RFA-TS-13-0010501SUPP15 02 05 15.pdf

Centers for Disease Control and Prevention

Agency for Toxic Substances and Disease Registry Extramural Research Program Office

Continuing Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation

RFA-TS-13-0010501SUPP15

Application Due Date: 02/05/2015

Continuing Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation

RFA-TS-13-0010501SUPP15

TABLE OF CONTENTS

Part 1. Overview Information

Key Dates Required Application Instructions Executive Summary

Part 2. Full Text

Section I. Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 1. Overview Information Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Agency for Toxic Substances and Disease Registry Extramural Research Program Office (ATSDR ERPO) Agency for Toxic Substances and Disease Registry (ATSDR) Funding Opportunity Announcement (FOA) Title Continuing Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation Activity Code U01; Cooperative Agreement

Funding Opportunity Announcement Type Reissue of TS13-001 Funding Opportunity Announcement Number

RFA-TS-13-0010501SUPP15

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.161 Category of Funding Activity:

Health FOA Purpose The purpose of this FOA is to support investigator-initiated research that will continue to expand and advance our understanding of exposures to uranium among Navajo mothers and their infants. Priority areas for this supplement are to conduct detailed environmental home assessments to characterize potential exposures.

Key Dates Publication Date: To receive notification of any changes to RFA-TS-13-0010501SUPP15, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link. An email address is needed for this service.

Letter of Intent Due Date: N/A

Application Due Date: 02/05/2015

On-time submission requires that electronic applications be error-free and made available to CDC for processing from eRA Commons on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov/eRA Commons no later than 5:00 PM U.S. Eastern Time. Note:

HHS/CDC grant submission procedures do not provide a period of time beyond the application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review: 02/25/2015 This is an estimated date. The review will be conducted in February or March, 2015.

Secondary Review: 03/13/2015 http://www.grants.gov

This is an estimated date. The review will be conducted in February or March, 2015.

Estimated Start Date: 04/13/2015 This is an estimated date. The actual start date will be in March or April, 2015.

Expiration Date: 02/06/2015 Due Dates for E.O. 12372: Due no later than 60 days after the application receipt date.

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note: The Research Strategy component of the Research Plan is limited to 10 pages.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose: The purpose of this FOA is to support investigator-initiated research that will continue to expand and advance our understanding of exposures to uranium among Navajo mothers and their infants. Priority areas for this supplement are to conduct detailed environmental home assessments to characterize potential exposures.

Mechanism of Support: U01; Cooperative Agreement

Funds Available and Anticipated Number of Awards. The total level of funding available for this FOA is $360,000 (indirect and direct costs). One award is expected. The actual award level is contingent upon availability of funds and a meritorious application. The total award depends upon the project quality, duration and cost proposed.

Budget and Project Period. The estimated total funding (direct and indirect) for the single 12 month budget period is $360,000. The estimated project period will run from 04/13/2015 to 08/31/2015.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. Application and Submission Information of this announcement.

Eligible Institutions/Organizations. Institutions/organizations listed in Section III.1 are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

Number of PDs/PIs. One.

Number of Applications. Institutions may submit only one application.

Application Type. Revision.

Special Date(s). None.

Application Materials. See Section IV.1 for application materials.

Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (770) 488-2783.

http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority

This program is authorized under Section 104(i)(15) of the Comprehensive Environmental Response Compensation and Liability Act (CERCLA),[42 U.S.C. Section 9604(i)(15)], as amended.

1. Background and Purpose

The Navajo Nation Reservation encompasses 16 million acres of New Mexico, Utah and Arizona, and is the largest Alaska Native / American Indian Reservation in the United States (1). From 1948 to 1986, hundreds of uranium mining and milling operations were conducted on the Navajo Nation (2). These mining and processing operations have left a legacy of potential uranium exposure from abandoned uranium mines/mills, drinking water and soil contamination, and homes and structures built with mining waste (3,4). Uranium is a naturally-occurring radioactive metal and may cause adverse health effects related to both its radiological and chemical properties (5,6). Exposure to uranium as a heavy metal, primarily damages the kidneys and urinary system (7,8). Although the renal health effects of uranium have been studied extensively, there have been very few studies to examine the reproductive toxicity from non-occupational exposure to natural uranium.

