From owner-sci-resources@net.bio.net Fri Dec 01 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 24, no. 41, pt. 1of1, 1 December 1995 Date: 1 Dec 1995 20:27:22 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 489 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <49okja$lo5@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19951201 V24N41 P1O1 ************************************ X-comment: RFAS described: HL-96-005, DA-96-003, HL-96-006, PA-96-008, PA-96- X-URL: gopher://gopher.nih.gov:70/11/res/nih-guide/guide-files/95.12.01 NIH GUIDE - Vol. 24, No. 41 - December 1, 1995 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$INDEX R1 ********************************************************** CORTICAL CONTROL OF NEURAL PROTHESES (RFP NIH-NINDS-96-02) National Institute of Neurological Disorders and Stroke INDEX: NEUROLOGICAL DISORDERS, STROKE $$INDEX R2 02/09/96 ************************************************* THE ETIOLOGY OF EXCESS CARDIOVASCULAR DISEASE IN DIABETES MELLITUS (RFA HL-96-005) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R3 02/21/96 ************************************************* NOVEL PHARMACOTHERAPIES FOR COCAINE AND OTHER PSYCHOSTIMULANT DEPENDENCE (RFA DA-96-003) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX R4 03/12/96 ************************************************* SLEEP ACADEMIC AWARD (RFA HL-96-006) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX P1 ********************************************************** EPIDEMIOLOGY OF LUNG CANCER: INTERDISCIPLINARY STUDIES (PA-96-008) National Cancer Institute National Institute of Environmental Health Sciences INDEX: CANCER; ENVIRONMENTAL HEALTH SCIENCES $$INDEX P2 ********************************************************** CENTRAL AUDITORY SYSTEM PLASTICITY IN ADULTS (PA-96-009) National Institute on Deafness and Other Communication Disorders INDEX: DEAFNESS, OTHER COMMUNICATION DISORDERS THIS PUBLICATION IS AVAILABLE ELECTRONICALLY VIA BITNET OR INTERNET, BY SUBSCRIPTION, AND IS ALSO ON THE NIH GOPHER (GOPHER.NIH.GOV). ALTERNATIVE ACCESS IS THROUGH THE NIH GRANT LINE USING A PERSONAL COMPUTER (DATA LINE 301/402-2221); CONTACT DR. JOHN JAMES AT 301/435- 0692 FOR DETAILS. 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. THE DIVISION OF RESEARCH GRANTS (DRG) HAS MOVED TO A NEW LOCATION. ALL COMPETING GRANT APPLICATIONS SUBMITTED TO THE NATIONAL INSTITUTES OF HEALTH MUST BE SENT TO: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$R1 BEGIN NIH-NINDS-96-02 ****************************************** CORTICAL CONTROL OF NEURAL PROTHESES NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFP AVAILABLE: NIH-NINDS-96-02 P.T. 34; K.W. 1002030, 0710085 National Institute of Neurological Disorders and Stroke The Neural Prosthesis Program of the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), supports research and development on functional neuromuscular stimulation (FNS) to restore hand and arm function in quadriplegic individuals. These FNS systems must operate under the voluntary control of the individual. Providing a means for the individual to produce the control signals represents a critical part of any potential FNS system. Presently, control signals are generated by voluntary movements of unparalyzed muscles such as the contralateral shoulder. This project will investigate the ability of cortical cells in a neurologically intact animal to control an artificial output device on a chronic basis. The goal of this work is to establish the feasibility of generating control signals through voluntary control of neurons in the central nervous system (CNS). To demonstrate cortical control, it is necessary to show that the neural activity in selected cell populations in the CNS can be trained to reliably control an electromechanical device. It is anticipated that one award, on a cost-reimbursement basis, will be made for a period of three years. INQUIRIES This is not a Request for Proposals. Request for Proposals (RFP) No. NIH-NINDS-96-02 will be issued on or about November 20, 1995, with responses due on or about January 22, 1996. Interested organizations may request either a streamlined version or an entire RFP document. If no selection is made, a streamlined version of the RFP will be provided. The streamlined version includes only the Statement of Work, deliverable and reporting requirements, special requirements, and technical evaluation criteria. After examination of these documents, any organization interested in responding to the RFP must request the entire RFP either in writing or by FAX request. Requests must cite the RFP number referenced above. Supply this office with two self-addressed mailing labels. All responsible sources may submit a proposal that will be considered by the Government. Laurie Leonard ATTN: RFP NIH-NINDS-95-14 Contracts Management Branch, DEA National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 901 - MSC 9190 Bethesda, MD 20892 FAX: (301) 402-4225 $$R1 END ************************************************************ $$R2 BEGIN HL-96-005 FULL-TEXT ************************************** THE ETIOLOGY OF EXCESS CARDIOVASCULAR DISEASE IN DIABETES MELLITUS NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA AVAILABLE: HL-96-005 P.T. 34; K.W. 0715040, 0715075, 0755030 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 2, 1996 Application Receipt Date: February 9, 1996 PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites applications for program project grants (P01) for research on the etiology of cardiovascular diseases (CVD) associated with diabetes mellitus. This is a reissue of an RFA originally published in October 1994 (HL-95-005). This initiative will support investigators with outstanding programs of basic and human subjects research on one or more diabetes associated cardiovascular complications. In addition, with the encouragement of the NHLBI, the research programs that secure awards will participate in a coordinated effort to evaluate the metabolic and environmental factors responsible for the pathogenesis of CVD in existing, defined population groups. A program project (P01) grant is for the support of a broadly-based multidisciplinary or multifaceted research program that has a specific major objective or central theme. Each program project application and award in response to this solicitation must have both basic research and human subjects components. Applications should be submitted to and will be reviewed by the NIH according to the usual NIH peer review procedures. Applications judged meritorious will be jointly funded by NHLBI and the Juvenile Diabetes Foundation International (JDFI). To have an application considered for funding by the JDFI, an applicant must authorize, in writing, the NHLBI to provide a copy of the letter of intent, application, and NIH prepared summary statement of the initial review to the JDFI. 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 RFA, The Etiology of Excess Cardiovascular Disease in Diabetes Mellitus, is related to the priority areas of heart disease and stroke and diabetes and chronic disabling 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). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221) and the NIH GOPHER (gopher.nih.gov), and by mail and email from the program contact listed below. Peter J. Savage, M.D. Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 8154 Bethesda, MD 20892-7934 Telephone: (301) 435-0702 FAX: (301) 480-1667 Email: Peter_Savage@NIH.GOV $$R2 END ************************************************************ $$R3 BEGIN DA-96-003 FULL-TEXT ************************************** NOVEL PHARMACOTHERAPIES FOR COCAINE AND OTHER PSYCHOSTIMULANT DEPENDENCE NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA AVAILABLE: DA-96-003 P.T. 34; K.W. 0404009, 0740020 National Institute on Drug Abuse Letter of Intent Receipt Date: January 19, 1996 Application Receipt Date: February 21, 1996 PURPOSE The purpose of this Request for Applications (RFA) is to encourage clinical testing of innovative and non-traditional pharmacotherapies for treatment of cocaine/psychostimulant (amphetamines) dependence. Two types of medications will be considered: (1) traditional pharmacotherapies addressing novel neurochemical mechanisms (beyond classical biogenic amines or compounds previously extensively tested); (2) non-traditional (alternative) pharmacotherapies selected to restore brain homeostasis or to repair/compensate for existing neurological/neurochemical deficits in chronic psychostimulant abusers (e.g., special nutritional factors, amino acids, neurotransmitter precursors, hormones, antihormones, supplements). Special emphasis will be put on testing natural compounds with very low or no toxicity, which could be potentially also utilized for treatment of children and pregnant women. Investigators should study the safety and efficacy of novel medications in either relapse prevention in detoxified cocaine/psychostimulant dependent participants or reduction of drug use. The primary focus will be on relapse prevention. Applications will be also required to assess the impact of investigational agent on HIV risk behaviors. Applications that propose to evaluate compounds already extensively studied in psychostimulant dependence (traditional medications that act at dopamine, noradrenaline, or serotonin systems, or carbamazepine, etc.) will not be considered responsive. It is anticipated that approximately $4 million will be available to support between 12 and 20 new research project grants (R01), First Independent Research Support and Transition (FIRST) (R29), or exploratory/developmental (R21) grants under this RFA. 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 RFA, Novel Pharmacotherapies for Cocaine and Other Psychostimulant Dependence, is related to the priority areas of health promotion, and alcohol and other drugs. 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). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221) and the NIH GOPHER (gopher.nih.gov), and by mail and email from the program contact listed below. Maria Dorota Majewska, Ph.D. Medications Development Division National Institute on Drug Abuse 5600 Fishers Lane, Room 11A-55 Rockville, MD 20857 Telephone: (301) 443-3318 FAX: (301) 443-2599 Email: mm158w@nih.gov $$R3 END ************************************************************ $$R4 BEGIN HL-96-006 FULL-TEXT ************************************** SLEEP ACADEMIC AWARD NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA AVAILABLE: HL-96-006 P.T. 34; K.W. 0715187 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 29, 1995 Application Receipt Date: March 12, 1996 PURPOSE The primary objective of this initiative is to encourage the development and/or improvement of the quality of medical curricula, physician/patient/nurse and community education, and clinical practice for the prevention, management, and control of sleep disorders. A secondary objective is to promote high quality clinical research on sleep. The candidate for the Sleep Academic Award must have knowledge and skills in sleep and sleep disorders medicine and be an established member of a medical faculty in an accredited school of medicine or osteopathy in the United States, its territories, or its possessions. The candidate must also have had experience and sufficient training in clinical sleep research, clinical practice, and/or medical education as well as the unqualified support of the Dean and the educational leadership of the applicant institution. The mechanism of support is the Academic Award Program (K07) of the National Heart, Lung, and Blood Institute. The total project period may not exceed five years and is non-renewable. The estimated funds (total costs) available for fiscal year 1996 will be $300,000. It is anticipated that three to four new grants will be awarded in FY 1996 and in each of the next two years through an additional competition in each of fiscal years 1997 and 1998. 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 RFA, Sleep Academic Award, is related to the priority areas of heart disease and stroke, diabetes, chronic disabling conditions, mental health and disorders, and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No.017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202- 512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301-402-2221) and the NIH GOPHER (gopher.nih.gov) and by mail and Email from the program contact listed below. James P. Kiley, Ph.D. National Center on Sleep Disorders Research National Heart, Lung, Blood Institute 6701 Rockledge Drive, Suite 7024 - MSC-7920 Bethesda, MD 20892-7920 Telephone: (301) 435-0199 FAX: (301) 480-3451 Email: Kileyj@NIH.GOV $$R4 END ************************************************************ $$P1 BEGIN PA-96-008 FULL-TEXT ************************************** EPIDEMIOLOGY OF LUNG CANCER: INTERDISCIPLINARY STUDIES NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA AVAILABLE: PA-96-008 P.T. 34; K.W. 0715035, 0785055, 0715165 National Cancer Institute National Institute of Environmental Health Sciences PURPOSE The National Cancer Institute (NCI) and the National Institute of Environmental Health Sciences invite investigator-initiated research project grant (R01) applications for innovative interdisciplinary studies to better understand the etiology of adenocarcinoma and small cell carcinoma of the lung and the means of prevention. 