kristoff@GENBANK.BIO.NET (Dave Kristofferson) (11/10/90)
NOTE: The NIH Guide may be split into more than one mail message to
avoid truncation during e-mail distribution. The first message always
begins with the RFP/RFA summary sections followed by the appended
texts of the full RFP/RFAs.
----------------------------------------------------------------------
NIH GUIDE - Vol. 19, No. 40, November 9, 1990
NOTICES OF AVAILABILITY (RFPs AND RFAs)
A REPOSITORY OF MOUSE MODELS FOR CYTOGENETIC DISORDERS (RFP) ..(84/119)...... 1
National Institute of Child Health and Human Development
Index: CHILD HEALTH, HUMAN DEVELOPMENT
INSULIN, INSULIN RESISTANCE, HYPERGLYCEMIA AND CARDIOVASCULAR DISEASE:
FIELD CENTERS, COORDINATING CENTER AND CENTRAL LABORATORIES
(RFA HL-91-03-P) .......................(122/184, 1044/2354)................. 1
National Heart, Lung, and Blood Institute
Index: HEART, LUNG, BLOOD
ALZHEIMER'S DISEASE CENTER CORE GRANTS (RFA AG-91-02) ..(187/272)............ 2
National Institute on Aging (2357/2559)
Index: AGING
MECHANISMS OF RESTENOSIS AFTER CORONARY ANGIOPLASTY (RFA HL-91-02-H) ........ 3
National Heart, Lung, and Blood Institute (275/311, 2562/2978)
Index: HEART, LUNG, BLOOD
COLLABORATIVE RESEARCH PLANNING GRANT - DIABETES IN AMERICAN INDIANS
AND ALASKA NATIVES (RFA DK-91-01) ..............(321/418, 2981/3387)......... 4
National Institute of Diabetes and Digestive and Kidney Diseases
Index: DIABETES, DIGESTIVE DISEASES, KIDNEY DISEASES
ONGOING PROGRAM ANNOUNCEMENTS
RAPID ASSESSMENT POST-IMPACT OF DISASTER (PA-91-04) ...(424/465)............. 5
National Institute of Mental Health
Index: MENTAL HEALTH
STUDIES ON THE EFFECT OF CYTOKINES ON IMMUNE CELLS INVOLVED IN
HYPERSENSITIVITY AND INFLAMMATION (PA-91-05) ..........(468/624)............. 5
National Institute of Allergy and Infectious Diseases
Index: ALLERGY, INFECTIOUS DISEASES
SMALL GRANTS PROGRAM FOR BIOETHICS AND CLINICAL DECISION MAKING
RESEARCH (PA-91-06) ...................................(627/754)............. 7
National Center for Nursing Research
Index: NURSING RESEARCH
MECHANISMS OF UNCONTROLLED ETHANOL INTAKE (PA-91-07) ..(757/1014)............ 9
National Institute of Alcohol Abuse and Alcoholism
Index: ALCOHOL ABUSE, ALCOHOLISM
NOTICES OF AVAILABILITY (RFPs AND RFAs)
A REPOSITORY OF MOUSE MODELS FOR CYTOGENETIC DISORDERS
RFP AVAILABLE: NICHD-CRMC-91-01
P.T. 34; K.W. 1002002, 1002019
National Institute of Child Health and Human Development
The National Institute of Child Health and Human Development (NICHD) is
seeking proposals from organizations to continue developing a repository for
the production, maintenance, and distribution of aneuploid mice with a primary
emphasis on trisomy sixteen (16). The organization will be responsible for
refining methodologies to produce segmental (partial) trisomies and improving
the production of chimeric mice with a trisomic 16 component. The selected
source will be required to breed various strains of mice to produce trisomic
or monosomic embryos with emphasis on chromosome 16, continue developing the
process of freezing, rescuing, and reimplanting embryos into pseudo-pregnant
mice, continue development of methods to improve the production of chimeric
mice with a trisomic component, and distribute the mice to requestors.
The Request for Proposals (RFP) will be issued on or about November 1, 1990.
Proposals will be due January 15, 1991, no later than 4:00 p.m. (Local Time).
Organizations desiring a copy of the solicitation may send their written
requests to the following address:
Mrs. Dorothy McKelvin
NIH, NICHD, OGC, CMB
9000 Rockville Pike
Executive Plaza North, Room 515
Bethesda, MD 20892
Telephone: (301) 496-4611
All requests must cite the RFP number above and include two self-addressed
mailing labels. All sources who consider themselves qualified are encouraged
to submit proposals. The Institute plans to make one award from this
solicitation.
INSULIN, INSULIN RESISTANCE, HYPERGLYCEMIA AND CARDIOVASCULAR DISEASE: FIELD
CENTERS, COORDINATING CENTER AND CENTRAL LABORATORIES
RFA AVAILABLE: HL-91-03-P
P.T. 34; K.W. 0715075, 0715040, 0755018
National Heart, Lung, and Blood Institute
Application Receipt Date: April 5, 1991
The Clinical and Genetic Epidemiology Branch of the Division of Epidemiology
and Clinical Applications, National Heart, Lung, and Blood Institute (NHLBI),
announces the availability of a Request for Applications (RFA) on the above
subject.