The majority of studies examining the reproductive toxicity of natural uranium have been in animals. These studies have shown that uranium exposure in mice resulted in decreased numbers of offspring, reduced fetal growth, and congenital malformations (7,9). In one study, female mice that drank water containing uranium at or below the US Environmental Protection Agency (EPA) maximum contaminant level (30 µg/L) exhibited indicators of early onset of puberty (10). The authors concluded that uranium is an endocrine-disrupting chemical and suggested that populations exposed to environmental uranium should be studied for elevated risk of reproductive cancers and fertility complications (10). Research shows that endocrine disruptors may pose the greatest risk to infants during prenatal and early postnatal development when organ and neural systems are developing (11,12). These early exposures have been associated with reproductive cancers later in life (12). The findings from these previous animal studies indicate further epidemiologic investigations are warranted.

There is a paucity of recent studies examining uranium exposure and subsequent maternal and child health outcomes on the Navajo Reservation. A 1992 nested case-control study examined congenital anomalies, developmental disorders, and other adverse birth outcomes among Navajos born at the Shiprock Indian Health Service Hospital. The study found a statistically significant association between adverse birth outcomes and the mother’s residence within 0.5 miles of uranium mill tailings or uranium mine waste dumps (13). In another study, the average age-adjusted incidence of reproductive cancer in New Mexico Native American children was eight times the incidence non-Native American children (14). Although cultural and social factors may influence birth and/or reproductive health outcomes among Navajo women (15), further study is warranted to better understand the potential associations between exposure of pregnant Navajo mothers and infants to environmental uranium and adverse birth outcomes and developmental delays.

American Indians and Alaska Natives experience considerable health disparities compared to the general U.S. population (16,17). These disparities are evident in maternal and child health on the Navajo Nation.

Only 61 percent of Navajo mothers with live births received prenatal care in the first trimester as compared to 83 percent of all US mothers (18). The infant mortality rate among Navajos is 8.5 deaths per 1000 live births, compared to 6.9 deaths per 1000 live births among all races. Postnatal mortality rates for Navajo infants are 2.1 times higher than all races in the US, and the mortality rate for sudden infant death syndrome was 2.3 times the rate for the US in 2000. Additionally, congenital anomalies are the leading cause of infant death among Navajos (18). Several potential health effects of uranium are of particular concern to susceptible populations such as infants, children, and those of reproductive age (18). Although uranium is a suspected teratogen, epidemiological studies are needed to document individual biomarker exposure to uranium and to differentiate the health effects of uranium from that of other teratogens (19,20).

The research efforts requested in this FOA complement and support current environmental investigations and possible future exposure mitigation efforts being conducted by a consortium of federal agencies to address uranium contamination on the Navajo Nation. In August 2008, the consortium, led by EPA and the Navajo Nation released the “Health and Environmental Impacts of Uranium Contamination in the Navajo Nation, Five-Year Plan”. This plan was developed at the request of the US House Committee on Oversight and Government Reform. The objectives of the plan fall into three categories: assess structures and water sources that are likely to be contaminated, cleanup and/or mitigate harmful exposures, and assess health risks faced by individuals residing near mill sites or abandoned mine sites (3).

As part of the response to the Congressional charge, ATSDR awarded a research cooperative agreement to the University of New Mexico Community Environmental Health Program (UNM-CEHP) entitled “A Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation” in August 2010. In partnership with the Navajo Nation and Indian Health Service, this cooperative agreement supported the design and initial epidemiological studies of health conditions among Navajo mothers and their infants caused by non-occupational exposures to uranium released from past mining and milling operations on the Navajo Nation. In September 2013, ATSDR awarded a continuation cooperative agreement to the University of New Mexico Community Environmental Health Program (UNM-CEHP) entitled “Continuing Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation”.

This cooperative agreement was awarded to continue work on an epidemiologic study focusing on pregnant Navajo mothers and their infants and includes several important initiatives. As pregnant women are enrolled in the study they provide biological specimens (blood and urine). Additional samples are collected from the mother prior to delivery and from the infant at the time of delivery. The biological specimens are analyzed for body burden levels of heavy metals, including uranium. Post-partum and infant developmental surveys are administered following birth and when the infant is 2, 6, 9, and 12 months old. Additionally, home environmental assessments are conducted to assist with the characterization of potential sources of exposure to environmental contaminants. At the end of the first budget year (September 1, 2013 to August 31, 2014), 333 mother-infant pairs were participating in the study. The target enrollment for the second budget year (September 1, 2014 to August 31, 2015) is an additional 300 mother-infant pairs.

