Full Text HD-95-005

LEARNING DISABILITIES:  MULTIDISCIPLINARY RESEARCH CENTERS

NIH GUIDE, Volume 23, Number 37, October 21, 1994

RFA:  HD-95-005

P.T. 04, AA

Keywords: 
  Learning Disorders+ 
  Etiology 
  Disease Prevention+ 
  Handicapped Education 
  Epidemiology 

0710030

National Institute of Child Health and Human Development
National Institute of Neurological Disorders and Stroke

Application Receipt Date:  February 14, 1995

PURPOSE

The Human Learning and Behavior Branch (HLB) of the Center for
Research for Mothers and Children (CRMC) of the National Institute of
Child Health and Human Development (NICHD) and the Developmental
Neurology Branch (DNB) of the Division of Convulsive, Developmental,
and Neuromuscular Disorders (DCDND) of the National Institute of
Neurological Disorders and Stroke (NINDS) invite research grant
applications to develop new knowledge in the areas of definition,
classification, epidemiology, prevention (and preventive strategies),
early intervention, etiology, diagnosis, and treatment of children
who display learning disabilities (LD) in component oral language
abilities (phonology, morphology, semantics, syntax, pragmatics),
reading (word attack skills, word recognition skills, reading
comprehension), written expression abilities (spelling, composition),
and mathematics (basic calculation skills, mathematical reasoning),
and combinations and relationships among them (e.g., combined
deficits in phonology, word attack skills, spelling behavior and
mathematics).  An emphasis should also be placed on identifying the
distinctions and interrelationships (comorbidities) between well
defined types of learning disabilities and other well defined
disorders to include disorders of attention, oppositional/conduct
disorders, genetic disorders affecting learning (e.g., Fragile X
syndrome, Asperger's syndrome, etc.).  In addition, of significant
interest are longitudinal studies of treatment effectiveness with
children with LD who are well defined in terms of age, gender,
ethnicity, SES, primary LD, comorbid LD, severity of disability,
intensity and duration of any previous intervention(s), familial
and/or genetic findings, intellectual status, cognitive-linguistic
status, neuropsychological status, neurophysiological status,
educational status, and social/behavioral competencies.

Specialized research center grant applications should propose, for
the purposes of this request for applications (RFA), an integrated
and synergistic research program that includes, at a minimum: (1)
studies of basic biological (neurobiological and genetic) factors
relevant to the etiology, developmental course, and outcomes of LD;
(2) cognitive-information processing, neuropsychological, and
behavioral factors relevant to the phenotypic expression of different
types of LD at different developmental periods and the predictive
capability of these factors for purposes of early intervention and
treatment; and, (3) factors related to response to treatment.  Up to
four Specialized Research Centers may be supported in response to
this RFA.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Learning Disabilities:  Multidisciplinary Research Centers,
specifically addresses those priorities that are concerned with the
developmental problems in children that are related to developmental
and learning problems in children, and particularly those that
require psychosocial interventions.  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 public and private, non-
profit and for-profit organizations such as universities, colleges,
hospitals, schools, laboratories, units of State and local
governments, and eligible agencies of the Federal government.  Women
and minority investigators are encouraged to apply.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Specialized
Research Center Grant (P50).  Policies that govern the grant-in-aid
award programs covered by the PHS will apply.  Responsibility for the
planning, direction, and execution of the proposed project will be
solely that of the applicant.  The total project period for
applications submitted in response to this RFA may not exceed five
years.

FUNDS AVAILABLE

The NICHD has set aside 2.1 million dollars for direct costs for the
first year of support and the NINDS has set aside 0.7 million
dollars.  It is anticipated that up to four awards will be made.
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 the Institutes,
awards pursuant to this RFA are contingent upon the availability of
funds for this purpose.

