessive sleepiness. Sleep disorders can alter the severity of cardiovascular, behavioral, and immunological diseases. Defining the basic role of sleep in health and disease represents a significant unmet biomedical challenge yet it remains a relatively understudied area of research. Little is known about the molecular and genetic basis of sleep control, the relationships between sleep and the function of major physiological systems, and changes in the sleep process during development, growth, and aging. Objectives and Scope Descriptive approaches have demonstrated for many years that sleep can be objectively defined and its properties measured. Much has been learned about specific humoral factors, neural pathways, and the physiology of sleep and circadian rhythms using traditional behavioral and systems techniques. An essential step is to build on what has been learned in other mammals by analyzing the component molecular and cellular events of sleep using models in which the contribution of specific genes and their encoded proteins can be identified and well-characterized. In order to accomplish this goal, it is necessary to establish and validate properties of sleep and wakefulness in the mouse including sleep staging, regulation of sleep onset and arousal from sleep, seasonal and daily patterns of sleep, and biological substrates of sleep such as electrophysiological, neurochemical, and neuroanatomical correlates. With the expected elucidation of the mouse genome and the availability of techniques to alter the expression and composition of genes in this species, the mouse offers an excellent model for investigations into the biochemical basis of sleep. However, research is greatly hampered by the lack of detailed investigations into the normal and abnormal sleep of this species. Existing approaches to studying sleep in cats, rats, and other mammalian species need to be extended to the mouse through studies which test and validate well-established properties and methods in other species. New protocols that simplify the investigation of sleep parameters such as total sleep time, sleep stage distribution and sleep latency are needed to facilitate the characterization of sleep phenotypes. Inbred and genomically well-characterized mouse strains can be used as benchmarks against which novel sleep mutants and variants can be compared. Carefully controlled descriptions of traditional and novel sleep phenotypes, as well as differences in sleep phenotypes between strains and responses to sleep-relevant pharmaceuticals, should facilitate future research efforts to define the responsible genes and their roles in sleep mechanisms. There are a number of research directions that could be pursued using the mouse as a model for the investigation of sleep and circadian rhythms. Molecular and genetic approaches combined with neurophysiological, behavioral, neuroanatomical, or pharmacological techniques are encouraged. The following are examples of studies using mouse models that would be responsive to this program: o Development of new technologies for phenotype characterization and the physiological and behavioral analysis of sleep and wakefulness in the mouse; o Validation in the mouse of known electrophysiological, neuropharmacological, and neuroanatomical indicators of sleep; o Elucidation of mechanisms that regulate sleep such as somnogenic factors; o Identification of molecular and cellular mechanisms responsible for the altered properties of neural networks contributing to cardiorespiratory regulation, sensory perception, and cognition during the sleep state; o Relationship of circadian rhythms to the basic developmental and restorative functions of sleep including how circadian rhythm and sleep/wake cycles are established, and how sleep and sleepiness affect behavioral performance and the function of the brain, heart, lung, and blood; o Characterization of normal and disordered changes in sleep and circadian rhythms during development or aging of the biological clock and the investigation of interventions that may enhance the function of clock components or somnogenic factors. o Tissue-specific maps of gene expression influencing the sleep characteristics of inbred or transgenic mice. o Elucidation of mechanisms linking sleep to diurnal variations in cardiopulmonary function, endocrine function, immunological responses, and other physiological functions. These topics serve as examples and are not a comprehensive or exclusive list of the areas that could be considered under this announcement. Not all areas are required in an application. Applicants are encouraged to propose other topics consistent with the goals of this program. SPECIAL REQUIREMENTS In order to be considered responsive to this announcement, applications must propose hypothesis-driven studies that focus on developing the mouse as a platform for sleep research. Studies that are needed to overcome technical barriers such as the scaling of methods for use in the mouse should be integrated into the proposed research program. However, applications focused solely on the transfer of established methods to the mouse will not be accepted. In addition to traditional research programs, applications may propose necessary developmental approaches to test innovative and conceptually creative hypotheses forming the basis of future sleep research project applications using mouse models. Applications should propose strategies that combine molecular and genetic approaches with physiological, behavioral, neuroanatomical, or pharmacological techniques. Collaborations and consortia promoting interdisciplinary approaches between scientists studying sleep, circadian biology, and mouse genetics are strongly encouraged. In such cases, each participant's contribution should be identified and well-integrated into the overall experimental design. Production of inbred or transgenic mice is not a requirement. Transgenic mice already produced in other studies may be used to address the research goals of this RFA. However, studies directed solely at either the production or screening of mutant mice unaccompanied by studies of sleep mechanisms will not be accepted. Applications proposing to include data collection from species other than the mouse or from human subjects must provide a strong rationale that is clearly relevant to the goal of developing the mouse as a platform for sleep research. Studies in mice must be the principal focus of the