The project is currently funded through the budget year 2 (September 1, 2014-August 31, 2015). The funding level for the current budget year is sufficient to complete the targeted enrollment, collect and analyze the biological samples from the mothers and infants, and administer the infant developmental surveys. However, the funding is not sufficient to conduct the home environmental assessments for a portion of the women who enrolled during the first budget year or any of the women who enroll during the second budget year;

approximately 350 women will need a home environmental assessment this year.

The research conducted under the current cooperative agreement will provide information about the body burden of uranium and other heavy metals in pregnant women and the infant's development during the first year for the study population. This FOA seeks research to provide information on whether the home environment contributes to the participant's exposure to uranium or heavy metals. The results of the research from this FOA may provide information on whether potential sources of uranium exposure exist in the homes of study participants at levels that could harm human health.

Purpose

The purpose of the program is to support investigator-initiated research that will continue to expand and advance our understanding of exposures to uranium among Navajo mothers and their infants. Priority areas for this supplement are to conduct detailed environmental home assessments to characterize potential exposures. This program addresses the “Healthy People 2020” priority areas of Environmental Health and

Public Health Infrastructure, and is in alignment with ATSDR’s performance goals to determine human health effects associated with exposures at hazardous waste sites to Superfund-related priority hazardous substances.

References

1. Panikkar, B and Brugge, D. The Ethical Issues in Uranium Mining Research in the Navajo Nation.

Accountability in Research. 2007:12:121-153

2. Brugge D, Goble R. The history of uranium mining and the Navajo people. Am. J. Public Health. Sep 2002;92(9):1410-1419.

3. Bureau of Indian Affairs, Department Of Energy, Nuclear Regulatory Commission, Environmental Protection Agency, Indian Health Service. Health and Environmental Impacts of Uranium Contamination in the Navajo Nation; Five-Year Plan. In: Bureau of Indian Affairs, Department of Energy, Nuclear Regulatory Commission, Environmental Protection Agency, Indian Health Service, eds2008.

4. Brugge D, Goble R. The history of uranium mining and the Navajo people. Am. J. Public Health. Sep 2002;92(9):1410-1419.

5. Brugge D, de Lemos JL, Oldmixon B. Exposure pathways and health effects associated with chemical and radiological toxicity of natural uranium: a review. Rev. Environ. Health. Jul-Sep 2005;20(3):177-193.

6. Ribera D; Labrot F; Tisnerat G; Narbonne J F. Uranium in the environment: occurrence, transfer, and biological effects. Reviews of Environmental Contamination and Toxicology 1996;146():53-89.

7. Kurttio P, Auvinen A, Salonen L, et al. Renal effects of uranium in drinking water. Environ. Health Perspect. Apr 2002;110(4):337-342.

8. D.M. Taylor and S.K. Taylor, Environmental uranium and human health, Rev Environ Health 12 (1997),

pp. 147–157

9. Domingo, Jose L., Reproductive and developmental toxicity of natural and depleted uranium: a review.

Reproductive Toxicology,2001 Nov, 603-609

10. Raymond-Whish S, Mayer LP, O'Neal T, Martinez A, Sellers MA, Christian PJ, Marion SL, Begay C, Propper CR, Hoyer PB, Dyer CA. Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor-dependent responses in female mice. Environ Health Perspect. 2007 Dec;115(12):1711-6

11. Newbold, RR, Padilla-Banks, E, Jefferson, WN 2006. Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations. Endocrinology 147(6): S11-S17

12. Birnbaum LS, Fenton SE. Cancer and developmental exposure to endocrine disruptors. Environ Health Perspect 2003;111:389–94

13. Shields LM, Wiese WH, Skipper BJ, Charley B, Benally L. Navajo birth outcomes in the Shiprock uranium mining area. Health Phys. Nov 1992;63(5):542-551.