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), Epidemiology of Lung Cancer: Interdisciplinary Studies, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001000473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). INQUIRIES The PA, which describes the research objectives, application procedures, review considerations, and award criteria for this program, may be obtained electronically through the NIH Grant Line (data line 301-402-2221) and the NIH GOPHER (gopher.nih.gov) and by mail and email from the program contact listed below. Dr. A.R. Patel Division of Cancer Epidemiology and Genetics National Cancer Institute 6130 Executive Boulevard, Suite 535, MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 FAX: (301) 402-4279 Email: Jasonc@EPNDCE.NCI.NIH.GOV Dr. Gwen W. Collman Chemical Exposures and Molecular Biology Branch National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-4980 FAX: (919) 541-2843 Email: collman@niehs.nih.gov $$P1 END ************************************************************ $$P2 BEGIN PA-96-009 FULL-TEXT ************************************** CENTRAL AUDITORY SYSTEM PLASTICITY IN ADULTS NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA AVAILABLE: PA-96-009 P.T. 34; K.W. 0775005 National Institute on Deafness and Other Communication Disorders PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) invites applications for the support of research on central auditory system plasticity in adults. This program announcement (PA) encourages research on plasticity in the adult auditory system at any level(s) of biological organization, from the level of the molecule to behavior, and at any processing station(s), from the cochlea to higher-order areas of auditory cortex, and beyond. Such studies may lead to a better understanding of normal brain function and development as well as an explanation for the recovery of auditory function sometimes seen following injury to the auditory system. In addition, these studies have the potential to reveal how auditory learning occurs, including that often seen following cochlear implantation. Findings from these studies may also guide the development of therapies for recovery of function following brain injuries, diseases, and disorders that affect auditory perception. The support mechanism for grants in this area will be the individual investigator-initiated research project grant (R01) and First Independent Research Support and Transition (FIRST) (R29) awards. 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 PA, Central Auditory System Plasticity in Adults, is related to the priority area of diabetes and chronic disabling conditions. 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). INQUIRIES The PA, which describes the research objectives, application procedures, review considerations, and award criteria for this program, may be obtained electronically through the NIH Grant Line (data line 301-402-2221) and the NIH GOPHER (gopher.nih.gov), and by mail and email from the program contact listed below. Lynn E. Huerta, Ph.D. 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) 402-3458 FAX: (301) 402-6251 Email: Lynn_Huerta@nih.gov $$P2 END ************************************************************ From owner-sci-resources@net.bio.net Tue Dec 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-96-009 - V24(41) 12/01/95 Date: 5 Dec 1995 21:13:13 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 297 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <4a38p9$15q@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA96009 PA-96-009 P1O1 *************************************** CENTRAL AUDITORY SYSTEM PLASTICITY IN ADULTS NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA NUMBER: PA-96-009 P.T. 34; K.W. 0775005 National Institute on Deafness and Other Communication Disorders PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) invites applications for the support of research on central auditory system plasticity in adults. Such studies may lead to a better understanding of normal brain function and development as well as an explanation of the recovery of auditory function sometimes seen following injury to the auditory system. In addition, these studies have the potential to reveal how auditory learning occurs, including that often seen following cochlear implantation. Findings from these studies may also guide the development of therapies for recovery of function following brain injuries, diseases, and disorders that affect auditory perception. 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 PA, Central Auditory System Plasticity in Adults, is related to the priority area of diabetes and chronic disabling conditions. 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 and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals, women, and individuals with disabilities are encouraged. MECHANISM OF SUPPORT The support mechanism for grants in this area will be the individual investigator-initiated research project grant (R01) and the FIRST (R29) award. RESEARCH OBJECTIVES Background Change in synaptic strength has long been invoked as a possible mechanism underlying learning and memory throughout the lifespan. While it has also been recognized that major features of functional organization of neural structures, such as representation of the body surface in somatosensory cortex, are modifiable during specific periods of development, these maps were considered to be "hard-wired" in adults and incapable of change. Over the last decade, however, studies of several sensory- and motor-related regions of neocortex have revealed that such maps undergo significant reorganization in response to injury and learning in adults. Despite the potential significance that such research holds for understanding a host of basic and clinical issues regarding auditory function, few studies of plasticity have been carried out in the mature auditory system. This program announcement (PA) encourages research on plasticity in the adult auditory system at any level(s) of biological organization, >From the level of the molecule to behavior, and at any processing station(s), from the cochlea to higher-order areas of auditory cortex, and beyond. Changes in the organization of representations of the periphery at the cortical level have been demonstrated following cochlear damage, retinal damage, limb amputation, and disruption of sensory innervation of the skin in adults. Following such peripheral perturbations, regions of cortex that are deprived of normal input do not become "silent," but typically respond to the remaining (usually adjacent) sensory inputs that are still intact. This often results in a shrinkage or elimination of the representation of the perturbed periphery and an enlargement of the representation of the intact periphery. Although most investigations of this type have examined changes in neocortex, subcortical structures have also been studied using these experimental approaches. The effects of learning on sensory cortex have been documented in the auditory system. For example, frequency receptive fields of neurons in the adult primary auditory cortex can be modified to that of a conditioned stimulus using classical conditioning paradigms. These changes have been shown to develop rapidly, are highly specific, can last indefinitely, and occur for different learning paradigms. Subcortical plasticity in the adult animal is also seen in changes in the receptive fields of midbrain neurons during sound localization tasks. While it is accepted that the central nervous system remains plastic throughout the lifespan, the mechanisms underlying this plasticity are unclear. The time course for these changes is variable, and may be due to the growth of axons and the formation of new connections over long distances or due to alterations in synaptic strength and the "unmasking" or activation of subthreshold pathways. The involvement of different forms of synaptic change, such as short- and long-term depression and potentiation, appears to vary for different brain regions. This suggests that, although the brain has a variety of means of modifying synapses, all regions do not achieve these modifications in the same way. The molecular mechanisms underlying the various forms of synaptic change also vary across brain regions. There are many possible explanations for these differences, but it is clear that understanding the implications of adult plasticity for auditory function would be best served by examining this specifically in the auditory system. The roles of drug and nondrug therapies for the recovery of function following peripheral or central injury or disease and their relationships to plastic changes in the central nervous system are under investigation. For example, the ability of nerve growth factors to enhance functional brain recovery following stroke is being studied in humans. The role of physical therapy in the recovery of motor function and observed changes in motor cortical regions is also being examined. Studies of such therapies offer great promise for improving and speeding recovery from brain and sensory and motor system diseases and disorders, but have thus far received little attention in the auditory system. Research Goals and Scope Current research related to central auditory plasticity in adults is yielding exciting insights into the nature of this phenomenon, and promises to improve understanding of the auditory system. Research on adult plasticity of the auditory system is, however, still in its infancy, and many areas need to be explored. Fulfilling the ultimate hope that this phenomenon will be harnessed to improve the lives of those with hearing impairment depends upon a sophisticated understanding of plasticity of the adult auditory system. The purpose of this PA is to encourage applications for research on topics such as, but not limited to, the following: o determination of the limits (e.g., time course, neural distance, effects of training) of central auditory nervous system plasticity following damage to the auditory system; o determination of the limits (e.g., time course, neural distance, effects of training) of central auditory nervous system plasticity induced by auditory training and deprivation; o elucidation of the relationship between central auditory nervous system plasticity and functional recovery following damage to the auditory system; o comparison of the nature and extent of plasticity occurring at different processing stations of the central auditory nervous system; o identification and characterization of the various forms of synaptic change (e.g., long- and short-term potentiation and depression) involved in central auditory nervous system plasticity; o identification and characterization of candidate neurochemical mechanisms for central auditory nervous system plasticity; and o development of new or improvement of existing therapies (both drug and nondrug) for the recovery of function following damage to the auditory system or for the enhancement of plasticity in the intact auditory system. 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 new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. 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 reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. 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. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301/435-0714, email: girg@drgpo.drg.nih.gov. The completed original and five legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) REVIEW CONSIDERATIONS Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with 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 or board. The review criteria are: scientific, technical, or medical significance and originality of proposed research; appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; availability of the resources necessary to perform the research; appropriateness of the proposed budget and duration in relation to the proposed research; and adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. AWARD CRITERIA Applications will compete for available funds with all other applications assigned to that Institute or Center. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review; availability of funds; and program priorities among research areas of the program announcement. INQUIRIES Written, telephone, and email inquiries concerning this PA are encouraged; the opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific content to: Lynn E. Huerta, Ph.D. Division of Human Communication National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-C 6120 Executive Boulevard MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-3458 FAX: (301) 402-6251 Email: Lynn_Huerta@nih.gov Direct inquiries regarding fiscal matters to: Sharon Hunt Grants Management Office National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400-B, MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: Sharon_Hunt@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.173. Awards are made under authorization 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 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. From owner-sci-resources@net.bio.net Tue Dec 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA DA-96-003 - V24(41) 12/01/95 Date: 5 Dec 1995 21:11:43 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 469 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <4a38mf$11f@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA DA96003 DA-96-003 P1O1 *************************************** NOVEL PHARMACOTHERAPIES FOR COCAINE AND OTHER PSYCHOSTIMULANT DEPENDENCE NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA: DA-96-003 P.T. 34; K.W. 0404009, 0740020 National Institute on Drug Abuse Letter of Intent Receipt Date: January 19, 1996 Application Receipt Date: February 21, 1996 PURPOSE The purpose of this Request for Applications (RFA) is to encourage clinical testing of innovative and non-traditional pharmacotherapies for treatment of cocaine/psychostimulant (amphetamines) dependence. Two types of medications will be considered: (1) traditional pharmacotherapies addressing novel neurochemical mechanisms (beyond classical biogenic amines or compounds previously extensively tested); (2) non-traditional (alternative) pharmacotherapies selected to restore brain homeostasis or to repair/compensate for existing neurological/neurochemical deficits in chronic psychostimulant abusers (e.g., special nutritional factors, amino acids, neurotransmitter precursors, hormones, antihormones, supplements, etc.). Special emphasis will be put on testing natural compounds with very low or no toxicity, which could be potentially also utilized for treatment of children and pregnant women. Investigators should study the safety and efficacy of novel medications in either relapse prevention in detoxified cocaine/psychostimulant dependent participants or reduction of drug use. The primary focus will be on relapse prevention. Applications will be also required to assess the impact of investigational agent on HIV risk behaviors. Applications that propose to evaluate compounds already extensively studied in psychostimulant dependence (traditional medications that act at dopamine, noradrenaline, or serotonin systems, or carbamazepine, etc.) will not be considered responsive. 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 RFA, Novel Pharmacotherapies for Cocaine and Other Psychostimulant Dependence, is related to the priority areas of alcohol and other drugs. Potential applicants may obtain a copy of Healthy People 2000 (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State 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. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). International collaborative studies, which must include a U.S. principal investigator, will also be considered. For example, if the investigational compound is not available on the U.S. market, but is available in European or Asian pharmacopeias, the pilot studies may be conducted in a foreign country. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01), FIRST (29) award, exploratory/developmental grant (R21), and small grant (R03). Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. Because the small grants and FIRST awards have special eligibility requirements, application formats, and review criteria, applicants are strongly encouraged to consult with the program staff (listed under INQUIRIES) and to obtain the appropriate additional guidelines/announcements for those grant mechanisms. FUNDS AVAILABLE It is anticipated that approximately $4 million will be available to support projects submitted under this RFA. Because the nature and scope of the research proposed in response to this RFA may vary, the size of an award will vary also. However, it is anticipated that between 12 and 20 new awards will be made under this RFA. About 70 percent of funds will be directed toward projects testing novel medications for relapse prevention, and about 30 percent toward projects testing effects of novel medications on reduction of drug use. RESEARCH OBJECTIVES Recent findings in clinical and preclinical neurosciences reveal complex biological determinants underlying psychostimulant dependence. These include psychopathological, neuroanatomical, pathophysiological, neuroadaptive, neurochemical, and hormonal factors, and may involve a variety of nutritional, environmental and toxicological substrates as underlying causes of drug addictions. Psychostimulant dependence is associated with various degrees of neuropathology and significant comorbidity with other neurological and psychiatric disorders, including attention and mood disorders, hypodopaminergia, hyposerotonergia, and hypofrontalism, manifested in perfusion and metabolic/bioenergetic deficits, among others. The bioenergetic deficits induced by psychostimulants may promote brain aging and facilitate neurodegenerative disorders in chronic psychostimulant abusers. Rational pharmacological interventions in these biological/pathological substrates could be effective in treating psychostimulant dependence. Moreover, recent reemergence, reported therapeutic success and safety of non-traditional pharmacotherapies, including medically designed nutrition, supplements, vitamins, amino acids, hormones and other natural compounds, in treating variety of chronic disorders suggest exploration of non-traditional treatments as potential therapies for cocaine/psychostimulant dependence. Such natural therapies, designed to normalize brain functions may be more acceptable to treatment-seeking addicts, who often refuse to be treated with conventional medications, and be more beneficial than traditional pharmacotherapies, which often produce undesirable side effects. It is expected that such therapies may be safe enough to be used for treatment of addicted children, adolescents or pregnant women. The main objective of this RFA is to encourage clinical evaluation of: (1) novel traditional medications with compounds and classes of compounds previously not studied in clinical trials to treat psychostimulant dependence, and; (2) non-traditional pharmacotherapies, in relapse prevention designs in detoxified cocaine/stimulant dependent participants, or reduction of drug use in psychostimulant addicts. The hypothesis and rationale for testing these novel medications should address one or more of the following research/clinical aspects: 1. the persistent neurochemical imbalance and/or neuroadaptive/neuropathological changes that have been described in cocaine/psychostimulant dependent individuals or in animals treated chronically with stimulants; 2. the pharmacological intervention in neurochemical and psychological factors contributing to vulnerability to stimulant dependence (e.g., attention deficit hyperactivity disorder, post-traumatic stress disorder); 3. the hormonal abnormalities in cocaine/stimulant dependent persons; 4. the biochemical mechanism relevant for behavioral outcomes for cocaine dependence (e.g., drug craving); 5. neurochemical factors involved in expression of euphorigenic and dependence-producing effects of psychostimulants; 6. neurochemical factors responsible for persistent anhedonia, depression, and anxiety, associated with psychostimulant withdrawal and accompanying abstinence in chronic psychostimulant abusers; 7. the availability of open clinical trial data or promising preclinical results; 8. other scientific or clinical rationales. Investigators are encouraged to study novel medications, yet untested for treatment of psychostimulant dependence (including those not approved in the U.S., but approved in European and Asian pharmacopeias) as well as a variety of nutritional factors, supplements, and naturally occurring substances, rationally selected to compensate for biochemical and functional deficits reported in stimulant addicts (e.g., apparent deficiency of biogenic amines, an imbalance in endogenous opioid peptides and other neurotransmitters) and to restore the brain homeostasis in psychostimulant dependent individuals. We are soliciting applications that test the hypothesis that correcting for persistent or permanent neuropathologies that are associated with psychostimulant dependence with novel pharmacotherapies may be effective in treating this disorder. Possible examples of such treatments include: precursors of biogenic amines and other neurotransmitters, vitamins and supplements that modify neurotransmitter metabolism and energy metabolism, and herbs of known therapeutic profile. Examples of potential therapeutic herbs may include: Ginkgo Biloba, Kudzu, Ginseng, Gotu Cola, and Kelp, among others. Encouraged also are pharmacological and natural interventions in hormonal systems (e.g., hypothalamo-pituitary-adrenal axis, hypothalamo-pituitary-gonadal axis, thyroid system, endogenous opioid peptides) that have been shown to play a role in drug dependence. Medications designed to improve deficient brain circulation, energy and phospholipid metabolism, and cognition, will be also considered along with rational combinations of treatments. Because no pharmacotherapy is expected to be optimally effective without concurrent behavioral therapy, adjunct therapies may concentrate on psychological, behavioral processes such as motivation building, relapse prevention skills, coping skills, skills for utilization of alternative reinforcers, as well as meditation, or imagery. Drug dependence encompasses both physical and psychological symptomatology; therefore, developing and testing integrative approaches for treatment of psychostimulant dependence is encouraged (i.e., treatments that stress pharmacotherapy, psychological support, behavioral and nutritional adjustments, and social adaptations). In addition to testing potential treatments that affect primary psychostimulant dependence, applications are encouraged to evaluate novel treatments for disorders comorbid with drug dependence; these include anxiety, depression, anhedonia, attention deficit and cognitive impairments, antisocial behavior, post-traumatic stress disorder, and other diagnoses that may contribute to continued psychostimulant abuse and relapse. The proposed studies should test the safety and efficacy of novel therapeutic approaches in rigorously designed and executed clinical trials to prevent relapse in persons detoxified from cocaine/psychostimulant dependence or to reduce drug use in addicts. Identified treatment modalities may be assessed in clinical pharmacologic-therapeutic paradigms (laboratory clinical assessments) and/or in phase I/II clinical trials that meet accepted standards for Good Clinical Practice (GCP) guidelines established by FDA (21 CFR). Because most psychostimulant abusers also co-abuse other substances (alcohol, benzodiazepines, opiates), evaluation of the impact of proposed new therapies on the use of the above drugs, in addition to psychostimulants, will be also required. Applications will be also required to assess impact of the investigational agent on HIV risk behaviors. Proposals must seek and obtain IRB review and approval prior to submission or review of the application. SPECIAL REQUIREMENTS The exploratory, developmental (R21) and Small Grant (R03) applications are limited to two years, are non-renewable, and are limited in direct cost amount per year (R03, $50,000; R21, $90,000). The R03 mechanism is intended for new, inexperienced investigators and both are intended for established investigators exploring new areas or departing from their usual research topics. There are special requirements for these mechanisms. An applicant intending to apply for them under this RFA should contact the named program person in the INQUIRIES section for further information. 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 new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. This new policy contains some new provisions that are substantially different from the 1990 policies. 