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17: Appendix - Biology

17: Appendix - Biology


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Answer Key for End-of-Chapter Review Questions

Chapter 1

#1. A #2. D #3. E #4. B #5. A #6. C #7. C #8. A #9. B #10. B

Chapter 2

#1. B #2. B #3. C #4. C #6. D #7. A #8. D #9. A #10. B

Chapter 3

#1. C #2. A #3. A #4. D #5. C #6. A #7. D #8. A #9. E #10. A

Chapter 4

#1. D #2. B #3. A #4. A #5. B #6. A #7. B #8. B #9. C #10. A

Chapter 5

#1. E #2. D #3. C #4. D #5. E #6. B #7. B #8. C #9. B #10. A

Chapter 6

#1. C #2. C #3. B #4. B #5. D #6. A #7. A #8. E #9. C #10. D

Chapter 7

#1. A #2. E #3. A #4. A #5. E #6. A #7. B #8. C #9. A #10. D

Chapter 8

#1. D #2. C #3. A #4. D #5. A

Chapter 9

#1. D #2. B #3. A #4. B #5. A #6. C #7. E #8. E #9. D #10. E

Chapter 10

#1. C #2. B #3. A #4. B #5. B #6. C #7. A #8. E #9. A #10. E

Chapter 11

#1. A #2. A #3. B #4. E #5. C #6. B #7. C #8. B #9. D #10. D

Attribution

This work is licensed under CC BY 4.0 by Matthew R. Fisher.

Thumbnail image - This work is in the Public Domain, CC0


17: Appendix - Biology

National Institutes of Health (NIH)

National Institute on Aging (NIA)
National Institute on Minority Health and Health Disparities (NIMHD)

Aging Biology Research to Address Health Disparities (Admin Supp)

Additional funds may be awarded as supplements to parent awards using the following Activity Code(s):

Administrative supplement requests must be submitted on paper for the following activity codes:

Administrative supplement requests may be submitted electronically for the following activity codes:

K08 Clinical Investigator Award (CIA)
K23 Mentored Patient-Oriented Research Career Development Award
R01 Research Project Grant
R25 Education Projects

    - Notice of Participation in PA-17-164. See Notice NOT-MD-17-002. -Notice of Change to the Eligible Activity Codes for PA-17-164. See Notice NOT-AG-17-006.

This Funding Opportunity Announcement (FOA) announces the availability of administrative supplements to support aging biology research that addresses disparities in health.

May 3, 2017, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Application Guide (SF424 (R&R) Application Guide, eRA Commons Administrative Supplement User Guide or PHS 398 Application Guide, as appropriate) except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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. Applications that do not comply with these instructions may be delayed or not accepted for review.

This FY 2017 Administrative Supplement program is offered to support research that addresses disparities in aging and health, with specific focus on biological processes and mechanisms that are relevant to health disparities in aging.

Health disparities are differences in the incidence, prevalence and burden of diseases and differences in life expectancy, mortality rates and causes of death that exist among population groups in the United States. Health disparities are associated with a broad, complex, and interrelated array of factors that influence health, accelerate aging and reduce life expectancy. Exposure to unique stressors, enduring chronic stress, socioeconomic disadvantage and other forms of environmental adversity have been posited as important determinants of health disparities in the United States.

A current research direction is the examination of biological mechanisms - such as cellular function and communication, physiological indicators, and genetic stability - that may link with environmental factors to account for accelerated aging among specific populations that experience health disparities.

NIA's health disparities research goals are to (1) understand environmental factors and related biological mechanisms that diminish health and reduce life expectancy for populations that experience health disparities, (2) develop strategies to increase life expectancy and healthspan among aging adults and improve the health status of older adults from underserved and disadvantaged populations, and (3) use research insights and advances to inform policies that address and reduce health disparities.

NIA is interested in aging biology research to explore mechanisms through which environmental factors create and sustain health disparities related to aging. For example, chronic stress linked to living in harsh environmental conditions for certain racial/ethnic or socioeconomic position groups may influence key aging biology processes such as genetic stability and proteostasis. The accumulation of DNA damage throughout life may be important to biological aging. One important question is whether this genetic damage may be accelerated in the face of chronic stress. Rapid attrition of telomere regions has been used as a marker of genetic stability, providing a gauge for premature development of diseases such as aplastic anemia.