RESEARCH OBJECTIVES

Background

The NICHD and the NINDS have had a long-standing interest in the
study of learning disabilities and disorders that adversely affect
the development of listening, speaking, reading, writing and
mathematics abilities in approximately 15 to 20 percent of children
in the United States.  Since its inception in 1963, the NICHD has
funded research to delineate the basic biological and behavioral
mechanisms that underlie specific deficits in attention, perception,
language, cognition, and academic skills, particularly reading.  In
January 1987, a National Conference on Learning Disabilities, co-
sponsored by the Interagency Committee on Learning Disabilities (of
which the NICHD was designated as the lead agency and of which the
NINDS was a member) and the Foundation for Children with Learning
Disabilities was held on the NIH campus.  The proceedings of this
conference were combined with other sources to provide a
comprehensive document titled "Learning Disabilities: A Report to the
U.S. Congress" (1987).  A major recommendation included in this
report called for a systematic effort to conduct research to develop
a valid and reliable definition and classification system that could
provide a theoretical, conceptual, and empirical framework for the
identification of different types of learning disabilities, as well
as the identification of distinctions and interrelationships
(comorbidities) between types of LD and other childhood disorders
including general academic underachievement, disorders of attention,
mental retardation, and emotional disturbance. In addition, the
"Report to Congress" called for a systematic effort to develop
rigorous research strategies and intervention trials to examine the
responses of children with LD to different forms of treatment.

Based on the 1987 "Report to Congress" recommendations, NICHD funded
three Multidisciplinary Learning Disability Research Centers (LDRCs)
in 1988 to initiate studies on the definition, classification and
etiology of LD and related disorders.  NINDS was at this time funding
the Center for the Study of the Neurological Basis of Language, which
serves as a model for these recommendations.  The three NICHD centers
joined several NICHD Program Projects that focussed on the specific
study of dyslexia.  In 1993, two additional research programs were
funded to study the effects of treatment interventions on children
with language-based reading deficits.  Studies conducted at the LDRCs
and Program Projects over the past five years have yielded
discoveries in several domains, and these are summarized below
according to research targets.

Classification/Definition

o  The definition and classification of LD, dyslexia, and disorders
of attention (i.e., attention deficit hyperactivity disorder (ADHD))
should be accomplished within a longitudinal developmental framework
that does not require adherence to a priori assumptions reflected in
current definitions.  The development of valid definitions requires
that studies be conducted with representative groups of children over
time that document, with robust measurements and measurement models,
how differences among children emerge, change, respond to treatment,
and influence further development.  In developing definitions, a
critical emphasis must be placed on the identification of valid
inclusionary criteria.

o  Current exclusionary definitions of LD in reading appear to be
invalid if discrepancy criteria are used.  Reading disabled (RD)
children with and without a discrepancy between IQ and reading
achievement do not differ in the information processing subskills
(e.g., phonological and orthographic processing) that are critical to
the reading of single words.  Likewise, genetic and
neurophysiological studies have not indicated differential etiologies
for RD children with and without IQ achievement discrepancies. It
remains to be seen whether or not discrepancies between IQ and
achievement constitute valid markers in the areas of oral language,
written expression, mathematics, or whether or not discrepancies are
worthwhile predictors of response to treatment/interventions.

Reading and Language-Related Processes

o  LDRC longitudinal, epidemiological studies show that RD (dyslexia)
affect at least 10 million children, or approximately 1 child in 5.

o  While public schools identify approximately four times as many
boys as girls as RD, LDRC and Program Project longitudinal and
epidemiological studies show that as many girls manifest RD as boys.
What is not as well understood are the factors that predispose boys
to a higher rate of identification.  Questions related to severity,
classroom behavior, teacher expectations and perceptions, and the
influence of comorbidities need to be addressed.

o  RD reflects a persistent deficit rather than a developmental lag
in linguistic (phonological) skills and basic reading skills.  LDRC
longitudinal studies show that of the children who are diagnosed RD
in the third grade, 74 percent remain disabled in the ninth grade.
Given these findings, several questions remain.  For example, what
are the characteristics of those children who are no longer diagnosed
RD?  Was their disability less severe in contrast to children with
persistent RD?  Were particular treatment/interventions more
effective with the compensated RD children than with those children
who remained RD?  Do compensated RD children show differences in
neurophysiological, linguistic, cognitive, and behavioral features?
What are the best predictors of outcome?  Do predictors change as a
function of type of intervention/treatment?