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 reprinted 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. This RFA requires that proposed studies conduct gender comparisons of clinical responses (side effects, efficacy, etc.) to the new medications and strongly encourages examination of menstrual cycle effects on the pharmacokinetics and pharmacodynamics of proposed new therapies. LETTER OF INTENT Prospective applicants are asked to submit, by January 19, 1996, a letter of intent that includes a descriptive title of the proposed research, the proposed mechanism of support, the telephone number of the Principal Investigator, the identities of other key personnel and participating institution, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIDA staff to estimate the potential review workload and to avoid conflict of interest review. The letter of intent is to be sent to: Director Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 FAX: (301) 443-0538 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone (301) 435-0714; email: girg@drgpo.drg.nih.gov. FIRST applications must include at least three sealed letters of reference attached to the Face Page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The RFA label in the form PHS 398 application kit must be affixed to the bottom of the original face page. Failure to use the RFA label and to follow instructions 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 in Item 2 of the face page and YES box marked. Submit a signed, typewritten original of the application, including Checklist, and three signed photocopies in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for overnight/courier service) At the time of submission, two additional copies of the application must also be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by NIDA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned without review. Applications that are complete and responsive to the RFA will be evaluated for scientific/technical merit by an appropriate peer review group convened by NIDA in accordance with the review criteria stated below. As part of the initial merit review, a streamlined review will be used by the initial review group in which application will be determined to be competitive or noncompetitive based on their scientific merit relative to other applications received in response to this RFA. Applications determined to be non-competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the application will be notified. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator could be included with the application. Review Criteria o merit, scientific, technical or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area or proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; and o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. o adequacy of plans regarding assessment of effects of proposed new medications on HIV risk behaviors. Plans for recruitment and retention of subjects will also be evaluated. 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 recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the proposal as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. Schedule Letter of Intent Receipt Date: January 19, 1996 Application Receipt Date: February 21, 1996 Initial Review Date: April 1996 Advisory Council Date: May 1996 Earliest Start Date: July 1996 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Maria Dorota Majewska, Ph.D. Medications Development Division National Institute on Drug Abuse 5600 Fishers Lane, Room 11A-55 Rockville, MD 20857 Telephone: (301) 443-3318 FAX: (301) 443-2599 Email: mm158w@nih.gov Direct inquiries regarding fiscal and grants management issues to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 Email: gfleming@aoada1.ssw.dhhs.gov AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public health Service Act, Section 301, and administered under PHS grants policies and federal regulations at Title 42 CFR 52 "Grants for Research projects", Title 45 CFR Part 74 & 92 "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR part 2, "Confidentiality of Alcohol and Drug Abuse patient records" may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health System Agency review. Sections of the Code of Federal regulation are available in booklet form from the U.S. Government Printing Office. Grants must be administered in accordance with the PHS Grants Policy Statement (revised 4/94), which may be available from your office of sponsored research. 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 of 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. From owner-sci-resources@net.bio.net Tue Dec 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-96-005 - V24(41) 12/01/95 Date: 5 Dec 1995 21:11:19 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 876 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <4a38ln$10o@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HL96005 HL-96-005 P1O1 *************************************** THE ETIOLOGY OF EXCESS CARDIOVASCULAR DISEASE IN DIABETES MELLITUS NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA: HL-96-005 P.T. 34; K.W. 0715040, 0715075, 0755030 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 2, 1996 Application Receipt Date: February 9, 1996 PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites applications for program project grants for research on the etiology of cardiovascular diseases (CVD) associated with diabetes mellitus. This initiative will support investigators with outstanding programs of basic and human subjects research on one or more diabetes associated cardiovascular complications. In addition, with the encouragement of the NHLBI, the programs that receive awards will participate in a coordinated effort to evaluate the metabolic and environmental factors responsible for the pathogenesis of CVD in existing, defined population groups. A program project grant (P01) is for the support of a broadly-based multidisciplinary or multifaceted research program that has a specific major objective or central theme. Each program project application and award in response to this solicitation must have both basic research and human subjects components. Applications should be submitted to and will be reviewed by the NIH according to the usual NIH peer review procedures. Applications judged meritorious will be jointly funded by NHLBI and the Juvenile Diabetes Foundation International (JDFI). To have an application considered for funding by the JDFI, an applicant must authorize in writing the NHLBI to provide a copy of the letter of intent, application, and NIH prepared summary statement of the initial review to the JDFI. 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 RFA, The Etiology of Excess Cardiovascular Disease in Diabetes Mellitus, is related to the priority areas of heart disease and stroke and diabetes and chronic disabling 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 for-profit and non-profit domestic institutions, public and private, such as universities, colleges, hospitals, laboratories, units of State and local government and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Although program project awards cannot be made to foreign institutions, a subproject of high scientific merit may be eligible for support. The principal investigator should be an established research scientist with the expertise and experience to provide scientific leadership, ensure quality control, and effectively administer and integrate all components of the program. A minimum time commitment of 25 percent is expected for this individual. The principal investigator must also be the project leader of one of the component research projects. If, the research project for which the principal investigator is the project leader is not recommended for further consideration, the entire program project application will not be considered further. If the project of the principal investigator is judged by peer review to be of low scientific merit, the overall scientific merit ranking assigned to the entire application by the review committee will be markedly reduced. Project leaders must agree to commit at least 20 percent effort to each project for which they are responsible. Exclusions This RFA is intended to support program project grants that have both a basic research and human population component. Therefore, applications that include only basic or only clinical research will not be responsive to this RFA. This solicitation is intended to redress the inadequate information on the etiology of excess cardiovascular disease in patients with diabetes mellitus. Therefore, applications that do not focus on this aspect of diabetes and cardiovascular disease will not be considered. Large population studies or large clinical trials will be considered unresponsive to this RFA. MECHANISM OF SUPPORT It is the intention of NHLBI and JDFI to stimulate collaboration among investigators with different but complementary areas of expertise. This research will be supported by the National Institutes of Health (NIH) Program Project research grant mechanism (P01). Responsibility for planning the proposed project will be solely that of the applicant. The total project period requested by an application submitted in response to the present RFA may not exceed five years. A program project grant is for the support of a broadly-based multidisciplinary or multifaceted research program that has a specific major objective or central theme. The award may support research components and core functions. Collectively, these components should demonstrate essential elements of unity and interdependence and result in a greater contribution to program goals than if each activity were pursued individually. Each applicant will be expected to propose both basic and human subjects based research components, with concentration on one or more major risk factors as related to the increased risk of CVD in diabetic patients. Efforts will be made by the NHLBI to facilitate collaboration both during development of applications and after the program is established. Applications must be prepared and awards will be made according to NHLBI Program Project policies. NHLBI Guidelines for the preparation of Program Project Grant applications may be obtained from Dr C. James Scheirer at the address listed under LETTER OF INTENT. Approximately 50 percent of the total costs of each grant will be funded by the NHLBI and the same amount by the JDFI. Funding rules, including the determination of allowable indirect costs, will take into consideration those of each sponsor. Post award administration will be according to current policies and requirements that govern the research grant programs of the NIH and the JDFI as appropriate. Although multidisciplinary approaches are required, it is not the intent of this announcement to solicit applications for large clinical trials or large epidemiological studies. In general, funds will not be provided for the purchase and installation of expensive, new equipment. Upon initiation of this program, the NHLBI and JDFI plan to sponsor a meeting to encourage the exchange of information among investigators, foster collaborative efforts among program grantees, and identify resources that would enhance the productivity of several grantees. In many cases, combining proposed measures in highly characterized population subgroups may provide the most information. Where appropriate, additional joint protocols will be developed. After this planning phase, collaborative investigations will be conducted. Subsequent meetings will take place approximately yearly. For this purpose, requests for travel funds for a two-day meeting (two in year 01 and one per year thereafter) should be included in the budget section of the application (assume meeting will be held in Bethesda, MD). Applicants should include a statement in their applications indicating their willingness to participate in such meetings and to cooperate with other researchers at other interdisciplinary research program sites. Support will be provided for up to five years. Continued funding will be contingent on satisfactory completion of proposed investigations. In addition to a continuing series of reports on results of individual investigations, an overall report will be produced at the conclusion of the program. Consortium Arrangements If a grant application includes research activities that involve institutions other than the grantee institution, the program is considered a consortium effort. Such activities may be included in a Program Project grant application, but it is imperative that a consortium application be prepared so that the programmatic, fiscal, and administrative considerations are explained fully. The published policy governing consortia is available in the business offices of institutions that are eligible to receive Federal grants-in-aid. Consult the latest published policy governing consortia before developing the application. If clarification of the policy is needed, contact William Darby, (301) 435-0177. Applicants for Program Project grants should clearly describe the interactions of the participants and the integration of the consortium project(s) with those of the parent institution, because synergism and cohesiveness can be diminished when projects are located outside the group at the parent institution. Indirect costs paid as part of a consortium agreement are excluded from the limit on the amount of direct costs that can be requested. FUNDS AVAILABLE Approximately $1.4 million in total costs will be provided for the first year of support for the program by NHLBI with an equivalent amount provided by JDFI. Applicants may request up to $650,000 direct costs, not including indirect costs for collaborating institutions, in the first year with a maximum increase of no more than four percent in each additional year requested in the application. Funding rules, including the determination of allowable indirect costs, will take into consideration those of each sponsor. It is anticipated that three to four grants will be awarded under this program. Although this program is provided for in the financial plan of the NHLBI, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. Administrative adjustments in project period and/or amount of support may be required at the time of the award. Equipment is included in the budget limitation. However, requests for special equipment that cause an application to exceed this limit may be permitted on a case-by-case basis following staff consultation. Such equipment requires strong justification. Final decisions will depend on the nature of the justification and the availability of funds. RESEARCH OBJECTIVES General Background Additional investigations of the etiology of macrovascular complications of diabetes mellitus are needed. Such studies should include population, clinical, and basic research and involve experts in both diabetes and cardiovascular diseases. JDFI has embarked on a major long term capital fund raising campaign to establish programs of excellence in diabetes research. Diabetes mellitus is a complex metabolic disorder that affects not only glucose metabolism but several other metabolic processes. Some of these effects are acute and appear related to concentrations of glucose and/or insulin. Other effects develop over many years and are related to other metabolic derangements of diabetes or are of uncertain etiology. Recent advances in understanding the process of atherogenesis and the pathogenesis of chronic diabetic complications indicate that diabetes may accelerate atherosclerosis and the development of clinical cardiovascular disease through several mechanisms. Scientific Background The association between overt diabetes mellitus and excess risk of cardiovascular disease (CVD) has been documented in diabetic populations throughout the world, but the pathogenic mechanisms for the relationship are only partially understood. Among diabetic patients, both the incidence and mortality rates from myocardial infarction are increased, as are the risks of recurrent infarction, congestive heart failure, cerebrovascular disease, and peripheral vascular disease. The increased risk of CVD associated with diabetes appears to be greater in women than in men. In general, about 50 percent of excess heart disease in diabetics is attributed to associated abnormalities in other known CVD risk factors but levels of these factors may be in part determined by the degree of diabetic control. Milder abnormalities of glucose tolerance are also associated with an increased risk of cardiovascular disease, but glucose level in this group generally has not been an independent CVD risk factor. In these patients, an underlying multiple risk factor syndrome may be a major contributor to accelerated macrovascular disease. Approximately 12 to 14 million Americans have diabetes and up to an additional 18 million may have impaired glucose tolerance or glucose levels between those of diabetes and normoglycemia. Cardiovascular disease is the cause of death in 60 to 75 percent of this combined group. Insulin dependent diabetes mellitus (IDDM) is a leading cause of premature cardiovascular disease. Non-insulin dependent diabetes (NIDDM) is a significant risk factor for cardiovascular disease in middle and older ages. As the U.S. population ages, the importance of glucose intolerance as a risk factor for CVD will increase since its prevalence increases markedly with age, reaching over 50 percent in those above age 65 years. Moreover, with improved methods of glucose control, the anticipated decline in chronic microvascular complications of diabetes may be offset by an increase in the rates of major cardiovascular complications. It is not clear whether the pathogenesis of excess CVD is the same in IDDM and NIDDM. It is also important to recognize that improved glucose control in diabetic patients may not by itself be sufficient to eliminate the excess risk of diabetic cardiovascular complications. While recent data from the Diabetes Control and Complication Trial (DCCT) suggest a reduction in cardiovascular events in the group achieving near normoglycemia, the number of CVD events in this generally young cohort is small. Preliminary results >From a pilot study of intensive treatment of hyperglycemia in Type II diabetic veterans fail to suggest any short term benefit of improved glucose control, showing fewer cardiovascular events in the conventional than in the intensive treatment group. No relative reduction in CVD was observed in the variable dose insulin treated group of the University Group Diabetes Program that achieved the best degree of glucose control. These observations may be particularly relevant to the Type II diabetic patient with the multiple cardiovascular risk factor syndrome (Syndrome X of Reaven) where control of hyperglycemia only partially ameliorates the other CVD risk factor abnormalities. Finally, the relative benefits of glucose control and other CVD risk factor control may vary depending upon the race and gender of the patient and whether or not atherosclerotic disease is already advanced. Thus, the treatment most appropriate to prevent long term macrovascular complications in a young Type I diabetic with labile hyperglycemia may not be best for an elderly Type II diabetic with mild hyperglycemia. More information is needed in all of these areas to design better and more specific treatment and prevention regimens. Available data on hyperglycemia and insulin levels as risk factors for CVD have numerous limitations. Many of the frequently cited studies are old and utilized techniques of risk factor and disease measurement that are crude by today's standards. Until recently, most population studies of diabetes have included only rudimentary measures of vascular disease. Many studies of CVD and associated risk factors measured diabetes crudely and, in others, particularly several large clinical trials, diabetics were excluded. Among several early studies that indicated a risk for CVD associated with hyperglycemia, it is now probable that at least part of the risk can be explained by subsequently identified risk factors that were not measured at the time of the studies, such as hyperinsulinemia, elevated insulin resistance, abnormalities in coagulation factors, platelet function, or lipoprotein particle size or composition. In fact, two of the frequently cited studies indicating elevated insulin level is an independent risk factor for CVD did not measure HDL-cholesterol. The relative importance of hyperglycemia, hyperinsulinemia, and elevated insulin resistance as factors in the excess CVD of diabetes has not been assessed in prospective studies. Relative to studies on other major CVD risk factors such as hypertension and hypercholesterolemia, evaluations of the role of glucose intolerance and its related abnormalities as causes of CVD have been limited. The many complex metabolic abnormalities associated with diabetes and their potential interactions with risk factors for atherosclerosis make collaboration among investigators with different expertise essential. While diabetes increases the risk of CVD in all populations studied, the observed CVD event rates vary widely, suggesting that important environmental and probably genetic factors may modify the adverse effects of hyperglycemia. Collaboration between experts in cardiovascular disease and diabetes and among basic researchers, clinical investigators, and epidemiologists will be essential to maximize progress in understanding the causes of cardiovascular disease among diabetic patients and to develop new therapeutic approaches for preventing this major chronic complication. Objectives The primary objective of this initiative is to understand how the presence of diabetes increases the risk of cardiovascular disease. To accelerate this understanding, this initiative will bring together basic, clinical, and population based investigators to develop a research program to address this question at the laboratory, clinical, and population levels. Although the control of hyperglycemia is clearly associated with a reduction in the development of microvascular complications of diabetes, its role in the prevention of the macrovascular complications of diabetes is less certain. As a consequence, optimal interventions to prevent these two major categories of complications may differ. Proposed studies should focus on how diabetes increases the risk of macrovascular disease and the relative importance of hyperglycemia compared to other cardiovascular disease risk factors associated with glucose intolerance in the pathogenesis of the macrovascular disease in diabetic patients. Key questions include: o Does hyperglycemia directly cause the macrovascular disease? o Does hyperglycemia increase the risk of macrovascular disease primarily by altering other CVD risk factors? o Is the excess risk of CVD in diabetics largely independent of the level of glucose? o Does hyperglycemia have differing importance as a CVD risk factor in Type I (insulin dependent) compared to Type II (non-insulin dependent) diabetic patients? o Is the observed variation in rates of cardiovascular complications among diabetic patients in different populations secondary to genetic and/or environmental factors? Answers to these questions will be important in formulating recommendations for therapy of diabetic patients and, potentially, for the design of a future clinical trial to test treatment to prevent diabetes associated CVD. Investigators selected for participation in this program will be expected both to direct innovative research at their institutions and to collaborate with other members of the study group to apply this information to human populations. This initiative will support a broad program to understand the etiology of the accelerated macrovascular disease found in diabetic patients. It will not necessarily support investigations in all relevant areas, but will attempt to select and promote collaboration among the most promising applicant groups. Applicants will be selected for participation based upon, among other things, the overall evaluation of the importance and innovative aspects of their proposed program and their plans for evaluating these findings in defined populations. Specifically, this initiative may support research in several areas, for example: o To evaluate the roles of hyperglycemia, glycosylation of proteins, and advanced glycosylation end products (AGEs) in the development of diabetic macrovascular disease. o To evaluate the role of hypertension and its interactions with other risk factors in the development of diabetic macrovascular disease. o To evaluate the role of modifications of lipids and lipoproteins (oxidation and glycosylation) in the development of diabetic macrovascular disease. o To evaluate the role of altered coagulation factors, abnormalities in platelet function, and alterations in blood viscosity in the development of diabetic macrovascular disease. To evaluate the role of hyperinsulinemia and/or insulin resistance in the development of diabetic macrovascular disease. o To evaluate the role of vascular wall factors in the development of vascular disease in the presence of hyperglycemia. o To evaluate the role of the co-occurrence or "clustering" of CVD risk factor abnormalities including hypertension, dyslipidemia, hyperglycemia, and obesity in the development of diabetic macrovascular disease. o To evaluate the role of genetic and environmental factors in the variation in prevalence of diabetic macrovascular disease among racial and ethnic groups. A unique aspect of this RFA is the recognition that much relevant work on the pathogenesis of atherosclerosis has been conducted that has not yet been related to the link between diabetes and atherosclerosis. A goal of this initiative is to establish collaborations among groups who have been pursuing separate paths. For example, extensive work on lipid oxidation has taken place, the importance of this process in diabetes has been recognized, but research to assess its importance in diabetic vascular disease is limited. Similarly, extensive work has been done on insulin and insulin resistance. The potential importance of these factors in the multiple CVD risk factor syndrome and in atherosclerosis has been recognized, but research to assess their atherogenicity in the diabetic is limited. Many additional examples were evident in the presentations at the 1992 Workshop on Diabetes and Mechanisms of Atherogenesis (Getz, 1993). Advances in basic research during the past decade have greatly improved understanding of the metabolic abnormalities of diabetes and the process of