PULMONARY IMMUNE DEFENSES AND THEIR REGULATION: UNDERSTANDING DYSFUNCTION ASSOCIATED WITH HIV DISEASE Release Date: January 16, 1998 RFA: HL-98-006 P.T. National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 17, 1998 Application Receipt Date: April 28, 1998 THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS AND INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS AND MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE This solicitation invites research grant applications focused on regulation of local immunity in the lung in the context of human immunodeficiency virus (HIV). Studies might be directed at cellular and molecular mechanisms of regulation of local immunity in the airways and the lung tissue. Ultimately, the goal of the program is aimed at developing strategies for selectively regulating mucosal or surface immunity (cellular and humoral), both of which might be helpful in understanding acquired immunodeficiency syndrome (AIDS) related pulmonary complications. However, since lung immunity in AIDS is still poorly understood, research could be directed at understanding normal local immune responses of the lung as a framework for understanding abnormal responses. For example, projects aimed at assessing the integrity of the immune apparatus in the naso-oropharynx, along the conducting airways, and in the alveolar spaces might be included. Human studies, e.g., in subjects with varying stages of HIV infection as compared to healthy persons, and studies in animal models would be of interest. Among the disciplines and expertise that may be appropriate for this research program are immunology, molecular immunology, cell biology, molecular biology, virology, mycology, bacteriology, genetics, infectious diseases, pathology, pulmonary medicine, and pediatrics. 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 Request for Applications (RFA), Pulmonary Immune Defenses and Their Regulation, is related to the priority areas of HIV infection and immunization and infectious diseases. 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 and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units 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. All current policies and requirements that govern the research grant programs of the National Institutes of Health (NIH) will apply to grants awarded under this RFA. Awards under this RFA to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. MECHANISM OF SUPPORT This RFA will use the NIH individual research project grant (R01) mechanism of support. Investigators without prior R29 or R01 support are encouraged to apply for this RFA and to identify their status in a cover letter. Specific R01 application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts 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 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. Although multidisciplinary approaches are encouraged, it is not the intent of this RFA to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed under INQUIRIES. For this RFA, funds must be requested in $25,000 direct cost modules and a maximum of eight modules ($200,000 direct costs) per year may be requested. A feature of the modular grant concept is that no escalation is provided for future years, and all anticipated expenses for all years of the project must be included within the number of modules being requested. Only limited budgetary 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 NHLBI staff following the initial review. The APPLICATION PROCEDURES section of this RFA provides specific details of modifications to standard PHS 398 application kit instructions. Applicants are expected to furnish their own estimates of time required to achieve the objectives of the proposed research project. Since a variety of approaches would represent valid responses to this RFA, it is anticipated that there will be a range of costs among individual grants awarded. Up to 5 years of support may be requested on R01 applications. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator- initiated applications and be reviewed according to the customary peer review procedures. It is anticipated that support for this program will begin in September, 1998. Administrative adjustments in project period and/or amount may be required at the time of the award. 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. The National Institute of Allergy and Infectious Diseases (NIAID) has interest in regulation of immunity in health and disease. Therefore, applications that are of mutual interest are likely to be given a secondary assignment to NIAID in accordance with the NIH referral guidelines. A program announcement "Mucosal Immunity in Pathogenesis/Prevention of Human Disease" (PA-97--073), NIH Guide Vol 26, 23, 7/18/97, sponsored by many institutes at NIH covers areas of research complementary to this RFA. PA-97-073 may be of interest to some investigators. FUNDS AVAILABLE It is anticipated that for fiscal year 1998, approximately $2,000,000 total costs will be available for the first year of support for this initiative. Award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. It is anticipated that approximately 8 new grants will be awarded under this program. The specific number to be funded will, 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 or other necessary administrative adjustments. Indirect costs will be awarded based on the negotiated rates. Applicants may request up to 5 years of support. RESEARCH OBJECTIVES Background Patients with AIDS continue to die predominantly as a result of respiratory infections. It is well recognized that the tubercle bacillus is deposited in the lower respiratory tract via aerosol and there is increasing evidence that other pathogens such as Pneumocystis carinii can also be transferred by the aerosol route from one infected subject to another. In addition, common bacteria such as S. pneumoniae are increasingly the cause of death in patients with AIDS. Systemic vaccination as a way to control respiratory infections has been attempted since the turn of the century. However, up to our recent attempts to protect high risk patients from pneumococcal pneumonia, using Pneumovax, systemic vaccination has not been very effective in controlling respiratory infections. Most AIDS lung research is based on bronchoalveolar lavage fluid analysis of cells retrieved from the lower respiratory tract and on in vitro cultured cells. Important information is known about macrophage-lymphocyte interactions, release of cytokines, activation status of macrophages, etc. However, less is known about