Path: utzoo!utgpu!watserv1!watmath!uunet!bionet!GENBANK.BIO.NET!kristoff From: kristoff@GENBANK.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: Additional RFAs from vol. 19, no. 42 Message-ID: Date: 5 Dec 90 00:49:26 GMT Sender: kristoff@genbank.bio.net Lines: 1084 REQUEST FOR APPLICATIONS RFA: HL-91-01-H P.T. 34, FC; K.W. 0715115, 0755030, 1002019, 1002004, 1002008, 1002030, 0785025 MECHANISMS OF HYPERTENSION IN BLACK MEN AND WOMEN National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 6, 1991 Application Receipt Date: April 8, 1991 PURPOSE The purpose of this Request for Applications (RFA) is to stimulate studies to elucidate specific mechanisms underlying the excessive prevalence of hypertension in black men and women, and to delineate mechanisms that direct the pathogenesis of hypertension in blacks, including vascular sequelae such as nephropathy, cerebral vascular disease, coronary artery disease, and atherosclerosis in other vascular beds. This RFA also seeks to encourage investigations that will examine gender-related mechanisms associated with the development of hypertension in blacks. Due to the multiple dimensions of the disease, a variety of disciplines and approaches are encouraged, such as genetic linkage analysis, molecular biology, biochemistry, physiology, neurobiology, pharmacology, cell and structural biology, cardiology, and nephrology. BACKGROUND In the United States, hypertension in blacks is a significant clinical and public health problem. Not only are blacks more likely to develop hypertension, but the disease develops earlier, is often more severe, and is more likely to be fatal at an earlier age. Mortality associated with hypertension in blacks is substantially higher than in whites; there is a six-fold greater incidence of hypertension-related deaths in middle-aged blacks compared to middle-aged whites. Even among blacks who do not die of hypertension, there is an increased prevalence of the morbid consequences of this disease: stroke is 50 percent higher in blacks compared to whites; left ventricular hypertrophy or an enlarged heart as a consequence of hypertension is 30 percent greater in blacks compared to whites; and kidney failure or end-stage renal disease is 3 times higher in blacks compared to whites. Abnormalities in glucose and insulin metabolism are common in hypertensive patients, both white and black. Early aberrations in insulin-stimulated glucose metabolism or insulin resistance need to be detected and delineated by race. There is a well-recognized association of hyperinsulinemia with elevated cholesterol, elevated low- density lipoprotein, and decreased high-density lipoprotein that potentially contributes to cardiovascular disease through progressive atherosclerosis. Little is known regarding abnormalities in lipid metabolism in blacks, independent of, or in association with, insulin resistance. Recently, Williams et al. described a syndrome ("Familial Dyslipidemic Hypertension"), that is present in 12 percent of hypertensive whites. Multigenerational studies on familial transmission may be able to detect distinctive phenotypes of black hypertension in which metabolic pathways are linked to hypertension. Compared with whites, blacks have alterations in renal function including blunted sodium excretion, blood pressure sensitivity to sodium load, lower rate of renal blood flow, higher vascular resistance, and reduced excretion of kallikrein. Of particular interest in hypertensive nephropathy is the observation that some hypertensive blacks exhibit a reduction in renal function despite seemingly adequate pharmacologic control of blood pressure. There is also evidence of excess end-stage renal disease among diabetic blacks. Blood pressure is generally higher in diabetic blacks than diabetic whites. It is not known whether the greater predisposition to hypertension among blacks contributes to the increased rate of diabetic renal failure. Alternatively, a single mechanism may be determining both the hemodynamic and metabolic expressions of a vascular disease more common in the black race. Several reports have described racial differences in cellular cation transport rates. Sodium-potassium cotransport is lower in blacks, whereas the hypertension-associated increase in sodium-lithium countertransport is greater in hypertensive whites. Other transport mechanisms that may be related to biochemical or metabolic variations among blacks include sodium-hydrogen exchange, sodium-calcium exchange, and sodium-potassium ATPase. Sympathetic nervous system activity influences blood pressure, arteriolar tone, glucose/insulin, and lipid metabolism. Several studies have shown greater blood pressure and vasoconstrictor responses to standardized stimuli in blacks. The results of these investigations have provided early evidence of augmented alpha receptor sensitivity in blacks compared to whites. These data suggest differences in peripheral vascular function or structure resulting in greater vascular resistance in blacks. Another possible avenue in the pathogenesis of hypertension and vascular disease in blacks consists of abnormalities in sympathetic activity that, in turn, lead to concurrent derangements of metabolic regulation and blood pressure. Alternatively, the chronic pressor effect of augmented adrenergic activity could occur as a sequela to the metabolic derangement via the mitogenic effects of insulin or related growth factors on the vasculature. In the young, there are detectable racial differences in some of these biochemical and physiologic parameters related to hypertension in black adults. Black children have lower rates of aldosterone excretion and lower urinary kallikrein. Racial differences have been reported in cardiovascular responses