atherogenesis. Further work may lead to unique ways of preventing or treating the atherosclerosis associated with diabetes. Because of this, a major portion of this initiative will be devoted to advancing fundamental knowledge of the atherosclerotic process in diabetics and to clarifying whether the same processes are responsible for the excess risk in all diabetic patients. A key question is whether the process in diabetic patients is the same or different from that in nondiabetics. Many research opportunities, many of which are interrelated, were identified in the workshop mentioned above (Getz, 1993). Several areas appear appropriate for emphasis: Dyslipidemias and diabetes: Prevalence rates of cardiovascular disease are low among diabetic patients in populations with low levels of total and LDL cholesterol. Several studies have shown alterations in the levels and composition of lipid particles in diabetic subjects. In addition to the long recognized abnormalities such as elevated triglyceride and lowered HDL-cholesterol levels, numerous other abnormalities including changes in lipoprotein particle size and composition, protein glycosylation and oxidation of lipoproteins have recently been reported. While the basic lipid changes have been found in all populations studied, their magnitude varies considerably, both within groups and within individual diabetic patients, suggesting the effects of diabetes can be substantially modified by environmental or underlying genetic factors. The reasons some individuals and groups appear to be protected are unknown and represent a promising area for further investigations. Lipid metabolism is also an area where differences occur between Type I and Type II diabetic patients with more adverse alterations generally found in Type II diabetics. Hypertension and diabetes: Hypertension is more common in diabetic patients than in age-matched normoglycemics and its presence increases the risk of both micro- and macrovascular complications of diabetes. Many questions need further exploration in this area including the origins of the excess hypertension. The relationship of elevated blood pressure to subclinical renal disease and to the multiple CVD risk factor syndrome are promising areas for further investigation. In addition, recent studies have suggested that the choice of drugs to treat hypertension may be important in postponing both micro- and macrovascular complications of diabetes. The role of renal dysfunction and the significance of microalbuminuria as a predictor of both micro- and macrovascular disease needs to be evaluated. Hemostasis and diabetes: Several abnormalities in the coagulation system of diabetics have been identified. Abnormalities include changes in level and structure of coagulation factors, alterations in platelet function, and alterations in blood and plasma viscosity. Many of the studies are small and the techniques used for measurement were sometimes controversial. The associations among coagulation factors and other recognized CVD risk factors require clarification. This is one of the least explored areas of diabetes associated CVD risk, but potentially very important and much work remains to be done. Hyperglycemia, insulinemia, and insulin sensitivity and diabetes: These risk factors have generally been the province of diabetologists studying the development of diabetes but recent reports have suggested they may be independent cardiovascular disease risk factors. Critical questions center around the absolute and relative importance of each of these factors in the acceleration of atherosclerosis. If hyperglycemia is "atherogenic," then improved blood glucose levels should lead to a decrease in the risk of CVD. In contrast, if hyperinsulinemia is "atherogenic," improvement of blood glucose levels by intensive insulin treatment may reduce the risk of microvascular disease (as demonstrated in the DCCT) but might increase the risk of macrovascular disease. Treatment regimens may have different effects in Type I and Type II diabetic patients. Vascular biology: The past decade has produced major advances in the understanding of atherogenesis at the cellular and molecular level. It is now recognized that the vascular endothelium is a complex organ that senses its environment and responds in numerous ways to injury and to recognized CVD risk factors. Independently, major advances have occurred in understanding how diabetes produces modifications at the cellular and molecular level. Much less is known about how these diabetic modifications may interact with other atherogenic factors in the local environment of the vessel wall to initiate and propagate atherosclerotic plaques in diabetic patients. In fact, it is not known whether atherosclerosis in diabetics is simply a more rapidly progressing common atherosclerotic plaque or whether differences exist in its composition and in the pattern of cellular responses and gene expression. An area of particular opportunity is the study of the regulation of growth factor and cytokine expression by mildly oxidized low density lipoprotein and advanced glycosylation end products (AGEs). Genetic and Environmental Factors: Rates of diabetic macrovascular complications vary widely in different populations. For example, some American Indian tribes, despite extraordinary rates of diabetes, appear relatively protected against cardiovascular complications. Some potential explanations for these differences have been outlined above. Clarifying the effects of genetic and environmental factors on risk factor levels (and/or composition) and on the susceptibility of the vascular wall to atherosclerosis is of critical importance for the design of future preventive measures. In addition to improving understanding of the basic processes that lead to excess macrovascular disease in diabetic patients, a major goal of this initiative is to apply this information to human studies. This initiative will also provide support for limited clinical and population studies which can either enhance understanding of the pathophysiology of cardiovascular complications of diabetes or provide information important for developing new therapeutic interventions. Because of their cost, support for establishing new epidemiologic studies of populations or clinical trials to test reduction of disease risk cannot be provided through this initiative. The NHLBI has already established several large populations to study risk factors for cardiovascular disease. Many of these studies have collected information on glucose tolerance and historical information on diagnosis and treatment of diabetes. They include extensive characterization of CVD risk factors and assessments of clinical and subclinical cardiovascular disease, making it possible to describe risk factor patterns prior to their alteration by drug therapy or clinical disease. In addition, these studies include men and women and representatives of multiple racial and ethnic groups, providing an opportunity to look at the contrast in risk of cardiovascular complications among different diabetic groups. Overall, they represent a valuable resource for studies of cardiovascular complications in Type II diabetic patients. Other important populations have been identified and characterized with support from other funding sources. Some include substantial numbers of Type I diabetic patients. Investigators applying for support from this initiative are strongly encouraged to propose collaborative efforts with existing population studies since this will be the most efficient way to develop a clinical component. Investigators are free to propose other clinical components, especially if they offer unique advantages. To obtain further information on NHLBI supported population studies, contact Dr. Peter Savage at the address listed under INQUIRIES. It is anticipated that each program project will have several discrete subprojects conducted by several investigators under the overall direction of the Principal Investigator. Each application should include laboratory investigations and also include a clinical and/or population component. Studies initiated in one of these components should lead to application in the others. For example, lipid abnormalities described in a population study could be studied further in the laboratory using cell or animal models, then translated into small clinical trials of drug efficacy. Other examples could involve investigations of the effects of hyperinsulinemia or elevated insulin resistance that include studies of their effect on the isolated vascular wall lesion, induction of hyperinsulinemia in animal models, pharmacologic alteration of levels of insulin resistance in small clinical studies, and assessment of the relative importance of insulin and insulin resistance on other risk factors in population studies containing several racial or ethnic groups. Such examples are not meant to suggest specific studies, but to indicate the spectrum of research and type of collaboration that this initiative is designed to support. In most cases, human subjects will be selected from an existing population on the basis of previously measured evidence of clinical or subclinical disease or risk factor profiles. In many cases, such studies may be conducted on stored samples. For more complex tests requiring extensive subject participation or collection of additional samples, care must be taken to not interfere with the ongoing study. Existing policies in current multicenter population studies for approval and reporting of ancillary studies will apply. NHLBI Project Scientists will expedite the collaborative aspects of study design and will facilitate joint research with existing NHLBI funded studies, as appropriate. SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES 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 new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (concerning the Inclusion of Women in Study Populations, and concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research," which was reprinted in the Federal Register of March 28, 1994 (59 FR 14508-14513) to correct typesetting errors in the earlier publication, and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from the program staff or contact person listed below. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by January 2, 1996, 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 NHLBI staff to estimate the potential review workload and avoid conflict of interest in the review. Letters of intent may be sent by U.S. mail or by fax. The letter of intent is to be sent to: Dr. C. James Scheirer, Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: James_Scheirer@NIH.GOV Letter of Authorization To be considered for funding by the JDFI, applicants must submit a brief letter to the NHLBI indicating that they will allow their applications to be considered by the JDFI. All materials relating to the application will be promptly forwarded to the JDFI by NHLBI. The summary statements for such applications will be shared with the JDFI at the time of their availability. Letters of authorization should be prepared by the Principal Investigator and co-signed by the official signing for the applicant institution. This letter may be combined with the letter of intent or may be submitted directly to Dr. Savage or Dr. Robinson 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. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301-435-0714, email: girg@drgpo.drg.nih.gov. Applicants must follow the instructions provided in the RFA. The RFA label available 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, to identify the application as a response to this RFA, check "YES", enter the title, "Etiology of Excess Cardiovascular Disease in Diabetes Mellitus" and the RFA number HL-96-005 on Line 2 of the face page of the application. Send or deliver a signed, typewritten original of the application, including the checklist, and three signed photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) Send two additional copies of the application to Dr. James Scheirer, Chief, Review Branch, Centers and Special Projects Section at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants, otherwise the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by February 9, 1996. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, or 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 DRG and for responsiveness by the NHLBI. 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 in accordance with the review criteria stated below by an appropriate peer group convened by the NHLBI. 