This program will support epidemiologic and clinical investigators and
supporting staff to collaboratively plan and execute a study to assess the
relationships of insulin and insulin resistance to cardiovascular disease
(CVD) and its risk factors over a range of glucose tolerance from normal to
overt diabetes. Major aims of the study are to employ a common protocol to
assess the associations of increasing concentrations of glucose and changing
levels of insulin and insulin resistance with levels of other CVD risk factors
and prevalence of CVD, using a population-derived, stratified sample so there
are adequate numbers to assess variations in individual CVD risk factors and
evidence of disease over a range of glucose tolerance from normal through
overt diabetes. This survey will provide insight into the reasons for the
changing risk of CVD at increasing glucose levels and may help to explain the
apparent difference in the contribution of hyperglycemia to the risk of CVD in
men and women.
In view of the size of this study and the anticipation that some needs will
not be identified until the protocol is developed, central functions of the
collaborative activity, a Coordinating Center and a Central Laboratory will be
performed by or under the direction of one or more of the examination centers.
Each Field Center applicant is invited to apply to serve as one or more of
these support units for the study. A separate application should be submitted
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 1
for each support unit. Applicants should discuss the special functions of any
proposed support activity, including methodology and quality control
assessment, and provide an estimated time for the work to be completed.
Investigators should be aware that NIH requires applicants to give added
attention, where feasible and appropriate, to the inclusion of minorities and
women in study populations. Gender and minority population differences must
be noted and analyzed whenever possible. If minorities and/or women are not
included in a given study, a clear reason for their exclusion must be
provided. Merely including an arbitrary number of minority group and women
participants in a given study is insufficient to guarantee generalization of
results.
Interested institutions may request copies of the RFA. Requests for copies of
the RFA should be addressed to:
Peter J. Savage, M.D.
Clinical and Genetic Epidemiology Branch
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Federal Building, Room 300
7550 Wisconsin Ave.
Bethesda, MD 20892
Telephone: (301) 496-4333
ALZHEIMER'S DISEASE CENTER CORE GRANTS
RFA AVAILABLE: AG-91-02
P.T. 04; K.W. 0715180, 0710010, 0715138
National Institute on Aging
Letter of Intent Receipt Date: December 3, 1990
Application Receipt Date: February 11, 1991
BACKGROUND
The National Institute on Aging (NIA) is inviting applications from qualified
institutions for Alzheimer's Disease Center Core grants (ADCC), which are
designed to serve as shared research resources, to facilitate research in
Alzheimer's disease (AD). The NIA currently supports five ADCCs. This
one-time solicitation is designed to increase the number of ADCCs. The NIA
Alzheimer's Disease Centers program is authorized by the Public Health Service
Act, Section 445.
An ADCC will provide support for cores, which are shared resources, to be used
by ongoing and to-be-developed research projects. An ADCC is required to have
an administrative, clinical, neuropathological, and education and information
transfer core. Additional cores can be proposed. Each ADCC will fund two
pilot research projects.
ELIGIBILITY
Institutions eligible for Center Core Grants (P30s) are those at which there
are (1) at least three prinicipal investigators with any PHS agency grant or
comparable peer-reviewed research project (including those funded by State
governments or private foundations) related to Alzheimer's disease, each with
at least two years of committed support remaining at the time of application;
or (2) one or more program projects (P01) grants related to AD, which also
have at least two years of committed support remaining. Institutions that can
demonstrate the ability to launch such a research effort are also eligible.
MECHANISM OF SUPPORT
The support mechanism for this program will be the Center Core Grant (P30).
Investigators may request up to five years of support. The intent is to fund
up to five ADCC grants in Fiscal Year 1991. The total costs (direct plus
indirect) for each ADCC are limited to $600,000 for the first year.
REVIEW PROCEDURES
In preparing proposals, instructions for PHS Form 398 (10/88 revision) and
specific supplemental guidelines available from NIA program staff should be
used. Proposals judged by staff to be nonresponsive to the RFA will be
administratively withdrawn and returned to the applicant without review.
Responsive proposals may then receive a preliminary review by a subcommittee
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 2
of the review panel to establish those applications deemed to be competitive.
Those judged noncompetitive will be so designated, and an abbreviated summary
statement noting the major areas of concern will be sent to the principal
investigator. Applications judged to be competitive will be given full
review. Following review by the initial review group, the applications will
be considered by the National Advisory Council on Aging.
NIH requires applicants for grants to give added attention (where feasible and
appropriate) to the inclusion of women and minorities in study populations and
as units of analysis. If minorities and women are not included in a study
population, a clear and convincing rationale for their exclusion must be
provided.