to sympathetic stimuli in childhood. The Bogalusa Heart Study has demonstrated racial differences in cardiovascular development in the young. Black adolescent males have greater vascular resistance and there is echocardiographic evidence of hypertensive changes in cardiac structure at blood pressure levels in the upper quartiles of the normal blood pressure distribution. Thus, another question is whether or not a metabolic process is directing early vascular changes, the rise in blood pressure occurring concomitantly as a consequence of increased peripheral vascular resistance. It is also important to note that there are indications that differences in the prevalence and effects of hypertension may be associated with gender. Premenopausal women, at any arterial pressure, have a total peripheral resistance that is lower than men of the same chronological age. Furthermore, clinical and epidemiological studies show essential hypertension to result in lower mortality in women than in men. To complicate these findings, black women show higher prevalence of hypertension than white women, particularly as age increases, and black women have a higher prevalence of obesity - a risk factor for hypertension - than do black men. Little attention has been paid to fundamental differences between males and females regarding homeostatic mechanisms that determine arterial blood pressure, vascular tone, and resistance. Finally, there is evidence that a significant component of the hypertensive state is inherited. Molecular genetic approaches utilizing family studies (genetic linkage) offer new approaches for dissecting out the genetic components of hypertension by providing DNA-based markers. These genetic markers can lead to a cascade of important and illuminating findings on the molecular and pathophysiological bases of hypertension by providing direct access to the altered genes in suitably configured American black families. The choice of phenotype is central to the success of genetic linkage analysis. The clearest possible results occur with the use of a discrete, reproducibly measurable trait that can distinguish affected individuals from non-affected individuals. Blood pressure measurements are difficult to use for phenotype characterization because blood pressure is unimodally distributed throughout the population, varies in its day-to-day levels, and is subject to other influences, such as alterations with age. One way to minimize this difficulty is to use "intermediate phenotypes" that are commonly associated with the hypertensive state and have a major gene effect. Some examples that may prove feasible include cationic transport measurements, hormone levels, and challenge-response tests. Another way to minimize the problems associated with the use of blood pressure as a phenotype is to do linkage studies with sibling-pairs. This approach is advantageous for a variety of reasons: there are no assumptions about the mode of inheritance; it is possible to minimize some variability effects (for example, the investigator could study siblings who were all about the same age); there are a lot of siblings, and they are easier to locate and recruit than extended families. Although not as powerful as linkage in extended families, this is a viable approach that operates under the assumption that siblings have inherited the same genetic predisposition. OBJECTIVES AND SCOPE Further research is needed to investigate the mechanisms underlying the excessive prevalence, morbidity, and mortality of hypertension in blacks, and to determine the mechanisms that may underlie disparate findings between black women and men. Recent data have identified racial differences in biochemical, neural, endocrine, and hemodynamic function. Further investigations are needed to fill the gaps in understanding the pathways that link these biochemical, neuroendocrine, or physiologic variations with progressive hypertensive disease in blacks. A number of examples of suitable research approaches are given below. These are meant to be illustrative only, and are not in any way meant to exclude other MECHANISTICALLY oriented topics. o elucidate pathophysiological mechanisms underlying excessive prevalence, morbidity, and mortality in blacks o examine gender-related mechanisms associated with the development of hypertension in blacks o build on observational data to develop and test mechanistically oriented hypotheses, such as hypertension in blacks is primarily: a. a disorder of membrane transport systems with major sequelae cascading from altered handling of calcium by vascular smooth muscle cells b. a renal disorder characterized by an impaired ability to efficiently excrete a sodium load c. a metabolic problem, such as insulin resistance and hyperinsulinemia, that leads to increased peripheral vascular resistance d. a neurogenic abnormality, leading to altered adrenergic sensitivity e. an endocrine defect that diminishes vasodilation or augments vasoconstriction o initiate studies to determine specific gene abnormalities responsible for this polygenic disorder in black families and use this knowledge to elucidate molecular, biochemical, and pathophysiological mechanisms. This approach would include studies to select and identify appropriate, black family configurations (for example, sibling-pairs or pedigrees); to phenotypically characterize their members, to collect, analyze, immortalize, and store cell lines from these individuals; and to use the DNA to identify markers and genes for hypertension. MULTIDISCIPLINARY APPROACHES, STUDY DESIGN, AND INCLUSION OF WOMEN Due to the multifactorial nature of the disease, a combination of disciplines would be appropriate. Relevant disciplines may include, but are not limited to: biochemistry, physiology, genetics, molecular biology, cardiology, nephrology, endocrinology, neurology, pharmacology, cellular and structural biology. Similarly, multiple designs and groups (young, middle age, elderly) may be appropriate. Studies, which may combine disciplines, should incorporate into the investigative design controls for age, body mass, and environmental factors. Investigators should be aware that NIH requires applicants to give added attention, where feasible and appropriate, to the inclusion of women in study populations. Gender differences must be noted and analyzed whenever possible. If women are not included in a given study, a clear reason for their exclusion must be provided. Merely including an arbitrary number of women participants in a given study is insufficient to guarantee generalization of results. Collaborative work may involve individuals from within an institution or it may be inter-institutional. EXCLUSIONS Although multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies that would encompass a variety of independent projects, i.e., program projects. This program will not support clinical trials or large epidemiological studies. In general, funds will not be provided for the purchase and installation of expensive, new equipment. Awards under this announcement to foreign institutions will be made only for research of very unusual merit, need and promise, and in accordance with Public Health Service policy governing such awards. MECHANISM OF SUPPORT The support mechanism for this program will be the traditional, individual research grant. Although approximately $1.5 million in total costs for this program is included in the financial plans for fiscal year 1991, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that 4 to 6 grants will be awarded under this program. The specific number to be funded, however, will depend on the merit and scope of the applications received and the availability of funds. Because a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. Upon initiation of the program, the Division of Heart and Vascular Diseases will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program and to stimulate collaboration. Applicants should request ADDITIONAL TRAVEL FUNDS for a one-day meeting each year, most likely to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Applicants, who will plan and execute their own research programs, are requested to furnish their own estimates of the time required to achieve the objectives of the proposed research project. Up to FIVE YEARS of support may be requested. At the end of the official award period, renewal applications may be submitted for peer review and competition for support through the regular grant program of the National Institutes of Health (NIH). It is anticipated that support for the present program will begin in September 1991. Administrative adjustments in project period and/or amount of support may be required at the time of the award. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operation Branch should be consulted regarding procedures to be followed (Tel: 301- 496-7257). All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. REVIEW PROCEDURES AND CRITERIA Review Method: All applications submitted in response to this RFA will be evaluated for scientific and technical merit by an initial review group, which will be convened for this purpose by the Division of Extramural Affairs, NHLBI. Upon receipt, applications will be reviewed for their responsiveness to the objectives of this RFA. If an application is judged unresponsive, the applicant will be contacted and given the opportunity to withdraw the application, or have it considered for the regular NIH grant program. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but that has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA which is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an Introduction addressing the previous critique. Review Criteria: The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research project grant applications, including: o the novelty, originality, and feasibility of the approach and the adequacy of the experimental design, including the suitability and composition of the study population o the competence of the Principal Investigator and collaborators to accomplish the proposed research, and the commitment and time they will devote to the project o the suitability of the facilities to perform the proposed research, including laboratories, instrumentation, and data management systems o the appropriateness of the requested budget for the work proposed o adequate plans for interaction and communication of information and concepts among investigators involved in collaborative studies METHOD OF APPLICATION Letter of Intent: Prospective applicants are asked to submit a letter of intent that includes the names of participating institutions and all investigators, together with a descriptive title. Such a letter of intent is not binding and will not enter into the review of any application subsequently submitted, nor is it a necessary requirement for application. Letters of intent are requested solely for planning purposes. The NHLBI Staff will not provide responses to such letters. Letters of intent should be received no later than March 6, 1991, and be addressed to: Dr. Charles L. Turbyfill Review Branch Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 553 National Institutes of Health Bethesda, MD 20892 Format for Applications: Submit applications on form PHS-398 (revised 10/88), the application form for the traditional NIH research project grant. Copies of this form are available in the applicant institution's office of sponsored research, or may be obtained from: Office of Grants Inquiries Division of Research Grants Westwood Building, Room 449 National Institutes of Health Bethesda, MD 20892 Use the conventional format for research project grant applications and ensure that the points identified in the section above on "Review Procedures and Criteria" are fulfilled. To identify the application as a response to this RFA, CHECK "YES" on item 2 of page 1 of the application and enter the title "Mechanisms of Hypertension in Black Men and Women" and enter the RFA number HL-91-01-H in the space provided. THE RFA LABEL FOUND IN THE FORM PHS-398 APPLICATION KIT MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED APPLICATION FORM PHS-398. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. Application Procedure: Send or deliver the completed, signed application and four (4) complete photocopies of it to the following, making sure that the original application with the RFA label attached is on top: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, MD 20892** SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO DR. CHARLES TURBYFILL AT THE ADDRESS LISTED UNDER "LETTER OF INTENT". IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH GRANTS, OR THE NHLBI CANNOT GUARANTEE THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA. Applications must be received by April 8, 1991. An application not received by this date will be considered ineligible. Timetable: Letter of Intent March 6, 1991 Application Receipt Date April 8, 1991 Review by National Heart, Lung, and Blood Advisory Council September 12-13, 1991 Anticipated Award Date September 30, 1991 Inquiries: Inquiries regarding this announcement may be directed to: Dr. Stephen C. Mockrin Chief Hypertension and Kidney Diseases Branch Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute Federal Building, Room 4C10 National Institutes of Health Bethesda, MD 20892 Telephone: (301) 496-1857 Fax: (301) 496-9882 *This program is described in the Catalog of Federal Domestic Assistance number 93.837, Heart and Vascular Diseases. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR part 52 and 45 CFR part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. ANIMAL RESOURCES PROGRAM INFORMATION FOR APPLICANTS RFA: RR-91-01 P.T. 34; K.W. 1002002, 1014006 DEVELOPING AND IMPROVING INSTITUTIONAL ANIMAL RESOURCES An Administrative Document Issued By: Animal Resources Program National Center for Research Resources National Institutes of Health Department of Health and Human Services This is a reissuance of the Request for Applications (RFA) RR-90-02, which was originally published in the NIH Guide for Grants and Contracts (Volume 19, Number 18, May 4, 1990, and clarified in Volume 19, Number 21, June 8, 1990). A related RFA, "Animal Facility Improvements for Small Research Programs," RR-90-03 was published in the NIH Guide for Grants and Contracts on August 14, 1990, Vol. 19, No. 31. INTRODUCTION The Animal Resources Program (ARP) of the National Center for Research Resources (NCRR), National Institutes of Health (NIH), assists institutions in developing and improving animal resources for biomedical research and research training through the award of research and resource grants. For the purpose of this program, animal resources are defined as all animals and the associated animal facilities and staff that support biomedical research activities. This document relates to institutional animal resource improvement projects that will be supported with funds anticipated to be made available to the Department of Health and Human Services (DHHS) in Fiscal Year 1991 for this activity. Other types of projects supported by ARP include developing and defining animal models, animal resource laboratories, and research and training related to laboratory animal science and medicine. Additional information on these latter grant programs may be requested from the Animal Resources Program, NCRR (see address at end of this document). RESEARCH GOALS AND SCOPE Animal resource improvement grants are awarded to assist biomedical research and educational institutions in upgrading their animal facilities and in developing administratively centralized programs of animal care. Another major objective is to enable institutions to comply with the USDA Animal Welfare Act and DHHS policies related to the care and use of laboratory animals. Requests should describe a discrete project, the total cost of which is no greater than approximately twice the PHS request. If this project is part of a larger renovation plan, the larger plan can be described in the body of the grant. Requests are limited to alterations and renovations (A&R) to improve laboratory animal facilities and major resource equipment related to the improvement, such as animal cage systems and cage washers. Large pieces of basic equipment for centralized surgeries or diagnostic laboratories are allowable if well justified. This improvement grant is not intended to provide general operational support for the resource (e.g., funding for personnel, consumable supplies for routine animal care, or small equipment items) or to provide specialized research equipment or facilities for use by only a few investigators. To gain approval and support, both the need for resource improvements and a sound plan to bring the entire animal resource up to required standards must be demonstrated and well-described in the context of the biomedical research programs of the institution. ELIGIBILITY AND SUPPORT NCRR anticipates that $9.4 million may be available to support animal resource improvement grants in Fiscal Year 1991. It is anticipated that approximately 40 grant awards will be made. The number and specific amounts of these awards will depend on the merit and scope of the applications received and the availability