Other biological processes may be linked to harsh environmental conditions and are thus relevant for health disparities research related to aging. Research has shown that as an individual perceives stress, the brain’s hypothalamus sounds an alert to the adrenal glands indicating a physiological need to respond to a potentially harmful threat by the hypothalamus-pituitary-adrenal axis (HPA). The adrenal glands then produce cortisol that replenishes energy stores that have been depleted by the initial adrenaline rush. The HPA ultimately determines whether the stress will be handled by physiologic response or by HPA overload. Chronic HPA overload - which may be caused by an individual's chronic, routine perceptions of stress in harsh environmental conditions - has been linked to poor health outcomes such as diabetes mellitus, depression, asthma, and chronic fatigue syndrome.

Specifically, for this Funding Opportunity Announcement (FOA) we are interested in projects that explore processes - including cellular function and communication, physiological indicators, and genetic stability - that enable harsh environmental conditions to become biologically embedded.

Appropriate topics/studies include:

  • Studies on age x gene x environment interactions where the genotype (allelic variant) or environmental conditions (e.g., relative exposure to hazards often more common in disadvantaged neighborhoods) are recapitulated in laboratory organisms.
  • Studies focused on identifying molecular differences that contribute to racial, ethnic or gender disparities in stress responses, including differences in stress pathways such as nutrient sensing, hormones, inflammation, immune-senescence, metabolomics or genetics/epigenetics.
  • Studies focused on differences in metabolomes that can be linked to racial or ethnic disparities in functional, physiologic, or metabolic outcomes across the lifespan and in old age
  • Research that will examine biological mechanisms underlying health disparities in aging-related declines of function in organ systems (e.g., liver, lung, heart, kidneys).

The intent of this FOA covers, but is not limited to, the following types of applications:

Applications that propose to add studies using human tissues or cells to ongoing basic studies on aging in order to conduct exploratory and comparative analyses.

The funding instrument will be the same as the parent award.

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Non-competing Administrative Supplements

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

NIA intends to commit $250,000 in FY 2017 to fund 4 awards.

Budget requests may be for no more than $45,500 in direct costs.

The funding mechanism being used to support this program, administrative supplements, can be used to cover cost increases that are associated with achieving certain new research objectives, as long as the research objectives are within the original scope of the peer reviewed and approved project, or the cost increases are for unanticipated expenses within the original scope of the project. Any cost increases need to result from making modifications to the project that would increase or preserve the overall impact of the project consistent with its originally approved objectives and purposes.

The project and budget periods must be within the currently approved project period for the existing parent award. All awards are for a one-year period

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

All organizations administering an eligible parent award may apply for a supplement under this announcement.

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations

This announcement is for supplements to existing projects. To be eligible, the parent award must be active and the research proposed in the supplement must be accomplished within the competitive segment. The proposed supplement must be to provide for an increase in costs due to unforeseen circumstances. All additional costs must be within the scope of the peer reviewed and approved project.

IMPORTANT: The research proposed by the NIH grantee in the supplement application must be within the original scope of the NIH-supported grant project.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Since administrative supplements are made against active grants and cooperative agreements, many of these registrations may already be in place. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration. Grants.gov registration is only required if you plan to submit using the 'Electronic Application Submission through Grants.gov' option.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Individual(s) must hold an active grant or cooperative agreement, and the research proposed in the supplement must be accomplished within the competitive segment of the active award. Individuals are encouraged to work with their organizations to develop applications for support.

For supplements to parent awards that include multiple PDs/PIs, the supplement may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award. Do not use this administrative supplement application to add, delete, or change the PDs/PIs listed on the parent award. Visit the Multiple Program Director/Principal Investigator Policy in the SF424 (R&R) Application Guide for more information.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per NIA parent award may be submitted.

Applicant organizations may submit more than one application, provided that each is sufficiently distinct from any other administrative supplement currently under consideration by the awarding NIH Institute or Center.

Only active NIA awards with at least 18 months remaining at the time of submission will be considered. Awards in no-cost extension periods are not allowed to submit an application in response to this FOA.

Applicants must prepare applications using current forms in accordance with the Application Guide.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

All forms must be completed for the supplemental activities only and must not reflect funding or activities for the previously awarded parent award.

