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The purpose of this Program Announcement with set-aside funds (PAS) is to invite applications to study the biological basis of vascular cognitive impairment (VCI). VCI causes a burden of illness similar to that caused by Alzheimer’s disease (AD), but has been far less well-studied. Recently, however, some important strides have been made in understanding the etiology of VCI. These include the discovery of a monogenic form of vascular dementia, CADASIL, and identification of the causative gene as Notch 3. In addition, MRI and other pathological data have provided a clearer delineation of the various clinical subtypes of VCI, and awareness of the synergistic interaction between vascular and classical Alzheimer’s pathologies in producing cognitive impairment. The goal of this PAS is to build on these first critical achievements to obtain a better understanding of the cellular and molecular mechanisms causing vascular, neural, and glial dysfunction in human VCI and animal models of VCI.

The Office of Research Integrity (ORI, DHHS), the National Institute of Neurological Disorders and Stroke (NINDS, NIH), the National Institute of Nursing Research (NINR, NIH), the National Institute on Drug Abuse (NIDA, NIH), and the Agency for Healthcare Research and Quality (AHRQ, DHHS) invite applications to support research on research integrity. The purpose of the proposed grant program is to foster empirical research on societal, organizational, group, and individual factors that affect, both positively and negatively, integrity in research. Proposals must have clear relevance to biomedical, behavioral health sciences, and health services research. Applicants are strongly encouraged to take into consideration problems or issues that are relevant to the missions of DHHS, NIH, AHRQ, or specific NIH institutes and programs. For the purposes of this RFA, "research" is interpreted broadly to include societal, organizational, group, and individual aspects of the enterprise. "Integrity" is understood as "the use of honest and verifiable methods in proposing, performing, and evaluating research and reporting research results with particular attention to adherence to rules, regulations, guidelines, and commonly accepted professional codes or norms."

PURPOSE OF THIS RFA Ischemic stroke is the third leading cause of death in the United States. With the aging of the population, the number of stroke patients in the US is likely to grow. There is a critical need to develop safe and effective therapies to improve the clinical management of stroke patients. Thus, the NHLBI and the NINDS invite research applications that will improve the understanding of brain hemostasis, identify new molecular targets, explore promising agents, and develop novel therapeutics for cerebral ischemia. This program intends to support basic, translational, and early clinical studies.

This Program Announcement with Set-Aside fosters co-operation between investigators and joint research projects to understand how fate choices are made by stem and precursor cells in the nervous system, and to design, refine, and improve upon the use of stem cells for diagnostic or therapeutic applications for neurological disorders. The National Institute of Neurological Disorders and Stroke (NINDS) is interested in supporting research that combines the unique and complementary expertise of laboratories from the United States and abroad, applying different disciplines, techniques, model systems or tissues. We anticipate that such research will ultimately lead to innovative approaches for the prevention, management and treatment of disorders of the nervous system, and encourage collaborations from disparate scientific areas and disciplines, including those not traditionally supported by the NINDS. It is essential, however, that the proposed activities be within the mission of the NINDS.

The participating Institutes and Centers of the National Institutes of Health (NIH) along with the Office of Research on Women’s Health announces a continuing program for administrative supplements to research grants to support individuals with high potential to reenter an active research career after taking time off to care for children or attend to other family responsibilities. The aim of these supplements is to encourage such individuals to reenter research careers within the missions of all the program areas of NIH. This program will provide administrative supplements to existing NIH research grants for the purpose of supporting full-time or part-time research by these individuals in a program geared to bring their existing research skills and knowledge up to date. It is anticipated that at the completion of the supplement, the reentry scientist will be in a position to apply for a career development (K) award, a research award, or some other form of independent research support. The NIH recognizes the need to increase the number of underrepresented racial and ethnic groups, women, individuals with disabilities, and people from disadvantaged backgrounds in biomedical, behavioral, clinical and social science research careers. Among the reasons for the low representation of women may be the fact that women bear a majority of the responsibilities surrounding child and family care. To address this issue, this program is designed to offer opportunities to women and men who have interrupted their research careers to care for children or parents or to attend to other family responsibilities. A second objective of the program is to mentor and guide those who receive support to reestablish careers in biomedical, behavioral, clinical or social science research. Participating NIH institutes and centers are listed at the end of the announcement.

The purpose of this program announcement (PA) is to encourage the submission of applications for research to enhance animal stem cells as model biological systems. Innovative approaches to isolate, characterize and identify totipotent and multipotent stem cells from nonhuman biomedical research animal models, as well as to generate reagents and techniques to characterize and separate those stem cells from other cell types is encouraged. Studies involving human subjects are not allowed under this PA. This PA supersedes PA-02-147 issued earlier by the NCRR.

The goal of this Program Announcement is to solicit applications on lysosomal storage disorders (LSDs) focused on improving CNS treatment outcomes, enhancing the effectiveness of delivery and targeting of cells, enzymes, drugs and genes into the brain, and developing novel therapeutic modalities, such as implantable biocapsules and micro-electro-mechanical systems (MEMS)-based devices. Lysosomal storage disorders constitute a group of recessive genetic diseases resulting from cellular enzymatic deficiencies of acid hydrolases that normally catalyze the metabolism of glycoproteins, glycolipids and other macromolecules, or from defects in transporter proteins leading to pathogenic accumulation of these substances in lysosomes. Treatment modalities for LSDs are currently limited to bone marrow transplantation (BMT) and enzyme replacement therapy (ERT). These approaches while providing significant promise for treatment of the visceral manifestations of LSDs, do little to address CNS pathologies for this group of disorders. Thus this announcement specifically encourages the transition from basic studies in LSDs to translational research for improved delivery of therapeutic cells, proteins, genes, and small molecules across the blood-brain barrier.

