EXPIRED
EXPLORATORY GRANTS IN PEDIATRIC BRAIN DISORDERS: INTEGRATING THE SCIENCE Release Date: July 14, 2000 (Revision of June 10, 1999 version See NOT-NS-00-009 for revisions.) PA NUMBER: PAS-99-080 (Inactive, see NOT-NS-03-010) National Institute of Neurological Disorders and Stroke National Institute of Child Health and Human Development National Institute of Mental Health THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTION THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA. PURPOSE The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Child Health Human Development (NICHD) and the National Institute of Mental Health (NIMH) invite exploratory/developmental research grant applications (R21) to facilitate the translation of fundamental neurobiology to pediatric brain disorders of anomalous development, neurodegeneration, and injury. Emphasis is placed on cross-discipline collaborations, novel hypotheses, and unique approaches in applying fundamental neurobiological concepts to pediatric brain disorders. Special consideration will be given to proposals that enhance the application of our scientific knowledge to understanding the pathobiology and treatment of these clinical disorders. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000", a PHS-led national activity for setting priority areas. This Program Announcement (PA), Exploratory Grants in Pediatric Brain Disorders: Integrating the Science, is related to the priority area chronic disabling conditions. Potential applicants may obtain a copy of Healthy People 2000 at http://www.crisny.org/health/us/health7.html. ELIGIBILITY REQUIREMENTS Applications can be submitted by foreign or domestic, for-profit and nonprofit organizations, public and private, such as universities, colleges, hospitals, laboratories, of State or local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT The Exploratory/Developmental (R21) research mechanism is used for support of creative, novel, and/or high risk/high payoff approaches that could produce innovative advances in this field. This includes feasibility studies, protocol planning, and the incorporation of new disciplines and technologies. This mechanism provides the means to acquire the necessary pilot information, to attract talented new investigators from related disciplines, and to foster the development of interdisciplinary, inter-institutional collaborative efforts among investigators with diverse training and expertise. All applications will be reviewed according to the customary NIH peer-review procedures. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Applicants may request up to three years of support. Applications for research at a single institution may request up to a maximum of $125,000 direct costs per year. Applications that include a consortium/contractual arrangement may request up to a maximum of $150,000 direct costs, including the facilities and administrative costs (indirect costs) of the consortium institution. R21 grants are non-renewable, and may not be used to supplement an ongoing project. Relevant applications and amended applications are welcome throughout the duration of this PA (3 years). Specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts. The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. Complete and detailed instructions and information on Modular Grants can be found at http://www.nih.gov/grants/funding/modular/modular.htm. Applications will request direct costs in $25,000 modules, up to a total direct cost of $125,000 per year for up to three years for applications proposing research at a single institution and up to a total direct cost of $150,000 per year for up to three years for applications that include a subcontract/consortium arrangement. The cost of equipment is included in the budget limitation. Application budgets will be simplified. Detailed categorical budget information will not be submitted with the application; budget form pages of the application kits will not be used. Instead, total direct costs requested for each year will be presented. Information, in narrative form, will be provided only for Personnel and, when applicable, for Consortium/Contractual Costs. See section on APPLICATION PROCEDURES below. There will be no routine escalation for future years. In determining the total for each budget year, applicants should first consider the direct cost of the entire project period. Well-justified modular increments or decrements in the total direct costs for any year of the project that reflect substantial changes in expected future activities may be requested. For example, purchase of major equipment in the first year may justify a higher overall budget in the first, but not in succeeding years. Other Support pages of the PHS 398 will not be submitted with the application. Information on research projects ongoing or completed during the last three years of the principal investigator and key personnel will be provided as part of the "Biographical Sketch." This information will include the specific aims, overall goals and responsibilities, and should include Federal and non-Federal support. This information will be used by reviewers in the assessment of each individual's qualifications for a specific role in the proposed project. Following peer review, information about Other Research Support will be requested by NIH from the applicant for applications being considered for award. Additional budget information will be requested only under special circumstances. FUNDS AVAILABLE NINDS has set aside 2.5 million total costs, NICHD has set aside $500,000 total costs, NIMH has set aside $500,000 total costs to support research grants responsive to this PA, depending on the overall scientific merit of the applications and the availability of funds throughout the duration of this solicitation (3 years). RESEARCH OBJECTIVES The purpose of this initiative is to: 1) focus the attention of the neuroscientist on the detrimental processes that affect the developing brain, 2)promote the interaction of developmental neurobiologists and clinical scientists, and 3) provide preliminary information necessary to unravel the complexities of developmental pathogenesis. The ultimate goal is to effect meaningful advances in understanding the pathogenesis of neurological