It is critical that applicants follow the instructions for their submission option (SF424 (R&R) Application Guide, eRA Commons Administrative Supplement User Guide or PHS 398 Application Guide, as appropriate) including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to documented requirements is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

All page limitations applicable to the parent award as described in the Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

The Research Strategy section of the administrative supplement application may not exceed 5 pages.

Administrative supplement requests for most single-project activity codes can be submitted using either paper or electronic submission processes. Administrative supplement requests for multi-project activity codes must be submitted using the paper submission process. See Activity Code section in Part 1 to determine if electronic submission is an option for your activity code.

Applicants submitting paper applications must use the PHS 398 Application Forms and the PHS 398 Application Guide.

Instructions for Electronic Application Submission through Grants.gov

Use the “Apply” button(s) in Part I of this announcement to access the application forms package posted at Grants.gov. If presented with more than one form package, use the Competition ID and Competition Titles provided to determine the most appropriate application forms package for your situation.

Prepare applications using the SF424 (R&R) forms associated with the chosen package. Please note that some forms marked optional in the application package are required for submission of applications for this announcement. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate required and optional forms, with the following additional guidance:

  • R&R Cover form: Select “Revision” in the “Type of Application” field.
  • Research Plan form: At a minimum, the Research Strategy section should be completed and must include a summary or abstract of the funded parent award or project. Other sections should also be included if they are being changed by the proposed supplement activities.
  • Project/Performance Site Location form: Include the primary site where the proposed supplement activities will be performed. If a portion of the proposed supplement activities will be performed at any other site(s), identify the locations in the fields provided.
  • Sr/Key Personnel form: List the PD/PI as the first person (regardless of their role on the supplement activities). List any other Senior/Key Personnel who are being added through this supplement, or for whom additional funds are being requested through this supplement include a biographical sketch for each.
  • Budget forms (e.g., R&R Budget, PHS 398 Training Budget): Only include funds requested for the additional supplement activities.
  • R&R Other Project Information form: If applicable, attach PDF documents in the “Other Attachments” field indicating that the proposed research experience was approved by the Institutional Animal Care and Use Committee (IACUC) or human subjects Institutional Review Board (IRB) at the grantee institution. Name the documents “IACUC Documentation.pdf” and/or “IRB Documentation.pdf”. Adherence to the NIH policy for including women and minorities in clinical studies must also be ensured, if additional human subjects’ involvement is planned for the supplement.

Special Instructions for Streamlined Submissions using the eRA Commons for electronic-based submissions

NIH offers a streamlined system through the eRA Commons for submitting administrative supplements. Login to the eRA Commons, identify the parent award, and prepare an administrative supplement request. A User’s Guide for submitting through this system is available, with the following additional guidance:

  • Budget information should be entered for the grantee institution in the tabs provided for each selected budget period.
  • Since there is no template or form available for subaward budget information, all subaward information must be included as a PDF attachment in the Subrecipient Budgets section showing the funds requested (by budget period) and using the same categories provided for the grantee institution. The attachment must also include any related budget justification information.
  • Use the “Add Other Attachments” function to include the following PDF documents:
  • Research Strategy including a summary or abstract of the funded parent award or project.
  • If applicable, attach documents indicating that the proposed research experience was approved by the Institutional Animal Care and Use Committee (IACUC) or human subjects Institutional Review Board (IRB) at the grantee institution. Adherence to the NIH policy for including women and minorities in clinical studies must also be ensured, if additional human subjects’ involvement is planned for the supplement component.

Instructions for Paper-based Submissions using the PHS 398 Application Forms

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application, with the following additional guidance:

  • Checklist: Select “Revision” in the “Type of Application” field.
  • Face Page (Form Page 1): On the face page of the application form, note that your application is in response to a specific program announcement, and enter the title and number of this announcement.
  • Research Plan: At a minimum, the Research Strategy section should be completed and must include a summary or abstract of the funded parent award or project. Other sections should also be included if they are being changed by the proposed supplement activities.
  • Project/Performance Sites section (Form Page 2): Include the primary site where the proposed supplement activities will be performed. If a portion of the proposed supplement activities will be performed at any other site(s), identify the locations in the fields provided.
  • Sr/Key Personnel section (Form Page 2): List the PD/PI as the first person (regardless of their role on the supplement activities). List any other Senior/Key Personnel who are being added through this supplement, or for whom additional funds are being requested through this supplement include a biographical sketch for each.
  • Budget for Entire Proposed Project Period (Form Page 5): A proposed budget should be submitted using the PHS 398 budget forms and should only include funds requested for the additional supplement activities.
  • If applicable, attach documentation in the Appendix section indicating that the proposed research experience was approved by the Institutional Animal Care and Use Committee (IACUC) or human subjects Institutional Review Board (IRB) at the grantee institution. Adherence to the NIH policy for including women and minorities in clinical studies must also be ensured, if additional human subjects’ involvement is planned for the supplement component.