functions of cells along the conducting airways in HIV disease. This is in contrast to asthma studies in which endobronchial biopsy methods in conjunction with bronchoscopy (in asthma and healthy controls) have elucidated lymphocyte subpopulations, cytokine production and interactions with the ciliated epithelium. A specific aspect of lung immunity that is poorly understood is the role of pulmonary lymphoid tissue in HIV infection. Much has been learned recently of the relationship between blood virus and lymphoid tissue, but little is currently known about the pulmonary lymphoid tissues, and whether virus/infected cells circulate between the alveolar space, interstitium, and lung lymphoid tissue. It is not known whether virus residing locally within the lung contributes to pulmonary immune dysfunction or simply reflects systemic immune damage. Another question is whether the lung, which is recognized as an important antigen-immune cell interface, is also an important site of lymphocyte killing. To what extent might the HIV-lymphocyte interactions in the lung lymphoid tissue contribute to local immune depletion, or even to systemic immune depletion? Delayed type hypersensitivity (Th1-like responses) are clearly important in granulomatous diseases such as mycobacterial and fungal infection. Responses of T cells to specific antigens are the first to deteriorate in HIV-infected people. Lack of knowledge concerning interstitial macrophages and dendritic cells has been identified as a major gap in understanding lung defenses. The alveolar macrophages serve as accessory cells for T lymphocyte responses to stimuli. This function is up-regulated by HIV infection. Almost nothing is known about the role of lung interstitial macrophages and dendritic cells in HIV infection. Strategies to reconstitute the immune apparatus or manipulate selective features to produce antibodies against microbes or to prevent microbial adhesion should be explored. Considerations for mucosal immunization include: appropriate antigen, local application of antigen, primary immunization versus repeated application, antigen processing, manipulation of cytokine networks to maximize antibody output, type of antibody needed and persistence of memory cells. Studies might focus on stimulating a specific IgA. Objectives and Scope The objective of this program is to understand regulation of local immunity in the lung at molecular and cellular levels in the context of HIV infection and HIV-associated opportunistic infections. Research applicable to this initiative could include studies of regulation of local immunity in the normal lung and airways in human subjects, animals, in vitro models or mathematical models to provide a frame of reference for what occurs in the immunodeficient state. However, the emphasis is on how HIV affects lung immunity. Investigations might address how HIV infection and other immunosupressed states perturb local immunity in the lung. If sufficient data are available to justify them, projects might include studies aimed at manipulating local lung immunity to restore function, to prevent or treat opportunistic infections or lung complications associated with HIV infection. In responding to this initiative expertise might be needed in the following areas: pathogenesis of infections; lung and respiratory tract immunology; and principles of vaccination. Expertise in aerosol delivery might also be necessary to develop or adapt delivery techniques to insure accuracy in deposition. If successful, new approaches to augmenting lung defenses might be developed which could reduce the incidence or severity of pulmonary infections in immunocompromised subjects such as patients with AIDS. Examples of areas of research (in HIV-infected, other immunodeficient or "normal" human subjects, suitable animal models, in vitro models, or non-linear mathematical models) that might be included under this RFA are as follows: o determine effect of HIV infection (or appropriate model of HIV infection) on respiratory tract lymphocyte subpopulations, local cytokine regulation and interactions with ciliated epithelium; o investigate the HIV-lymphocyte interactions in pulmonary lymphoid tissue and the regulation of local lymphocyte killing in the pathogenesis of lung complications of HIV and overall progression of HIV disease; o elucidate the role of lung interstitial macrophages dendritic cells in determining T lymphocyte responses to antigenic stimuli in HIV disease; o investigate regulation of specific immunoglobulins (e.g., IgA) including the function of cytokines in Ig switching and elucidate role(s) in the pathogenesis of specific HIV-related opportunistic infections; o investigate strategies for reconstituting local pulmonary immune function and preventing lung disease in HIV infection and other immunodeficient conditions relevant to pulmonary immunity in HIV infections. These are examples only. Investigators should not feel limited to the subjects mentioned above and are encouraged to submit other topics pertinent to the objectives of the RFA. Of great concern, is that any attempt to augment immune function might potentially upregulate HIV replication. Progress in understanding the issues outlined in this initiative will help in determining the role of concomitant antiretroviral therapy with immunomodulatory therapy. It is anticipated that human, animal, in vitro studies and studies that include non-linear mathematical models would be appropriate. Investigators are encouraged to apply findings from theoretical and in vitro work to in vivo studies when this is feasible. The initiative is relevant to black and Hispanic minority populations who are disproportionately affected by HIV in comparison to the total population. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget of the grant application, travel funds for a one day meeting each year, most likely to be held in Bethesda, Maryland, should be included in the modules. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Applications that focus exclusively on normal pulmonary immunity are not acceptable. However, studies of normal pulmonary immune responses may be included, for comparison purposes, along with studies of local pulmonary immunity in HIV infection, HIV- associated pulmonary opportunistic infections and complications and models pertaining to these. Applications that propose descriptive studies and do not contain hypothesis driven studies directed at understanding the mechanisms that influence pulmonary immune defenses and their regulation will not be acceptable. Applications that focus on mechanisms of local immunity in the lung at the molecular level are of particular interest. Although studies in human subjects are strongly encouraged, large clinical studies are not within the scope of this RFA. Applicants who propose to test hypotheses in animal, in vitro models or theoretical models must provide a strong rationale for relevance to the human host. This program will not support studies directed at development of animal models alone. Therefore, models must be applied to the study of pulmonary immunity regulation in "normals," in HIV-infection and in other immunodeficient states relevant to elucidating dysfunction of pulmonary immunity in HIV-infection. 