Although not a prerequisite for applying, potential applicants are encouraged
to submit to the Chief, Dementias of Aging, Neuroscience and Neuropsychology
of Aging Program (NNA), at the address indicated below, a non-binding letter
of intent to apply no later than December 3, 1990. The letter of intent
should include a brief descriptive title, the names of the principal
investigator(s) and other key investigators, and any other participating
institutions. Applications must be received by February 11, 1991 for an
earliest start date of September 30, l991. Applicants are strongly encouraged
to obtain the complete Request for Applications (RFA) and supplemental
information and to discuss their plans with and direct any other inquirires
to:
Chief, Dementias of Aging
NNA, NIA, NIH
Building 31, Room 5C35
9000 Rockville Pike
Bethesda, MD 20892
Telephone: (301) 496-9350
FAX: (301) 496-1494
MECHANISMS OF RESTENOSIS AFTER CORONARY ANGIOPLASTY
RFA AVAILABLE: HL-91-02-H
P.T. 34; K.W. 0715040, 1002004, 0760020
National Heart, Lung, and Blood Institute
Application Receipt Date: March 18, 1991
The Division of Heart and Vascular Diseases of the National Heart, Lung, and
Blood Institute, NIH, announces the availability of a Request for Applications
(RFA) on the above mentioned topic. Applicants may request up to five years
of support for studies of the restenosis after coronary angioplasty.
Investigations may focus on the roles of growth factors, cell-cell
communications, cell adhesion molecules, and on other factors involved in
regulation of cellular and metabolic responses to mechanical
revascularization.
Investigators should be aware that NIH requires applicants to give added
attention, where feasible and appropriate, to the inclusion of minorities and
women in study populations. Gender and minority population differences must
be noted and analyzed whenever possible. If minorities and/or women are not
included in a given study, a clear reason for their exclusion must be
provided. Merely including an arbitrary number of minority group and women
participants in a given study is insufficient to guarantee generalization of
results.
Potential applicants are advised to obtain the full RFA announcement from:
George Sopko, M.D., M.P.H.
Cardiac Diseases Branch
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Federal Building, Room 3C06
Bethesda, MD 20892
Telephone: (301) 496-1081
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 3
COLLABORATIVE RESEARCH PLANNING GRANT - DIABETES IN AMERICAN INDIANS AND
ALASKA NATIVES
RFA AVAILABLE: DK-91-01
P.T. 34, FE; K.W. 0715075, 0755030, 0765033, 0745070, 0745027
National Institute of Diabetes and Digestive and Kidney Diseases
Letter of Intent Receipt Date: December 15, 1990
Application Receipt Date: February 15, 1991
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
and the Indian Health Service (IHS) have initiated a joint program on Diabetes
in American Indians and Alaska Natives to help improve the health status of
these populations. In this Request for Applications (RFA), NIDDK invites
applications for Collaborative Research Planning Grants to support the
development of plans for collaborative research projects that address critical
questions related specifically to the etiology, pathogenesis, diagnosis,
treatment, cure, and prevention of diabetes mellitus and its complications in
American Indians and Alaska Natives.
Collaborative research studies proposed in response to this RFA may involve
basic biomedical research, clinical research, behavioral research, education
research, clinical trials, and epidemiologic research. Accordingly, the
applicant research team should include individuals with the appropriate
scientific, medical, and sociocultural expertise to pursue the proposed
research project. In this regard, special consideration should be given to
including team members with demonstrated access, knowledge, and cultural
sensitivity to the specified study population.
This RFA is a one-time solicitation by NIDDK for applications for
Collaborative Research Planning Grants (R21) to help support the unique
short-term needs of investigators planning research studies related to
diabetes in American Indians and Alaska Natives. The award of these
Collaborative Research Planning Grants will be followed within approximately
one year by an RFA for investigator-initiated research project grant
applications (RO1) related to this same program area.
Teams of applicants are encouraged that could include universities, public
health departments, IHS Hospitals, voluntary organizations, health clinics,
and federally recognized Indian tribe or tribal organizations as defined in
P.L. 93-638 and amended by P.L. 100-472, etc., or combinations thereof. Among
a team of applicants, one institution must be proposed as the lead
organization to serve as the Grantee Institution and assume responsibility for
the fiscal and programmatic conduct of the project.
Applicants are encouraged to submit and describe their own ideas on how best
to meet the objective of this RFA. Applications will be judged primarily on
(1) the likelihood that the new knowledge that may be gained will subsequently
help to reduce the burden of diabetes and its complications on the health
status of American Indians and Alaska Natives; (2) the potential scientific
and technical merit of the proposed project including the significance of the
scientific question(s), rationale, appropriateness of the proposed planning
process, consideration of appropriate ethical issues, and availability of
preliminary data; (3) the agreement of a suitable American Indian population
to participate in planning the proposed study, and potential to establish
collaboration with the tribal groups and other agencies involved in health
care of the selected populations; and (4) the qualifications and experience of
the proposed investigators.