The grantee institution, on behalf of the PD/PI of the parent award, must submit the request for supplemental funds directly to the awarding component that supports the parent award. Submit a signed, typewritten original of the application, including the checklist, to:

Carl V. Hill, Ph.D., M.P.H.
National Institute on Aging
Director, Office of Special Populations
31 Center Drive, MSC-2292
Bethesda, MD 20892
Email: [email protected]

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and Times. Applicants are encouraged to submit electronic applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

For electronic application submission, information on the submission process and a definition of on-time submission are provided in the SF424(R&R) Application Guide.

For paper-based application submission, information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted using the instructions specified above.

Applicants must complete all required registrations prior to submission. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission contact the Application Submission Contacts in Section VII.

Important reminders:
For applications submitted electronically on the SF424 (R&R) Application forms, all PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form 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 NIH.

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 (SAM). Additional information may be found in the Application Guide.

See more tips for avoiding common errors.

Administrative Supplements do not receive peer review. Instead, the administrative criteria described below will be considered in the administrative evaluation process.

The staff of the NIH awarding component will evaluate requests for a supplement to determine its overall merit. The following general criteria will be used:

Budget and Period of Support

NIH staff will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

NIH staff will consider the ability of the proposed supplement activities to increase or preserve the parent award’s overall impact within the original scope of award:

For Research and Research Center Awards Only (P50, R01, R03, R25): Will the administrative supplement increase or preserve the likelihood for the project to exert a sustained, powerful influence on aging biology research that addresses health disparities related to aging?

For Career Development Awards Only (K23, K08): Will the administrative supplement increase or preserve the likelihood for the candidate to maintain a strong aging research program that addresses health disparities related to aging?

In addition, each of the following criteria will be evaluated as applicable for the proposed supplement.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, NIH staff will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, NIH staff will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

NIH staff will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed (3) interventions to minimize discomfort, distress, pain and injury and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

NIH staff will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Administrative supplement requests will undergo an administrative evaluation by NIH staff, but not a full peer review. Applications submitted for this funding opportunity will be assigned to the awarding component for the parent award and will be administratively evaluated using the criteria shown above.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. This may be as an NoA for the supplemental activities only alternatively, it may be as either a revision to the current year NoA or included as part of a future year NoA. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website. When calculating the award for additional funds, NIH will 1) prorate funding if the requested budget period is adjusted at the time of award, and 2) use the institution’s current F&A rate i.e., the rate in effect when the new funding is provided.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Any supplements to Cooperative Agreements will be subject to the same Cooperative Agreement terms and conditions as the parent award.

Reporting requirements will be specified in the terms and conditions of award as applicable to the supplemental activities. In most non-competing continuation applications, the progress report and budget for the supplement must be included with, but clearly delineated from, the progress report and budget for the parent award. The progress report must include information about the activities supported by the supplement even if support for future years is not requested. Continuation of support for the supplement activities in the remaining years of the competitive segment of the grant will depend upon satisfactory review by the NIH awarding component of progress for both the parent award and the supplement project, the research proposed for the next budget period, and the appropriateness of the proposed budget for the proposed effort. This information is submitted with the Research Performance Progress Report (RPPR) and financial statements as required in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Felipe Sierra, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: [email protected]

Ron Kohanski, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: [email protected]

Lesa McQueen, M.Sc.
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals.

Single gene disorders are among the most well-understood genetic disorders given their straightforward inheritance patterns (recessive or dominant) and relatively simple genetic etiology. Although the majority of these diseases are rare, in total, they affect millions of Americans. Some of the more common single-gene disorders include cystic fibrosis, hemochromatosis, Tay-Sachs, and sickle cell anemia.