14. Duncan MH, Wiggins CL, Samet JM, Key CR. Childhood cancer epidemiology in New Mexico's American Indians, Hispanic whites, and non-Hispanic whites, 1970–82. J Natl Cancer Inst 1986, 76:1013–1018

15. Boyce WT, Schaefer C, Harrison HR, et al. Social and cultural factors in pregnancy complications among Navajo women. Am J Epidemiol 1986;124:242-53

16. Alexander GR, Wingate MS, Boulet S. Pregnancy outcomes of American Indians: contrasts among regions and with other ethnic groups. Matern Child Health J, 2008, 12:S5-S11

17. Grossman DC, Baldwin LM, Casey S, Nixon B, Hollow W, Hart LG. Disparities in infant health among American Indians and Alaska Natives in US metropolitan areas. Pediatrics. 2002;109:627–633

18. Indian Health Service. Regional Differences in Indian Health 2002-2003 Edition Rockville, Md: US Department of Health and Human Services, Indian Health Service; 2003.

19. Magdo HS, Forman J, Graber N, Newman B, Klein K, Satlin L, Amler RW, Winston JA, Landrigan PJ.

Grand Rounds: Nephrotoxicity in a Young Child Exposed to Uranium from Contaminated Well Water Environ Health Perspect. 2007 Aug;115(8):1237-41

20. Hindin R, Brugge D, Panikar B. Teratogenicity of depleted uranium aerosols: A review from an epidemiological perspective. Environmental Health: A Global Access Science Source, 4:17, September 30, 2005.

Healthy People 2020 and other National Strategic Priorities

This program addresses the “Healthy People 2020” priority areas of Environmental Health and Public Health Infrastructure, and is in alignment with ATSDR’s performance goals to determine human health effects associated with exposures at hazardous waste sites to Superfund-related priority hazardous substances.

Public Health Impact

Previous uranium mining and milling activities in the Navajo Nation have resulted in contamination of soil and drinking water near homes throughout the area. Uranium exposure is associated with adverse health effects related to both its radiological and chemical properties; however, most studies have focused on the renal system. Toxicological studies of uranium exposure in mice have documented health effects in the reproductive system that include reduced fetal growth and congenital malformation. A few epidemiological studies have documented adverse birth outcomes and a higher incidence of reproductive cancer amoung Navajo women. This study will provide additional information on non-occupational exposure to environmental uranium and subsequent health effects on the Navajo Nation. This knowledge is essential to prevent and mitigate current and future exposures and adverse health outcomes on the Navajo Nation.

Relevant Work

ATSDR is directed by congressional mandate to perform specific functions concerning the effect on public health of hazardous substances in the environment. ATSDR works with communities, environmental groups, tribal governments and local, state and federal agencies to evaluate exposures to hazardous substances in communities to protect the public’s health. ATSDR’s work on the Navajo Nation Reservation began in September 2008, when CDC and ATSDR were asked to participate in an effort requested by Rep. Henry Waxman (D-CA), then-Chair of the House Oversight & Government Reform Committee. Initially, NCEH collaborated with EPA Region 9 on a water quality study to investigate public health impacts of hauling water from unregulated water wells. In 2009, ATSDR initiated what has now known as the Navajo Birth Cohort Study.

ATSDR’s involvement with the Navajo Nation Birth Cohort Study is only one aspect of ATSDR’s work to identify, evaluate and offer mitigation recommendations for communities exposed to harmful levels of environmental contaminants. Additional examples about ATSDR’s evaluations are available and can be found at http://www.atsdr.cdc.gov/stories/index.html.

Previous related research efforts funded by ATSDR have evaluated the level of PCB and DDE in mothers consuming contaminated fish from the Great Lakes region during pregnancy, and whether their exposure was associated with adverse health effects in the children. The health outcomes evaluated include neurobehavioral deficits in children and adolescents, and the gene activity involved in sex steroid production and breakdown.

2. Approach

Research funded under this FOA will continue to expand and advance our understanding of exposures to uranium among Navajo mothers and their infants. Specifically, this FOA is to conduct detailed environmental home assessments to characterize potential exposures at the home of pregnant women enrolled in the Navajo Nation Birth Cohort study.

http://www.atsdr.cdc.gov/stories/index.html

Objectives/Outcomes

Research Objectives

The epidemiologic study conducted under the current cooperative agreement focuses on pregnant Navajo mothers and their infants and includes several important initiatives. As pregnant women are enrolled in the study they provide biological specimens (blood and urine). Additional samples are collected from the mother prior to delivery and from the infant at the time of delivery. The biological specimens are analyzed for body burden levels of heavy metals, including uranium. Post-partum and infant developmental surveys are administered following birth and when the infant is 2, 6, 9, and 12 months old. Home environmental assessments are conducted to assist with the characterization of potential sources of exposure to environmental contaminants.