Prospective applicants are requested to submit a letter of intent by December
15, 1990, that includes a descriptive title of the proposed research, the
name, telephone number and mailing address of the Principal Investigator, the
names of other key personnel, the name of the applicant institution and other
collaborating entities, and the number and title of this RFA.
This letter of intent should be sent to:
Dr. Robert D. Hammond
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Westwood Building, Room 406
Bethesda, MD 20892
Requests for the full text of this RFA and inquiries should be directed to the
following NIDDK Program Staff:
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 4
Dr. Robert E. Silverman
Chief, Diabetes Programs Branch
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Westwood Building, Room 626
Bethesda, MD 20892
Telephone: (301) 496-7888
OR
Dr. Joan T. Harmon
Executive Director, Diabetes Research Program
Diabetes Program Branch
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Westwood Building, Room 622
Bethesda, MD 20892
Telephone: (301) 496-7731
ONGOING PROGRAM ANNOUNCEMENTS
RAPID ASSESSMENT POST-IMPACT OF DISASTER
PA: PA-91-04
P.T. 34; K.W. 0715095, 0730050
National Institute of Mental Health
The National Institute of Mental Health is issuing a new announcement, the
Rapid Assessment Post-Impact of Disaster (RAPID), whose purpose is to provide
a mechanism to support research requiring rapid funding to permit access to a
disaster area in the immediate aftermath of the event. When an emergency
event of potential significance for mental health occurs with little or no
warning, prompt assessment of the situation may be crucial.
Applications may be submitted by any public or nonprofit institution such as a
university, college, hospital, or community agency, units of State or local
government, and authorized units of the Federal Government and to for-profit
institutions and entities. Women and minorities and investigators without
previous NIMH support are encouraged to apply. NIMH requires applicants to
give added attention (where feasible and appropriate) to the inclusion of
women and minorities in study populations. If women and minorities are not to
be included, a clear rationale for their exclusion should be provided.
Applications may be submitted at any time and need not await the regular
research grant submission dates. RAPID applications will be handled on an
expedited external peer review and award basis to meet the goals for this
program. RAPID awards are not to exceed $50,000 in direct costs. RAPID
awards are nonrenewable and are not to exceed 1 year. Continued support may
be requested only through a regular research applications that will be fully
reviewed.
Potential applicants are strongly encouraged to contact the Program Officer
before submitting a RAPID applications:
Susan D. Solomon, Ph.D.
Coordinator, Emergency/Disaster Research Program
Epidemiology and Psychopathology Research Branch
National Institute of Mental Health
5600 Fishers Lane
Rockville, MD 20857
Telephone: (301) 443-3728
STUDIES ON THE EFFECT OF CYTOKINES ON IMMUNE CELLS INVOLVED IN
HYPERSENSITIVITY AND INFLAMMATION
PA: PA-91-05
P.T. 34; K.W. 0710070, 0715110, 0715026, 1002004, 0755035
National Institute of Allergy and Infectious Diseases
The Division of Allergy, Immunology, and Transplantation (DAIT) of the
National Institute of Allergy and Infectious Diseases (NIAID), a component of
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 5
the National Institute of Health, invites research project grant applications
(R01s) for support of basic and preclinical studies on the role of cytokines
on immune cells involved in allergy and inflammation.
BACKGROUND INFORMATION
In recent years, substantial progress has been made in elucidating the
mechanisms by which cytokines modulate the immune response in lymphocytes.
Use of newer molecular biologic and biochemical techniques has allowed great
success in identifying and defining the diverse functional properties of
cytokines such as the interleukins and gamma interferon, and cellular factors
such as TGF-alpha and beta, and GM-CSF. An understanding of what role
cytokines play in the regulation of cells involved in hypersensitivity and
inflammation, has been slower to develop. A picture rich with complexity but
providing numerous potential opportunities to intervene in these disease
processes has begun to emerge.
There is substantial experimental evidence which defines functional and
morphological differences between tissue and circulating macrophages, mast
cells, and basophils. Further, recent research has identified subsets of
these cells which differ in their biological and physiological functions.
Representative examples are pulmonary and peripheral blood macrophages in
humans, and tissue and mucosal mast cells in rats in mice. As a group, these
cells are important in the etiology and pathology of numerous acute and
chronic inflammatory and allergic diseases. Recent evidence indicates that a
wide variety of known cytokines are involved in the maturation,
differentiation, proliferation, and growth of these cells which mediate
inflammation and allergy. For instance, interleukin-4 and gamma interferon
have been shown to regulate serum IgE and IgG. But by the same token
cytokines are thought to account in great part for the observed cell
activation that appears not to be IgE-mediated. Eosinophil proliferation is
elicited by GM-CSF and eosinophil differentiating factor (IL-5). Most
recently, mast cells themselves have been shown to secrete cytokines such as
IL-3, IL-4, IL-5, and IL-6 upon activation by cross-linking to IgE or by
treatment with calcium ionophores. This opens the possibility that mast cells
may regulate themselves and/or be involved in the regulation of other cells of
the immune system. Thus although progress is being made on determining the
roles of known cytokines on these cells, more information is needed, such as
whether other known cytokines are involved with these cells.