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 follow 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 of March 18, 1994, Volume 23, Number 11. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by March 17, 1998, 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 subsequent applications, the information that it contains allows NIH staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be faxed or sent to Dr. C. James Scheirer, at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev 5/95) is to be used in applying for these grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20898-7910, telephone 301-710-0267, Email: ASKNIH@od.nih.gov. The RFA label found in the PHS 398 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. This RFA is restricted to R01 grants. All will be awarded as modular grants. The modular grant concept establishes specific modules (increments) in which direct costs may be requested and a maximum level for requested direct cost. Only limited budgetary information is required in the application; a detailed budget need not be provided. BUDGET INSTRUCTIONS Sample budgets and justification page will be provided upon request from Mr. Raymond Zimmerman at the address 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 described below: o FACE PAGE As a reminder, Item 7 should be completed to indicate Modular Direct Costs requested and Item 8 should reflect Total Costs (Modular Direct plus F&A costs). o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD Do not complete Form Page 4 of the PHS 398 (rev 5/95). 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. 5/95). 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 EIGHT modules ($200,000 direct costs) per year may be requested and each applicant may request up to FIVE years of support for this RFA. 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 his/her role on the project. Under the justification for the principal investigator, indicate if you are a new investigator (i.e. an investigator without prior R29 or R01 support). - 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. o 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 and indirect) 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). Please 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 indirect costs for all years of the consortium. Please 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. o 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. o 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 NHLBI staff if there is a possibility for an award. o CHECKLIST - No "Checklist" page is required as part of the initial application. A completed Checklist will be requested by NHLBI staff if there is a possibility for an award. o The applicant should provide the name and phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. Applications not conforming to these guidelines will be considered unresponsive to this RFA and will be returned without further review. Submit a signed, typewritten original of the application and three signed, photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to Dr. C. James Scheirer at the listed under INQUIRIES. Applications must be received by April 28, 1998. 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. o If an application is determined to be unresponsive to the RFA, the principal investigator will be notified and may request that the application be returned or sent to CSR where it will be processed in the next available cycle as a regular grant application. REVIEW CONSIDERATIONS Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NHLBI, in accordance with NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a review in which only those applications deemed to have the highest scientific merit of the applications under review (usually two to three times the number of applications that the NHLBI anticipates being able to fund under the program) will be discussed, assigned a priority score, and receive a second level review by the National Heart, Lung, and Blood Advisory Council. 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. 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 review, comments on the following aspects of the application will be made 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 the assignment of the overall score. (1) Significance Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition, the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research will be reviewed. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects, the safety of the research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. The roster of the initial review group will be available, via the NHLBI homepage, at the following address: http://www.nhlbi.nih.gov/nhlbi/meet/sep/develop.asc. AWARD CRITERIA 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. Applications from new investigators will be strongly considered. The anticipated date of award is September 29, 1998. INQUIRIES Inquiries concerning this RFA are encouraged. Potential applicants may request a copy of sample budget and justification pages, as previously stated. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct requests for sample budget pages to: Melonie Shine Division of Lung Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 10018, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0222 FAX: (301) 480-3557 Email: melonie_shine@nih.gov Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 10018, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0222 FAX: (301) 480-3557 Email: hannah_peavy@nih.gov Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 7154, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0171 FAX: (301) 480-3310 Email: zimmermr@gwgate.nhlbi.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 U.S.C. 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 a 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.
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |