GENE DISCOVERY FOR NEUROLOGICAL AND NEUROBEHAVIORAL DISORDERS Release Date: March 26, 2001 RFA: RFA-NS-02-002 National Institute of Neurological Disorders and Stroke National Institute on Aging National Institute of Mental Health Letter of Intent Receipt Date: June 7, 2001 Application Receipt Date: July 10, 2001 THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE The goal of this Request for Applications (RFA) is to promote the identification of genes that cause or contribute to human neurological and neurobehavioral diseases. It is intended to encourage applications for genetics research projects with one or more of the following objectives: (1) to identify the gene or genes that produce disease susceptibility (2) to identify modifier genes that affect disease susceptibility or outcome and (3) to investigate the relationship between genotype and disease phenotype. Because of the interdisciplinary nature of such projects, collaborative studies are encouraged. Studies using invertebrate or vertebrate animal models are appropriate if they directly promote the identification of human disease susceptibility genes. RESEARCH OBJECTIVES Background Genetic factors contribute to a broad spectrum of neurological and neurobehavioral diseases. During the last decade, genes that cause many single-gene neurological disorders have been identified (e.g. Huntington’s disease, neurofibromatosis, and Rett Syndrome). For these disorders, familial inheritance patterns follow the rules of Mendelian segregation. For common disorders (e.g. Parkinson’s disease, epilepsy, Alzheimer’s disease, frontotemporal dementia and autism), progress in identifying genes that affect susceptibility and outcome has been slow. Such disorders may be caused by multiple genes or by a combination of environmental and genetic factors. The role of genetics in the response to environmental trauma (e.g. brain or spinal cord injury) or to age-related metabolic dysfunction in the brain (e.g. oxidative stress) is also poorly understood. The wealth of genomic information becoming available through the Human Genome Project will provide an increasingly powerful tool for gene discovery. Once disease susceptibility genes are identified, it will be possible to study gene function, investigate disease pathophysiology, and explore strategies for therapeutic intervention. Gene identification will also provide a basis for genetic counseling and improved diagnostic classification. Scope Applications submitted in response to this announcement should focus on gene discovery or genotype-phenotype analysis. For gene discovery studies, proposals can focus on either single-gene or multigenic disorders. Proposed studies can involve the initial collection of biomaterials and clinical information from a patient population and/or the application of molecular genetic strategies for disease gene identification. Possible methodologies include, but are not limited to, traditional linkage analysis, sib-pair and affected-pedigree-member methods, case-control or family-based association studies, linkage disequilibrium mapping in genetically isolated populations, candidate gene analysis, cytogenetic studies to identify chromosomal abnormalities associated with a disorder, and positional cloning techniques. The use of invertebrate or vertebrate animal models is also appropriate, if this will facilitate the identification of genes that contribute to a specific human disorder. Such models may, for example, permit the identification of modifier genes where a primary disease gene has already been identified (e.g. for neurofibromatosis, triplet repeat disorders, etc.). In the area of genotype-phenotype analysis, studies should be designed to correlate the mutations present in individual patients (in primary disease genes or modifier genes) with clinical outcome. Projects in which a strong case can be made that such correlations will be useful for diagnosis or genetic counseling are particularly encouraged. Since gene discovery requires collaborations among epidemiologists, geneticists, clinicians, molecular biologists, and other researchers, multidisciplinary projects are encouraged. Because progress in gene identification is driven by technological advances in these fields, it is important that proposals use state of the art methodologies. Applications should focus on disorders relevant to the research missions of NINDS, NIA, or NIMH. A partial list of diseases of interest to NINDS is given in Appendix A of the planning document Neuroscience at the New Millennium; http://www.ninds.nih.gov/about_ninds/plans/strategic_plan.htm). These include common disorders (Parkinson’s disease, Alzheimer’s disease, epilepsy, etc.) and a broad range of rarer disorders of the nervous system. Disorders of interest to NIA for this RFA include Alzheimer’s disease and other age- associated neurodegenerative, cognitive, and motor system disorders (see http://www.nia.nih.gov/ResearchInformation/ExtramuralPrograms/NeuroscienceOfAging/Research+Areas.htm and http://www.nia.nih.gov/AboutNIA/StrategicPlan/). Disorders of interest to NIMH for this RFA include autism and autism spectrum disorders, attention deficit hyperactivity disorder, late-onset Alzheimer’s disease, Fragile X Syndrome, and Tourette Syndrome. Disorders not included under this solicitation are bipolar disorder or related mood disorders, recurrent early-onset depression, eating disorders, obsessive-compulsive disorder