From owner-sci-resources@net.bio.net Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-95-074 - V24(24) 06/30/95 Date: 3 Jul 1995 14:59:23 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 413 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p7r$ajv@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA95074 PA-95-074 P1O1 *************************************** AGING, VASCULAR STIFFNESS, AND CARDIOVASCULAR FUNCTION NIH GUIDE, Volume 24, Number 24, June 30, 1995 PA NUMBER: PA-95-074 P.T. 34; K.W. 0710010, 0715040, 0411005 National Institute on Aging PURPOSE The purpose of this program announcement (PA) is to foster research that will enhance our understanding of vascular stiffness in aging and in cardiovascular disease. Ascertaining the importance of vascular stiffness, as a risk factor for cardiovascular morbidity and mortality, may suggest approaches to prevention and treatment including early modification of risk factors and/or adverse lifestyles to prevent, delay, and/or reverse vascular stiffening and its potential deleterious sequelae as well as novel treatment in persons with established stiffness or cardiac disease. The Geriatrics Program, National Institute on Aging (NIA), invites grant applications on clinically-relevant research focusing on aging and vascular stiffness. 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, Aging, Vascular Stiffness, and Cardiovascular Function, is related to the priority area of heart disease and stroke. 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 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC Program Director or Principal Investigator should be included with the application. MECHANISM OF SUPPORT This program will use the NIH investigator-initiated research project grant (R01) and FIRST (R29) award mechanisms. The total project period for an application submitted in response to this program may not exceed five years. Because the nature and scope of the research proposed in response to this program may vary, it is anticipated that the size of awards will vary as well. It is not the intent of this program to encourage submission of large, multi-center, clinical trials. Awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 94-50,000 (rev. 4/1/94). RESEARCH OBJECTIVES Background Cardiovascular diseases are the most common cause of death among the elderly and the percentage of deaths due to these diseases increases significantly with age throughout the later years of life. Age is the main risk factor for cardiovascular diseases, including heart attacks and stroke. Age-related changes in cardiac function, circulatory hemodynamics, blood pressure regulation, and lipid metabolism all contribute significantly to morbidity and mortality in the elderly. Although age is a potent risk factor for high blood pressure, stroke, coronary artery disease, and heart failure, the precise reasons for this observation are presently unknown. Other than age per se, a potential risk factor that may underlie cardiovascular morbidity in the elderly is a stiffening of the large and medium-sized elastic arteries (e.g., the aorta). Arterial stiffening increases during aging in healthy persons and is accompanied by an elevation in systolic blood pressure, within the normal range, which averages 25-35 mm Hg between the third and eighth decades of life. In approximately half of older Americans age 65 and beyond, the degree of vascular stiffening may become large enough to lead to the development of isolated systolic hypertension (defined as a systolic blood pressure of 140 mm Hg or greater and a diastolic blood pressure less than 90 mm Hg). This observation is important because high blood pressure is the major risk factor for stroke and is also an important independent risk factor for coronary artery disease, myocardial infarction, and heart failure in older Americans regardless of gender or racial/ethnic background. The increased arterial pressure (i.e., increased afterload) may affect cardiac function in aging. For example, the moderate increase in left ventricular mass in many individuals observed between the third and ninth decades of life may, in part, be mediated by the increased arterial pressure and/or vascular stiffness. Importantly, left ventricular hypertrophy represents a major independent risk factor for morbid cardiovascular events including myocardial infarction and cardiac death. According to The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, African Americans have one of the highest frequencies of high blood pressure in the world. The Third National Health and Nutrition Examination Survey (NHANES III) reports that in non- Hispanic blacks, age 60 and older, high blood pressure is present in approximately 71 percent of the population. Moreover, in comparison to whites, high blood pressure in African Americans is earlier in onset and of greater severity at any decade of life. As a result, African Americans have a greater rate of stroke, heart disease, and end-stage renal disease than whites. Yet, the importance of vascular stiffening during aging, in contributing to the development of these morbid cardiovascular events in African Americans is currently unknown. Taken together, the available data suggest that vascular stiffening may be implicated in the etiology and progression of several cardiovascular disorders that affect a high proportion of older Americans regardless of gender or racial/ethnic background. Vascular stiffening has been considered a part of "normal" aging and neither treatment for increased arterial stiffness nor lifestyle modification nor pharmacologic intervention has been advocated to blunt vascular stiffening and its potential deleterious sequelae. Recent data from the literature, including data from the Baltimore Longitudinal Study of Aging (BLSA) suggest that measurement of aortic pulse wave velocity (i.e., the speed of transmission with which the arterial pulse wave is propagated down the arterial tree) and applanation tonometry (i.e., measurement of late systolic amplification of the carotid artery pressure pulse) are important markers for age-associated changes in vascular stiffness. In a normotensive, carefully screened, healthy population of BLSA volunteers (age range: 21-90), increasing age is associated with progressive vascular stiffening. Importantly, at any age, men and women who have higher aerobic capacity (as indexed by maximal oxygen consumption during exercise), demonstrate lower vascular stiffness than their less aerobically fit peers. Moreover, when compared to their untrained age matched peers, endurance trained older men demonstrate a markedly lower arterial stiffness. These data suggest an important inverse relationship between maximal oxygen consumption and vascular stiffness and also imply that physical conditioning to improve aerobic capacity in older Americans may blunt the arterial stiffening that accompanies aging (Vaitkevicius et al., Circulation 88 (part 1): 1456-1462, 1993). Other ongoing collaborative studies suggest that novel pharmacologic therapy (vasodilators) in older subjects, by decreasing central arterial stiffness, eliminates the age- associated difference in cardiac volumes and ejection parameters seen in older versus younger individuals during maximal exercise. Thus, pharmacologic therapy may have potential for improving both vascular stiffness and cardiac performance in older persons. In other clinical studies, data have accumulated suggesting that differences in chronic dietary salt intake may affect vascular stiffness. In a rural Chinese population who consume approximately 50 percent less salt than an urban Chinese population with a higher prevalence of high blood pressure, arterial pulse wave velocity is consistently lower and increases by a smaller amount with age when compared to the urban group. Moreover, arterial pulse wave velocity is lower in rural group subjects, as compared to age-matched urban group subjects with the same arterial pressure (Avolio et al. Circulation 71: 202-210, 1985). In a different study population, normotensive adult volunteers who follow a low salt diet for an average of two years demonstrate a reduced vascular stiffness, as indexed by arterial pulse wave velocity, when compared to age- and arterial pressure-matched control subjects consuming a regular salt diet (Avolio et al. Arteriosclerosis 6:166-169, 1986). Collectively, these data suggest that differences in dietary salt intake may affect vascular stiffness and moreover, that the effect of salt may be independent of arterial pressure. Thus, modification of diet may also prove beneficial in altering age-associated increases in vascular stiffness. Another focus of this program is to stimulate research on the development of new indices of vascular stiffness and how these new indices compare to well established indices currently in use. Although arterial pulse wave velocity methodology is well established, reproducible, easy to use, and amenable to study in humans due to its non-invasiveness it does, like any other methodology, have its limitations. Ultrasound imaging has gained popularity as a more direct measure of vascular stiffness but suffers >From having the requirement to also measure arterial blood pressure changes concurrently from a different vascular site. It has been suggested that future progress in this field may require a consensus for the best overall measurement of vascular stiffness, including comparisons among various methodologies (both indirect and direct) in prospective clinical studies (Arnett et al., Am. J. Epidemiol. 140(8): 669-682, 1994). This program is particularly interested in the development of new non-invasive measures of aortic impedance. Ascertaining the importance of vascular stiffening in aging, and its potential as a risk factor for cardiovascular morbidity and mortality in older persons, may lead to development of preventive strategies (e.g., early modification of risk factors and adverse lifestyles through exercise and diet interventions) or new therapeutic strategies (e.g., novel pharmacologic therapy) to prevent, delay, and/or reverse vascular stiffening in aging and its potential deleterious sequelae. The potential public health benefit of treating age-associated vascular stiffening, in terms of both cost savings and improving the quality of life of older Americans, may be considerable. Objectives The NIA encourages submission of clinically-relevant research projects on vascular stiffening and the potential for vascular stiffening as a risk factor for cardiovascular morbidity and mortality in aging persons. Topics of interest include, but are not limited to: o Relationship between changes in vascular stiffness, arterial blood pressure, and cardiovascular function with age in heterogenous populations including women and ethnic/minority subgroups; o Relationship between vascular stiffness, arterial blood pressure, and cardiac structure/function including left ventricular mass and ejection parameters (i.e., systolic function) in older populations; o Relationship between vascular stiffness, arterial blood pressure, and diastolic dysfunction in older populations with normal systolic function; o Role of interventions including aerobic exercise, novel pharmacologic agents, dietary modification, and/or smoking cessation in modifying vascular stiffening (and the rate of increase in stiffening), arterial blood pressure, and cardiac performance in older populations; o Importance of vascular stiffness as a predictor of morbid cardiovascular events in aging populations including hypertension, atherosclerosis, stroke, coronary heart disease, and heart failure; o Relationship between vascular stiffness, arterial blood pressure, atherogenic lipoproteins, and susceptibility to atherosclerosis in aging persons; o Physiologic, nutritional, and genetic risk factors affecting the rate of increase in vascular stiffening with age in humans; o Clinico-pathologic studies relating clinical measurements of vascular stiffness to tissue properties of autopsy material or other specimens; o Development of new indices of vascular stiffness; and o Comparisons between established indices of vascular stiffness and newly developed indices in the same study population of older persons. These topics are neither prioritized nor meant to be restrictive. Investigators are encouraged to submit applications in any meritorious area of research responsive to the general research objectives of this program. 