Even though these diseases are primarily caused by a single gene, several different mutations can result in the same disease but with varying degrees of severity and phenotype. But even the same mutation can result in slightly different phenotypes. This may be caused by differences in the patient’s environment and/or other genetic variations that may influence the disease phenotype or outcome. For example, other genes have been shown to modify the cystic fibrosis phenotype in children who carry the same CFTR mutation. In addition, for some disorders such as galactosemia, mutations in different genes can result in similar phenotypes.

Genetic testing is available for many single-gene disorders, however, the clinical examination is extremely important in the differential diagnosis particularly in patients with no family history. For some genetic conditions, patients can often be treated for their symptoms or modify their diets to prevent the onset of symptoms if diagnosed at an early age (newborn screening). However, despite advancements in the understanding of genetic etiology and improved diagnostic capabilities, no treatments are available to prevent disease onset or slow disease progression for a number of these disorders.

Some useful resources to bookmark include GeneTests and OMIM. GeneTests (http://www.genetests.org) is an online genetic testing laboratory database providing information about conditions and laboratory testing services. The Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) database is a comprehensive resource that provides information about the genetic etiology, clinical symptoms, and a bibliography. Of over 5,000 known genetic conditions, the molecular basis is known in almost 2,000.

ConditionGene (Chr. Location)Inheritance Pattern
Congenital Deafness
(nonsyndromic)
Connexin 26 (13q11)Recessive
Tay-Sachs hexosaminidase A (15q23)Recessive
Familial hypercholesterolemia LDL receptor (19p13)Dominant
Sickle cell anemia Beta-globin (11p15)Recessive
Duchenne muscular dystrophy Dystrophin (Xq21)X-linked Recessive
Cystic Fibrosis CFTR (7q31)Recessive
HemochromatosisHFE (6p21)Recessive
Huntington disease Huntington (4p16)Dominant

All Genetic Alliance content, except where otherwise noted, is licensed under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The evolutionary perspective

In attempting to discover a plausible function of the human appendix, there has been a search for homology with that of other mammalians. The fact that the appendix is much larger in certain ‘lower’ mammalians such as rabbits has, for a long time, resulted in the human appendix being considered a vestigial organ. The lack of a clear morphological caecal appendage in some evolutionarily more closely related primates, however, seems to contradict this hypothesis 5.

In the assessment of its evolution, the human appendix is generally considered as a remnant of the mammalian caecum. Originally, this part of the intestine had a digestive function, primarily facilitating the digestion of cellulose with the aid of residential micro‐organisms 6. This cellulose digestive trait is lost in the human caecum, although in the human appendix a relative abundance of micro‐organisms present in biofilms still exists alongside the presence of lymphoid tissue 3. The vermiform appendix in rabbits is found to be essential for the development of the gut associated lymphoid tissue (GALT). After the initial independent development of follicle centres, presence of the commensal intestinal flora is required for diversification of the primary antibody repertoire and for further development of T and B cell areas of follicles within the lymphoid tissue 7, 8, 9. In some non‐human primates, such as tamarins and white𠄎yelid mangabeys 5, and other mammals such as mice 10 and rats 11 that lack a caecal diverticulum, a high concentration of lymphoid tissue is found in the caecal apex 5, referred to as the �l patch’. Moreover, the proximal large bowel of amphibians and reptiles, that lack both the presence of a caecum and appendix and the need of cellulose digestion, also functions as the site where most of the interaction between host and symbiotic bacteria is seen 12. This gives rise to the idea that the appendix, with its excellent conditions for sheltering the commensal gut flora, may have evolved prior to the caecum, rather than having derived from it. Therefore, the digestive trait could have been developed in conjunction with the bulging of the proximal large intestine that eventually became the caecum, which would imply that the immunological function existed before the digestive one. The worm‐like morphology of the appendix and its location in the gut could indicate its long‐lasting immunological function by providing a ‘safe house’ for the commensal intestinal flora, instead of being evidence for its vestigial nature 3, 12.


17: Appendix - Biology

National Institutes of Health (NIH)

National Cancer Institute (NCI)
National Institute on Dental and Craniofacial Research ( NIDCR )

Biology of Lung, and Head and Neck Preneoplasias (R21 - Clinical Trial Not Allowed)

R21 Exploratory/Developmental Grant (formerly R01)

  • March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077.
  • August 23, 2019 - Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137.
  • July 26, 2019 - Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128.
  • November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228. - Notice of NIDCR's Participation in PA-17-460. See Notice NOT-DE-18-013.
  • NOT-OD-18-009 - Reminder: FORMS-E Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2018.
  • September 20, 2017 - Updates to Active Funding Opportunity Announcements to Prepare for Policy Changes Impacting Due Dates On or After January 25, 2018. See NOT-OD-17-114. - Notice of Correction to Activity Code in PA-17-460 "Biology of Lung, and Head and Neck Preneoplasias (R21 - Clinical Trial Not Allowed)" See Notice NOT-CA-17-078.