dysfunction and develop interventions and effective treatments that improve the quality of life for children and young adults. Effective research strategies will have untold ramifications as affected children have a reduced lifetime potential, families have physical, emotional and financial burdens, and society makes a staggering commitment of resources. Background The areas of emphasis covered in this program announcement- disorders of anomalous development, neurodegeneration during development, and injury to the developing brain have not received the same degree of focused attention as the more common adult disorders of neurodegenerative, ischemic, hemorrhagic, and traumatic brain injury. There are a number of reasons for this: 1) many of these pediatric disorders, taken in isolation, are rare autosomal recessive disorders and have been perceived as obscure genetic entities; 2) there has been a lag in acquiring the basic knowledge and tools for understanding both normal neurodevelopment and abnormal developmental processes; and 3) research involving children as subjects has not been as aggressively pursued. However, recent advances in molecular biology, genetics, neuroimaging, and clinical detection (diagnostic capabilities) have now opened the door to fruitful investigations of pediatric brain disorders. Similarly, these advances have also demonstrated that anomalies of brain development may be implicated in the etiology of major mental disorders such as schizophrenia. In parallel, there is increased awareness and support for research addressing childhood disorders/diseases. A brief description of the areas of emphasis follows: Disorders of Anomalous Development - Normal development of the central nervous system is a closely coordinated process of neuronal and non neuronal cell development (e.g., neurogenesis, cell growth and differentiation, migration, synaptogenesis, regressive events-cell death, axonal pruning, synaptic elimination, neuron-glia interactions, etc.). Aberrations in one or more of these processes have been shown to lead to a number of disorders of neurological development. Some recent cases of newly discovered genes, such as those involved in the lissencephalies, holoprosencephaly, Fragile X, and X-linked mental retardation, are examples of new contributions of fundamental neurobiology to our understanding clinical disorders. It is hoped that these examples will encourage investigations into the genetic basis of other developmental disorders, such as, cerebral, cerebellar, and brainstem hypoplasias/dysplasias (e.g., agenesis of the Corpus Callosum, developmental heterotopias, Joubert Syndrome, Moebius Syndrome)and more complex disorders involving anomalous developmental processes, (e.g., mental retardation, autism, cerebral palsy, epilepsy, and childhood onset movement disorders (dystonia, Tourette syndrome, motor stereopathies)). Neurodegeneration During Development - Recently identified genes of childhood neurodegenerative disorders - Friedreich Ataxia (FA), Ataxia-Telangiectasia (A-T), neuronal ceroid lipofuscinoses (NCL or Batten Disease), childhood neuromuscular disorders-the dystrophies and spinal-muscular atrophies (SMAs), and a number of childhood metabolic disorders - are providing new information and insights into molecular and cellular biology (complex DNA conformations/triplet repeat disorders, cell cycle signaling/repair, mitochondrial respiratory functions, and altered ion channel biology). These fascinating discoveries are bringing scientists from multiple disciplines together to elucidate disease pathogenesis. New insights resulting from these gene identifications regarding protein functions and cellular events are changing the appreciation of disease pathogenesis in a number of inherited and sporadic childhood and adult disorders for which we have previously had little understanding. The information gained through understanding these genetic disorders is also rapidly advancing our knowledge of how the normal brain functions and processes information on a number of levels. It has also made possible the development of relevant animal models that mimic the neurogenetic defect known to occur in children. Studies on model systems from yeast to flies to mammals, are now being employed to understand the pathology and neurodegenerative progression in these disorders. Exploratory studies will speed the pace of progress for developing meaningful insights for clinical and laboratory research of fundamental mechanisms of childhood neurodegeneration, will provide opportunities for effective scientific exchange of rapidly evolving molecular, biochemical, biological, and behavioral research results, and will allow for development of rational candidates for eventual utilization in therapeutic trials. Injury To The Developing Brain - Injury to the pre and postnatal brain is a leading cause of death and disability in children. This includes 1) injury induced by adverse fetal/perinatal environments, 2) traumatic brain injury, and 3) injuries due to infectious, vascular, and ischemic causes. Childhood cerebral vascular disease is generally secondary or related to vascular abnormalities such as Sturge-Weber Syndrome, Moya-moya, disease, fibromuscular hyperplasia/dysplasia (FMH)), metabolic disorders (such as mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS),homocystinuria, auto-immune disorders), conditions resulting from blood dyscrasias (such as sickle cell disease, hypercoagulable states), and congenital heart disease (resulting in emboli to the cerebral vascular system). We currently do not have therapeutic regimens that are successful for the treatment of brain injury in children. The general belief that the immature brain recovers more fully by virtue of its greater "neural plasticity" has been challenged by more recent studies that suggest that brain injury in young children (less than 4 year olds) may result in higher mortality and more severe motor, communicative, and cognitive deficits than the same injury in older children and adults. In traumatic brain injury, there may be biomechanical issues that are peculiar to the infant brain and skull and types of injuries sustained at developmental ages that are not comparable to the adult. In addition, limited animal research suggests