In addition, new groups of cytokines derived both from immune and non-immune
cell sources have now been shown to affect mast cells, basophils and
eosinophils. Neither the number nor the biochemical and physical properties
of the newly discovered cytokines that act on these cells has been adequately
defined. Further, the effects of these new cytokines on other cell lineages
and their roles in instigating and perpetuating inflammatory/allergic diseases
are not known. Identifying newer cytokines and determining their functions
holds great potential benefit. Modification or abrogation of their effects,
should be of value in controlling inflammatory disease in general. The
application of modern molecular methodologies will allow the identification of
new mediators that play a role in inflammatory disease. The isolation and
further phenotypic characterization of subsets of the cells which participate
in these diseases should be valuable prognostically, and provide selective
points of attack for intervention therapy.
RESEARCH GOALS AND SCOPE
The NIAID is soliciting regular research grant applications directed toward
identifying, isolating, and characterizing novel cytokines and the cells upon
which they act, the subsets of mast cells, eosinophils, and macrophages which
participate in or instigate acute and chronic inflammatory and/or allergic
diseases. Information concerned with the action of known cytokines on these
cells is also sought. Accordingly, there is interest in sponsoring research
projects that deal with, but are not limited to, the following topics:
a) Determining the mechanisms of action of known cytokines on mast cells,
macrophages, eosinophils, or basophils.
b) Identifying and developing means to isolate or enrich, and culture (either
long- or short-term) subsets of the above cells that are involved in
inflammatory and/or allergic responses and determining unique markers or
biological functions which define their clonotypic and phenotypic properties.
c) Determining what additional cytokines are secreted by mast cells,
basophils, and eosinophils and how this secretion may regulate the function of
these cells and other immune cells.
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 6
d) Identifying, isolating, and characterizing new cytokines that are secreted
by or have influence on eosinophils, mast cells, and basophils.
e) Cloning the genes that encode such new cytokines and determining how they
are regulated at various stages during the inflammatory and allergic
processes.
In these proposals the use of newer techniques of molecular and cellular
biology and protein biochemistry is strongly encouraged.
MECHANISMS OF SUPPORT
The mechanism of support will be the individual research project grant (R01).
Policies that govern research grant programs of the National Institutes of
Health will prevail.
APPLICATION AND REVIEW PROCEDURES
Applicants should use the standard research grant application form PHS 398
(Rev. 10/88). For purposes of identification and processing, check yes on
item 2 of the face page and enter the title: "STUDIES ON CYTOKINES INVOLVED
IN HYPERSENSITIVITY AND INFLAMMATION, PA-91-05". Applications will be
accepted in accordance with the standard submission dates for new
applications: February 1, June 1, and October 1. All applications will be
assigned by the Division of Research Grants for review on the basis of
established Public Health Service referral guidelines. Applications will be
reviewed for scientific and technical merit by a study section in the Division
of Research Grants. Following study section review, applications will receive
a second-level review by the appropriate national advisory council.
Applications recommended for approval will compete for available funds with
all other approved applications.
Applicants should include, where feasible and appropriate, minorities and
women as well as men in study populations for all clinical research efforts
and to analyze, where appropriate, differences between these populations. If
women and minorities are not to be included, a clear rationale for their
exclusion should be provided.
The original and six copies of the application should be submitted to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
Requests for additional information or questions regarding this program may be
directed to Dr. Prograis.
Lawrence J. Prograis, Jr., M.D.
Chief, Asthma and Allergy Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Westwood Building, Room 752
Bethesda, MD 20892
Telephone: (301) 496-8973
FAX: (301) 402-0175
This program is described in the Catalog of Federal Domestic Assistance No.
93.855. Grants will be awarded under the authority of the Public Health
Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC
241) and administered under PHS grant policies and Federal Regulations at 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.
SMALL GRANTS PROGRAM FOR BIOETHICS AND CLINICAL DECISION MAKING RESEARCH
PA: PA-91-06
P.T. 34; K.W. 0785130, 0783010
National Center for Nursing Research
BACKGROUND AND GOALS
The mission of the National Center for Nursing Research (NCNR) is to conduct,
support, and disseminate information respecting basic and clinical nursing
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 7
research, research training, and other programs in patient care research. The
National Advisory Council for Nursing Research recognizes the importance of
research in the area of bioethics in clinical practice and has developed a
statement of research in this area that is available from NCNR at the address
below.
NCNR also sponsored an interdisciplinary bioethics workshop as a means of
exploring the research opportunities in bioethics and clinical practice.