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 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 the Grants Information Office, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Suite 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301-435-0714. The title and number of this program announcement must be typed in Section 2a on the face page of the application. Applications for the FIRST (R29) award must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) award applications submitted without the required number reference letters will be considered incomplete and will be returned without review. 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 20817-7710 (for express/courier service) REVIEW CONSIDERATIONS Applications will be assigned on the basis of established Public Health Service 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. Review Criteria o Scientific, technical, or medical significance and originality of the 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 the resources necessary to perform the research; o Appropriateness of the proposed budget and duration in relation to the proposed research; o Adequacy of the provisions for the protection of human and animal subjects and safety of the research environment; and 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 Scored applications will compete for available funds with all other scored applications assigned to that Institute/Center. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review; o Availability of funds; and o Program balance among research areas of the program announcement. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Andre J. Premen, Ph.D. Geriatrics Program National Institute on Aging Gateway Building, Suite 3E327 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-6761 FAX: (301) 402-1784 Email: PremenA@gw.nia.nih.gov Direct inquires regarding fiscal matters to: Mr. Joseph Ellis Grants and Contracts Management Office National Institute on Aging Gateway Building, Suite 2N212 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: EllisJ@gw.nia.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866. 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, USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AA-95-005 - V24(24) 06/30/95 Date: 3 Jul 1995 14:59:20 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 489 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p7o$ajl@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA AA95005 AA-95-005 P1O1 *************************************** ROLE OF TOBACCO DEPENDENCE IN ALCOHOLISM TREATMENT NIH GUIDE, Volume 24, Number 24, June 30, 1995 RFA: AA-95-005 P.T. 34; K.W. 0404003, 0404001, 0404019, 0745070 National Institute On Alcohol Abuse And Alcoholism Letter of Intent Receipt Date: October 18, 1995 Application Receipt Date: November 21, 1995 PURPOSE The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research applications to study the alcohol tobacco interaction in its implications for alcoholism treatment. The objective of this RFA is to encourage research that will lead to improved strategies for treating alcohol and nicotine dependence in patients receiving care for problem drinking. Such research may identify and test relevant clinical intervention strategies; identify interactions between the two substances that have implications for relapse prevention, or further understanding of the alcoholism treatment process by investigating reinforcement mechanisms underlying conjoint abuse of the two substances. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), is related to the priority areas of alcohol abuse reduction and alcoholism treatment. 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 202-783-3238). ELIGIBILITY 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Foreign applicants are not eligible for First Independent Research Support and Transition (FIRST) (R29) Awards. MECHANISM OF SUPPORT Research support may be requested through applications for a regular research project grant (R01), FIRST Award (R29), exploratory/developmental grant (R21), and small grant (R03). An applicant for an R01 may request support for up to five years. In FY 1995, the average total cost per year for new R01s funded by the NIAAA was approximately $200,000. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. FIRST Award applications must be for five years. Total direct costs for the five-year period may not exceed $350,000 or $100,000 in any one budget period. Small grants (R03) and exploratory/developmental grants (R21) are limited to two years for up to $50,000/year and $70,000/year, respectively, for direct costs. FIRST Awards, small grants and exploratory/developmental grants cannot be renewed, but grantees may apply for R01 support to continue research on the same topics. Potential applicants for FIRST Awards (R29), small grants (R03), and exploratory/developmental grants (R21) should obtain copies of the specific announcement for these programs from the National Clearinghouse for Alcohol and Drug Information, P.O. Box 2345, Rockville, MD 20852, telephone (301) 468-2600 or 1-800-729-6686. Investigators submitting applications that exceed $500,000 for direct costs in any one year must contact program staff prior to submitting an application. Applicants may also submit applications for Investigator-Initiated Interactive Research Project Grants (IRPG) (refer to PA-94-086, Vol. 23, No. 28, July 29, 1994). Interactive Research Project Grants require the coordinated submission of related research project grants (R01) and, to a limited extent, FIRST Award (R29) applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of, for example, ideas, data, and materials among the collaborating investigators. A minimum of two independent investigators with related research objectives may submit concurrent, collaborative, cross-referenced individual R01 and R29 applications. Applicants may be from one or several institutions. Further information on these and other grant mechanisms may be obtained from the program staff listed under INQUIRIES. FUNDS AVAILABLE It is estimated that $2 million in total costs will be available to support approximately 8 to 10 grants under this RFA. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plan of NIAAA, the award of grants pursuant to this RFA is also contingent upon the availability of funds. The earliest possible award date is July 1, 1996. RESEARCH OBJECTIVES Background Behavioral Research During the past decade many lines of converging data have suggested that alcohol and tobacco consumption are correlated. For example, smokers consume two times as much alcohol per capita as do non- smokers (Carmody et al., 1985) and their risk of excessive drinking is also twice that of non-smokers, a relationship that holds across a broad range of demographic variables (Henningfield et al., 1990; Johnson and Jennison, 1992). Alcoholism itself is estimated as 10 to 14 times more prevalent among those who smoke than those who do not (DiFranza and Guerrera, 1990). In addition, heavy drinking tends to be associated with heavy smoking with 85 percent of currently drinking alcoholics smoking daily. Although smoking has substantially declined in the United States to approximately 30 percent of adults it has diminished very little among alcoholics. Co-occurrence of smoking and excessive drinking has important treatment implications. For example, previous or current problems with alcohol and alcohol treatment bodes negatively for success in smoking cessation (Bobo et al., 1987; DiFranza and Guerrera, 1990; Sandor, 1991). On the other hand, smoking cessation prior to formal alcoholism treatment (Miller et al., 1983) appears to improve subsequent drinking outcome. Conversely, reducing drinking appears to improve the prospects for successful smoking cessation (Burling et al., 1982). Curiously, participation in a stop-smoking program conducted during the course of alcoholism treatment was found to enhance maintenance of sobriety, even though the intervention had little impact on smoking behavior itself (Burling et al., 1991). Discontinuation of smoking and long-term abstinence from drinking are also associated. Alcoholics who maintain sobriety longer have been reported as more successful in smoking cessation (Bobo et al., 1987; Hughes, 1993). Similarly, relapse to drinking may prompt smoking relapse (Shiffman et al., 1985; Sees and Clark, 1993). Several pharmacologic and behavioral mechanisms have been proposed to explain the association between smoking and drinking. At a pharmacologic level some degree of cross-tolerance seems to occur between nicotine and alcohol as sympathetic nervous system agents, each of which has both depressant and stimulant effects. Second, conjoint use of the two substances may also be due to accelerated metabolism of one substance following ingestion of the other. Third, nicotine and alcohol may somewhat counteract the aversive effects of each other, while potentiating reinforcing effects. Basic Science Administration of both alcohol and nicotine together to laboratory animals alters the responses to either drug when administered alone. For example, prior exposure to a low dose of nicotine increases alcohol consumption, whereas a high dose decreases consumption (Gauvin, Morre and Holloway, 1993). Animals respond more for lateral hypothalamic stimulation after nicotine treatment and less after ethanol treatment, compared to controls (Schaefer and Michael, 1992). However, when both agents are given together, responding is higher than after nicotine alone suggesting that alcohol is enhancing the reinforcing properties of nicotine. In discriminative stimulus studies, nicotine enhances the alcohol-like effects of nicotine in alcohol-preferring rats compared to non-preferring rats (Gordon, Meehan and Schecter, 1993). Further evidence of interactions between alcohol and nicotine derives >From comparative sensitivity and cross-tolerance studies suggesting that the sensitivities to alcohol and nicotine are related. Mice selectively bred for alcohol sensitivity are also more sensitive to nicotine compared to alcohol-insensitive mice. In addition, alcohol- sensitive mice rendered tolerant to alcohol are also tolerant to nicotine (de Fiebre and Collins, 1993; Luo, Marks and Collins, 1994 and Majchrzak and Dilsaver, 1992) and nicotine-tolerant, alcohol- sensitive mice display cross-tolerance to alcohol (Collins et al., 1993). These effects are not observed in alcohol-insensitive mice. In other studies, nicotine can antagonize the motor incoordinating effect of alcohol (Dar and Bowman, 1994), whereas a nicotinic receptor antagonist partially blocks increased locomotor activity induced by alcohol (Blomqvist, Soderpalm and Engel, 1992). To better understand the treatment implications of alcohol and tobacco co-dependence, it is necessary to determine the mechanism of interaction of these two agents and how the actions are modified when both drugs are co-administered. Several lines of evidence suggest that although alcohol and nicotine have different molecular structures, they have actions in common. For example, both substances