o  Children with RD differ from one another and from other non-
disabled readers along a continuous distribution, and do not cluster
to form a bimodal distribution or a distinctive "hump" at the tail of
the normal distribution.  Given that RD occurs along a continuum, it
will be important to understand in future studies which "cut-off
points" are most valid and useful for establishing levels of severity
for diagnostic and treatment planning purposes.  Treatment/
intervention studies would be helpful in this regard.

o  The ability to read and comprehend depends upon rapid and
automatic recognition and decoding of single words, and slow and
inaccurate decoding are the best predictors of difficulties in
reading comprehension.  While this finding has been replicated across
the LDRCs and other projects, an identification of the multiple
cognitive and linguistic sources that are required for comprehension
and their relative importance to comprehension is not fully
understood.  More detailed and comprehensive studies are needed in
this area.

o  The ability to decode single words accurately and fluently is
dependent upon the ability to segment words and syllables into
abstract constituent sound units (phonemes).  Converging evidence
from all the LDRCs and other projects show that deficits in
phonological awareness reflect the core deficit in RD or dyslexia.
In future studies, it will be critical to determine whether the
phonological deficit reflects a specific linguistic deficiency that
interferes with the development of reading in and of itself, or
whether deficits in phonology actually reflect deficiencies at lower
levels of processing (e.g., rapid temporal processing of information
irrespective of modality).  It is also critical to establish the
neurobiological underpinnings of the phonological deficit and
temporal processing deficiencies, if in fact, the latter are strongly
implicated in the developmental reading process.

o  In addition, some LDRC data and studies from other sources
continue to find that orthographic processing influences how reading
develops in children.  Given this consistent finding, research is
needed to fully define and identify the role of orthographic
processing in both single-word reading and comprehension, as well as
to identify and delineate other visual processing factors that may
contribute to the developmental reading process.  Neurobiological,
cognitive, and treatment studies would be instrumental in this
regard.

o  At this time, the best single predictor of RD from kindergarten
and first grade test performance is phoneme segmentation ability.
However it remains to be determined whether other phonological skills
are equally robust, or whether combinations of tasks are most
efficacious.

Attention

o  The reviews of the literature conducted by the LDRCs and Program
Projects indicate that a precise classification system and definition
of disorders of attention is not yet available.  A classification
methodology that assesses BOTH internal and external validity of
dimensional AND categorical models must be applied to the task.
Thus, any findings discussed with respect to ADD or ADHD must be
interpreted with the type of caution that should accompany any ill-
defined construct.

o  Disorders of attention and RD often coexist, but the two disorders
appear distinct and separable with respect to the effects of ADD on
cognitive tasks.  For example, it has been found that ADD children
perform poorly on rote verbal learning and memory tasks, but
relatively well on naming and phonological awareness tasks.  The
converse appears to be the case for children with RD.  Clearly,
research is needed to understand whether differential neurobiological
and genetic mechanisms underlie disorders of attention versus other
types of learning disabilities.  It will also be critical to
understand whether comorbidity between RD and disorders of attention
predispose a child to particular treatment-response patterns.

o  Disorders of attention, which occur more frequently among males,
exacerbate the severity and cognitive morbidity of RD.  Thus, level
of severity may be one reason that more males than females are
identified as RD.  Again, neurobiological and genetic research will
be critical to understanding the gender difference for ADD and ADHD,
and treatment studies will be critical in determining the types of
interventions necessary to remediate severe RD with ADD/ADHD.