differential vulnerability of the immature brain response to injury. To address these issues, research must be focused on developing appropriate animal models (reflecting neuronal and glial disruptions), on characterizing the etiological factors, degree, type, and extent of injury, both acutely and later brain processes. In addition, epidemiological studies support the need to consider the roles of neuroendocrine/neuroimmune/environmental factors to the immediate state and long term outcomes of age-dependent brain injury. Exploratory research studies in this important area will hopefully provide the necessary information for preventative strategies and rational therapeutic designs. Scope Applications submitted in response to this PA may address any of the above areas of emphasis. Examples of approaches responsive (but not restrictive) to this PA include: Adaptation of recently produced models of adult nervous system injury or degeneration to disorders of the developing nervous system; the creation of new models of anomalous brain development, of injury to the developing brain, and of degeneration of the developing brain. Collaborations resulting in the development of novel strategies, hypotheses to enhance understanding of the mechanisms of pathogenesis in disorders of anomalous brain development, injury or degeneration in development. For clinical studies that require the consideration of processes in brain development that occur in utero but may not be recognized till the neonatal period or later; collaborations which foster obstetrical, neonatal, neurological, neuroimaging, expertise. Studies which seek to identify pre- and/or post-natal brain developmental mechanisms which may be linked to the pathophysiology of mental disorders. Proposals to identify genes involved in anomalous development, degeneration or injury processes by exploiting growing knowledge of neurogenetics in development, cell cycle regulation, and the cascades evoked by injury. Exploratory studies of maturational/organizational brain development having sound rationale and related to one of the areas of emphasis in this initiative. Very preliminary studies, new collaborations, to acquire knowledge for the purposes of eventually developing therapeutic regimens. This could include identification of appropriate clinical markers (neuroimaging, neurophysiologic, neurochemical), or preliminary information for developing clinical protocols, methodologies, and/or pharmacological agents. Development of new technologies relevant to studies in the areas of emphasis in this initiative. Given that the purpose of this R21 initiative is to broaden the base of inquiry in underserved areas of pediatric brain research, the focus of review will be on innovation in the development of novel concepts, new methodologies, and/or new, cross-disciplinary collaborations. Bearing in mind that the developmental research projects proposed under this program announcement may well contain preliminary tests of feasibility, substantial risks, and challenges to current concepts, and may lack the amount of preliminary data and background experience normally found in an R01 application, reviewers will weigh the following standard review criteria accordingly. The Research Plan must be soundly developed in the context of the current knowledge/research base, with well-defined and clear objectives. The Approach should utilize appropriate concepts and current methodology. Applicants should elaborate on innovative aspects of the proposed research, novel collaborations, and special attributes of the resources and environment. In addition, applicants must identify how the exploratory studies could result in new insights or capabilities for research into anomalous neurodevelopment, neurodegeneration, or injury in development. 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 the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "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) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994, and are available on the web at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not94-100.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 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 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: http://www.nih.gov/grants/guide/notice-files/not98-024.html Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: [email protected]. They may also be downloaded from the Internet at http://www.nih.gov/grants/forms.htm. In preparing Modular Grant Applications, standard instructions for specific award mechanisms should be followed: (PHS 398 and R21), with these specific modifications reflecting modular budget and just-in-time concepts: Face Page - Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $125,000 for research at a single institution, or up to a maximum of $150,000 for research involving a consortium/contractual arrangement) and Total costs (Modular Total Direct plus Facilities and Administrative (F&A) Costs) for the initial budget period. Items 8a and 8b should be completed indicating the Direct and Total Costs for the entire proposed period of support, which is not to exceed 3 years. Detailed Budget for the Initial Budget Period - Do not complete Form Page 4 of the PHS 398. It is not required and will not be accepted with the application. Budget for the Entire Proposed Period of Support - Do not complete the categorical budget table on Form Page 5 of the PHS 398. It is not required and will not be accepted with the application. Narrative Budget Justification - Use a Modular Grant Budget Narrative page. (See http://www.nih.gov/grants/funding/modular/modular.htm for sample pages.) At the top of the page, enter the total direct costs requested for each year. Under Personnel, list key project personnel, including their names, percent of effort, and roles on the project. No individual salary information should be provided, however, the applicant must be mindful of the DHHS appropriation language regarding the salary cap and the NIH policy applicable to graduate student compensation. For Consortium/Contractual costs, provide an estimate of total costs (direct plus facilities and administrative) for each year, each rounded to the nearest $1,000. List the individuals/organizations with whom