stimulate the release of dopamine in the nucleus accumbens, (Imperato and Di Chiara, 1986a, 1986b) an area of the brain involved with the reinforcing properties of drugs. A role for dopamine is also suggested by the observation that blockade of dopamine receptors increases both alcohol and nicotine intake (Gauvin, et al, 1993; Dawe et al, 1995) . Acetaldehyde is a pyrolysis product of tobacco and has been suggested to play a role in the reinforcing effects of alcohol. The rapid transport of acetaldehyde in an unmetabolized and undiluted form from the lungs through the heart to the brain may enhance the reinforcing properties of smoking. Areas of Research Interest The following list of topics is intended only to illustrate NIAAA interests; topics not specified should not be viewed as excluded from consideration. The primary objective of the RFA is to enhance the efficacy of treatment for nicotine addicted, alcohol dependent patients. To that end, research studies are solicited in the following areas. Research is needed to determine the conditions under which tobacco use serves as a salient risk factor for alcohol relapse. Research suggests several hypothesized mechanisms for the linkage in conjoint alcohol-tobacco use. Studies are needed to more clearly specify these putative mechanisms and understand their interactions. Studies are needed that identify the optimal sequencing of alcohol and smoking cessation in treatment programs. Studies are needed that investigate the use of new/existing pharmacologic agents as adjuncts to alcohol and smoking cessation and in the maintenance of abstinence. Our understanding of treatment issues would be advanced by the identification of the cellular and molecular mechanisms that underlie initiation, maintenance and relapse in conjoint alcohol and tobacco consumption. Studies that seek to advance the transfer of basic research findings toward treatment intervention applications are expressly encouraged. Research is needed that elucidates factors that underlie the joint vulnerability to alcohol and nicotine dependence. Research is needed to develop common assessment methodologies for alcohol and tobacco dependence that will lead to improved treatment efficacy. Research is needed to determine the extent to which alcohol acts through nicotinic receptors and other receptors and whether chronic nicotine exposure can alter those actions. Research is needed using gene knockout technology against the nicotinic receptor, examine the interactions of alcohol and nicotine. Studies are needed that clarify the nature of the discriminative stimuli for alcohol and nicotine and how these stimuli interact. Studies are needed to determine whether conditioned cues associated with smoking enhance alcohol reinforcement. Studies are needed that assess the role of acetaldehyde in alcohol- nicotine interactions. 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 affect 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 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. LETTER OF INTENT Prospective applicants are asked to submit, by October 18, 1995, 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 of title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIAAA staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: RFA: AA-95-005 Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 409 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 FAX: (301) 443-6077 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; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892, telephone 301-435-0714; and from the NIAAA program administrators listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Page limits and limits on size of type are strictly enforced. Applications for the FIRST award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST award (R29) applications submitted without the required number reference letters will be considered incomplete and will be returned without review. Submit 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 mail) At the time of submission, two additional copies of the application must also be sent to: Mark Green, Ph.D. Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 409 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 (20852 for express mail) Applications must be received by November 21, 1995. If an application is received after that date, it will be returned to the applicant without review. 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, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must be prepared as a revised application and include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and for responsiveness by the NIAAA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, DRG staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Institute in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non- competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. The second level of review will be provided by the appropriate National Advisory Council or Board. Review Criteria Criteria to be used in the scientific and technical merit review of alcohol research grant applications will include the following: 1. The scientific, technical, or medical significance and originality of the proposed research. 2. The appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research. 3. The adequacy of the qualifications (including level of education and training) and relevant research experience of the principal investigator and key research personnel. 4. The availability of adequate facilities, general environment for the conduct of the proposed research, other resources, and collaborative arrangements necessary for the research. 5. The reasonableness of budget estimates and duration in relation to the proposed research. 6. 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. 7. Where applicable, the adequacy of procedures to protect or minimize effects on human and animal subjects and the environment. The review criteria for Small Grants (R03), Exploratory/Developmental Grants (R21), and FIRST Awards (R29) are contained in their program announcements. AWARD CRITERIA Applications recommended for approval by the National Advisory Council on Alcohol Abuse and Alcoholism will be considered for funding on the basis of the overall scientific and technical merit of the proposal as determined by peer review, NIAAA programmatic needs and balance, and the availability of funds. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding treatment aspects of proposed research to: Joanne Fertig, Ph.D. Division of Clinical and Prevention Research National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 402 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-0796 FAX: (301) 443-8744 Email: jfertig@willco.niaaa.nih.gov Direct inquiries regarding the neuroscience and behavioral aspects of proposed research to: Walter Hunt, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 402 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-4223 FAX: (301) 594-0673 Email: whunt@willco.niaaa.nih.gov Direct inquiries regarding fiscal matters to: Joseph Weeda Office of Planning and Resource Management National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 504 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-4703 FAX: (301) 443-3891 Email: jweeda@willco.niaaa.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.273. Awards are made under the authorization of the Public Health Service Act, Sections 301 and 464H, and administered under the PHS policies and Federal Regulations at Title 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing 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 Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-95-073 - V24(24) 06/30/95 Date: 3 Jul 1995 14:59:15 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 548 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p7j$ajb@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA95073 PA-95-073 P1O1 *************************************** MECHANISMS OF ADOLESCENT ALCOHOL ABUSE AND ALCOHOLISM NIH GUIDE, Volume 24, Number 24, June 30, 1995 PA NUMBER: PA-95-073 P.T. 34; K.W. 0404003, 0403001, 0705048 National Institute on Alcohol Abuse and Alcoholism PURPOSE The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research grant proposals to conduct basic research, using animal models and state-of-the-art imaging techniques in humans, to identify the neurobiological, physiological, and genetic factors that lead to adolescent alcohol abuse and dependence. Despite the fact that alcohol use is high among secondary school students, relatively few studies to date define the neurobiologic and physiologic mechanisms of high alcohol intake or the effects of excessive drinking in adolescents. Studies of neurobiologic mechanisms and risk factors for alcoholism during late childhood through adolescence would increase our ability to predict which individuals will be most likely to develop alcoholism early in life. In addition, evaluation of the effects of alcohol ingestion during postnatal development, particularly during adolescence, would further our understanding of alcohol's immediate consequences and the contribution of early alcohol exposure to excessive drinking and abnormal cognitive and social functioning during subsequent developmental stages. Finally, results obtained will help develop strategies for treatment and prevention of adolescent alcohol abuse and alcoholism. 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, Mechanisms of Adolescent Alcohol Abuse and Alcoholism, is related to the priority area of alcohol abuse and alcoholism. 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 202-783-3238) ELIGIBILITY Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). MECHANISM OF SUPPORT Research support may be requested through applications for a regular research project grant (R01), FIRST Award (R29), exploratory/developmental grant (R21), and small grant (R03). Applicants for R01s may request support for up to five years. In FY 1994, the average total cost per year for new and competing renewal R01s funded by the Division of Basic Research was approximately $170,000. FIRST Award applications must be for five years. Total direct costs for the five-year period may not exceed $350,000 or $100,000 in any one budget period. Small grants (R03) and exploratory/ developmental grants (R21) are limited to two years for up to $50,000 per year and $70,000 per year, respectively, for direct costs. FIRST Awards, exploratory/developmental grants, and small grants cannot be renewed, but grantees may apply for R01 support to continue research on the same topics. Potential applicants for the FIRST Award (R29), exploratory/developmental grant (R21), and small grant (R03) should obtain copies of the specific announcements for these programs from the National Clearinghouse for Alcohol and Drug Information, P.O. Box 2345, Rockville, MD 20847-2345, telephone 301-468-2600 or 1-800-729-6686. Investigators submitting applications that exceed $500,000 for direct costs in any one year should contact program staff before submitting an application. Applicants may also submit applications for Investigator-Initiated Interactive Research Project Grants (IRPG) (PA-94-086, NIH Guide, Vol. 23, No. 28, July 29, 1994). Interactive Research Project Grants require the coordinated submission of related research project grant (R01) and, to a limited extent, FIRST Award (R29) applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of, for example, ideas, data, and materials among the collaborating investigators. A minimum of two independent investigators with related research objectives may submit concurrent, collaborative, cross-referenced individual R01 and R29 applications. Applicants may be from one or several institutions. Further information on these