This Funding Opportunity Announcement (FOA) seeks applications investigating mechanistic and biological aspects of preneoplasia leading to lung, and head and neck (HN) cancers. Despite improved therapies and a deeper molecular understanding of lung and HN cancers, these tumors remain a major health problem in the United States and globally. While molecular markers of early injury to the aerodigestive epithelial field have been found, relatively little is known about the molecular mechanisms that initiate these preneoplasias and drive their progression to invasive cancer. A functional understanding of the key molecular changes involved in the formation and progression of lung and HN preneoplasias will enhance our knowledge of oncogenic progression and accelerate development of effective preventive and therapeutic strategies.

30 days prior to the application due date

Standard dates apply , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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. Applications that do not comply with these instructions may be delayed or not accepted for review.

This Funding Opportunity Announcement (FOA) seeks applications investigating mechanistic and biological aspects of preneoplasia leading to lung, and head and neck (HN) cancers. Despite improved therapies and a deeper molecular understanding of lung and HN cancers, these tumors remain a major health problem in the United States and globally. While molecular markers of early injury of the aerodigestive epithelial field have been found, relatively little is known about the molecular mechanisms that initiate these preneoplasias and drive their progression to invasive cancer. A functional understanding of the key molecular changes involved in the formation and progression of lung and HN preneoplasias will enhance our knowledge of oncogenic progression and accelerate development of effective preventive and therapeutic strategies.

This FOA utilizes the Exploratory/Developmental Grant (R21) mechanism, which supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical research.

An R21 grant application should not have extensive background material or preliminary information. Extensive preliminary data demonstrating feasibility is an indication that the project is beyond the scope of this FOA. Reviewers' determinations of merit will rely instead on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding or practice. Applicants can provide appropriate justification for the proposed work through literature citations, data from other sources, or analytical and computational models. The proposed research could involve considerable risk that the work may not be successful and applicants should clearly explain the significance of the work in order to allow the reviewers to determine whether the potential impact justifies these risks.

This FOA runs in parallel with an FOA of similar scientific scope, PA-17-459 which utilizes the Research Project Grant (R01) mechanism.

Lung cancer

Lung cancer continues to be a significant health burden in the United States where over 220,000 new cases are expected in 2017, constituting about 25% of all cancer diagnoses. While the incidence of lung cancer has been declining, the mortality rates (156,000 are estimated for 2017) remain high and lung cancer continues to be a leading cause of cancer deaths in Americans. In general, lung cancers are divided into two groups, non-small cell lung carcinoma (NSCLC), constituting 84% of lung cancers, and small cell lung carcinoma (SCLC), accounting for 13%. NSCLC is composed mainly of two histologic subtypes, adenocarcinoma (AC), which arises in peripheral regions of the lung, and squamous cell carcinoma (SCC), which are found more centrally. Despite the development of novel targeted and immune therapies that have prolonged survival in some NSCLC patients, many lung cancer patients do not benefit from these therapies and the five-year survival rate following diagnosis remains poor (18%).

Most lung cancers are attributed to cigarette smoking and all three tumor subtypes (AC, SCC, and SCLC) are commonly found in cigarette smokers. Most lung malignancies are thought to arise from airway epithelia that have been damaged through smoke exposure, an idea termed the airway field of injury. Although this field may appear morphologically normal, molecular changes have been identified that distinguish it from undamaged lung epithelium from never-smokers. Further damage to the epithelium causes histologic preneoplasias to emerge from this field, as seen in NSCLC, and eventually, invasive carcinomas arise.

Preneoplastic stages have been best defined for SCC where a series of progressive changes have been identified by histopathology. Bronchial hyperplasia and squamous metaplasia are seen first, followed by increasing grades of dysplasia and carcinoma in situ (CIS), after which invasive carcinoma develops. Some molecular alterations have been associated with particular stages of SCC preneoplasia—loss of heterozygosity at 3p21 in morphologically normal epithelium, p16 methylation in squamous dysplasia, and p53 loss in CIS— suggesting that SCC arises through a multistage progression process. However, not all preneoplasias are destined to progress to invasive cancer and it is not known which molecular changes establish each stage and drive progression.