consortium or contractual arrangements have been made, the percent effort of key personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost for a consortium/contractual arrangement is included in the overall requested modular direct cost amount. Provide an additional narrative budget justification for any variation in the number of modules requested. Biographical Sketch - The Biographical Sketch provides information used by reviewers in the assessment of each individual's qualifications for a specific role in the proposed project, as well as to evaluate the overall qualifications of the research team. A biographical sketch is required for all key personnel, following the instructions below. No more than three pages may be used for each person. A sample biographical sketch may be viewed at: http://www.nih.gov/grants/funding/modular/modular.htm - Complete the educational block at the top of the form page; - List current position(s) and then previous positions; - List selected peer-reviewed publications, with full citations; - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years. Other Support - Do not submit the 'other support' pages. Selected other support 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 NINDS or collaborating Institutes if there is a possibility for an award. Checklist - This page should be completed and submitted with the application. Page Limitation - In keeping with the pilot/feasibility nature of the requested studies the application (aims, background and significance, preliminary data and experimental design and methods) is limited to 20 pages. Tables and figures are included in the 20-page limitation. Appendix - An appendix or additional supporting materials will not be accepted with the exception of originals of photos used in the application. 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. Comments and inquiries concerning this notice are encouraged. Nevertheless, the instructions and procedures described in this notice must be observed. Additional information, including sample budget narratives and biographical sketch, may be found at this site: http://www.nih.gov/grants/funding/modular/modular.htm. The title and number of the program announcement must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and five 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) The Center for Scientific Review (CSR) will not accept any application in response to this PA 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 an application already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be evaluated for scientific and technical merit by an appropriate scientific review group in accordance with the standard NIH peer review procedures. 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 appropriate national 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 the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry important work that by its nature is not innovative but is essential to move a field forward. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? In the context of the R21 mechanism, a strong rationale and conceptual framework are normally sufficient for establishing the feasibility of the project, in lieu of preliminary data. (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? If the project is not innovative but is essential to move the field forward, the applicant should mention and discuss this aspect in the proposal. (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The reasonableness of the proposed budget and duration in relation to the proposed research. 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. The initial review group will also examine the provisions for the protection of human subjects and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. The anticipated date of the first awards is February 2000. INQUIRIES Inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from the potential applicants is welcomed. Direct inquiries regarding programmatic and scientific issues to: Giovanna M. Spinella, M.D. Division of Fundamental Neuroscience and Developmental Disorders National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 2132 Bethesda, MD 20892 Telephone: (301) 496-5821 FAX: (301) 402-0887 Email: [email protected] Felix F. De La Cruz, M.D., M.P.H. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B-09 Bethesda, MD 20892 Telephone: (301) 496-1383 FAX: (301) 496-3791 Email: [email protected] Inquiries about studies addressing developmental mechanisms involved in the etiology of mental disorders should contact: Douglas L. Meinecke, Ph.D. Division of Neuroscience and Basic Behavioral Science National Institute of Mental Health Neuroscience Center, Room 7183 6001 Executive Boulevard Telephone: (301) 443-5288 FAX: (301) 443-4822 Email: [email protected] Direct inquiries regarding fiscal matters to: Karen D. Shields Grants Management Branch National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 3264 Bethesda, MD 20892 Telephone: (301) 496-9231 FAX: (301) 402-0219 Email: [email protected] Mr. Edgar D. Shawver Office of grants and contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A-17 Bethesda, MD 20892 Telephone: (301) 496-1303 FAX: (301) 402-0915 Email: [email protected] Diana S. Trunnell Grants Management Branch National Institute of Mental Health 6001 Executive Boulevard, Room 6115 Bethesda, MD 20892-9605 Telephone: (301) 443-2805 FAX: (301) 443-6885 Email: [email protected] Although NINDS, NICHD and NIMH are issuing this PA, the NIDCD has interest in supporting research in the area of communication processes and disorders, covered in this program announcement. For further information, applicants may wish to contact: Beth M. Ansel, Ph.D., CCC-SLP Division of Human Communication National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400-C, MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-3461 FAX: (301) 402-6251 Email: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853 and 93.854 (NINDS), 93.855 and 93.856 (NICHD) and 93.242 (NIMH). Awards are made under the authority of the Public Health Service Act, Title IV, Part A (Public Law 78-410 as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant 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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