Proceedings from the workshop are available from NCNR staff. As a result of
both endeavors, NCNR is reissuing this program announcement to encourage
qualified researchers and multidisciplinary research teams to submit
applications for small-scale studies and pilot projects that focus on the
bioethical issues and dilemmas central to clinical decision making that relate
to clinical practice. Submitted studies must be empirically based, include an
interdisciplinary perspective, and examine questions in the clinical settings
where the problem exists. Moreover, it is the National Institutes of Health
policy that, if women or minorities are not included in a given study, a clear
rationale for this exclusion must be provided. It is anticipated that
findings from pilot projects, feasibility studies, or small scale studies will
provide a basis from which investigators can build larger studies.
MECHANISM OF SUPPORT
As a means of laying the groundwork for bioethics and clinical decision making
research, NCNR announces the Small Grants (R03) Program for Bioethics. The
R03 is a nonrenewable award limited to a total of $35,000 in direct costs for
the entire project period. The project period may be up to two years. The
purpose of the R03 is to provide research support for empirically-based
small-scale studies, pilot projects, or feasibility studies in the area of
bioethics and clinical decision making research. However, applicants may
utilize alternative existing mechanisms such as the R01 or R29 for other
bioethical and clinical practice studies.
ELIGIBILITY
Application to the Small Grants Program (R03) is open to both new and
experienced investigators engaged in clinical research from nonprofit
organizations and institutions, state and local governments and their
agencies, and profit-making organizations. Submission of an R03 application
precludes concurrent submission of another research grant application
containing the same research proposal during that particular review cycle.
APPLICATION AND REVIEW PROCEDURES
Applications for the Small Grants Program (R03) should be submitted to the
Division of Research Grants on Application Form PHS 398 (Rev. 10/88) for an
annual August 23 receipt date. The mailing address is as follows:
Division of Research Grants, NIH
Westwood Building, Room 240
Bethesda, Maryland 20892**
Read GENERAL INFORMATION of the PHS 398, follow the GENERAL INSTRUCTIONS on
pages 1-11 of the application kit, and use SPECIFIC INSTRUCTIONS on pages
12-22, except as indicated below. The application should be written as
succinctly as possible. Appendices should not be submitted.
Page 12 - Item 2 - Check "Yes" and enter Bioethics and Clinical Decision
Making, PA-91-06.
Page 14 - Item 6 - The proposed project period may be up to, but must not
exceed, two years.
Page 14 - Item 8a - The amount for the total project period is $35,000 in
direct costs.
Page 19 - Biographical Sketch - Do not exceed one page per biographical
sketch.
Pages 20 through 22 - Follow general instructions.
Page 23 - Appendix - Do not submit an appendix.
REVIEW PROCEDURE AND CRITERIA
Applications submitted in response to this announcement will be reviewed in
competition by an appropriate initial review group in NCNR in accord with the
usual NIH peer review procedures and criteria. Applications will be evaluated
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 8
with respect to the following criteria: the significance and scientific merit
of the proposed project; level of innovation; the probability that the study
will provide a basis for more extended research in the scientific area; the
investigator's background and training for carrying out the project; and the
adequacy and availability of resources and facilities to carry out the
project.
REPORTING REQUIREMENTS
When an award is made in response to a Small Grant (R03) application, an
annual progress report and Financial Status Report must be submitted. Within
90 days after the termination of the award, a Final Progress Report is
required. This final reporting requirement is the same as that for other
types of research grants and is in accord with 42 CFR Part 52 and 45 CFR Part
74.
CONSULTATION WITH PROGRAM STAFF
Before preparing the R03 in bioethics and clinical decision making research,
applicants should consult with the NCNR program staff about their proposed
project under this announcement. Applicants should contact:
Dr. Patricia Moritz
Chief, Nursing Systems Branch
National Center for Nursing Research
Building 31, Room 5B09
Bethesda, MD 20892
Telephone: (301) 496-0523
This program is described in the Catalog of Federal Domestic Assistance No.
93.361, Nursing Research. Awards are made under the authority of the PHS Act,
Sections 301, 483, 484, and 485, as amended by Public Law 99-158 and 97-219.
Awards are administered under PHS grant policies and Federal regulations 42
CFR Part 52 and 45 Part 74.
MECHANISMS OF UNCONTROLLED ETHANOL INTAKE
PA: PA-91-07
P.T. 34; K.W. 0404003, 0404001, 0404000, 0710085, 1002030
National Institute on Alcohol Abuse and Alcoholism
PURPOSE
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking
applications using single or multidisciplinary approaches to study the
mechanisms underlying uncontrolled intake of ethanol. Of particular interest
is the development of behavioral models that will allow investigations of the
mechanisms of ethanol craving and reinforcement. These models should be able
to integrate neuropharmacological, neurochemical, neurophysiological, and
neuroanatomical measures with genetic and environmental factors that may
contribute to ethanol self-administration.
BACKGROUND
Nearly two-thirds of the adult population in the United States consumes
alcoholic beverages. Most of these consumers have no problems with their
drinking. However, 10 percent are problem drinkers and some are classified as
alcoholics.