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 or board. Neither site visits nor reverse site visits are planned as a part of the review process. Therefore, each application should be complete on submission. Following the initial review group consideration, secondary review of applications will be conducted by the National Heart, Lung and Blood Advisory Council and the Juvenile Diabetes Foundation International Advisory Board. The criteria for review of applications will be those used regularly for the review of program project grant applications by the NHLBI. A complete and detailed description of these criteria is contained in "Program Project Grant: Preparation of the Application", NHLBI, US DHHS, August 1992, a copy of which may be obtained from Dr Scheirer at the address listed under LETTER OF INTENT. Awardees will be selected on the basis of the priority score of their individual applications, subproject scores, and the ability of that proposal to contribute to a comprehensive investigation of diabetic cardiovascular disease. Review criteria for RFAs are generally the same as those for unsolicited interdisciplinary research grant applications, and include: o the scientific merit of each proposed project in the application, including originality, feasibility of the approach, and adequacy of the experimental design; o the integration of the clinical and fundamental research into a coherent enterprise with adequate plans for interaction and communication of information and concepts among the collaborating investigators; o if applicable, the technical merit and justification of each core unit; o the qualifications, experience, and commitment of the Program Project Principal Investigator and his/her ability to devote adequate time and effort to provide effective leadership; o the competence of the subproject investigators to accomplish the proposed research goals, their commitment, and the time they will devote to the program; o the adequacy of facilities to perform the proposed research including the laboratory and clinical facilities, access to subjects, instrumentation, and data management systems when needed; o the scientific and administrative structure of the program, including adequate internal and external arrangements and procedures for monitoring and evaluating the proposed research and for providing ongoing quality control and scientific review; o the institutional commitment to the program and the appropriateness of the institutional resources and policies for the administration of a research program of the type proposed; and of the appropriateness of the budget for the proposed program. o Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. AWARD CRITERIA The most important criterion in selecting awardees will be the scientific merit as reflected in the priority score. However, factors such as program balance and available funds may enter into selection >From among meritorious applications. Applications must be received by February 9, 1996. An application not received by this date will be considered ineligible. Schedule Letter of Intent Receipt Date: January 2, 1996 Application Receipt Date: February 9, 1996 Initial Review: March/April 1996 Review by NHLB Advisory Council: June 1996 Review by JDFI Advisory Board: June 1996 Anticipated Award Date: June 28, 1996 INQUIRIES Inquiries regarding this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Peter J. Savage, M.D. Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 8154 Bethesda, MD 20892-7934 Telephone: (301) 435-0702 FAX: (301) 480-1667 Email: Peter_Savage@NIH.GOV David M. Robinson, Ph.D. Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive,, Room 10193, MSC 7956 Bethesda, MD 20892-7956 Telephone: (301) 435-0545 FAX: (301) 480-2849 Email: drw@cu.nih.gov Direct inquiries regarding fiscal and administrative matters to: Mr. William Darby Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7128 Bethesda, MD 20892-7926 Telephone: (301) 435-0177 FAX: (301) 480-3310 Email: William_Darby@NIH.GOV AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance number 93.387, Heart and Vascular Diseases. Awards are made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency Review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Dec 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-96-008 - V24(41) 12/01/95 Date: 5 Dec 1995 21:12:51 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 426 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <4a38oj$14t@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA96008 PA-96-008 P1O1 *************************************** EPIDEMIOLOGY OF LUNG CANCER: INTERDISCIPLINARY STUDIES NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA NUMBER: PA-96-008 P.T. 34; K.W. 0715035, 0785055, 0715165 National Cancer Institute National Institute of Environmental Health Sciences PURPOSE The Division of Cancer Epidemiology and Genetics of the National Cancer Institute (NCI) invites grant applications for innovative interdisciplinary studies to better understand the etiology of adenocarcinoma and small cell carcinoma of the lung and the means of prevention. 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), Epidemiology of Lung Cancer: Interdisciplinary Studies, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001000473-1) 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, research laboratories, units of State and local governments, eligible agencies of the Federal government, and small businesses. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. RESEARCH OBJECTIVES Background Lung cancer is now a leading cause of cancer death in industrialized countries and is rising in many developing countries. Thun et al. (1), who examined changes in smoking-specific death rates from the 1960s to the 1980s in the U.S. reported that lung cancer surpassed coronary heart disease as the largest single contributor to smoking-attributable death among White middle-class smokers. In 1930, the age-adjusted lung cancer death rate among U.S. males was about 5/100,000 per year; it rose to 55.9 in 1970 and to 74.9 in 1987. Among females in the U.S., the corresponding lung cancer death rates were 3.0, 12.2 and 28.5, respectively (2). In 1994, lung cancer accounted for an estimated 172,000 incident cases (100,000 males and 72,000 females) and 153,000 deaths (94,000 males and 59,000 females) (3). Cigarette smoking is the leading cause of lung cancer. While smoking cessation programs are critical to reduce the burden of lung cancer in our society, additional research is also warranted to clarify the reasons for changes in the distribution of the major histologic types during the last 40 years and gender and racial differences in risk. Our lack of understanding of the reasons for these patterns reflects the inadequacy of our knowledge of lung carcinogenesis at the histology-specific level. This level of understanding will also impact clearly on our ability to prevent the disease. Several investigators have reported on time trends. Vincent (4) found adenocarcinoma and squamous cell carcinoma to be the more common histologic types among lung cancer patients presenting to the thoracic surgery department of Roswell Park Memorial Institute between 1962 and 1975. Adenocarcinoma increased progressively from 17.6 percent of the total cases in 1962 to 29.8 percent by 1975, while squamous cell carcinoma represented 48.6 percent of the total cases in 1962 but decreased to 25.5 percent in 1975. Devesa et al. (5), reporting on changing patterns of lung cancer by histologic type for the period 1969-1986 for five geographic areas (Atlanta, Connecticut, Detroit, Iowa and San Francisco- Oakland) covering seven percent of the U.S. population, indicated that for all sex-race groups combined, age-adjusted incidence of lung cancer increased three percent per year from 38.6/100,000 person-years during 1969-71 to 58.4/100,000 person-years during 1984-86. The rate rose 25 percent among white men, about 50 percent among black men, and over 150 percent among both black and white women. Squamous cell carcinoma rates increased 50 percent or less among men and more than doubled among women. Adenocarcinoma and small cell carcinoma rates doubled among men and more than tripled among women. As a result, the histologic distribution of lung cancer changed over time. Squamous cell carcinoma remains the most common type among men. Among women, however, adenocarcinoma is the most frequent type; the rates of small cell carcinoma exceeds slightly those of squamous cell carcinoma among white women only. Recently, Travis et al (6) reported analyses of Surveillance, Epidemiology, and End Results (SEER) Program data on lung cancer for the period 1973-1987. The percentage of lung cancers that were adenocarcinoma in all race-sex groups combined increased to 32 percent, surpassing squamous cell carcinoma as the most frequently occurring histologic type. Squamous cell carcinoma, however, continues to constitute a large proportion (29 percent) of lung tumors. The race, gender and time patterns of adenocarcinoma and small cell carcinoma cannot be readily explained. It has been suggested that advances in techniques for establishing the diagnosis of lung cancer should be considered in interpreting temporal trends of incidence by histologic type. Changing patterns of classification by pathologists may also have influenced the reported increase in frequency of adenocarcinoma. Cigarette smoking is a stronger risk factor for squamous cell carcinoma and small cell carcinoma than for adenocarcinoma of the lung (5). Smoking intensity, duration, types of cigarette smoked, cessation, or different degree of susceptibility to carcinogens present in tobacco smoke may differentially affect the development of the various histologic types of lung tumors. Newer cigarettes containing lower amounts of tar, as determined by the Federal Trade Commission method, may be more harmful than older brands. Women may be at a higher elevated risk of lung cancer than men due to greater exposure to newer brands and/or to gender-related susceptibility (7,8). The greater lung cancer risk in blacks compared to that in whites may be due to racial differences in carcinogen metabolism or for reasons similar to those responsible for gender differences. Occupational determinants of lung adenocarcinoma have not been well investigated. Few studies have examined the differences in occupational risks for histologic types of lung cancer, but associations between occupations and specific histologic types have been suggested. Adenocarcinoma of the lung was elevated among carpenters, and cabinet and furniture makers (9). Occupational exposure to bischloromethyl ether (10) and radon (11) preferentially influence small cell carcinoma. With regard to diet, positive associations have been seen with lipid consumption, fat and cholesterol, and inverse associations with various carotenoids, vitamin C, and retinol, and with fruits and vegetables as a group (12). Immunologic and hormonal factors have been suggested to affect risk of adenocarcinoma (13,14), and familial patterns have been observed (15). Findings from a multicenter case-control study of lung cancer in nonsmoking women indicated an overall 30 percent increased risk associated with exposure to environmental tobacco smoke from a spouse, with a 50 percent elevated risk of lung adenocarcinoma (16). Other adult life exposures in household, occupational and social settings were each associated with a 40 to 60 percent increased risk of lung adenocarcinoma (16). Approximately half of all lung cancers among current nonsmokers could be attributed to a history of smoking, dietary intake of saturated fat, nonmalignant lung disease, environmental tobacco smoke, occupational exposures including asbestos, a family history of lung cancer and domestic radon (17). Thus half of the lung cancer incidence among nonsmokers remains unexplained. Research Scope and Goals The reasons for the increases in adenocarcinoma and small cell carcinoma of the lung in the U.S. remain to be fully explained. Changing diagnostic trends should be considered as one possible reason, and examined through standardized review of a sample series of cases that are representative of those occurring since the 1950s. There is a paucity of understanding of the environmental and host factors and the mechanisms of induction for specific types of lung cancer. In particular, further research is needed to elucidate the etiologic factors that influence the upwards time trends in lung adenocarcinoma and small cell carcinoma. The areas of research listed below are not intended to be all- inclusive, but are designed to give the applicant some direction for the types of research that the NCI is interested in stimulating to enhance knowledge about the etiology of lung adenocarcinoma and small cell carcinoma and means for their prevention. 1. Epidemiologic studies of lung adenocarcinoma and/or small cell carcinoma in smokers, with detailed collection of tobacco use data, assessment of risk modifiers, and evaluation of susceptibility factors; pooled analysis of existing data sets for lung adenocarcinoma and small cell carcinoma; studies of non- tobacco environmental/occupational exposures and lung adenocarcinoma and small cell carcinoma risk. 2. Studies of host susceptibility factors in relation to lung cancer type, such as P450 expression/polymorphisms, glutathione S-transferase enzymes, hormonal factors, and diet. 3. Studies of the molecular mechanisms of lung adenocarcinoma and/or small cell carcinoma in laboratory animals and humans to assess the role of novel oncogenes or tumor suppressor genes; investigation of carcinogen metabolic activation and detoxification in human pulmonary cells; development of biomarkers of chemicals in tobacco products, in the general environment or in occupational settings that induce lung adenocarcinoma, and small cell carcinoma, including DNA adducts. Consideration should also be given to DNA adduct repair in human pulmonary cells. 