The funding level for the current budget year is not sufficient to conduct the home environmental assessments. The research objectives of this FOA focus on the objectives of the home environmental assessments. The research to be conducted under this supplement will characterize the potential exposures study participants have to environmental contaminants at their home environment. The results will improve our understanding of whether and how the home environment contributes to the mother and infant’s exposure to uranium and other environmental contaminants. The home environmental sampling will include, but is not limited to:

Collection and analysis of at least one indoor air radon test.

Collection and analysis of at least one vacuum and one swipe dust sample from the floor and work surfaces.

Collection and analysis of gamma radiation scans.

Target Population

Navajo women who receive care at one of the five clinic sites located in the Navajo Nation Reservation.

Collaboration/Partnerships

The applicant shall work in coordination with ATSDR, the Indian Health Service and Navajo Nation to identify study participants eligible for the home environment assessment, and to conduct the assessments and review the results.

Evaluation/Performance Measurement

Applicants should include an analytical plan that describes the research design, data collection measures, and data analysis design. Outcomes to be evaluated should be clearly specified.

Translation Plan

Research findings should be disseminated through publications, including articles in peer reviewed journals and “Research Briefs” for diverse audiences, as well as presentations at professional conferences and other venues. An explanation for how the scientific findings will be translated into public health programs, policies or practice should be included in the application.

Section II. Award Information

Funding Instrument Type: Cooperative Agreement A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

Revision (formerly Competing Supplement) - Request for additional funds for a current award to expand the scope of work. Applicants should contact the awarding agency for advice on submitting any revision/supplement application.

Estimated Total Funding: $360,000

The ceiling is $360,000 for a single 12-month budget period (including direct and indirect costs).

Anticipated Number of Awards: 1

Awards issued under this FOA are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling: $360,000 Per Project Period Award Floor: $360,000 Per Project Period Total Project Period Length: 1 year(s) Throughout the project period, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (http://www.hhs.gov/ asfr/ogapa/aboutog/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: Public and State controlled institutions of higher education

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Special Eligibility Requirements

Limited eligibility. This FOA is intended to provide supplemental funds to complete efforts proposed in the original scope of the approved project for FOA #TS13-001. The University of New Mexico is uniquely qualified to conduct this research. They have the technical expertise to conduct the required sampling, scientific background to analyze the results, and established partnerships within the community to achieve the necessary level of participation by pregnant mothers.

4. Justification for Less than Maximum Competition http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

The University of New Mexico (UNM) is uniquely qualified to conduct the efforts requested in this supplemental FOA. UNM has established partnerships to coordinate with area health clinics sponsored by the Indian Health Service (IHS) to ensure the biomonitoring samples obtained from the pregnant women and infants are properly collected and prepared for laboratory analyses. UNM established partnerships with the Navajo Nation health and environmental agencies and community members to be able to recruit pregnant women to the study.

UNM successfully worked with ATSDR on the earlier cooperative agreement funded under TS10-001, A Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation. UNM worked with Navajo Nation agencies and community, IHS, and ATSDR to investigate community concerns about living in close proximity to elevated levels of uranium. The research from TS10-001 resulted in the design and initial epidemiological studies of health conditions among Navajo mothers and their infants caused by non-occupational exposures to uranium released from past mining and milling operations on the Navajo Nation. This study was designed to both address the community's greatest concerns regarding birth outcomes and provide valuable epidemiological information to the scientific community about the reproductive effects of exposure to elevated levels of environmental uranium.

During the first budget year of the current cooperative agreement funded by TS13-001, UNM successfully enrolled over 333 mother-infant pairs and conducted home environmental assessments for most of the enrollees (approximately 50 women did not receive the home evaluation assessment). The mother-infant pairs provide urine samples that will be analyzed to assess their body burden of uranium and other heavy metals. The infants are periodically assessed to evaluate their development according to medical norms. The home environmental assessments are conducted to determine whether and how the home environment contributes to the mother and infant's exposure to uranium and other heavy metals.