of funds. Awards will be made for a project period of one year. All policies and requirements which govern PHS grant programs will apply. Any domestic public or private institution, organization, or association with one or more research projects supported by the Public Health Service (PHS) that involve the use of laboratory animals is eligible to apply. For the purposes of this program, an institution is defined as the organizational component covered under a single Biomedical Research Support Grant code. Separate applications may be submitted from different colleges or schools on the same campus of a university within the same fiscal year. However, if this is done, documentation from an appropriate institutional official, stating that the applications are part of a coordinated, campus-wide plan to improve the animal facilities must be provided. The applicant institution is strongly encouraged to develop a single proposal for a campus-wide program with a single, centralized animal care program whenever possible. The total request for PHS support and the award are limited to $700,000. Within this limit, the equipment request may be of any size, but the A&R portion cannot exceed $500,000. Matching funds from non-Federal sources, and equal to the total award, are required. These matching funds must be applied to the specific project described in the application and cannot be met by citing other expenditures. A letter of assurance of matching funds and the projected source of these funds, signed by the responsible institutional official, must be included in the body of the application. Support for construction is not authorized. REVIEW PROCEDURES AND CRITERIA Applications will be received by the Division of Research Grants (DRG). There will be a single receipt date of February 12, 1991. Applications received after this deadline will be returned without further processing. All applications submitted in response to this RFA will be reviewed for scientific merit by an appropriate review committee managed by the Office of Review, NCRR, and by the National Advisory Research Resources Council for program considerations. Final funding decisions will be made during the summer of 1991. Review of animal resource improvement projects will be based on the request itself, as well as on the entire animal resource program of the submitting institution. Factors entering into the appraisal of an animal resource improvement project include: A The Improvement Request 1 Need - Evidence of the need of resource grant support for improvements for the institution to meet or maintain the standards of the Animal Welfare Act and DHHS policies on the care and use of animals should be demonstrated. The amount and source(s) of funding for animal-related biomedical research utilizing the resource will also be evaluated. 2 Procedural Plans - Evidence of institution-wide planning to assure a comprehensive and acceptable research animal program will be evaluated. The specific methods proposed will be judged for scientific and technical soundness and their ability to meet the applicable standards. 3 Budget - The budget will be evaluated in relationship to the responsiveness to the RFA, justification provided for each of the requested items, cost effectiveness and institutional commitment. 4 Animal Welfare - The extent to which the project will enhance the welfare of animals maintained in the facility to be served by the resource will be an important part of the evaluation. An assessment of the benefit of the improvements to the welfare of animals in the facility, including advances in the humane treatment of the animals due to husbandry changes allowed by the improvements, should be described. Increases above the minimum space recommendations for laboratory animals (as set forth in the Guide for the Care and Use of Laboratory Animals, (Guide), HHS, NIH Publication No. 85-23, 1985 edition or succeeding revised editions), may be requested by the applicant from the ARP, NCRR office noted later in this document. The overall application will be evaluated for its scientific merit, technical soundness, and cost effectiveness. B The Animal Resources Program The scope of coverage of the animal resources program to be enhanced by this facility improvement request should be carefully defined. Normally, it should cover the applicant institution. 1 Animal Care - The quality of the animal husbandry program will be assessed, including training of the animal technical staff, housing, caging, feeding, record keeping, sanitation, and other animal care practices. Consideration of the animal health program will include clinical services, laboratory support, preventive medicine programs, and any relevant specialized procedures. 2 Personnel - The adequacy of the staff will be evaluated. There should be a sufficient number of professional staff with appropriate qualifications to operate the animal resource in a competent manner. Provisions should be made for an adequate number of appropriately trained non-professional staff and supporting services. An appropriate preventive health program should be in place. 3 Administrative Arrangements - An evaluation will be made of the administrative arrangements for planning and day-by-day management of the animal resource. There should be a sound plan for financial support of the resource, through a recharge system, per diems, institutional support, or other means. Previous expenditures by the institution for capital improvements of the animal resource program should be described. 