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- sponsored 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 new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women and Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research," which was reprinted in the Federal Register on March 28, 1994 (59 FR 14508-14513) to correct typesetting errors in the earlier publication, and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from the program staff or contact person listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) 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 may be obtained from Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301-435-0714. The completed original application and five legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD, 20817 (for courier/overnight service) REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened 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 or board. Review Criteria o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. 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 subjects and animal welfare and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to the NCI. 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. INQUIRIES Inquiries are encouraged, particularly during the planning phase of the grant applications. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. A.R. Patel Division of Cancer Epidemiology and Genetics National Cancer Institute 6130 Executive Boulevard, Suite 535, MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 FAX: (301) 402-4279 Email: Jasonc@EPNDCE.NCI.NIH.GOV Dr. Gwen W. Collman Chemical Exposures and Molecular Biology Branch National Institute of Environmental Health Sciences P.O, Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-4980 FAX: (919) 541-2843 Email: collman@niehs.nih.gov Direct inquiries regarding fiscal matters to: Mr. E. C. Melvin Grants Administration Branch National Cancer Institute Executive Plaza South 6120 Executive Boulevard, Suite 243, MSC 7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, EXT 258 FAX: (301) 496-860 David L. Mineo Grants Management Branch National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-7628 FAX: (919) 541-2860 Email: MELVINE@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.393. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-140, as amended by Public Law 99.158, 42 USC 241 and 285) and administered under HHS policies and grant regulations. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health System Agency review. The Public Health Service (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. References: 1.Thun, M.J., Day-Lally, C.A., Calle, E.E., et al. Excess mortality among cigarette smokers: changes in a 20-year interval. Am. J Public Health, 85: 1223-1230, 1995. 2. Wynder, E.L. and Hoffmann, D. Smoking and lung cancer: scientific challenges and opportunities. Cancer Res., 54: 5284- 5295, 1994. 3. Boring, C.C., Squires, T.S., Tong, T., et al. Cancer statistics, 1994. Ca. Cancer J. Clin., 44: 7-26, 1994. 4. Vincent, R. G., Pickren, J.W., Lane, W.W. et al. The changing histopathology of lung cancer: a review of 1682 cases. Cancer, 39: 1647-1655, 1977. 5. Devesa, S. S., Shaw, G.L., and Blot, W.J. Changing patterns of lung cancer by histologic type. Cancer Epidemiol., Biomarkers Prev., 1: 29-34, 1991. 6. Travis, W.D., Travis, L.B., and Devesa, S.S. Lung cancer. Cancer, 75: 191-202, 1995. 7. Risch, H.A., Howe, G.R., Jain, M., et al. Are female smokers at higher risk of lung cancer than male smokers? A case-control analysis by histologic type. Am. J. Epidemiol., 138: 281-293, 1993. 8. Harris, R.E., Zang, E.A., Anderson, J.I., et al. Race and sex differences in lung cancer risk associated with cigarette smoking. Int. J. Epidemiol., 22: 592-599, 1993. 9. Zahm, S.H., Brownson, R.C., Chang, J.C., et al. Study of lung cancer histologic types, occupation and smoking in Missouri. Am. J. Ind. Med., 15: 565-578, 1989. 10. Pasternack, B.S., Shore, R.E., and Albert, R.E. Occupational exposure to chloromethyl ethers. J. Occup. Med., 19: 741-746, 1977. 11. Samet, J.M. Radon and lung cancer. J. Natl. Cancer Inst., 81: 745-757, 1989. 12. Patel, A.R. and Obrams, G.I. Meeting Report: Adenocarcinoma of the lung. Cancer Epidemiol., Biomarkers Prev., 4: 175-180, 1995. 13. Fraumeni, J.F. Jr., Wertelecki, W., Blattner, W.A., et al. Varied manifestations of a familial lymphoproliferative disorder. Am. J. Med., 59: 145-151, 1975. 14. Gao, Y.T., Blot, W.J., Zheng, W., et al. Lung cancer among Chinese women. Int. J. Cancer, 40: 604-609, 1987. 15. Mulvihill, J.J. Host factors in human lung tumors: an example of ecogenetics in oncology. J. Natl. Cancer Inst., 57: 3-7, 1976. 16. Fontham, E. T. H., Correa, P., Wu-Williams, A., et al. Lung cancer in nonsmoking women: a multicenter case-control study. Cancer Epidemiol., Biomarkers Prev., 1: 35-43, 1991. 17. Alavanja, M.C.R., Brownson, R.C., Benichou, J., et al. Attributable risk of lung cancer in lifetime nonsmokers and long-term exsmokers. Cancer Causes and Control, 6: 209-216, 1995. From owner-sci-resources@net.bio.net Tue Dec 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-96-006 - V24(41) 12/01/95 Date: 5 Dec 1995 21:12:14 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 612 Sender: daemon@net.bio.net Approved: BIOSCI Administrator Distribution: world Message-ID: <4a38ne$12i@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HL96006 HL-96-006 P1O1 *************************************** SLEEP ACADEMIC AWARD NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA: HL-96-006 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 29, 1995 Application Receipt Date: March 12, 1996 THIS RFA USES "JUST-IN-TIME" PROCEDURES. THIS RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE FOLLOWED WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS RFA. PURPOSE The primary objective of this initiative is to encourage the development and/or improvement of the quality of medical curricula, physician/patient/nurse and community education, and clinical practice for the prevention, management, and control of sleep disorders. A secondary objective is to promote high quality clinical research on sleep. 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 RFA, Sleep Academic Award, is related to the priority areas of heart disease and stroke, diabetes, chronic disabling conditions, mental health and disorders, and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Institutions Applications may be submitted by any domestic university or school of medicine or osteopathy. In this competition, there is a special interest in institutions sponsoring candidates experienced in medical education and sleep and clinical sleep research. Also, minority institutions and institutions with eligible minority faculty members are encouraged to apply. Candidates A candidate for an award must: o Individuals who have or have had another NIH career development award (K series) or a regular research grant (R01) are eligible for a Sleep Academic Award if the individual meets the requirements of the Sleep Academic Award program. Applications from minority individuals and women are encouraged. o have knowledge and skills in sleep and sleep disorders medicine; o be an established member of a medical faculty in an accredited school of medicine or osteopathy in the United States, its territories, or its possessions; o have had formal clinical research training or post graduate clinical research training; o have had experience and sufficient training in clinical sleep research, clinical practice, and/or medical education to develop and implement a high quality curriculum in sleep and sleep disorders and provide leadership in clinical research on sleep; o have the unqualified support of the Dean and the educational leadership at the institution and demonstrate knowledge and commitment to medical education for medical students, physicians, patients, nurses, and the public; o be a citizen or non-citizen national of the United States or have been lawfully admitted to the United States for permanent residence at the time of application. MECHANISM OF SUPPORT This RFA is part of the Academic Award Program (K07) of the National Heart, Lung, and Blood Institute. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years and is non-renewable. Awards will be limited to a maximum of $62,500 for the salary of the Principal Investigator, plus applicable fringe benefits, and a maximum of $20,000 for technical support. Indirect costs may not exceed 8 percent. It is anticipated that support for this program will begin September 30, 1996. Application instructions have been modified to implement "just-in- time" streamlining efforts being considered by the NIH. This requires an applicant to submit certain information only when and if it is likely that an award will be made. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers, and NHLBI staff. For this RFA, no budgetary information is required in the application. However, the anticipated level of effort in all years and a brief description of responsibilities for the Principal Investigator and key personnel must be included in the research plan. In addition, instructions for completing the Biographical Sketch have been modified and no "Other Support" information or "Checklist" page is required in the initial application. If an award is likely, necessary budget, Other Support, and Checklist information will be requested by NHLBI staff. The SPECIAL REQUIREMENTS section of this RFA provides specific modifications to the instructions in the PHS 398 application kit. FUNDS AVAILABLE The estimated funds (total costs) available for this program for fiscal year 1996 will be $300,000. It is anticipated that three to four new grants will be awarded in FY 96 and in each of the next two years through an additional competition in each of fiscal years 1997 and 1998. The actual number each year, however, will depend upon the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background Recent estimates suggest that as many as 40 million people may suffer >From chronic or intermittent disorders of sleep. Many remain undiagnosed and untreated, the consequences of which include reduced productivity, lowered cognitive performance, increased likelihood of accidents, higher risk of morbidity and mortality, and decreased quality of life. It is now apparent that sleep disorders, disturbances of sleep, and sleep deprivation are major public health concerns. Sleep problems occur in both genders, in all races and socioeconomic groups, and increase with age. National attention has been directed to this problem. The National Commission on Sleep Disorders Research submitted their report entitled "Wake Up America: A National Sleep Alert" to the United States Congress in January 1993. The Commission's recommendations include encouraging broader awareness of sleep and training about sleep and the diagnosis and treatment of sleep disorders, spanning the full range of health care professions, particularly at the primary care level. Several surveys have documented that physician training and knowledge about sleep and sleep disorders is minimal. For example, in 1978, the American Sleep Disorders Association (ASDA) conducted a survey of medical school curricula and found that about one third of the medical schools provided one to four hours within the curricula for teaching about sleep. A more recent (1990) survey found that less than two hours were allocated to teaching about sleep at one third of the medical schools and one third of the medical schools reported no formal teaching about sleep. It was estimated that about 30 percent of all medical students receive no instruction about sleep. These results would suggest that there actually has been a decrease in the amount of medical school training about sleep. The American Thoracic Society (ATS) surveyed pulmonary residency training programs and found that 70 percent had laboratories, but only 29 percent had formal training programs about sleep. Of greater concern was that 90 percent of the trainees diagnosed patients with sleep apnea, but only 33 percent had any formal training on how to conduct sleep studies. The major obstacles cited for increasing the attention to sleep in medical schools included low administrative priority, lack of qualified faculty, and limited curriculum time. Given the limited medical school training about sleep and sleep disorders, it is not surprising that