Genetics

o  A multiple regression analytic procedure has been developed by the
Colorado LDRC that allows for the analysis of the genetic etiology of
deviant scores as well as individual differences in language/reading
functions.  This is a unique and highly flexible methodology that can
be extended to assess a wide range of possible main effects and
interactions and to test for differential genetic and environmental
influences.

o  Twin studies have found strong evidence for a genetic etiology of
reading disability, with deficits in phonological awareness
reflecting the greatest degree of heritability.  There is also
behavioral genetic evidence for degrees of heritability for
orthographic processing, but this genetic relationship is not well
understood.

o  Preliminary data suggest that at least one type of reading
disability can be linked to the HLA region of Chromosome 6 reflecting
a possible association with autoimmune disorders.  Recent evidence
obtained from twins and siblings with severe deficits in reading
performance show strong support for a Quantitative Trait Locus on
Chromosome 6.

Neurobiology (Neuroanatomy, Neurophysiology, Neuroimaging)

o  Several types of brain pathology, including microdysgenesis
(ectopias), cell loss, hippocampal anomalies, congenital
hydrocephalus, and abnormalities of the corpus callosum have been
reported in a number of strains of immune-defective mice.  There is a
similarity between the brain lesions seen in the animal models and in
the brains of individuals with dyslexia.

o  Data suggest that the microdysgenesis in the cortex of affected
animals is developmental in origin and begins prior to the end of
neuronal migration.  Comparable pathology occurring after the
completion of neuronal migration leads to cell loss and myelinated
gliosis - a finding also obtained in dyslexic brain samples.

o  At the macroscopic level, atypical neural organization in dyslexic
individuals is suggested by an absence of the normal left-greater-
than- right asymmetry in the region of the temporal planum.  This
observation requires substantial continued investigation using well
controlled structural neuroimaging procedures.

o  Converging evidence derived from anatomical microstructure
studies, gross morphology studies, and neuroimaging studies carried
out at the LDRCs and the LD Program Projects suggests that the
phenotypic expression in dyslexia is related to anomalous
organization of brain structures and processing systems within the
posterior left hemisphere. Substantial structural and functional
neuroimaging remain to be done with children with dyslexia to obtain
a valid signature for this hypothesized neurophysiological
difference.

Treatment/Intervention

o  Disabled readers do not readily acquire the alphabetic code when
learning to read, apparently due to deficiencies in the processing of
phonological information.  Further, some data suggest that explicit
instruction in phonological concepts and their relationship to early
reading skills is more efficacious than interventions that rely on
contextual or meaning-based approaches.

o  Of substantial importance is the need to extend these preliminary
treatment/intervention studies to identify specific child x treatment
interactions at early stages of development, and to further
investigate how positive or negative responses to different forms of
intervention are reflected in brain development and neural and
cognitive information processing.  Such aptitude x treatment studies
are clearly needed for all types of LD (reading, oral language,
mathematics, written expression).

Focus

The major focus of this RFA is to build upon the findings derived
from the studies conducted at the LDRCs, the LD Program Projects, and
other research programs in and outside of North America, and to
confirm, refute, and extend these findings with an eye toward
generating new knowledge relevant to the definition and
classification of all types of LD, their epidemiology, their
developmental course, their etiologies, their response to treatments,
and their outcomes, as well as the factors that explain different
outcomes.  Given the significant advances in neuroimaging technology,
particularly in the development and application of non-invasive
functional Magnetic Resonance Imaging technology to the study of
brain development and information processing in children, an emphasis
on investigating the neurobiology of different types of LD will be
critical.  Moreover, such non-invasive neurobiological studies should
be designed so that questions related to the etiologies and
developmental courses of different types of LD (with and without
comorbidities) can be examined in detail.  Of particular interest is
the effect that different forms of well-defined treatment/
interventions have on brain development and neural
processing.

It should be noted that current knowledge related to the etiologies,
developmental courses, and diagnostic characteristics of children
with LD who display primary deficits in written expression, reading
comprehension, and mathematics is less developed than that which is
now known about aspects of oral language (e.g., phonology) and basic
reading development.  As such, there exists a need to initiate
studies of these types of LD, particularly with reference to
establishing reliable and valid definitions and classification
systems.

Research Population:  The selection of the research population should
be based upon the need to conduct integrated prospective,
developmental, longitudinal investigations incorporating
neurobiological, cognitive/behavioral, and early (and later)
treatment/intervention studies with children who manifest LD in one
or more of several domains to include oral language, basic reading
skills, reading comprehension, written expression, and mathematics
development.  Within this context, longitudinal studies may be
initiated with preschool and kindergarten children, with the children
being followed as they enter and proceed through the early grades.
Cross-sectional studies of LD children of ages ranging across the
elementary and middle school age-span should also be considered, but
such studies must be related meaningfully to the questions being
asked within the longitudinal studies.

It is expected that not all children within the research population
will manifest the entire range of oral language, written language,
and mathematics deficits detailed above.  In fact, there will likely
be subgroups and subtypes of children with significantly different
patterns of academic deficits, different patterns of comorbidity,
levels of severity, and different psychological/cognitive processing
deficits.  As such, applicants should consider research protocols
that are capable of identifying well defined subgroups and subtypes
that exist within the sample.  Investigators should also consider
casting the sampling net wide enough to insure a representative
number of subtypes and contrast groups within the study population.
For example, of interest are subtypes of LD children of varying
intellectual abilities, with primary deficits in one or more academic
domains who display no comorbid deficits, a single comorbid deficit,
or a combination of comorbid deficits in attention, behavior, and
social competencies, etc.

Subject Selection Criteria:  The samples for study must be rigorously
defined so that complete replication in another site can be
accomplished.  Within this context, applicants should provide clearly
documented and operationalized definitions for their subject
selection criteria.  These definitions and criteria must be specified
in an a priori manner.  The selection of "school-identified" or
"clinic-identified learning disabled children is strongly discouraged
unless the diagnostic characteristics in these cases match the
applicant's a priori established selection criteria.  Likewise,
criteria for selection of contrast group(s) must be specified in a
priori.

All children selected for study must be defined with reference to
age, gender, grade level, length of time in special education
placement, type of current special education placement, previous
special education placement(s) to include intensity and duration,
ethnicity, socioeconomic status, primary learning disability,
comorbid disabilities, severity of disability, familial and/or
genetic findings, physical/neurological findings, intellectual
status, cognitive linguistic status, neurophysiological/
neuropsychological status, levels of academic achievement in oral
language, reading, mathematics, and written language, and presence or
absence of attention deficit disorder.

Measurement Criteria:  Standardized tests, laboratory tasks,
observational measures, and other assessment procedures (e.g.,
dynamic assessment procedures) must be selected on the basis of known
reliability and validity and appropriateness for the population under
study.  If reliability and validity characteristics are not yet known
for a particular assessment or measurement procedure, the application
should contain specific plans for establishing these features.  The
valid measurement of change over time is critical to the research
called for in this RFA since the study of developmental course and
treatment effectiveness are of primary concern.  As such, applicants
should be aware of and utilize robust procedures for separating
treatment effects from the effects of development in general.  The
use of growth curve models and longitudinal data are encouraged as is
the collection of sufficient data prior to the onset of any
experimental condition or treatment(s) to allow estimation of pre-and
post-treatment growth curves.  Measurement should also be carried out
across multiple time points.

Rationale and Research Questions

A critical public health task that continues to confront the field of
learning disabilities is the development of a set of operational
definitions and a classification system for different types of LD
that will provide the scientific context for their treatment and for
the identification of distinctions and interrelationships
(comorbidities) between the types, and other well defined disorders
to include disorders of attention, oppositional/conduct disorders,
and genetic disorders affecting learning.  There exists a compelling
need to apply state-of-the-art classification methodology to achieve
this goal, and to externally validate emerging definitions and
classification models via the conduct of neurobiological/neuroimaging
studies, cognitive studies, and treatment/intervention studies.  To
this end, examples of research questions and areas that need to be
addressed are provided below.  These examples are illustrative and
not restrictive.