4 Resources and Environment - The suitability of the institutional setting for achieving the goals of the program will be considered. This will include an appraisal of the academic environment and the support for the animal resource by the administration and faculty. The adequacy of the physical environment, buildings, and equipment for the animal resource will be evaluated. APPLICATION PROCEDURES There will be a single receipt date of February 12, 1991. Applications received after this date will be returned to the applicant. Applications must be submitted on Form PHS 398 (Rev. 10/88), the application form used for research grants. Application kits can be obtained from most institutional business offices, or from the Division of Research Grants, NIH (see address below). The RFA label included in Application Form PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. The format and details applicable to regular research grant applications should be followed, except for the following: SECTION 1 A Face Page of the Application - Item 2 - Check the box marked "yes" and type in the number and title of this RFA (RFA RR-91- 01, "Developing and Improving Institutional Animal Resources"). Item 5 - Check the box marked "No" at Item 5a. Item 5b - Not applicable. Item 7 - This figure refers to the direct costs requested from the PHS only and should not include the required matching dollars. B Key Personnel - Application Page 2 - Only key personnel should be listed here. This must include the chief or attending veterinarian, and may include the principal investigator, additional veterinarians, director of the animal facility, or chief animal technician, as appropriate. Biographical sketches must be provided for all people listed. C Table of Contents - Indicate page numbers for all major headings outlined under Section 1 and Section 2, Research Plan. This is an important aid in the review process for the application. D Detailed Budget - Application Page 4 - The total request for PHS support may not exceed $700,000. Of this, the request for A&R may not exceed $500,000. Matching funds, equal to the total award and from non-Federal sources, are required. Personnel Category - List only those individuals who will spend time on the execution of the facility improvement project and the time needed for this project. Salary support should not be requested. The requested budget should be limited to items of major equipment for animal care, or other aspects of facility function, and A&R. Equipment should be classified as movable or fixed using the institution's classification guidelines as provided by the institution's Business Office. Fixed equipment is considered as part of the A&R request. Small equipment items costing less than $1,000 per manufacturer's unit should not be requested. This includes multiple polycarbonate rodent cages for replacement or change-out purposes. However, as an exception to this, microisolator cages are acceptable if an appropriate change station is also purchased or already available. To avoid deletion, requests for items that may require the purchase of small component parts, e.g., a rack and cages, should be priced as a single item, but a description of the individual components must be provided (see below). Large pieces of basic surgical equipment, such as tables, lights, and gas anesthesia machines may be requested if the operating room is an integral part of the animal facility and is available to all investigators. Such a request must be justified by listing the number of investigators, case load, and types of surgeries involved. Similarly, basic diagnostic equipment to be used in support of the animal facility, but not for research, will be allowed if adequate justification is given. Office equipment (including data processing items), and research equipment should not be requested. Physical security systems are not allowable, but systems for environmental monitoring are acceptable. Each major equipment item must be fully described. The manufacturer, model number, size, capacity, or design criteria, total unit cost and facility where it will be used must be given. This information should be provided on a separate page immediately following the budget. It should not be in an appendix. On the budget page the total cost of the equipment and A&R needed for the discrete project described should be given in the rectangular space under the appropriate headings on the left. The right hand column should reflect only the PHS request. The Total Direct Costs (bottom right hand column total) should be the total application request to the PHS, not including the required matching funds. These data should be summarized in tabular form. (Contact the Animal Resources Program at address below for suggested format.) E Budget for Entire Proposed Project Period - Application, Page 5 - Not applicable (do not complete this section). F Justification - Application, Page 5 - Justification should be provided in this section for all equipment items requested in terms of the proposed improvement program. Failure to adequately justify why each requested item is needed will likely result in its deletion from the recommended budget. More extensive justification may be provided in the body of the narrative (SECTION 2, D.2.f.). As part of the justification, information such as the species and number of animals, cages, tests or surgeries involved, should be provided as appropriate. The location and use of each piece of equipment should be clearly described. The failure to adequately justify equipment items has been a major weakness of applications in the past. G Summary Sheets - (Contact the Animal Resources Program at address below for suggested format.) These sheets have been developed to assist investigators in the preparation of the application as well as to assist the reviewers in their review of the application. They should be completed and placed between the Budget Justification and the Biographical Sketches section of the