and other grant mechanisms may be obtained from the program staff listed under INQUIRIES. RESEARCH OBJECTIVES Alcohol remains the most commonly abused substance among adolescents. According to the National Adolescent Student Health Survey, 75.9 percent of 8th graders and 87.3 percent of 10th graders have used alcohol in their lifetime (Windle, 1990). Of greater significance is the widespread occurrence of heavy drinking (defined as consuming five or more drinks in a row during the past two weeks). Among high school seniors this statistic is 28 percent. Males have consistently reported more frequent and heavier use than females, but this difference has been gradually diminishing over the last decade (Johnston, et al., 1994). This is particularly important since females require less alcohol to achieve blood alcohol concentrations equivalent to males (Frezza, et al, 1990). Thus, if females begin drinking heavily during adolescence and continue throughout life, they may be at enhanced risk for the medical consequences of alcohol abuse including liver disease (Norton, et al, 1987), brain damage (Harper, et al., 1990), and associated behavioral deficits (Glenn & Parsons, 1992). Given the early onset of drinking and its frequency, the consequences of alcohol's acute and chronic effects on physiological growth and maturation, as well as its potential deleterious effects on the development of social and interpersonal competencies, are of major concern. During the period of late childhood and adolescence, development of neurobiologic systems is incomplete. Although final brain size and available neurons are largely fixed early in infancy, plasticity of the brain continues during adolescence through the processes of overproduction and elimination of synapses, progressive myelination, variation in the evolution of neurotransmitter systems, and changes in the rate of brain electrical and metabolic activity (Watkins and Williams, 1992). In addition, hormonal levels change dramatically during adolescence as a result of the onset of puberty. Corresponding to the shifts in brain and hormonal status are significant transitions in cognitive, psychological, and social development (Susman and Petersen, 1992). Adolescence is marked by the emergence of new thinking skills, reassessment of body image, focus on peer relationships, and a desire to establish self identity and distance from parents (Ingersoll, 1992). Thus, environmental influences during adolescence, including alcohol consumption, may interact with unique neurobiological and physiological strengths and weaknesses to predispose or protect an individual from alcohol abuse and/or dependence. A better understanding of alcohol's effects during adolescence on the complicated interaction among genetic, neurobiologic, psychosocial and environmental factors could lead to earlier and more effective prevention and treatment strategies. To date, relatively few studies define the neurobiological and physiological effects of alcohol in adolescents, in part due to ethical considerations that prohibit administering alcohol to youths. Neurobehavioral research in human adolescents has been largely limited to studies of children who are at high risk because of a positive family history of alcoholism. These investigations suggest that there are neurocognitive and neurophysiological abnormalities in children of recovering alcoholics that could be early indicators of risk for alcoholism (Begleiter, et al, 1984; Hill, et al, 1990; Porjesz and Begleiter, 1993; Whipple, et al, 1991). More importantly, the neurophysiological abnormalities are most pronounced during the prepubertal and late adolescent years, are highly dependent on the differential rates of nervous system development in boys and girls, and may reflect maturational lag in children who are at high risk for developing alcoholism (Hill and Steinhauer, 1993; Steinhauer and Hill, 1993). This latter finding underscores the importance of considering developmental stages, particularly adolescence, when trying to identify early risk markers for alcoholism. Evidence from animal studies indicates that unique neurochemical and behavioral changes are occurring during postnatal development, including adolescence, that could mediate the response to alcohol (see Witt, 1994, for review). While the various neurotransmitter systems develop at different rates, the ontogeny of several neurotransmitter systems extends into the adolescent period. For example, in the rat, neurochemical markers of dopamine activity in the striatum, such as levels of postsynaptic receptors and presynaptic dopamine content, show a gradual increase until adult levels are reached around puberty (Coyle and Harris, 1987; Noison and Thomas, 1988). Similarly, in animals and humans, presynaptic cholinergic markers in the cortex do not reach adult levels until the adolescent period (Coyle and Yamamura, 1976; Virgili, et al., 1990; Court et al., 1993). During the 7- to 10-day period just prior to the onset of puberty, referred to as "periadolescence", both male and female rats are behaviorally and pharmacologically distinct from younger and older animals (Spear and Brake, 1983). Periadolescent animals are more "hyperactive" as measured by tests of exploratory behavior and social play, and have difficulty with complex discrimination learning tasks. Pharmacologically, periadolescent animals are less responsive (hyposensitive) to drugs affecting the catecholaminergic system (Spear, et al., 1980; Shalaby and Spear, 1980), which may be due to functional immaturity of self-inhibitory presynaptic dopamine autoreceptors in mesolimbic brain regions during the periadolescent period (Spear et al., 1981). However, whether periadolescent animals drink more alcohol than early postpubertal or adult rats because of an immature dopaminergic system, are more susceptible to alcohol dependence, or fail to attain mature dopamine function following high early intakes are important research questions that need to be explored. Dopamine is one of many neurotransmitter systems that have been implicated in the alcohol addiction process. An understanding of the ontogeny of psychopharmacological responsiveness in neurotransmitter systems related to mechanisms of alcohol reinforcement, alcohol preference, or alcohol's subjective effects could be extremely important in understanding the development of alcohol addiction during adolescence. Finally, animal studies of the ontogeny of alcohol's acute effects on learning and memory have shown early age-dependent changes in alcohol's effect on selective learning tasks (e.g., sensory preconditioning) (Chen, et al., 1992). However, more studies are needed to look at ethanol's influence on age-related changes on other cognitive measures and the neurochemical mechanisms underlying these changes. Similarly, few studies have investigated the effects of chronic ethanol use on cognition and brain function. A recent study of alcohol-abusing teenagers found that both male and female adolescent alcohol abusers were inferior in language skills, but only females were impaired on tests of abstract reasoning and cognitive flexibility (Moss, et al., 1994). Furthermore, chronic ethanol treatment may lead to increased N-methyl-D-aspartate (NMDA)-mediated neurotoxicity (Crews & Chandler, 1993), which could be exacerbated by repeated withdrawals such as during binge drinking (Hunt, 1993). Since the immature brain is more susceptible to NMDA neurotoxicity (Garthwaite & Garthwaite, 1986) and since teenagers are more likely to engage in weekend binge drinking, it would be important to study the effects of such patterns of ethanol exposure on neurochemical parameters and cognitive functioning using adolescent animals models. More basic research is needed in humans and animals to elucidate the neurobiological mechanisms of alcoholism and the effects of alcohol ingestion throughout the period of postnatal maturation. Human studies would also be important to identify neurobiologic and behavioral risk factors for alcoholism during postnatal development, particularly adolescence. For example, with the advent of noninvasive imaging techniques such as PET and SPECT as well as the development of radioactive ligands to label dopamine and benzodiazepine receptors, it may be possible to study the functioning of various neurotransmitter systems in children at risk for developing alcoholism and, more importantly to identify those who are likely to become alcoholic during adolescence. Animal studies will be important for investigating the neurochemical, neuropharmacological, and behavioral mechanisms underlying the variable response to alcohol during ontogeny, examining the consequences of acute and chronic alcohol ingestion on the immature central nervous system, and for controlled studies of gene- environment interactions as they relate to patterns of adolescent drinking. Areas needing further research include, but are not limited to: Development of animal paradigms to study modes of initiation of alcohol-seeking behavior and alcohol's effects on reinforcement, drug discrimination, sensitization, tolerance, and dependence during the juvenile through adolescent period. Ontogenetic studies to compare patterns of alcohol-related behavior (e.g., alcohol reinforcement, sensitivity) as well as their neurochemical, neuropharmacological, neurophysiological, and neuroanatomical mechanisms during each stage of postnatal development through adulthood. Animal studies of the acute and chronic effects of alcohol on brain and behavioral functioning during adolescence, and the effects of early exposure on adult functioning. Studies of recovery of neural and behavioral function following alcohol consumption to determine if the adolescent brain is more or less vulnerable than the adult brain to alcohol's acute and chronic effects. Studies of gender differences in alcohol's effect on normal hormonal activation during puberty, mechanisms of alcohol's effect on neuroendocrine-neurotransmitter interactions, and the relationship of alcohol-induced hormonal/ neurotransmitter disturbances during adolescence on the development of gender differences in behavior (including mood, stress, peer relationships, sexual behavior, aggression, cognitive functioning). Human studies and animal studies using different genetically defined strains to examine the interaction among premorbid temperament/personality, cognitive functioning, neurobiological, environmental, and genetic factors in the development of addictive behaviors in adolescents. Use of noninvasive neuroimaging (MRI, MRS, PET, SPECT), neurophysiological (EEG, ERP, MEG), and neuropsychological/cognitive measures in adolescent humans/animals to study brain mechanisms of craving, intoxication, and withdrawal, and to assess progression of damage and recovery of function following abstinence. 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 affect 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 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 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. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Grants Information Office, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Suite 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301-435-0714. The title and number of the program announcement must be typed in section 2a on the face page of the application. Applications for the FIRST award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. 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 20817-7710 (for express/courier service) REVIEW CONSIDERATIONS 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 the applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council. Review Criteria Criteria for scientific/technical merit review of applications for regular research grants (R01) are as follows: 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 the 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 and animal subjects and the safety of the research environment. The review criteria for Small Grants (R03), Exploratory/Developmental Grants (R21), and FIRST Awards (R29) are contained in their program announcements. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to the Institute. 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. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquires regarding programmatic issues to: Ellen Witt, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 402 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-6545 FAX: (301) 594-0673 Email: EWitt@willco.niaaa.nih.gov Direct inquiries regarding fiscal matters to: Linda Hilley Office of Planning and Resource Management National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 504 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-0915 FAX: (301) 443-3891 Email: LHilley@willco.niaaa.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.273. Awards are made under authorization of the Public Health Service Act, Sections 301 and 464H, and administered under PHS policies and Federal Regulations at Title 42 CFR Part 52, and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing 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 Begleiter, H., Porjesz, B., Bihari, B., & Kissin, B. (1984). Event- related brain potentials in boys at risk for alcoholism. Science, 255, 1493-1496. Chen, W., Spear, L. P., & Spear, N. E. (1992). Enhancement of sensory preconditioning by a moderate dose of ethanol in infant and juvenile rats. Behavioral and Neural Biology, 57, 44-57. Coyle, J. T. & Harris, J. C. (1987). The development of neurotransmitters and neuropeptides. In J. D. Noshpitz (Ed.), Basic handbook of child psychiatry (pp. 14-25). New York: Basic Books, Inc. Coyle, J. & Yamamura, H. I. (1976). Neurochemical aspects of the ontogenesis of cholinergic neurons in the rat brain. Brain Research, 118, 429-440. Frezza, M., di Padova, C., Pozzato, G., Terpin, M., Barona, e., & Lieber, C. (1990). The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. New England Journal of Medicine, 322, 95-99. Glenn, S. W. & Parsons, O. A. (1992). Neuropsychological efficiency measures in male and female alcoholics. Journal of Studies on Alcohol, 53, 546-552. Harper, C. G., Smith, N. A., & Kril, J. J. (1990). The effects of alcohol on the human brain: A neuropathological study. Alcohol and Alcoholism, 25, 445-448. Hill, S. Y., Steinhauer, S., Park, J., & Zubin, J. (1990). Event- related potential characteristics in children of alcoholics from high density families. Alcoholism: Clinical and Experimental Research, 14, 6-16. Hill, S. Y. and Steinhauer, S. R. (1993). Assessment of prepubertal and postpubertal boys and girls at risk for developing alcoholism with P300 from a visual discrimination task. Journal of Studies on Alcohol, 54, 350-358. Hunt, W. A. (1993). Are binge drinkers more at risk for developing brain damage? Alcohol, 10, 559-561. Ingersoll, G. (1992). Psychological and social development. In E. R. McAnarney, R. E. Kreipe, D. P. Orr, & G D. Comerci (Eds.), Textbook of adolescent medicine (pp. 91-98). Philadelphia: W. B. Saunders Company. Johnston, L. D., O'Malley, P. M., & Bachman, J. G. (1994). National survey results on drug use from monitoring the future study, 1975-1993, Volume 1, secondary students. National Institute on Drug Abuse. NIH Pub. No.94-3809. Washington, D.C.: Supt. of Docs., U. S. Govt. Print. Off. Moss, H. B., Kirisci, L., Gordon, H. W, and Tarter, R. E. (1994) Neuropsychologic profile of adolescent alcoholics. Alcoholism: Clinical and Experimental Research, 18(1), 159-163. Noison, E. L. & Thomas, W. E. (1988). Ontogeny of dopaminergic function in the rat midbrain tegmentum, corpus striatum, and frontal cortex. Developmental Brain Research, 41, 241-252. Norton, R., Dwyer, T., & MacMahon, S. (1987). Alcohol consumption and the risk of alcohol related cirrhosis in women. British Medical Journal, 295, 80-82. Shalaby, I. A., Dendel, P. S., & Spear, L. T. (1981). Differential functional ontogeny of dopamine presynaptic receptor regulation. Developmental Brain Research, 1, 434-439. Shalaby, I. A. and Spear, L. P. (1980). Psychopharmacological effects of low and high doses of apomorphine during ontogeny. European Journal of Pharmacology, 67, 451-459. Spear, L. T. & Brake, S. C. (1983). Periadolescence: age- dependent behavior and psychopharmacological responsivity in the rat. Developmental Psychobiology, 16, 83-109. Steinhauer, S. R. and Hill, S. Y. (1993). Auditory event-related potentials in children at high risk for alcoholism. Journal of Studies on Alcohol, 54, 408-421. Sussman, J. & Petersen, A. C. (1992). Hormones and behavior. In E. R. McAnarney, R. E. Kreipe, D. P. Orr, & G. D. Comerci (Eds.), Textbook of adolescent medicine (pp. 125-130). Philadelphia: W. B. Saunders Company. Watkins, J. M. & Willams, M. E. (1992). Cognitive neuroscience and adolescent development. In E. R. McAnarney, R. E. Kreipe, D. P. Orr, & G. D. Comerci (Eds.), Textbook of adolescent medicine (pp. 99-106). Philadelphia: W. B. Saunders Company. Whipple, S. C., Berman, S. M., & Noble, E. P. (1991). Event- related potentials in alcoholic fathers and their sons. Alcohol, 8, 321-327. Windle, M. (1990). Alcohol use and abuse: some findings from the National Adolescent Student Health Survey. Alcohol Health and Research World, 15, 5-10. Witt, E. D. (1994). Mechanisms of alcohol abuse and alcoholism in adolescents: A case for developing animal models. Behavioral and Neural Biology, 62, 168-177. From owner-sci-resources@net.bio.net Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA CA/DA-95-013 - V24(24) 06/30/95 Date: 3 Jul 1995 14:59:11 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 406 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p7f$aj3@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA ADA95013 CA/DA-95-013 P1O1 *********************************** PHARMACO-BEHAVIORAL TREATMENT OF NICOTINE DEPENDENCE NIH GUIDE, Volume 24, Number 24, June 30, 1995 RFA: CA/DA-95-013 P.T. 34; K.W. 0404001, 0710100, 0414015 National Cancer Institute National Institute on Drug Abuse Letter of Intent Receipt Date: August 11, 1995 Application Receipt Date: September 21, 1995 PURPOSE The Division of Cancer Prevention and Control (DCPC) of the National Cancer Institute (NCI) and the Division of Clinical and Services Research at the National Institute on Drug Abuse (NIDA) seek applications for controlled, randomized trials to determine the most effective, generalizable, cost-efficient, and durable adjuvant behavioral therapies to support the pharmacological treatment of nicotine dependence. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Pharmaco-Behavioral Treatment of Nicotine Dependence, is related to the priority area of cancer prevention and control. 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 202-783-3238). 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01) award mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed four years. The anticipated award date is April 1, 1996. This RFA is one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE Approximately $1.2 million in total costs per year for four years will be committed by the NCI to specifically fund three to five applications submitted in response to this RFA. In addition, $800,000 per year in total costs will be committed by the NIDA to fund two to four applications. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the awards will also vary. The expected number of awards is five to nine. Although this RFA is provided for in the financial plans of the NCI and NIDA, the award of grants pursuant to it is contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Tobacco use, although slowly declining in most of the industrialized world, remains a significant public health problem. In the U.S., for example, while the prevalence of smoking has been reduced to approximately 25 percent of the adult population, 46 million adults remain current smokers (MMWR, 1994), accounting for more than 400,000 deaths per year. Worldwide, tobacco smoking accounts for more than three million deaths per year (Peto et al., 1994). Yet, despite such mortality, smoking not only continues in the industrialized countries, but is increasing in the developing world. There is wide agreement (DHHS, 1988; Benowitz, 1988) that nicotine dependence is the primary cause of the maintenance of this behavior. In 1987, the American Psychiatric Association, in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R), classified "nicotine dependence" as a psychoactive substance dependence disorder (American Psychiatric Association, 1987). Although a wide variety of approaches to reducing nicotine dependence have been used (e.g., Lichtenstein and Glasgow, 1992; Orleans and Slade, 1993; Richmond, 1994), the most common medical treatment in the U.S. over the past decade (i.e., more than six million users) has been pharmacotherapy - i.e., almost exclusively, either nicotine polacrilex (nicotine- containing gum, or NG) or transdermal nicotine patch (or TNP). The effectiveness of both NG and TNP as treatment aids in smoking cessation has been established in a wide range of research (e.g., Imperial Cancer Research Fund General Practice Research Group, 1993; Silagy et al., 1994; Foulds, 1994; Fiore et al., 1994). An important aspect of this treatment about which there is a lack of clarity, however, is the role of adjuvant counseling or behavioral therapy (defined here as any advice, counseling, or program - whether delivered in person, in print, or through other media - which employs basic behavior change principles in its delivery). As noted by Fiore et al. (1994), many insurers require that smokers who are prescribed NG or TNP participate in an adjuvant behavioral smoking cessation program. The manufacturers themselves encourage such participation (both in package inserts and, in some cases, by providing self-help cessation guides), and the U.S. Food and Drug Administration (FDA) requires that NG and TNP only be prescribed as "part of a comprehensive behavioral smoking cessation program". Yet, there is no consensus about the effectiveness, or the specific, necessary elements, of adjuvant behavioral therapy for smoking cessation (Hajek, in press). There is a great need to establish both the effectiveness and the specific required elements and necessary level of intensity of behavioral therapy when it is provided as an adjuvant to pharmacotherapy aimed at smoking cessation. The importance of smoking cessation as a public health problem, the millions of smokers who are prescribed NG or TNP, the implications for insurers and health care reform efforts, and the need for providers to be able to offer the most effective, cost-efficient, and durable treatment possible requires that this question be addressed. Research Goals The primary goal of the research being solicited is to determine the most effective, generalizable, cost-efficient, and durable adjuvant behavioral therapy in the pharmacological treatment of nicotine dependence. There appears to be general agreement that as the intensity of adjuvant behavioral therapy increases, so also does success in the pharmacological treatment of nicotine dependence (e.g., Fiore et al., 1994). It is not realistic, however, to assume that sufficient intensity for universal effectiveness will be achievable, due to fiscal, time, and/or personnel constraints. Therefore, controlled, randomized studies are sought that will address such questions as: Is there a behavioral therapy that offers the best balance among the four core aims of efficacy, generalizability, cost-efficiency, and durability? Is behavioral