1.  IQ-Achievement discrepancies have not been found to be meaningful
in differentiating between discrepant and non-discrepant poor readers
with deficits in single word reading.  Does this same finding hold
true for children who manifest LD in reading comprehension? written
expression?, mathematics?  Do IQ-Achievement discrepancies predict
response to treatment/intervention?  Are they related to LD
children's self-esteem and self-concept?  Are they related to teacher
and parent expectations?

2.  Are there more appropriate psychometric means to assess the
concept of "unexpected underachievement" that is central to most
existing definitions of LD and to the construct of LD?  If so, do
children who demonstrate "unexpected underachievement" differ from
children whose achievement is predicted to be subaverage on measures
of linguistic performance, neuropsychological abilities,
neurophysiological functioning, genetic factors, response to
instruction, etc.

3.  Are there demonstrable differences between children with
different types of LD (e.g., reading vs. mathematics, vs. written
language) with respect to brain structure and function as assessed by
non-invasive neuroimaging technology?  Does level of severity
influence any differences?  Do comorbidities influence any
differences?

4.  Are there demonstrable differences between children with
different types of LD with respect to cognitive and information
processing characteristics?  Does level of severity and/or
comorbidities influence any differences?

5.  Can neurobiological and genetic information obtained during the
early course of development (e.g., preschool/kindergarten years) be
useful in predicting the onset, course, and level of severity of
different types of LD?  Can neurobiological and genetic information
help to predict response to different forms of treatment?

6.  Given that disabilities in single word reading, and possibly
other types of LD, occur along a continuous distribution, what
methods, procedures, and/or strategies can be used to identify
precise levels of severity and the treatment intensity necessary to
remediate the deficit(s)?  This issue and its resolution is critical
to accurate identification and efficacious treatment/education of LD
children in schools.

7.  Is outcome for different types of LD related to severity?
comorbidity? gender? IQ? SES? neurobiological factors? genetic
factors? type, intensity, and amount of treatment?  onset of
treatment (early vs. late)?

8.  How do deficits in information processing abilities (e.g.,
phonological processing, listening comprehension, visual perception,
orthographic processing and memory, spatial and temporal processing)
relate to neurobiological data obtained via non-invasive structural
and functional neuroimaging studies, and to behavioral, genetic and
linkage studies?  How do such deficits interact with well defined
treatment/interventions to develop specific skills, concepts, and
strategies in different academic areas?

9.  Deficits in the development of phonological abilities have been
strongly linked to failure in developing basic reading skills.  Do
phonological deficits constitute the core deficit in reading, or is
the ability to process information rapidly, regardless of modality,
the major underlying factor in reading disability?

10.  What is the most robust definition and classification system for
disorders of attention?  Should a categorical model be employed?
Should a dimensional model be employed?  Should a combination of
models be used?

11.  Do different types of deficits in attention correspond reliably
to different neurophysiological signatures as measured by functional
MRI or other non-invasive functional neuroimaging modalities?  If so,
does the signature differ with age? severity? gender? degree of
comorbidity? IQ?

12.  Are there neurobiological or genetic factors that can explain
the greater frequency of attention disorders in males than females?

13.  Are different deficits in component oral language skills (e.g.,
phonology, semantics, syntax) related to different reading, written
language, and mathematics disabilities?

14.  Is there differential treatment response by gender? By SES? By
comorbidity? By degree of neurobiological involvement?

15.  How can treatment success and efficacy best be measured?  How
are growth curves best assessed?  Are static or dynamic measures best
suited for the monitoring of treatment effects?

16.  Are positive responses to treatment for component oral language,
written language or mathematics deficits accompanied by changes in
neurophysiological, neuropsychological, affective, social, and
attentional status?