People drink ethanol presumably because of its reinforcing properties --
properties that increase the desire to drink more and more ethanol. Progress
in understanding the brain mechanisms that mediate the reinforcement of
behavior in relation to ethanol drinking has come from the development of
animal models of ethanol self-administration that may be analogous to the
human condition. Such models include those in which animals will work for
ethanol and those where animals are selectively bred for ethanol preference.
More research is needed to validate these models of drug-seeking behavior.
Neurochemical studies have begun to identify specific neural pathways, as well
as alterations in neurotransmitter systems within particular brain structures
that could account for excessive ethanol intake. Although no clear consensus
exists on the exact mechanism, most researchers agree that the "brain reward
system" is somehow involved in ethanol reinforcement, and that multiple
structures play a role. Recent neurochemical and autoradiographic data have
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 9
linked high ethanol-seeking behavior to several neurotransmitters including
dopamine, serotonin, gamma-aminobutyric acid, opiates, and glutamate.
More integrative research is encouraged on the complex interrelationships
among neurobiological, genetic, environmental, and behavioral factors
underlying ethanol reinforcement to elucidate how the rewarding properties of
ethanol may contribute to excessive intake and the development of dependence,
particularly in humans.
RESEARCH AREAS OF INTEREST
Examples of important research related to this announcement include, but are
not limited to, the following:
1 Behavioral Models
Good behavioral models are needed for studying ethanol-seeking behavior. Some
existing models are based on consummatory behavior, operant responding
(progressive ratios, or preference ratios for multiple reinforcers), brain
stimulation reward, and taste and place preference conditioning. Models are
encouraged that are best suited to answer specific questions relevant to
ethanol-seeking behavior. Issues such as taste aversion, nutritional and
motivational factors, and psychomotor function should be taken into
consideration in designing behavioral models.
Research addressing the following related questions is also encouraged: What
brain areas are sensitive to brain stimulation reward following ethanol
administration? What is the role of anxiety in ethanol self-administration?
How can behavioral paradigms be used to elucidate the pharmacology and
neurobiology of ethanol self-administration? Can a model be developed to
study the transition to uncontrolled drinking? Does uncontrolled drinking
play a role in the development of tolerance and dependence?
2 Behavioral Genetics of Alcohol-seeking Behavior
Research is encouraged to explore the possible genetic relationships
underlying the brain reward system and its relation to ethanol-seeking
behavior.
The following are some important questions to be addressed: Are strain or
individual differences in high ethanol-seeking behavior (e.g., preference,
operant responding), genetically correlated with other ethanol-related
behaviors (i.e., seizure proneness, locomotor activity, neurosensitivity,
hypothermia)? Does high ethanol consumption correlate with high consumption
of other drugs of abuse? What are the neurochemical and neuroanatomical
substrates of high ethanol consumption?
3 Alcohol Reinforcement and Brain Systems
Experimental designs with multidisciplinary approaches are encouraged to
determine whether the mesocorticolimbic-accumbens-extrapyramidal pathway
and/or other neural pathways are brain reward systems that underlie alcohol
reinforcement, and whether these systems are specific for alcohol or are
common brain reward systems for other drugs of abuse.
The following research areas are also of interest: How agonists, antagonists,
and inverse agonists of the various neurotransmitters interact to alter
ethanol self-administration. Whether neurotransmitter systems are acting in
parallel or sequentially to control ethanol intake. Distinguishing between
the primary and secondary neurotransmitters for ethanol effects in a multiple
systems framework (e.g., whether serotonin effects are blocked by drugs acting
on the dopaminergic system). How the brain reinforcement system is related to
the development of physical dependence.
4 Environmental Factors
It is important to study how environmental factors interact with
neurobiological factors in ethanol reinforcement, craving, and relapse. In
particular, research is desirable to investigate how early environmental
history, current environment, i.e., aversive vs. nonaversive, and conditioned
stimuli, secondary reinforcers, route of administration, contingent vs.
noncontingent administration, and physiological state, are related to high
ethanol-seeking behavior in both animals and humans.
Other topics of interest include: How the methods of initiation of ethanol
consumption, including rate of acquisition and asymptote achieved, contribute
to high ethanol intake. The role of prior drug history, including dose and
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 10
exposure to other drugs of abuse. The role of environmental factors in
relapse.
5 Neurobiological Mechanisms
For each established behavioral model, it is crucial that causality be
established between changes at the molecular or cellular level and high
ethanol-seeking behavior. Research is encouraged to explore methods for
producing a neurochemical change at a cellular or molecular level that can
initiate ethanol-seeking behavior. Multidisciplinary approaches are highly
encouraged, including neurobehavioral genetics, molecular biology,
neurochemistry, neurophysiology, neuroanatomy, neuropharmacology, and
neuroimmunology. The use of the latest neurobiological techniques and models
are desirable, including transgenic mice, immunological techniques, in vivo
brain dialysis, voltammetry, brain imaging techniques, and quantitative
autoradiography.