The participating Institutes, Centers and Offices of the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ) invite investigators to submit R03 research grant applications on health literacy. The goal of this Program Announcement is to increase scientific understanding of the nature of health literacy and its relationship to healthy behaviors, illness prevention and treatment, chronic disease management, health disparities, risk assessment of environmental factors, and health outcomes including mental and oral health. Increased scientific knowledge of interventions that can strengthen health literacy and improve the positive health impacts of communications between healthcare and public health professionals (including dentists, healthcare delivery organizations, and public health entities), and consumer or patient audiences that vary in health literacy, is needed. Such knowledge will help enable healthcare and public health systems serve individuals and populations more effectively and employ strategies that reduce health disparities in the population. Healthy People 2010 defines health literacy as the “degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions” (U.S. Department of Health and Human Services, 2000). Many factors affect individuals’ ability to comprehend, and in turn use or act on, health information and communication. Proficiency in reading, writing, listening, interpreting, oral communication, and visual analysis is necessary as the modern health system typically relies on a variety of interpersonal, textual, and electronic media to present health information. Individuals and families both must be able to: communicate with health professionals; understand the health information in mass communication; understand how to use health- related print, audiovisual, graphical and electronic materials; understand basic health concepts (e.g., many health problems can be prevented or minimized) and vocabulary (e.g., about the body, diseases, medical treatments, etc.); and connect this health-related knowledge to health decision-making and action-taking. Access to and understanding of health information and services is a reciprocal process among health professionals, communication professionals and patients. For instance, these professionals must use science-based strategies and tactics, develop resources and materials, and understand communication interactions between providers and patients. Research on health literacy should assist NIH in its mission of communicating scientifically-based health information to the public and to the health care providers and related professionals who serve the public. The application of scientific knowledge from health literacy research may also strengthen the health information knowledge and communication skills of the public, and further one of the national goals of Healthy People 2010, to improve health literacy by the decade’s end.

The purpose of the Midcareer Investigator Award in Patient-Oriented Research is to provide support for clinician investigators to allow them protected time to devote to patient-oriented research (POR) and to act as research mentors primarily for clinical residents, clinical fellows and/or junior clinical faculty. This award is primarily intended for clinician investigators who are at the Associate Professor level or are functioning at that rank in an academic setting or equivalent non- academic setting, and who have an established record of independent, peer-reviewed Federal or private research grant funding in POR. This award is intended to advance both the research and the mentoring endeavors of outstanding patient-oriented investigators. It is expected, for example, that investigators will obtain new or additional independent peer-reviewed funding as the PI for POR and establish and assume leadership roles in collaborative POR programs; and that there will be an increased effort and commitment to mentor beginning clinician investigators in POR to enhance the research productivity of the investigator and increase the pool of well-trained clinical researchers of the future. With a view to achieving these objectives, the maximum level of allowable Research Development Costs has been increased in this announcement from $25,000 to $50,000 per year. For the purposes of this award, and in agreement with the recommendations of the NIH Director’s Panel on Clinical Research, (http://www.nih.gov/news/crp/97report/index.htm), patient-oriented research is defined as research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena)for which an investigator directly interacts with human subjects. This area of research includes 1) mechanisms of human disease; 2) therapeutic interventions; 3) clinical trials, and; 4) the development of new technologies. Studies falling under Exemption 4 for human subjects research are not included in this definition.

Stem cells appear to possess great plasticity, but the cellular mechanisms regulating their behavior and fate are not understood. If these mechanisms can be harnessed to obtain cells specifically required for therapy, diagnosis or drug discovery, it may be possible to restore function to tissues and organ systems that have been compromised by congenital disorders, developmental malfunction, age, injury, disease or drug exposure. The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute on Aging (NIA), the National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute of Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH) invite applications for studies on the characterization, behavior and plasticity of human and non-human stem cells, regulation of their replication, differentiation, integration and function in the nervous system, and the identification and characterization of normal and tumor stem cells. An understanding of intrinsic and extrinsic signals, especially those involved in the stem cell niche, age-dependent processes and genetic factors that govern the activities of pluripotent cells is crucial in order to utilize them to develop safe and effective treatments for the restoration of function, or to prevent their transformation into tumor-generating cells. Although animal studies demonstrate that stem or progenitor cells can be derived from a variety of tissues and from hosts of different ages, the requirements and potential for differentiation of each type of pluripotent cell appear to be unique. We lack a clear understanding of the intrinsic properties that distinguish one population from another, and how these populations differ in their response to similar conditions in vitro and in vivo. This Program Announcement, which replaces PA-01-078 (Biology of Non- Human Stem Cells in the Environment of the Nervous System) and PA-02-025 (Plasticity of Human Stem Cells in the Nervous System), encourages applications to study the fundamental properties of all classes of human and non-human stem cells, and to confirm, extend, and compare the behavior of stem cells that are derived from different sources and ages or exposed to different regimes in vitro and in vivo or derived from tumors. Of high priority are studies to develop methods for identifying, isolating and characterizing specific precursor populations at intermediate stages of differentiation into neurons and glia, and their relationship to tumor- generating cells. Projects that address comparisons between different classes of human stem cells and between human and non-human stem cells would also be directly relevant to this PA.