or other anxiety disorders, panic disorder, schizophrenia or other psychotic disorders, and personality disorders. An important resource available to applicants is the Center for Inherited Disease Research (CIDR), a centralized facility established to provide high- throughput genotyping and statistical genetics services. CIDR was established in 1996 as a joint effort of eight NIH Institutes, and is supported through a contract to Johns Hopkins University. CIDR is available to all investigators through competitive peer review by a chartered CIDR Access Committee (CAC). Projects are evaluated based on the need for high throughput genotyping and the likelihood that genotyping will lead to successful mapping of genes contributing to that disease. Since NINDS, NIA, and NIMH are supporting NIH Institutes, research projects funded under this RFA are eligible for no-cost genotyping at CIDR. Further information about CIDR may be found at http://www.cidr.jhmi.edu. Submission deadlines for applications requesting CIDR access are November 1, March 1 and July 1. An approval letter from the CAC may then be included in the application. SPECIAL REQUIREMENTS Plan for Dissemination of Data and Biomaterials Sharing of biomaterials, data, and software in a timely manner has been an essential element in the rapid progress that has been made in the genetic analysis of human diseases. PHS policy requires that investigators make unique research resources readily available for research purposes to qualified individuals within the scientific community when they have been published (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/guide/notice-files/not96-184.html) To promote dissemination of research results, applicants who respond to this RFA must propose detailed plans for sharing data and biomaterials generated through the grant. It is expected that the information to be shared will include all clinical, diagnostic, and pedigree structure information. The proposed plan may, at the applicant’s discretion, include biomaterials (e.g. DNA and cell lines). When possible, it is preferable that data generated through grants funded through this RFA be placed, stripped of personal identifiers, in common, public access databases that are widely accessible to investigators throughout the scientific community. When applicants propose to share biomaterials, it is preferable that these biomaterials be placed in a public access repository, if such a repository exists. NIH maintains several repositories as resources for the scientific community (see, for example, http://zork.wustl.edu/nimh/NIMH_initiative/NIMH%20Human %20Genetics%20Initiative%20Access%20Information.htm). Rapid sharing of data and biomaterials is strongly encouraged. The Initial Review Group will evaluate the proposed sharing plan and comment on its adequacy in an administrative note in the summary statement. The adequacy of the plan will be considered by NIH staff in determining whether the grant shall be awarded. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of renewal applications will include assessment of the effectiveness of data and biomaterial release. Informed Consent Procedures NIH, in consultation with the NIH Office of the General Counsel (OGC) and the Office for Human Research Protection (OHRP; formerly the Office for Protection From Research Risks (OPRR)), has developed a model consent form for human genetic research. This form will be provided to applicants for use in projects funded under this RFA. This may then serve as a template that is subject to modification and/or approval by local institutional review boards. It is expected that the applicant’s approved consent form address the following: (1) disclosure that clinical data (and biomaterials, if applicable) will be stored as part of a national resource of data and materials for the genetic analysis of the disease under investigation; (2) assurance that such data will be provided to researchers without personal identifiers; (3) disclosure that analyses of these data wil be conducted by other scientists currently not included within the current research team; and (4) disclosure that there is no plan to provide subjects with any financial benefits from commerical products derived from the data. NIH will review consent forms and IRB approvals for all projects prior to funding under this RFA. Phenotyping Issues Phenotyping subjects for complex diseases presents numerous challenges. Several methodological problems could significantly reduce the ability to detect linkage or linkage disequilibrium, and thereby thwart efforts to identify disease susceptibility loci. For example, efforts to replicate results and combine data across different samples may be hampered if diagnostic criteria are widely variable across multiple research projects. Minimizing phenotypic error and imprecision, especially that which contributes to false-positive diagnoses of affected status, requires the careful application of state-of-the-art diagnostic techniques. For many rare disorders, diagnostic criteria remain poorly defined or relatively imprecise. It is expected that applicants will use the most sophisticated methodologies currently available for a particular disorder. When possible, applicants are encouraged to include the following methodological features in their proposals: o Use of a structured or semi-structured diagnostic interview with patients or other informants. It is expected