application. Applicants are encouraged to contact the program officials listed under INQUIRIES for further information. Upon initiation of the program, the sponsoring Institutes will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. Travel funds for a two day meeting each year, most likely to be held in Bethesda, Maryland, must be included in the module calculation. Applicants must include a statement indicating their willingness to participate in these meetings. RESEARCH INVOLVING HUMAN SUBJECTS The primary objective of this RFA is to derive mouse models for sleep and circadian research. There may be instances in which applicants must collect or use pathology specimens derived from human subjects, or clinical or epidemiological data from projects involving human subjects, to design models or to derive the standards that validate them as models of human sleep or circadian rhythm disorders. In those instances, the NIH policies described below apply and must be addressed in the application. 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 subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of 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 "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), in the NIH Guide for Grants and Contracts of March 18, 1994, and is available at the following URL address: https://grants.nih.gov/grants/guide/notice-files/not94-105.html INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the 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 specific 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 LETTER OF INTENT Prospective applicants are asked to submit, by January 26, 1999, 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 staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be mailed, or faxed, to Dr. C. James Scheirer at the address listed under INQUIRIES. APPLICATION PROCEDURE Applications are to be submitted on the research grant application form PHS 398 (rev. 4/98). Application kits are available at most institutional offices of sponsored research or may be obtained 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. BUDGET INSTRUCTIONS Sample budgets and justification page for the for modular grants can be obtained by contacting Mr. Raymond Zimmerman listed under INQUIRIES. The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions as described below: o FACE PAGE Item 7 should be completed to indicate Modular Direct Costs requested and Item 8 should reflect Total Costs (Modular Direct plus facilities and administrative costs). o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD Do not complete Form Page 4 of the PHS 398 (rev 4/98). It is not required nor will it be accepted at the time of application. o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT Do not complete the categorical budget tables on Form page 5 of the PHS 398 (rev. 4/98). Only the requested total direct costs line for each year must be completed based on the number of $25,000 modules being requested. Applicants may not request a change in the amount of each module. A maximum of nine modules ($225,000 direct costs) per year may be requested and each applicant may request up to four years of support for this program. Direct cost budgets will remain constant throughout the life of the project (i.e., the same number of modules requested for all budget periods). Any necessary escalation should be considered when determining the number of modules to be requested. However, in the event that the number of modules requested must change in any future year due to the nature of the research proposed, appropriate justification must be provided. Total Direct Costs for the Entire Proposed Project Period should be shown in the box provided. o BUDGET JUSTIFICATION Budget justifications should be provided under "Justifications" on Form Page 5 of the PHS 398. List the names, role on the project, and proposed percent effort for all project personnel (salaried or unsalaried) and provide a narrative justification for each person based on their role on the project. Identify all consultants by name and organizational affiliation and describe the services to be performed. Provide a general narrative justification for individual categories (equipment, supplies, etc.) required to complete the work proposed. More detailed justifications should be provided for high cost items. Any large one-time purchases, such as large equipment requests, must be accommodated within these limits. No specific costs for items or categories should be shown. CONSORTIUM/CONTRACTUAL COSTS - If collaborations or subcontracts are involved that require transfer of funds from the grantee to other institutions, it is necessary to establish formal subcontract agreements with each collaborating institution. A letter of intent from each collaborating institution should be submitted with the application. Only the percentage of the consortium/contractual TOTAL COSTS (direct plus facilities and administrative costs) relative to the total DIRECT COSTS of the overall project needs to be stated at this time. The following example should be used to indicate the percentage cost of the consortium, "The consortium agreement represents 27% of overall $175,000 direct costs requested in the first year". A budget justification for the consortium should be provided as described in the "Budget Justification" section above (no Form Page 5 required for the consortium). Indicate whether the consortium will be in place for the entire project period and identify any future year changes in the percentage relative to the parent grant. If there is a possibility for an award, the applicant will be requested to identify actual direct and facilities and administrative costs for all years of the consortium. Note that total subcontract costs need not be calculated in $25,000 modules. However, when subcontract funds are added to the parent grant budget, the total direct cost amount must be included in the number of $25,000 modules requested. If clarification of the policy is needed, contact Mr. Raymond Zimmerman at the address listed under INQUIRIES. BIOGRAPHICAL SKETCH - A biographical sketch is required for all key personnel, following the modified instructions below. Do not exceed the two-page limit for each person. - Complete the educational block at the top of the form page; - List current position(s) and those previous positions directly relevant to the application; - List selected peer-reviewed publications directly relevant to the proposed project, with full citation; - The applicant has the option to provide information on research projects completed and/or research grants participated in during the last five years that are relevant to the proposed project. OTHER SUPPORT - Do not complete the "Other Support" pages (Form Page 7). Selected other support information relevant to the proposed research may be included in the Biographical Sketch as indicated above. Complete Other Support information will be requested by the staff of NHLBI or collaborating Institutes if there is a possibility for an award. CHECKLIST - No "Checklist" page is required as part of the initial application. A completed Checklist including a breakdown of facilities and administrative cost calculations (rate, base, and base exclusions) will be requested by the staff of NHLBI or collaborating Institutes if there is a possibility for an award. - 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. Applications not conforming to these guidelines will be considered unresponsive to this RFA and will be returned without further review. 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 could be included with the application. 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. 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. Send or deliver the completed application and three signed, exact photocopies of it to the following, making sure that the original application with the RFA label attached is on top: 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) Send an additional two copies of the application to Dr. Scheirer at the address listed under INQUIRIES. It is important to send these two copies at the same time as the original and three copies are sent to the Center for Scientific Review (CSR). Otherwise the sponsoring Institutes cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by February 26, 1999. If an application is received after that date, it will be returned to the applicant without review. The 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 also 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 for responsiveness to this RFA by the collaborating Institutes. 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 receive primary assignment to NHLBI and secondary assignment to NIMH, NIA, and/or NINDS. Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Affairs, NHLBI. Final Institute primary assignments will be determined by the collaborating Institutes. 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, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Advisory Councils of the sponsoring Institutes. Review Criteria The following criteria will be considered when assessing the scientific and technical merit of a research grant application: (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 key personnel? (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? Additional Considerations (1) Potential of the proposed study to extend existing knowledge about mammalian sleep and circadian rhythms to either the initial development of new interesting models in mice or the improved characterization of sleep phenotypes using inbred or transgenic mouse strains. (2) Experience of the key personnel in conducting sleep and circadian biology research using mice or other animal models. The personnel category will be reviewed for appropriate staffing based on the requested percent effort. The direct costs budget request will be reviewed for consistency with the proposed methods and specific aims. Any budgetary adjustments recommended by the reviewers will be in $25,000 modules. The duration of support will be reviewed to determine if it is appropriate to ensure successful completion of the requested scope of the project. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, relevance to the scientific programs of the participating Institutes, overall programmatic balance, and the availability of funds. Designated funding levels are subject to change at any time prior to award, due to unforeseen budgetary, administrative and/or scientific developments. Subject to the availability of necessary funds and consonant with the priorities of this RFA, the sponsoring Institutes of this RFA will provide funds for a project period up to four years. The anticipated date of award is September 30, 1999. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic issues may be directed to: Michael J. Twery, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 7024, MSC-7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0202 FAX: (301) 480-3557 Email: Twery@nih.gov Israel I. Lederhendler, Ph.D. Coordinator for Sleep Research National Institute of Mental Health 5600 Fishers Lane, Room 11C-16 Rockville, MD 20857 Telephone: (301) 443-1576 FAX: (301) 443-4822 Email: ilu@helix.nih.gov Andrew A. Monjan, Ph.D., M.P.H. Neuroscience and Neuropsychology of Aging Program National Institute on Aging 7201 Wisconsin Avenue, Suite 3C307 - MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 FAX: (301) 496-1494 Email: am39m@nih.gov Charlotte McCutchen, M.D. National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 516, MSC 9020 Bethesda, MD 20892-9020 Telephone: (301) 496-1917 FAX: (301) 496-9916 Email: cm69e@nih.gov Direct inquiries regarding the receipt and review of applications to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: ScheireJ@nih.gov Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Grants Operations Branch National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7154 Bethesda, MD 20892-7926 Telephone: (301) 435-0171 FAX: (301) 480-3310 Email: ZimmermR@gwgate.nhlbi.nih.gov Diana Trunnell Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-08 Rockville, MD 20857 Telephone: (301) 443-3065 Email: dt21a@nih.gov Joseph Ellis Grants Management Office National Institute on Aging 7201 Wisconsin Avenue, Suite 2C212, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 Email: EllisJ@exmur.nia.nih.gov Maurice Johnson Grants Management Branch National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 1004 Bethesda, MD 20892-9190 Telephone: (301) 496-9231 Email: mj34w@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.839 and 93.848. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to Health Systems Agency review. The PHS strongly encourages all grant and contract 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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