The funds available for the second year of the cooperative agreement funded by TS13-001 were not sufficient to conduct home environmental assessments for a portion of the women who enrolled in the first budget year or any of the 300 women who will be enrolled during the second year. This supplemental funding will ensure all women enrolled during the first or second year receive a home environmental assessment. Approximately 350 home environmental assessments will be conducted; this includes the homes of the 300 women expected to be enrolled this year (budget year 2) and a small number of women (approximately 50) enrolled during the end of budget year 1.

The University of New Mexico is a public institution of higher education. Similar limited or single-source eligibility requests were made prior to releasing the original TS10-001 FOA and the following TS13-001 FOA. Both were accepted.

With the research funded by this supplement, ATSDR will gain a better understanding of the relationship between the level of exposure the pregnant women have to uranium in their homes, the concentration of uranium in their urine, the concentration of uranium in the urine of infants, and the infants' development.

Without this supplement the research results will be unable to demonstrate whether the uranium levels measured in the mothers and infants are associated with exposures at home or from other locations; limiting the ability of the researchers to provide meaningful information to the community on actions they can take to reduce harmful exposures.

5. Responsiveness

Application must not exceed page limits

Application must clearly define methodolgy to meet research objects defined in this FOA

6. Required Registrations

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato. int/AC135Public/Docs/US%20Instructions%2 0for%20NSPA%20NCAGE.pdf System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/portal/SAM/#1.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes.

The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements.

The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM).

Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the grantee organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the grantee organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for HHS/CDC support.

9. Cost Sharing https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://www.sam.gov/portal/SAM/%231 http://www.Grants.gov https://public.era.nih.gov/commons/public/login.do?TYPE=33554433&REALMOID=06-1edb031f-46c7-44b3-b803-60b537de74d2&GUID=&SMAUTHREASON=0&METHOD=GET&SMAGENTNAME=-SM-938PYmoLVb4VrDeXo04LZUDVDvc%2b3899ByInEAjuSUvWNIGfB2zRpWiCivYGCogG&TARGET=-SM-http%3a%2f%2fpublic%2eera%2enih%2egov%2fcommons http://www.Grants.gov http://fedgov.dnb.com/webform https://www.sam.gov/index.html

This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http:// www.hhs.gov/ asfr/ ogapa/ aboutog/ hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement, (http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), applications received in response to the same funding opportunity announcement generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Only one application per institution (normally identified by having a unique DUNS number) is allowed.

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

If access to the Internet is not available or if the applicant encounters difficulty accessing the forms on-line, contact the HHS/CDC Procurement and Grants Office Technical Information Management Section (PGO TIMS) staff at (770) 488-2700 or pgotim@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern Standard Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/ 424/SF424_RR_Guide_General_VerC.pdf), except where instructed in this Funding Opportunity Announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

The forms package associated with this FOA includes all applicable components, mandatory and optional.

Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components.

All page limitations described in this individual FOA must be followed. For this FOA, the Research Strategy section is limited to 10 pages.

3. Letter of Intent Due Date for Letter of Intent:

N/A

4. Required and Optional Components http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.Grants.gov mailto:pgotim@cdc.gov

4. Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this FOA in Grants.gov includes all applicable components for this FOA, required and optional.

5. PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description).

Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings: Significance, Innovation and Approach. Describe the proposed research plan, including staffing and timeline.

4. Inclusion Enrollment Report (Renewal and Revision applications ONLY)

5. Progress Report Publication List (for Continuation ONLY)

Human Subjects Section

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

8. Targeted/Planned Enrollment Table (for New Application ONLY)

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

Component 4 (Inclusion Enrollment Report) applies only to Renewal and Revision applications for clinical research. Clinical research is that which is conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies). Follow the page limits in the SF 424 unless otherwise specified in the FOA.

All instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) must be followed along with any additional instructions provided in the FOA.

6. Appendix

6. Appendix Do not use the appendix to circumvent page limits. A maximum of 10 PDF documents are allowed in the appendix. Additionally, up to 3 publications may be included that are not publically available. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

7. Page Limitations All page limitations described in this individual FOA must be followed. For this specific FOA, the Research Strategy component of the Research Plan narrative is limited to 10 pages. Supporting materials for the Research Plan narrative included as appendices may not exceed 5 PDF files with a maximum of 30 pages for all appendices.