that such procedures will greatly facilitate the establishment of a reliable diagnosis, and thus will increase the statistical power and utility of the data set for genetic analysis. o Comprehensive synthesis of information systematically collected from laboratory procedures, structured or semi-structured clinical interviews of high reliability, medical records, and multiple informants. o Application of structured operational diagnostic criteria, based on the comprehensive synthesis of information for history, laboratory results, signs, and symptoms, to establish a final best estimate lifetime diagnosis. For example, operational criteria for the clinical diagnosis of Alzheimer’s disease have been developed to follow NINCDS-ADRDA Work Group guidelines. It is expected that applicants fully document their procedures for establishing such a final best estimate lifetime diagnosis. Subjects may be diagnosed in any one of multiple systems, but an ICD-10 diagnosis always should be established to permit pooling of these data with other pre-existing resources. o Entry of comprehensive phenotypic data described above into a computerized database that may be easily shared amongst other researchers. MECHANISM OF SUPPORT This RFA will use the research project grant (R01) and exploratory grant (R21) mechanisms. R01 applications should be submitted in the modular format, and their budgets limited to $250,000/year (direct costs), as specified under that format (see URL listed below for further description of modular applications). For this RFA, participating NIH Institutes will use the NINDS guidelines for the R21 mechanism, which can be found at http://www.ninds.nih.gov/funding/r21guidelines.htm. As described in these guidelines, R21 proposals should have the potential for truly groundbreaking impact, be restricted to a maximum of $125,000/year (direct costs), and limited in duration to a maximum of two years. Applicants are encouraged to contact program staff for advice about choosing the appropriate grant mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. 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. The earliest anticipated award date is April 1, 2002. Specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. Complete and detailed instructions and information on Modular Grant applications can be found at http://grants.nih.gov/grants/funding/modular/modular.htm For administrative reasons all applications received in response to this solicitation will be assigned initially to NINDS. After discussions among the participating Institutes following review, applications will be reassigned to the Institute(s) that are programmatically most appropriate. Because the scope of the research proposed in response to this RFA encompasses the interests of several NIH Institutes, applications may receive dual assignments based on the established PHS guidelines. Awards will be made and managed by one of the participating NIH institutes. FUNDS AVAILABLE The participating Institutes intend to commit a total of approximately $4,000,000 in FY2002 to fund approximately 10 to 14 new grants submitted in response to this RFA. The total project period for an application submitted in response to this RFA may not exceed 5 years. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award will also vary. Although the financial plans of the Institute provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, it is not known if this RFA will be reissued. 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 and local governments, and eligible agencies of the Federal government. Investigators from foreign institutions are strongly encouraged to contact program staff before preparing applications. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or answer questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Robert Finkelstein NINDS Neuroscience Center, Rm 2143 6001 Executive Blvd. Bethesda, MD 20892-9527 Telephone: (301) 496-5745 FAX: (301) 401-1501 Email: finkelsr@ninds.nih.gov Dr. Bradley C. Wise Neuroscience and Neuropsychology of Aging Program National Institute of Aging Gateway Building, Suite 3C307 7201 Wisconsin Avenue MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 FAX: (301) 496-1494 Email: WiseB@nia.nih.gov Dr. Steven O. Moldin Division of Neuroscience and Basic Behavioral Science NIMH 6001 Executive Boulevard, Room 7189, MSC 9643 Bethesda, MD 20892-9643 Telephone: (301) 443-2037 Fax: (301) 443-9890 Email: smoldin@mail.nih.gov Direct inquiries regarding review issues to: Dr. Lillian Pubols Scientific Review Branch NINDS Neuroscience Center, Rm 3208 Bethesda, MD 20892 Telephone: (301) 496-9223 FAX: (301) 402-0182 Email: LP28E@nih.gov Direct inquiries regarding fiscal matters to: Ms. Tina Carlisle Grants Management Branch NINDS 6001 Executive Boulevard, Rm 3290 Bethesda, MD 20892 Telephone: (301) 496-3938 Email: carlislt@ninds.nih.gov Ms. Linda Whipp Grants and Contracts Management Office National Institute of Aging Gateway Building, Suite 2N212 7201 Wisconsin Avenue MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: WhippL@nia.nih.gov Ms. Diana S. Trunnell Grants Management Branch NIMH 6001 Executive Blvd., Room 6115, MSC 9605 Bethesda, MD 20892-9605 Telephone: (301) 443-2805 Fax: (301) 443-6885 Email: Diana_Trunnell@nih.gov LETTER OF INTENT Prospective applicants are asked to submit 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 IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed below. SCHEDULE SUMMARY Letter of Intent Receipt Date: June 7, 2001 Application Receipt Date: July 10, 2001 Peer Review Date: November, 2001 Council Review: February, 2002 Earliest Anticipated Start Date: April 1, 2002 APPLICATION PROCEDURES 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, reviewers and Institute staff. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants, with the modifications noted below. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIO BUDGET INSTRUCTIONS Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $250,000 per year for R01s or $125,000 per year for R21s. 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: PHS 398 o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $250,000) 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. o 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. o 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. o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative page. (See http://grants.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. This is not a Form page. o Under Personnel, list all project personnel, including their names, percent of effort, and roles on the project. No individual salary information should be provided. However, the applicant should use the NIH appropriation language salary cap and the NIH policy for graduate student compensation in developing the budget request. 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 all 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. Include the Letter of Intent to establish a consortium. Provide an additional narrative budget justification for any variation in the number of modules requested. o 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://grants.nih.gov/grants/funding/modular/modular.htm Complete the educational block at the top of the form page; - List position(s) and any honors; - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years. - List selected peer-reviewed publications, with full citations; o CHECKLIST - This page should be completed and submitted with the application. If the F&A rate agreement has been established, indicate the type of agreement and the date. All appropriate exclusions must be applied in the calculation of the F&A costs for the initial budget period and all future budget years. 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. 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. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. A sample RFA label is available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is in pdf format. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Dr. Lillian M. Pubols Scientific Review Branch, NINDS 6001 Executive Blvd. NSC Rm 3208, MSC 9529 Bethesda, MD 20892-9529 (for courier delivery use: Rockville, MD 20852) Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by NIH staff. 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 be evaluated for scientific and technical merit by an appropriate peer review group convened by the NINDS Scientific Review Branch in accordance with the review criteria stated below. 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 the applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate National Advisory Council or Board. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of 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 out 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? (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? (6) Sharing plan: Has the investigator proposed an adequate plan to make all data and biological materials collected and produced as a result of the proposed research accessible in a timely manner to the biomedical research community? (7) R21 applications only: Does this project have the potential for groundbreaking impact? If successful, will this project achieve at least one of the following goals: 1) generate pilot data to assess the feasibility of a novel avenue of investigation? 2) involve high risk experiments that could lead to a breakthrough in a particular field? or 3) demonstrate the feasibility of new technologies that could have major impact in a specific area? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o 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. o The reasonableness of the proposed budget and duration in relation to the proposed research. o 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. AWARD CRITERIA Award criteria that will be used to make award decisions include: o scientific merit (as determined by peer review) o availability of funds o programmatic priorities o adequacy of proposed sharing plan 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 sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of 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 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: http://grants.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 the policy. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS- led national activity for setting priority areas. This Request for Applications (RFA), Gene Discovery for Neurological and Neurobehavioral Disorders, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853, (NINDS), 93.866 (NIA), and 93.242 (NIMH). Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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 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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