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

The research subjects will range in age from four to 12 years.
Investigators are encouraged to study male and female children
varying in their racial and socio-economic background.  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 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
relevant information concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on form PHS 398 (rev. 9/91).  This
application form is available in the office of sponsored research at
most academic and research institutions and from the Office of Grants
Information, Division of Research Grants, National Institutes of
Health, 5333 Westwood Avenue, Room 449, Bethesda, MD 20892, telephone
(301) 435-0714.  The receipt deadline for applications prepared in
response to this RFA is February 14, 1995.  Late applications will
not be accepted.

The RFA label available in the PHS 398 application form must be
affixed to the bottom of the face page of the application.  Failure
to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title, "Learning Disabilities:
Multidisciplinary Research Centers" and the 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
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two copies of the application must be sent
under separate cover to:

Susan Streufert, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03
Bethesda, MD  20892

Applications must be received by February 14, 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 the same as one already reviewed.
This does not preclude the submission of substantial revisions of an
application 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 NICHD and NINDS staff.  Incomplete or non-
responsive applications will be returned to the applicant without
further consideration.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the Institutes 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.  Those
applications judged to be competitive will be further evaluated for
technical and scientific merit by a peer review panel convened for
this purpose by the Division of Scientific Review, NICHD.

Review criteria for evaluating the applications will be those
normally used by reviewers as specified in the NICHD P50 Guidelines.

The review criteria for the overall program are:

o  significance of the research program proposed by the center to the
initiative on learning disabilities;

o  scope and breadth of the center's programs, the component research
projects, and core units;

o  suitability of the center's central theme and provisions for
coordinating the research projects and core units;

o  multidisciplinary scope of the center and provisions for
coordinating the research projects and cores; and

o  leadership ability and scientific stature of the center director
and his/her ability to meet the program's demands of time and effort.

The review criteria for the component research projects and core
units are:

o  scientific merit of each component research project and the
relation of the project to the center's overall theme;

o  cost effectiveness and quality control of core units;

o  the quality and productivity of research projects using the core
facilities. (each core should be used by at least three research
projects);

o  the appropriateness of the research projects' use of core
services;

o  qualifications, experience, and the commitment of the
investigator's responsible for the component research projects and
core units;

o  participation of a suitable number of responsible, experienced
investigators;

o  appropriateness of the budgetary requests;

o  accomplishments and progress to date of the component research
projects and core units, particularly for competing continuation
(renewal) and supplemental applications;

o  as appropriate, the adequacy of the means proposed for protecting
against risks to human subjects, animals, and/or the environment;

o  academic and physical environment as it bears on patients, space,
and equipment, and on the potential for interaction with scientists
from other departments and institutes;

o  arrangements for internal quality control of ongoing research, the
allocation of funds, day-to-day management, contractual agreements,
and internal communication and cooperation among the investigators in
the center's program;

o  presence of an administrative and organizational structure
conducive to attaining the center's objectives; and

o  institutional commitment.

o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

AWARD CRITERIA

The earliest anticipated date of award is December, 1995.  Scientific
merit, technical proficiency, and availability of funds as described
in the application, will be the predominant criteria for funding.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic and scientific issues to:

G. Reid Lyon, Ph.D.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Building, Room 4B05
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-6591
FAX:  (301) 402-2085
EMAIL:  LYONR@HD01.NICHD.NIH.GOV

Sarah H. Broman, Ph.D.
Division of Convulsive, Developmental, and Neuromuscular Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8C06
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-5821
FAX:  (301) 402-0887
EMAIL:  sb73f@nih.gov

Direct inquiries regarding fiscal and administrative matters to:

E. Douglas Shawver
Office of Grants and Contracts
National Institute of Child Health and Human Development
6100 Building, Room 8A17
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-1303

Angeline Wilson
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-9231

AUTHORITY AND REGULATION

This program is described in the Catalog of Federal Domestic
Assistance No. 93.365, Research for Mothers and Children.  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.  Awards are also made under
authorization of PHS Act, Title V, Part B.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or health System Agency review.

The Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.

.

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