6 Therapeutic Prototypes
The ultimate goal of these research initiatives is to enhance the treatment of
alcohol abuse and alcoholism. Possible treatments can include the use of
pharmacological agents or behavioral conditioning. New and novel approaches
to treatment of excessive or uncontrolled ethanol intake are encouraged.
Those approaches that might include a small-scale clinical trial and are
prototypic in nature are relevant to this announcement. Large-scale human
drug trials and other related clinical research are covered under other
announcements.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF ADAMHA POLICIES
CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY
POPULATIONS
Applications/proposals for ADAMHA grants and cooperative agreements are
required to include both women and minorities in study populations for
clinical research, unless compelling scientific or other justification for not
including either women or minorities is provided. This requirement is
intended to ensure that research findings will be of benefit to all persons at
risk of the disease, disorder, or condition under study. For the purpose of
these policies, clinical research involves human studies of etiology,
treatment, diagnosis, prevention, or epidemiology of diseases, disorders or
conditions, including but not limited to clinical trials; and minorities
include U.S. racial/ethnic minority populations (specifically: American
Indians or Alaskan Natives, Asian/Pacific Islanders, Blacks, and Hispanics).
ADAMHA recognizes that it may not be feasible or appropriate in all clinical
research projects to include representation of the full array of U.S.
racial/ethnic minority populations. However, applicants are urged to assess
carefully the feasibility of including the broadest possible representation of
minority groups.
Applications should include a description of the composition of the proposed
study population by gender and racial/ethnic group, and the rationale for the
numbers and kinds of people selected to participate. This information should
be included in the form PHS 398 in Section 2, A-D of the Research Plan AND
summarized in Section 2, E, Human Subjects.
Applications should incorporate in their study design gender and/or minority
representation appropriate to the scientific objectives of the work proposed.
If representation of women or minorities in sufficient numbers to permit
assessment of differential effects is not feasible or is not appropriate, the
reasons for this must be explained and justified. The rationale may relate to
the purpose of the research, the health of the subjects, or other compelling
circumstances (e.g., if in the only study population available there is a
disproportionate representation in terms of age distribution, risk factors,
incidence/prevalence, etc., of one gender or minority/majority group).
If the required information is not contained within the application, the
review will be deferred until it is complete. Peer reviewers will address
specifically whether the research plan in the application conforms to these
policies. If gender and/or minority representation/justification are judged
to be inadequate, reviewers will consider this as a deficiency in assigning
the priority score to the application.
All applications/proposals for clinical research submitted to ADAMHA are
required to address these policies. ADAMHA funding components will not award
grants that do not comply with these policies.
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 11
ELIGIBILITY
Applications for alcohol research grants may be made by public or private
nonprofit or for-profit organizations, such as universities, colleges,
hospitals, laboratories, units of State or local governments, and eligible
agencies of the Federal Government. Women and minority investigators are
encouraged to apply.
MECHANISMS OF SUPPORT
Studies conducted in response to this announcement can be performed under the
R01, R03, R29, and P01 mechanisms.
APPLICATION AND REVIEW PROCEDURES
Applicants should use the grant application form PHS 398 (Rev. 10/88). The
number and title of this announcement, PA 91-07 and "Mechanisms of
Uncontrolled Ethanol Intake," respectively, should be typed in item number 2
on the face page of the PHS 398 application form. Page limits and limits on
size of type are strictly enforced. Non-conforming applications will be
returned without being reviewed.
Receipt dates for applications are February 1, June, 1, and October 1.
The signed original and six permanent, legible copies of the completed
application should be sent to:
Division of Research Grants, NIH
Westwood Building, Room 240
Bethesda, MD 20892**
The Division of Research Grants, NIH, serves as a central point for receipt of
applications for most discretionary PHS grant programs. Applications received
under this announcement will be assigned to an Initial Review Group (IRG) in
accordance with established PHS Referral Guidelines. The IRG, consisting
primarily of non-Federal scientific and technical experts, will review the
applications for scientific and technical merit. Notification of the review
recommendations will be sent to the applicant after the initial review.
Applications will receive a second-level review by an appropriate national
advisory council whose review may be based on policy as well as considerations
of scientific merit. Only applications recommended for approval by the
Council may be considered for funding.
Applications submitted in response to this announcement are not subject to the
intergovernmental review requirements of Executive Order 12372, as implemented
through Department of Health and Human Services regulations at 45 CFR Part
100, and are not subject to Health Systems Agency review.
INQUIRIES
For further information, please contact:
Walter A. Hunt, Ph.D. (Neuroscience Research)
Ellen D. Witt, Ph.D. (Behavioral Research)
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
5600 Fishers Lane, Room 16C-05
Rockville, MD 20857
Telephone: (301) 443-4223
**THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF
RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE
CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO
USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S
REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD
BUILDING IS:
5333 Westbard Avenue
Bethesda, Maryland 20816
NIH GUIDE - Vol. 19, No. 40, November 9, 1990 - Page 12