The preneoplastic states of AC and SCLC are not well understood. In AC, only one preneoplasia type has been identified by histopathology, atypical adenomatous hyperplasia (AAH). Additionally, adenocarcinoma in situ and minimally invasive adenocarcinoma are recognizable histologic entities although their relationship to AAH is not clear. Early molecular alterations in AAH include mutations in K-ras, B-raf, EGFR, and p53. Whether AAH is a requisite step for AC development is not certain. K-ras and EGFR mutations are mutually exclusive in AC, yet some patients with EGFR-mutant AC have concomitant AAH with K-ras mutations present, suggesting that in these cases AC developed via a path distinct from AAH. No clear preneoplasias have been found yet in SCLC and SCLC may arise directly from morphologically-normal, damaged epithelium.

Head and Neck Cancer

HN cancer includes tumors that arise from multiple sites, including the oral cavity, pharynx, larynx, paranasal sinuses and nasal cavity. Most of these tumors are squamous cell carcinomas and are collectively referred to as HNSCC hereafter. In 2017, HNSCC is expected to account for approximately 63,000 new cases and 13,000 deaths in the United States. HNSCCs arising from different primary sites have distinct clinical presentations and outcomes. In general, about one-third of HNSCCs are diagnosed as a local disease, which is associated with an 80% five-year survival rate, while tumors diagnosed as regionally advanced and distantly metastatic are associated with survival rates of about 50% and 35%, respectively.

While individual subtypes of HNSCC have different etiologies, a common risk factor is tobacco use. Consumption of smokeless tobacco and betel quid, a preparation containing tobacco, is frequently associated with oral cavity HNSCC. Tobacco and alcohol use are implicated in about three-quarter of HNSCCs and heavy consumption of both agents increases risk by 30-fold. Oropharyngeal HNSCC is associated with oral infection by human papilloma virus (HPV). The incidence of HPV-positive oropharyngeal cancers has risen recently in the US whereas the incidence of HPV-negative oral cancer has declined.

HNSCC preneoplasia is not well understood. Like other tobacco-associated malignancies such as lung cancer, HNSCC often arises from the field of injured, normal-appearing epithelium. Approximately 20% of primary HNSCC is associated with a second or subsequent HNSCC. Evidence indicates that multiple oral lesions can arise independently within a field or be derived from a single clone that has spread within the epithelium. Because the entire aerodigestive epithelium is exposed to carcinogens from tobacco, HNSCC patients are also at risk for developing second primary tumors at other sites, such as the lung and esophagus. The predominant preneoplastic precursor for HNSCC is dysplasia, although the histopathological characteristics of dysplasia are not predictive of malignant progression or overall prognosis. Molecular studies have identified several common changes in HNSCC dysplasia including chromosomal loss at 9p (CDKN2A), 3p and 17p (TP53), although the clinical utility of these findings is uncertain.

Currently, we have a poor understanding of how lung and HN preneoplasias relate to cancer development. Gaining mechanistic insights into the biology of these preneoplasias would help to find conditions for likely progression. Such knowledge will allow the identification of high-risk individuals who may benefit from surveillance or early intervention.

Research areas of interest for this FOA include but are not limited to:

  • Mechanistic understanding of how the field of injury contributes to lung or HN preneoplasia formation or progression
  • Identifying which lung or HN preneoplasias are benign and which progress, and determining the key molecular or cellular factors that govern these outcomes
  • Development and validation of new and human-relevant models of preneoplasia, particularly for HNSCC, SCC, and SCLC, to enable functional characterization of preneoplasia initiation and progression to advanced stages. Model systems could utilize cell, organoid, ex vivo or whole animal approaches among others
  • Functional understanding of how distinct stromal components, such as immune cells, fibroblasts, and extracellular matrix, contribute to the formation or progression of lung or HN preneoplasia
  • Identifying functional drivers of lung or HN preneoplasia establishment or advancement Delineation of causative genetic and epigenetic changes that determine specific preneoplasia stages or their subsequent regression or progression
  • Discovering immune cell components that interact with lung or HN preneoplasia and understanding the molecular mechanisms that regulate the recognition and removal of preneoplasia
  • Identifying molecular signatures of preneoplasia formation or progression that indicate suitability for intervention and,
  • Finding functional barriers of preneoplasia regression and defining interventional targets to overcome these barriers.