therapy a necessary adjuvant to pharmacological treatment of nicotine dependence? What is the minimal behavioral therapy needed to achieve a 10%/25%/etc. difference between control and treatment groups prescribed NG or TNP? Since NG and TNP are physician/dentist- prescribed in the U.S., can physicians and/or dentists, particularly in a primary care setting, deliver a sufficiently effective behavioral therapy to address the four core aims above? What role should other primary care staff, especially nurses, play in the delivery of adjuvant behavioral therapy? Are there elements in adjuvant behavioral therapy that appear to be essential to reduction of nicotine dependence? What components of a primary care intervention could increase rates of patient participation in more intensive adjuvant therapies (which are presumably more effective, but limited by low participation rates)? Other Requirements Several requirements should be observed in preparing applications in response to this RFA: (1) "Pharmaco-therapy" and "pharmacological treatment of nicotine dependence" is defined as treatment with FDA- approved nicotine polacrilex (nicotine gum) and transdermal nicotine patch (subsequent solicitations may focus on other pharmacological treatment approaches); (2) Definitions of the four "core aims" cited above are: (a) efficacy = tobacco use cessation rate; (b) generalizability = ability of the intervention being tested to be adapted to, and used routinely and effectively in, a non-research setting; (c) cost-efficiency = cost comparisons, per successful quitter, of different adjuvant therapies (note: investigators may suggest alternative definitions of cost-efficiency in their proposals); and (d) durability = cessation for at least 6 months; (3) At least one adjuvant behavioral therapy to be tested in any study must be conducted in, or be readily adaptable to, primary care medical or dental settings and all adjuvant therapies should be adaptable to a variety of population characteristics (e.g., women, ethnic minorities, heavy smokers); (4) Minimum patient follow-up should be six months; and (5) At least one measure of treatment "success" shall be continuous non-smoking at all measurement points between the end of treatment (or other measurement point, if the investigator views treatment as an ongoing process) and the final follow-up. SPECIAL REQUIREMENTS Investigators should budget for two, two-day meetings in Bethesda for the PI and one other key staff in Years 1 and 4 and one meeting per year in Years 2 and 3. Additionally, investigators should be prepared to discuss the adoption of data elements and outcome measures common to all studies funded through this RFA. 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. LETTER OF INTENT Prospective applicants are asked to submit, by August 11, 1995, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Thomas J. Glynn 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; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, Bethesda, MD 20892-7762, telephone 301/435-0714; and from the program administrator listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed typewritten original of the application, including the Checklist, and 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) At the time of submission, two additional copies of the application must be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Rockville, MD 20852 (for express mail) Applications must be received by September 21, 1995. If an application is received after that date, it will be returned to the applicant without review. 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, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness by the NCI and NIDA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, DRG staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI, in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit 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 the 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 and animal subjects, and the safety of the research environment. AWARD CRITERIA Applications found to have significant and substantial merit will be considered for funding by the following criteria: o Quality of the proposed study as determined by peer review; o Availability of funds; and o Responsiveness to the goals and requirements of the RFA. 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: Thomas J. Glynn, Ph.D. Division of Cancer Prevention and Control National Cancer Institute Executive Plaza North, Room 320 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8520 FAX: (301) 496-8675 Email: glynnt@dcpcepn.nci.nih.gov Debra Grossman, M.A. Division of Clinical and Services Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10-A-10 Rockville, MD 20857 Telephone: (301) 443-0107 FAX: (301) 443-8674 Email: dgrossma@aoada.ssw.dhhs.gov Direct inquiries regarding fiscal matters to: Victoria Price Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 252 FAX: (301) 496-8601 Email: PriceV@GAB.NCI.NIH.GOV Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A54 Rockville, MD 20857 Telephone: (301) 443-6710 FAX: (301) 594-6847 Email: gfleming@aoada2.ssw.dhhs.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.399. 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 and Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant 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 routing 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 Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 24, no. 24, pt. 1of1, 30 June 1995 Date: 3 Jul 1995 14:59:06 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 325 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p7a$ail@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19950630 V24N24 P1O1 ************************************ X-comment: RFAs described: CA/DA-95-013, AA-95-005, PA-95-073, PA-95-074 X-URL: gopher://gopher.nih.gov/11/res/nih-guide/guide-files/95.06.30 NIH GUIDE - Vol. 24, No. 24 - June 30, 1995 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$INDEX R1 09/21/95 ************************************************* PHARMACO-BEHAVIORAL TREATMENT OF NICOTINE DEPENDENCE (RFA CA/DA-95-013) National Cancer Institute National Institute on Drug Abuse INDEX: CANCER, DRUG ABUSE $$INDEX R2 11/21/95 ************************************************* ROLE OF TOBACCO DEPENDENCE IN ALCOHOLISM TREATMENT (RFA AA-95-005) National Institute on Alcohol Abuse And Alcoholism INDEX: ALCOHOL ABUSE, ALCOHOLISM $$INDEX P1 ********************************************************** MECHANISMS OF ADOLESCENT ALCOHOL ABUSE AND ALCOHOLISM (PA-95-073) National Institute on Alcohol Abuse and Alcoholism INDEX: ALCOHOL ABUSE, ALCOHOLISM $$INDEX P2 ********************************************************** AGING, VASCULAR STIFFNESS, AND CARDIOVASCULAR FUNCTION (PA-95-074) National Institute on Aging INDEX: AGING 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 ROUTING 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) The NIH Guide for Grants & Contracts will not be published on July 7, 1995. The next issue of the NIH Guide will be on July 14, 1995. $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$R1 BEGIN CA/DA-95-013 FULL-TEXT *********************************** PHARMACO-BEHAVIORAL TREATMENT OF NICOTINE DEPENDENCE NIH GUIDE, Volume 24, Number 24, June 30, 1995 RFA AVAILABLE: CA/DA-95-013 P.T. 34; K.W. 0404001, 0710100, 0414015 National Cancer Institute National Institute on Drug Abuse Letter of Intent Receipt Date: August 11, 1995 Application Receipt Date: September 21, 1995 PURPOSE The National Cancer Institute (NCI) and the National Institute on Drug Abuse (NIDA) announce the availability of a Request for Applications (RFA) to develop controlled, randomized trials to determine the most effective, generalizable, cost-efficient, and durable adjuvant behavioral therapies to support the pharmacological treatment of nicotine dependence. Approximately $2 million in total costs per year for four years will be committed to specifically fund applications submitted in response to this RFA. It is anticipated that up to nine awards will be made. 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, Pharmaco-Behavioral Treatment of Nicotine Dependence, is related to the priority area of cancer prevention and control. 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 202-783-3238). 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 contacts listed below. Thomas J. Glynn, Ph.D. Division of Cancer Prevention and Control National Cancer Institute 6130 Executive Boulevard, Room 320 Bethesda, MD 20892 Telephone: (301) 496-8520 FAX: (301) 496-8675 Email: glynnt@dcpcepn.nci.nih.gov Debra Grossman, M.A. Division of Clinical and Services Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A10 Rockville, MD 20857 Telephone: (301) 443-0107 FAX: (301) 443-8674 Email: dgrossma@aoada.ssw.dhhs.gov $$R1 END ************************************************************ $$R2 BEGIN AA-95-005 FULL-TEXT ************************************** ROLE OF TOBACCO DEPENDENCE IN ALCOHOLISM TREATMENT NIH GUIDE, Volume 24, Number 24, June 30, 1995 RFA AVAILABLE: AA-95-005 P.T. 34; K.W. 0404003, 0404001, 0404019, 0745070 National Institute on Alcohol Abuse And Alcoholism Letter of Intent Receipt Date: October 18, 1995 Application Receipt Date: November 21, 1995 PURPOSE The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research applications to study the alcohol tobacco interaction in its implications for alcoholism treatment. The objective of this RFA is to encourage research that will lead to improved strategies for treating alcohol and nicotine dependence in patients receiving care for problem drinking. Such research may identify and test relevant clinical intervention strategies; identify interactions between the two substances that have implications for relapse prevention, or further understanding of the alcoholism treatment process by investigating reinforcement mechanisms underlying conjoint abuse of the two substances. It is estimated that up to $2 million in total costs will be available to support approximately 8 to 10 R01, R29, R21, and/or (R03) grants under this RFA. The earliest possible award date is July 1, 1996. 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, Role of Tobacco Dependence in Alcoholism Treatment, is related to the priority areas of alcohol abuse reduction and alcoholism treatment. 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 202-783-3238). 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. Joanne Fertig, Ph.D. Division of Clinical and Prevention Research National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-0796 FAX: (301) 443-8744 Email: jfertig@willco.niaaa.nih.gov $$R2 END ************************************************************ $$P1 BEGIN PA-95-073 FULL-TEXT ************************************** MECHANISMS OF ADOLESCENT ALCOHOL ABUSE AND ALCOHOLISM NIH GUIDE, Volume 24, Number 24, June 30, 1995 PA AVAILABLE: PA-95-073 P.T. 34; K.W. 0404003, 0403001, 0705048 National Institute on Alcohol Abuse and Alcoholism PURPOSE The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research grant applications to conduct basic research, using animal models and state-of-the-art imaging techniques in humans, to identify the neurobiological, physiological, and genetic factors that lead to adolescent alcohol abuse and dependence. Despite the fact that alcohol use is high among secondary school students, relatively few studies to date define the neurobiologic and physiologic mechanisms of high alcohol intake or the effects of excessive drinking in adolescents. Studies of neurobiologic mechanisms and risk factors for alcoholism during late childhood through adolescence would increase our ability to predict which individuals will be most likely to develop alcoholism early in life. In addition, evaluation of the effects of alcohol ingestion during postnatal development, particularly during adolescence, would further our understanding of alcohol's immediate consequences and the contribution of early alcohol exposure to excessive drinking and abnormal cognitive and social functioning during subsequent developmental stages. Finally, results obtained will help develop strategies for treatment and prevention of adolescent alcohol abuse and alcoholism. 