application. H Letter of Assurance - Provide assurance of matching funds for the total PHS award and the projected source(s) and amount of these funds in a separate letter or memorandum signed by a responsible institutional official. This letter should be placed before the start of SECTION 2. SECTION 2 Research Plan The points identified under Review Procedures and Criteria should be considered when this section is prepared. All information critical to the review should be in SECTION 2, and not in an appendix. Please note the instructions on Page 20 of Form PHS 398 concerning the limitation of 20 pages for Sections A-D of the Research Plan. A Specific Aims - (Limit to 1 page) Clearly present the aims of the animal resource improvement project and relate them to the short- and long-term goals of the institution's animal resource program. B Background and Significance - (Limit to 2-3 pages) This section should demonstrate the institution's overall involvement in animal related research. In addition, the following current information should be provided as shown on the sample Data Sheet (contact the Animal Resources Program at the address below for sample Data Sheet): 1) the institution's total annual research budget that involves the use of animals; 2) the annual dollar level of support (direct costs) from PHS vs. non-PHS sources that make up this budget; and 3) the institution's total number of projects using laboratory animals. Failure to provide these data will weaken the application. This section should also be used to relate the significance of the proposed resource improvement project to the institution's overall biomedical research programs as well as to the individual research projects that will be affected. If the resource will be used by a relatively small number of research projects, a brief description of those projects, including the source and amount of funding on an annual basis for each, must be indicated. C Progress Report/Preliminary Studies - Not applicable. D Experimental Design and Methods - This section should provide an overall description of the institution's animal care and use program. It should also demonstrate how the proposed facility improvement program will enhance the resource and how it fits into the institution's overall plan to meet or maintain PHS standards for animal care and use. The equipment items requested may be justified further in the context of the overall animal care program as part of this narrative. The A&R request should be described/justified as indicated in Paragraph 2.g. below. 1 Introduction - Provide relevant background information and a description of the current status of the institution's animal resource facilities and program as they relate to biomedical research and research training. Include relevant information regarding current deficiencies in the animal care program as cited by the American Association for Accreditation of Laboratory Animal Care (AAALAC), the Institutional Animal Care and Use Committee (IACUC) facility review reports, and the institution's PHS Animal Welfare Assurance Statement. Any problems in meeting the provisions of the Animal Welfare Act should also be addressed. This information is important for documenting the need for facility improvement support. 2 Project Plan - This section should describe how the requested improvements will accomplish the Specific Aims presented in Item A. It is important to describe how the requested improvements will correct the deficiencies and problems documented above. If the project is part of an overall larger facility improvement plan, the larger plan and how the project fits into it should be described. This section should also include a description of the following aspects of the animal resource: a Administrative arrangements and structure of the animal resource. The lines of authority and responsibility for administering the institution's program for the care and use of animals should be clearly presented. The role and composition of the IACUC and how compliance with relevant laws, policies, and guidelines is achieved should be included. If this proposal encompasses several institutions in a campus-wide program, the planning process that resulted in this proposal should be described. b Animal care procedures and the animal health program. This section should include information concerning veterinary oversight, vendor surveillance, conditioning programs, colony and environmental monitoring, and diagnostic capabilities in anatomic pathology, clinical chemistry, hematology, and microbiology. The general description of the animal care program should be supported by data that characterize various activities, such as numbers of laboratory procedures for monitoring and disease diagnosis, veterinary inspections for animal health, etc. If specialized equipment, such as microisolators, are requested, they should be part of an overall system, and the husbandry program to utilize this equipment should be carefully outlined. Failure to carefully describe the basic program of animal care, including veterinary care, has been a major weakness of many applications. c Outline the total staff and functional organization of the animal resource, both current and planned, following the requested improvements. Outline the qualifications of the animal care staff and the training opportunities available to them. d List all financial support for the animal resource, including sources and amounts (e.g., recharge, core funding from the institution, etc.) and the operating budget (listed by major categories). Provide a copy of per diem and service charge schedules and indicate their method of determination. The latter information may be included in an appendix. e Expenditures for capital improvements (facilities and equipment) during the past five years and future plans for such needs should be described. Any previous support for improvement of the institution's animal facilities from the ARP, NCRR should be noted. How the support was utilized and the effect on the animal care program should be described briefly. f Provide a brief description of all campus and off-campus animal facilities, including sites where experimental surgery is performed. Indicate the person responsible for the direction and day-to-day management of each animal facility. In this section, the need for specific items of equipment, in relation to the various facilities where they will be located, should be justified (See D.2.g. below for A&R). The reason for the need, the facility that will benefit, and the ultimate improvement of the overall animal care program should be clearly evident. As shown on the sample Data Sheet (contact the Animal Resources Program at address below for sample Data Sheet), indicate the number of animals (by species) used or produced per year, and the average daily census for each major component of the animal resource. If equipment is requested for surgical or diagnostic facilities, the case load, species, and types and numbers of surgeries or diagnostic tests must be documented on the Data Sheet. These data are important to the evaluation of the application, as well as for the justification of need. g For any proposed A&R, a narrative summary (as outlined below), line drawings, and cost estimates must be included. (Contact the Animal Resources Program at address below for sample format.) If multiple sites are involved, the A&R, including cost estimates proposed for each site, should be described separately for each site. The following narrative format should be followed: Narrative Summary (1) Relate the proposed renovation to projected animal populations by the species and research projects that will utilize the facility. Daily and annual census data (by species) must be provided. The animal care and use program for the animal facility that is to be renovated must be well described in D.2.b., Animal care procedures and animal health plan. (2) List the functional components, size, and square footage of each component (room, alcove, cubicle, etc.) that will be directly affected by the renovation project. (3) List engineering criteria applicable to each component (mechanical, electrical, and utilities). Include information such as the number of air changes per hour, electrical power, light levels, hot and cold water, and steam. (4) List appropriate architectural criteria, such as width of corridors and doors, and surface finishes. (5) List all fixed equipment requested for the renovated area. (6) List all movable equipment requested for the renovated area. Line Drawings (On 8-1/2" x 11" paper only, DO NOT SUBMIT BLUEPRINTS). These drawings will not be considered within the 20 page limit for Section 2. All floor plans must be legible, with the scale clearly indicated. (1) The plot plan should indicate the location of the proposed renovation area in the building. (2) Include the as-built drawings of the proposed renovation area and indicate any demolition. (3) Provide the architectural plan(s) of the proposed renovation. The plans should indicate size (dimensions), function, and net and gross square feet of space for each room. The total net and gross square feet of space to be renovated should also be given. (4) Changes or additions to existing mechanical and electrical systems should be clearly narrated in notes made directly on the plan or attached to the plan. (5) A Finish Schedule which indicates the type of new finishes to be applied to room surfaces should be included in the plan. SECTION 3 Appendix Material All information critical to the review must be included in Sections 1 and 2 of the application. Be very selective and include only relevant supplementary information in the appendix. Do not include standard references or other generally available information. Six collated sets of the appendix material must be included in the application package. All appendix material must be identified with the name of the Principal Investigator and the institution. Do not mail this appendix material separately, but include it with the original grant application. SUBMISSION PROCEDURE 1 The completed original application and four copies including appendix material should be mailed or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** 2 An additional two copies of the application and appendix material should be mailed to: Dr. Arthur Schaerdel, Executive Secretary Office of Review National Center for Research Resources National Institutes of Health Westwood Building, Room 10A16 5333 Westbard Avenue Bethesda, MD 20892** 3 Inquiries about specific instructions for application and other aspects of the program should be directed to: Animal Resources Program National Center for Research Resources National Institutes of Health Westwood Building, Room 857 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-5175 4 Application forms (PHS 398) may be obtained from grantee business or sponsored projects offices or from: Office of Grants Inquiries Division of Research Grants National Institutes of Health Westwood Building, Room 440 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7441 ** 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 NIH. 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. This program is described in the Catalog of Federal Domestic Assistance No. 93.306, Laboratory Animal Sciences and Primate Research. Awards will be made 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 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. Brought to you by Super Global Mega Corp .com