8. Format for Attachments Designed to maximize system-conducted validations, multiple separate attachments are required for a complete application. When the application is received by the agency, all submitted forms and all separate attachments are combined into a single document that is used by peer reviewers and agency staff. Applicants should ensure that all attachments are uploaded to the system.

CDC requires all text attachments to the Adobe application forms be submitted as PDFs and that all text attachments conform to the agency-specific formatting requirements noted in the SF424 (R&R) Application Guide (Part I, Section 2) (http://grants.nih.gov/ grants/funding/424/ SF424_RR_Guide_General_VerC.pdf).

9. Submission Dates & Times Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov (http://www.grants.gov), the online portal to find and apply for grants across all Federal agencies. The eRA Commons systems retrieve the application from Grants.gov and check the application against CDC business rules. If no errors are found, the application will be assembled in the eRA Commons for viewing by the applicant before moving on for further CDC processing.

If errors are found, the applicant will be notified in the eRA Commons. They must make required changes to the local copy of their application and submit again through Grants.gov.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Once you can see your application in the Commons, be sure to review it carefully as this is what the reviewer will see. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons (http:// grants.nih. gov/grants /guide/url_redirect .htm? id=11123).

Information on the submission process is provided in the SF424 (R&R) Application Guide.

Note: HHS/CDC grant submission procedures do not provide a period of time beyond the grant application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e. error correction window).

http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://www.grants.gov/ http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123

The application package is not complete until it has passed the Grants.gov/eRA Commons validation process. This process and email notifications of receipt, validation or rejection may take two (2) business days.

Applicants are strongly encouraged to allocate additional time prior to the submission deadline to submit their applications and to correct errors identified in the validation process. Applicants are encouraged also to check the status of their application submission to determine if the application packages are complete and error-free. Applicants who encounter system errors when submitting their applications must attempt to resolve them by contacting the Grants.gov Contact Center (1-800-518-4726; support@grants.gov). If the system errors cannot be resolved, applicants must contact CDC PGO TIMS at 770-488-2700; www.pgotim@cdc.gov for guidance at least 3 calendar days before the deadline date.

After submission of your application package, applicants will receive a “submission receipt” email generated by Grants.gov. Grants.gov will then generate a second e-mail message to applicants which will either validate or reject their submitted application package. This validation process may take as long as two (2) business days. A third and final e-mail message is generated once the applicant’s application package has passed validation and the grantor has confirmed receipt of the application.

Unsuccessful Submissions:

If an application submission was unsuccessful, the applicant must:

1. Track his/her submission and verify the submission status (tracking should be done initially regardless of rejection or success).

a. If the status states “rejected,” do #2a or #2b.

2. Check his/her emails from both Grants.gov and eRA Commons for rejection notices.

a. If the deadline has passed, he/she should email the Grant Management Specialist listed in the FOA (pgotim@cdc.gov) explaining why the submission failed.

b. If there is time before the deadline, he/she should correct the problem(s) and resubmit as soon as possible.

Due Date for Applications: 02/05/2015

Electronically submitted applications must be submitted no later than 5:00 p.m., ET, on the listed application due date.

10. Intergovernmental Review (E.O. 12372)

Your application is subject to Intergovernmental Review of Federal Programs, as governed by Executive Order 12372 (http://www.archives.gov/federal-register/codification/executive-order/12372.html). This order sets up a system for state and local review of proposed federal assistance applications. You should contact your state single point of contact (SPOC) as early as possible to alert the SPOC to prospective applications, and to receive instructions on your state’s process. Click on the following link to get the current SPOC list:

http://www.whitehouse.gov/omb/grants_spoc/.

11. Funding Restrictions All HHS/CDC awards are subject to the terms and conditions, cost principles, and other requirements described in the HHS Grants Policy Statement. Pre-award costs may be allowable as an expanded authority, but only if authorized by CDC.

For more information on expanded authority and pre-award costs, go mailto:support@grants.gov mailto:www.pgotim@cdc.gov http://www.archives.gov/federal-register/codification/executive-order/12372.html http://www.whitehouse.gov/omb/grants_spoc/ to: http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf.

12. Other Submission Requirements and Information

Application Submission Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

Applicants must complete all required registrations before the application due date. Section III.6 "Required Registrations" contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically (http://grants.nih.gov/grants/guide /url_ redirect.htm? id=11144).

Important reminders:

All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to CDC.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the…