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), Mechanisms of Adolescent Alcohol Abuse and Alcoholism, is related to the priority area of alcohol abuse and alcoholism. 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 202-783-3238). INQUIRIES The PA, 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. Ellen Witt, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-6545 FAX: (301) 594-0673 Email: EWitt@willco.niaaa.nih.gov $$P1 END ************************************************************ $$P2 BEGIN PA-95-074 FULL-TEXT ************************************** AGING, VASCULAR STIFFNESS, AND CARDIOVASCULAR FUNCTION NIH GUIDE, Volume 24, Number 24, June 30, 1995 PA AVAILABLE: PA-95-074 P.T. 34; K.W. 0710010, 0715040, 0411005 National Institute on Aging PURPOSE The purpose of this program announcement (PA) is to foster research that will enhance our understanding of vascular stiffness in aging and in cardiovascular disease. Ascertaining the importance of vascular stiffness, as a risk factor for cardiovascular morbidity and mortality, may suggest approaches to prevention and treatment including early modification of risk factors and/or adverse lifestyles to prevent, delay, and/or reverse vascular stiffening and its potential deleterious sequelae as well as novel treatment in persons with established stiffness or cardiac disease. The Geriatrics Program, National Institute on Aging (NIA), invites grant applications on clinically-relevant research focusing on aging and vascular stiffness. Support for this PA will be the traditional investigator-initiated research project grant (R01) and First Independent Research Support and Transition (FIRST) (R29) award. 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, Aging, Vascular Stiffness, and Cardiovascular Function, is related to the priority area of heart disease and stroke. 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 202-783-3238). INQUIRIES The full text of 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. Andre J. Premen, Ph.D. Geriatrics Program National Institute on Aging 7201 Wisconsin Avenue, Suite 3E327, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-6761 FAX: (301) 402-1784 Email: PremenA@gw.nia.nih.gov $$P2 END ************************************************************ From owner-sci-resources@net.bio.net Sun Jul 02 23:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AA-95-004 - V24(23) 06/23/95 Date: 3 Jul 1995 14:59:00 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 728 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3t9p74$aib@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA AA95004 AA-95-004 P1O1 *************************************** MODERATE ALCOHOL CONSUMPTION: BENEFITS AND RISKS NIH GUIDE, Volume 24, Number 23, June 23, 1995 RFA: AA-95-004 P.T. 34; K.W. 0404003, 0411005, 1002004, 1002008, 0785055 National Institute on Alcohol Abuse and Alcoholism Letter of Intent Receipt Date: October 18, 1995 Application Receipt Date: November 21, 1995 PURPOSE The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking applications for research to determine both the benefits and risks of moderate alcohol use. Several cultural and social definitions for "moderate" alcohol consumption exist, and epidemiological studies refer to a wide range of drinking as moderate. In addition to defining moderate drinking, many important questions remain unanswered. The cellular and molecular mechanisms of the positive association of moderate alcohol use and cardiac health need to be established. Further, any negative effects associated with long term moderate drinking in individuals or subpopulations need to be delineated. Answers to such questions will help identify the tradeoffs involved in an individual's decision about drinking, and will provide a solid base for formulating public health policies. Information obtained about moderate drinking will also provide a better understanding of the mechanisms involved in alcohol effects in general. The purpose of this request for applications (RFA) is to stimulate a wide range of molecular and cellular studies, as well as epidemiological, clinical and psychosocial studies on the benefits and the risks of moderate drinking. These areas include, but are not limited to: (1) coronary artery disease; (2) hypertension; (3) stroke; (4) osteoporosis and breast cancer; (5) interaction with various medications; (6) trade-offs (risk/benefit analysis); and (7) psychosocial issues. 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, Moderate Alcohol Consumption: Benefits and Risks, is related to the priority area of consequences of alcohol abuse and alcoholism. 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 202-783-3238). 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) Awards. MECHANISM OF SUPPORT Research support may be obtained through applications for a regular research project grant (R01), FIRST (R29) Award, exploratory/developmental grant (R21), and small grant (R03). Applicants for R01s may request support for up to five years. In FY 1995, the average total cost per year for new R01s funded by the NIAAA was approximately $200,000. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. A FIRST (R29) Award application must be for five years. Total direct costs for the five-year period may not exceed $350,000 or $100,000 in any one budget period. Small grants (R03) and exploratory/developmental grants (R21) are limited to two years for up to $50,000/year and $70,000/year, respectively for direct costs. FIRST (R29) Awards, small grants (R03) and exploratory/developmental grants (R21) cannot be renewed, but grantees may apply for R01 support to continue research on the same topics. Potential applicants for FIRST (R29) Awards, small grants (R03) and exploratory/developmental grants (R21) should obtain copies of the specific announcement for these programs from the National Clearinghouse for Alcohol and Drug Information, P.O. Box 2345, Rockville, MD 20852, telephone (301) 468-2600 or 1-800-729-6686. Investigators submitting applications that exceed $500,000 for direct costs in any one year should contact program staff prior to submitting an application. Applicants may submit applications for Investigator-Initiated Interactive Research Project Grants (IRPG) (refer to PA-94-086, Vol. 23, No. 28, July 29, 1994). Interactive Research Project Grants require the coordinated submission of related research project grants (R01) and, to a limited extent, FIRST Award (R29) applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of, for example, ideas, data, and materials among the collaborating investigators. A minimum of two independent investigators with related research objectives may submit concurrently collaborative, cross-referenced individual R01 and R29 applications. Applicants may be from one or several institutions. Further information on these and other grant mechanisms may be obtained from the program staff listed under INQUIRIES. FUNDS AVAILABLE It is estimated that up to $2.0 million in total costs will be available for approximately 10 grants under this RFA in FY 1996. This level of support is dependent on the receipt of sufficient number of applications of high scientific merit. Although this program is provided for in the financial plan of NIAAA, the award of grants pursuant to this RFA is also contingent upon the availability of funds. The earliest possible award date is July 1, 1996. RESEARCH OBJECTIVES A review of the psychological benefits of moderate drinking suggests that low levels of alcohol can reduce stress, promote conviviality, and reduce tension and self- consciousness (Baum-Baicker, 1985). This RFA focuses on the benefits and risks associated with moderate drinking. 1. Alcohol and Coronary Artery Disease Numerous epidemiologic studies indicate that moderate drinking is associated with a protective effect against coronary artery diseases (e.g., Klatsky et al., 1990; Rimm et al., 1991; Anderson et al., 1993; Serdula et al., 1995), but not longevity (Criqui and Ringel, 1994). A recent study showed that light to moderate alcohol consumption reduced mortality in women, but this benefit appears largely confined to women at greater risk for coronary heart disease (Fuchs et al., 1995). Most of these epidemiological studies consider the impact of total alcohol consumption over time versus heart disease. However, the influence of various drinking patterns (e.g., lifelong moderate consumption vs. heavy drinking in youth and abstinence later, vs. beginning consumption later in life) is not clear. In addition, the effects of acute versus chronic alcohol consumption and coronary artery disease needs clarification. The contribution of other life style factors (e.g., aspirin consumption, exercise, dietary habits, marital status, smoking, stressful events, and social class) to the observed effect on coronary arteries needs to be elucidated. A recent study has attributed some of the apparent protective effects of moderate drinking to physical activity and other health practices (Barrett et al., 1995). Understanding the cellular and molecular mechanisms by which alcohol reduces the risk of coronary artery disease is important. Research performed hitherto on the mechanisms of the protective effect is suggestive, but not conclusive. While some studies have shown that chronic alcohol consumption increases HDL cholesterol (Hartung et al., 1990; Langer et al., 1992), others have reported that the subspecies HDL3, which is associated with moderate drinking in several studies, has low protective effect (Miller et al., 1981). Yet other studies have shown that both HDL2 and HDL3 are associated with light drinking (Haffner et al., 1985). These studies suggest an effect of alcohol on HDL; however, the mechanism of action has not been firmly established. Some studies hypothesized that this effect is due to an alcohol-induced defect in cholesteryl ester transfer protein (CETP) (Savolainen et al., 1990; Hirano et al., 1992; Hannuksela et al., 1992). Further studies are needed to clarify the effects of alcohol on HDL, CETP and on lipoproteins. Results from a number of studies have demonstrated that acute alcohol consumption reduces platelet aggregation and coagulation (e.g., Renaud and deLorgeril, 1992), which may partly explain the decrease in risk of coronary artery disease associated with moderate drinking. Healthy volunteers who consumed alcohol in sufficient amounts to produce blood alcohol levels less than 100 mg/dL showed an increase in the blood concentration of prostacyclin, which counters the platelet-aggregating effects of thromboxane A2 (Landolfi and Steiner, 1984). The extent to which this effect contributes to the reduction in cardiac risk is unknown. Furthermore, the interaction between alcohol and anticoagulants (aspirin, coumarin derivatives, etc.), and the relative roles of endothelin, nitric oxide, thromboxane A2, prostacyclin and adenosine in the protective effect have not been extensively studied. Also, antioxidants, such as flavonoids (Demrow et al., 1995) or resveratrol (Siemann and Creasy, 1992) are claimed to contribute to the cardio-protective effect of wine, but this issue remains controversial. The role of antioxidants, if any, needs clarification. Epidemiologic studies have shown that all alcoholic beverages, i.e. beer, wine, and distilled spirits (even those that do not contain an appreciable amount of antioxidants) confer protective effects (Seigneur et al., 1990; Klatsky et al., 1992), although a recent study in Copenhagen found decreased risk only with wine (Gronbek, 1995). Other questions that need to be addressed include: Are there gender differences in the extent of alcohol-induced coronary artery protection? If so, what is the relative contribution of alcohol-induced increases in estrogens, especially in post-menopausal women, to the overall effect? What is the role of phytoestrogens that are present in certain drinks (e.g., Bourbon) in producing the observed effect? 