Research areas that are not appropriate for this FOA include:

  • Clinical trials and,
  • Biomarker discovery for early detection of lung or HN preneoplasias

See Section VIII. Other Information for award authorities and regulations.

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Not allowed: Only accepting applications that do not propose clinical trials

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Direct costs are limited to $275,000 over a two-year project period, with no more than $200,000 in direct costs allowed in any single year.

The maximum project period is 2 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Ron Johnson, Ph. D.
National Cancer Institute (NCI))
Telephone: 240 276 6250
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(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 NIH. See Section III of this FOA for information on registration requirements.

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 System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications however, they may be included if available.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise are their leadership approach, governance and organizational structure appropriate for the project?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed (3) interventions to minimize discomfort, distress, pain and injury and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan (2) Sharing Model Organisms and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

(For applications that relate to cancer biology)

Ron Johnson, Ph. D.
National Cancer Institute (NCI))
Telephone: 240 276 6250
Email: [email protected]

(For applications that relate to cancer prevention)

Eva Szabo, M. D.
National Cancer Institute (NCI)
Telephone: 240-276-7011
Email: [email protected]

(For applications that relate to cancer prevention)

Margaret Wojtowicz, M. D.
National Cancer Institute (NCI)
Telephone: 240-276-7012
Email: [email protected]

Chiayeng Wang, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4647
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Long Nguyen
National Cancer Institute (NCI)
Telephone: 240-276-5807
E-mail: [email protected]

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


What is the function of the human appendix? Did it once have a purpose that has since been lost?

"For years, the appendix was credited with very little physiological function. We now know, however, that the appendix serves an important role in the fetus and in young adults. Endocrine cells appear in the appendix of the human fetus at around the 11th week of development. These endocrine cells of the fetal appendix have been shown to produce various biogenic amines and peptide hormones, compounds that assist with various biological control (homeostatic) mechanisms. There had been little prior evidence of this or any other role of the appendix in animal research, because the appendix does not exist in domestic mammals.

"Among adult humans, the appendix is now thought to be involved primarily in immune functions. Lymphoid tissue begins to accumulate in the appendix shortly after birth and reaches a peak between the second and third decades of life, decreasing rapidly thereafter and practically disappearing after the age of 60. During the early years of development, however, the appendix has been shown to function as a lymphoid organ, assisting with the maturation of B lymphocytes (one variety of white blood cell) and in the production of the class of antibodies known as immunoglobulin A (IgA) antibodies. Researchers have also shown that the appendix is involved in the production of molecules that help to direct the movement of lymphocytes to various other locations in the body.

"In this context, the function of the appendix appears to be to expose white blood cells to the wide variety of antigens, or foreign substances, present in the gastrointestinal tract. Thus, the appendix probably helps to suppress potentially destructive humoral (blood- and lymph-borne) antibody responses while promoting local immunity. The appendix--like the tiny structures called Peyer's patches in other areas of the gastrointestinal tract--takes up antigens from the contents of the intestines and reacts to these contents. This local immune system plays a vital role in the physiological immune response and in the control of food, drug, microbial or viral antigens. The connection between these local immune reactions and inflammatory bowel diseases, as well as autoimmune reactions in which the individual's own tissues are attacked by the immune system, is currently under investigation.

"In the past, the appendix was often routinely removed and discarded during other abdominal surgeries to prevent any possibility of a later attack of appendicitis the appendix is now spared in case it is needed later for reconstructive surgery if the urinary bladder is removed. In such surgery, a section of the intestine is formed into a replacement bladder, and the appendix is used to re-create a 'sphincter muscle' so that the patient remains continent (able to retain urine). In addition, the appendix has been successfully fashioned into a makeshift replacement for a diseased ureter, allowing urine to flow from the kidneys to the bladder. As a result, the appendix, once regarded as a nonfunctional tissue, is now regarded as an important 'back-up' that can be used in a variety of reconstructive surgical techniques. It is no longer routinely removed and discarded if it is healthy.


Watch the video: Functions of Appendix #Science #Biology #Appendix (September 2022).


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