2. Alcohol and Hypertension Epidemiological studies from numerous countries have demonstrated that chronic heavy alcohol consumption is associated with hypertension (see review by McMahon, 1987). Although hypertension has not been directly associated with moderate drinking, some studies have shown a positive linear relationship between blood pressure and amount of alcohol consumed, especially in men (Paulin, 1985; Klatsky et al., 1986; Rimm et al., 1991). Does moderate consumption lead to hypertension over time? If so, what is the threshold level of consumption that does not produce hypertension? Women who consume moderate amounts of alcohol did not show tendency for developing hypertension. Why? Whether or not chronic moderate drinking results in hypertension is not clear. However, studies to determine the mechanisms by which heavy alcohol consumption induces hypertension are needed to design effective treatment protocols. 3. Alcohol and Stroke Stroke, both ischemic and hemorrhagic, is the third leading cause of death in the United States. Once stroke occurs, the prognosis is poor. Epidemiologic studies suggest that moderate alcohol consumption reduces the risk of ischemic stroke, especially in Caucasian populations of both genders (Gill et al., 1986, 1988; Stampfer et al., 1988). This effect was not observed in a Japanese population (Tanaka et al., 1982, 1985; Kono et al., 1986). In contrast, moderate alcohol consumption was associated with increases in the risk of hemorrhagic stroke in all populations (Donahue et al., 1986; Stampfer et al., 1988). The cellular and molecular mechanisms by which moderate drinking reduces the risk of ischemic stroke in certain populations, and increases the risk of hemorrhagic stroke are not clear. Are dietary factors involved? Why does alcohol increase risk from hemorrhagic stroke? Does interference with platelet function (Rand et al., 1988; Benistat and Rubin, 1990) play a role? Is alcohol-induced increase in prostacyclin levels (Mikhailidis et al., 1990) involved in this effect? Oral contraceptives use is associated with an appreciable increase in risk of subarachnoid hemorrhage (Petiti et al., 1979). Whether or not moderate alcohol consumption interacts with oral contraceptives to increase the risk of hemorrhagic stroke needs to be clarified? Alcohol intake by women at increased risk has not been examined. 4. Alcohol, Osteoporosis, and Breast Cancer Moderate alcohol consumption is positively correlated with bone mineral density in males and females, especially in post-menopausal women (Laitinen et al., 1991; Holbrook and Barrett-Conner, 1993). This finding suggests that moderate alcohol consumption may help in reducing osteoporosis and, consequently, decrease the risk of fractures. However, other studies indicated the opposite effect (Hernandez-Avila et al., 1991). Carefully designed cellular and molecular studies may elucidate the effects of alcohol on bone homeostasis. The association between moderate alcohol consumption and breast cancer is controversial. While some epidemiological studies have concluded that even modest alcohol consumption is associated with increased risk of breast cancer (Colditz, 1992) in women (Longnecker, 1994, estimated that four percent of the 150,000 cases/year is attributable to alcohol), others did not show such a relationship (Ewertz, 1991). The contribution of alcohol consumption to breast cancer risk needs to be delineated. If indeed moderate drinking increases the risk of breast cancer, what are the cellular and molecular mechanisms of such an effect? Does alcohol-induced increase in estrogen play a role? Do alcohol-induced microsomal enzymes affect the biotransformation of procarcinogens to carcinogens? 5. Interaction Between Moderate Alcohol Consumption and Various Medications Many medications (anesthetics, antibiotics, anticoagulants, antidepressants, oral hypoglycemics, antihistamines, antipsychotics, antiseizure, cardiovascular, narcotics, analgesics, sedatives, etc.) can interact with alcohol leading to serious consequences. Whether moderate drinking results in blood alcohol levels that may adversely interact with medications, especially in the elderly, is an issue of interest. 6. Trade-Offs (Risk/Benefit Analysis) In addition to defining what moderate drinking is, studies aimed at investigating possible trade-offs between the benefits and risks of moderate drinking (in terms of morbidity and mortality) for the population as a whole and for specific subgroups are encouraged. What are the benefits versus risks for different groups of people (e.g., elderly, young adults, smokers). 7. Psychosocial Issues Even modest amounts of alcohol may increase morbidity from existing physical disorders, cause relapse among abstaining alcoholics, affect performance or judgment in critical situations, increase accidents and falls among low tolerance populations (e.g., the elderly), and exacerbate existing family and work problems. For groups who do drink moderately, more detailed information is required to formulate appropriate advice. In particular, health care professionals are increasingly encouraged to advise patients about "safe drinking" limits. This may include selective advice to at-risk groups such as anticipatory guidance to adolescents and the elderly. Research is needed to: (a) understand how vulnerable populations, the population at large, and health-care professionals interpret moderate drinking messages of various types (e.g., promoting cardiovascular risk reduction, reduction of behavioral consequences of heavy drinking); (b) examine how patients respond to different types of advice from their health-care providers concerning the benefits and risks of moderate drinking; (c) increase knowledge on the psychosocial and environmental contexts in which moderate drinking occurs, how context mediates the consequences of moderate drinking, and what changes might be implemented to make moderate drinking patterns less hazardous INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of 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 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. LETTER OF INTENT Prospective applicants are asked to submit, by October 18, 1995, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIAAA staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: RFA: AA-95-004 Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 409 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 FAX: (301) 443-6077 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; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, msc 7762, Bethesda, MD 20892, telephone 301-435-0714; and from the NIAAA program administrators listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Page limits and limits on size of type are strictly enforced. Applications for the FIRST award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST award (R29) applications submitted without the required number reference letters will be considered incomplete and will be returned without review. Submit 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 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must also be sent to: Mark Green, Ph.D. Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 409 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 (20852 for express mail) Applications must be received by November 21, 1995. If an application is received after that date, it will be returned to the applicant without review. 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, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must be prepared as a revised application and include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and for responsiveness by the NIAAA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, DRG staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIAAA in accordance with the review criteria stated below. As part of the initial merit review, a triage process may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non-competitive will be withdrawn from further consideration, and the Principal Investigator and the official signing for the applicant organization will be notified. The second level of review will be provided by the National Advisory Alcoholism and Alcohol Abuse Council. Review Criteria Criteria to be used in the scientific and technical merit review of alcohol research grant applications are the following: 1. The scientific, technical, or medical significance and originality of the proposed research. 2. The appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research. 3. The adequacy of the qualifications (including level of education and training) and relevant research experience of the principal investigator and key research personnel. 4. The availability of adequate facilities, general environment for the conduct of the proposed research, other resources, and collaborative arrangements necessary for the research. 5. The reasonableness of budget estimates and duration in relation to the proposed research. 6. 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. 7. Where applicable, the adequacy of procedures to protect or minimize effects on human and animal subjects and the environment. The review criteria for FIRST Awards (R29), Small Grants (R03) and Exploratory/Developmental Grants (R21) are contained in their program announcements. AWARD CRITERIA Applications recommended for approval by the National Advisory Council on Alcohol Abuse and Alcoholism will be considered for funding on the basis of the overall scientific and technical merit of the application as determined by peer review, NIAAA programmatic needs and balance, and the availability of funds. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding biomedical aspects of proposed research to: Sam Zakhari, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 402 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-0799 FAX: (301) 594-0673 Email: SZakhari@Willco.NIAAA.NIH.Gov Direct inquiries regarding epidemiological aspects of proposed research to: Mary C. Dufour, M.D., M.P.H. Deputy Director National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 400 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-3851 FAX: (301) 443-7043 Email: MDufour@Willco.NIAAA.NIH.Gov Direct inquiries regarding psychosocial aspects of proposed research to: Kendall Bryant, Ph.D. Division of Clinical and Prevention Research National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 505 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-8820 FAX: (301) 443-8774 Email: KBryant@Willco.NIAAA.NIH.Gov Direct inquiries regarding fiscal matters to: Joseph Weeda Office of Planning and Resource Management National Institute on Alcohol Abuse and Alcoholism Willco Building, Suite 504 6000 Executive Boulevard MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-4703 FAX: (301) 443-3891 Email: JWeeda@Willco.NIAAA.NIH.Gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.273. Awards are made under the authorization of the Public Health Service Act, Sections 301 and 464H, and administered under the PHS policies and Federal Regulations at Title 42 CFR Part 52 and 45 CFR Part