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Participating Organization(s)
National Institutes of Health (NIH)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Human Genome Research Institute (NHGRI/NIH), (http://genome.gov) on behalf of the NIH.
Funding Opportunity Title
Clinical Sites for an Undiagnosed Diseases Network (UDN) (U01)
Activity Code
U01 Research Project – Cooperative Agreements
Announcement Type
Related Notices
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)
Funding Opportunity Purpose
To establish Clinical Sites for an Undiagnosed Diseases Network (UDN) added to and building upon the NIH Intramural Research Program's Undiagnosed Diseases Program (IRP-UDP).
Posted Date
January 29, 2013
Open Date (Earliest Submission Date)
May 19, 2013
Letter of Intent Due Date(s)
May 17, 2013
Application Due Date(s)
June 19, 2013, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Not Applicable
Scientific Merit Review
Advisory Council Review
Earliest Start Date
April 2014
Expiration Date
June 20, 2013
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the 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.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.
The purpose of this funding opportunity announcement (FOA) is to establish 5-7 Clinical Sites (CS) for a national network added to and building upon the NIH Intramural Research Program Undiagnosed Diseases Program (IRP-UDP). Together with the IRP-UDP and a separately funded Coordinating Center (CC), these sites will constitute the NIH Undiagnosed Diseases Network (UDN).
The purpose of the Network is to diagnose both rare and new diseases and, through the support of mechanistic studies, to suggest, where possible, management strategies for the patients. This program will advance laboratory and clinical research building upon the experience and expertise of the IRP-UDP and similar programs to enhance coordination and collaboration among laboratory and clinical researchers across multiple centers and to share resulting data and approaches widely throughout the scientific community.
The Clinical Sites will be selected and funded 3-4 months after award of the CC. This will allow the CC to assist and develop with IRP-UDP investigators a preliminary set of protocols and operating guidelines for consideration by the newly-formed UDN. These draft protocols and guidelines will begin to define an initial framework of common practices across the Network, to be refined and expanded as the Network grows and matures. To the degree possible, common protocols for data collection and common approaches to patient selection, evaluation, and diagnosis will facilitate pooled analyses and cross-site collaborations, ultimately advancing the clinical approach to undiagnosed diseases. Some of these best practices could be modeled after the IRP UDP.
For the purposes of this FOA, undiagnosed diseases are considered to be disorders with long-standing symptoms or signs that have not been diagnosed despite extensive clinical investigation. Undiagnosed diseases include 1) rare, previously described diseases, afflicting less than 200,000 individuals in the United States, that are often not recognized because they are so infrequent; 2) yet-to-be-described disorders, previously unknown to medicine also presumed to be rare; and 3) rare variants of more common diseases.
Rare and yet-to-be-described disorders are a difficult problem for patients, their families and their physicians. The NIH Office of Rare Diseases Research notes that about 6% of patients seeking their assistance have an undiagnosed disease. For those who were ultimately diagnosed, as many as 15% had persistent symptoms without diagnosis for at least 5 years, a difficult and costly delay for patient, family (including other afflicted family members), and physicians who struggle to identify and treat these disorders. This diagnostic odyssey is usually expensive with repeated, sequential diagnostic efforts involving a series of physicians pursuing similar duplicative imaging (with related increased X-ray exposure and other risks) and biomarker investigations.
In addition, these patients present compelling research questions since clarification of the underlying genetics, biochemistry and physiology of these disorders will lead to a better understanding of their disease processes and those of related disorders. Advances in the science of genetics and genomics in medicine have made it possible to understand the causes and potential targets for treatment of some of these diseases. Furthermore, as the cost of genotyping and sequencing continues to fall and the accuracy of these methods increases, these approaches become more attractive as potentially standard means to diagnose these disorders.
The Intramural Research Program – Undiagnosed Diseases Program (IRP-UDP) began in May 2008 and from modest initial recruitment numbers, has over a four-year period received approximately 6,300 inquiries. From these inquiries, the investigators were able to evaluate 2,300 medical records and admit 450 patients to the NIH Clinical Center for thorough, one-week evaluations. Despite the resource limitations of a new pilot program, NIH investigators over the four years since program initiation have responded each year to an average 1,575 inquiries, evaluated 575 medical records for potential participation and admitted 113 patients for evaluation. As these data reveal, even without a systematic approach to advertising the program, there is a substantial unmet demand for these capabilities. This justifies the creation of a Network that will be able to address more inquiries, and potentially be more accessible to patients throughout the country who require these services.
Over a four-year period, the IRP-UDP has made diagnoses in approximately 100 patients (20-25% of those evaluated) whose challenging conditions had perplexed and defeated the diagnostic efforts of many skilled physicians. The IRP-UDP has discovered and described two unknown diseases and identified 15 genes not previously associated with human disease. Much has been learned and many efficiencies gained in the evaluation of patient/family inquiries and of submitted medical records, in diagnostic approaches dictated by organ system involvement, and in engaging the expertise of laboratory scientists studying disease mechanisms.
This funding opportunity and a related FOA (RFA-RM-12-020, "Coordinating Center for an Undiagnosed Diseases Network"), together with the ongoing IRP-UDP and NIH program staff, will create the NIH Undiagnosed Diseases Network. The Network will increase the availability of diagnostic services, expand the geographic distribution of patient access sites, foster opportunities for collaboration between laboratory and clinical investigators, and provide resulting data and protocols to the broader community. These efforts will lead to new knowledge regarding the biochemistry, physiology, and mechanisms of these diseases and improve diagnostic and management options for patients afflicted with them.
The objectives of this program are to:
1. Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common protocols designed by an enlarged community of investigators;
2. Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures; and
3. Create an integrated and collaborative research community across multiple clinical sites and among laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases and share this understanding to identify improved options for optimal patient management.
This program seeks to provide improved patient access to state-of-the-art diagnostic methods, by expanding the available expertise and facilities serving patients with these unusual disorders and to accelerate discovery and innovation in diagnosing and treating these patients. The IRP-UDP will establish, as an additional element of this overall program, training programs in genomics and genetics of undiagnosed diseases at the NIH Clinical Center and potentially at other sites. In addition to the clinical infrastructure, gene function studies will be supported through a variety of funding mechanisms to elucidate the biologic mechanisms of identified genetic variants in disease causation, leading to potential pathways to improved treatments. Such funding mechanisms may include subsequent supplements to the CS supported by this FOA to foster collaboration among laboratory and clinical investigators.
The IRP-UDP investigators will assist in the development of the new Clinical Sites by sharing lessons learned over the past four years in approaches to inquiries, evaluation of medical records, and detailed assessment of phenotype, environment and genotype in patients and families selected for diagnostic investigation. To facilitate sharing this knowledge, the IRP-UDP will establish a Consultation Core, available by phone, internet, or visits to or from new CS, to advise on the processes of patient application, review and acceptance, as well as phenotyping, data collection and interpretation, ultimately leading to a diagnosis. The IRP-UDP will also establish and make available to the new CS specialized Core Laboratories for technologies such as DNA or RNA sequencing, gene expression, proteomics, lipidomics, and glycomics that it will establish in FY13 for investigation of its existing patient cohort. Once the new CS are established and running smoothly, they will be invited to compete, along with IRP-UDP, to provide these functions Network-wide.
It is hoped that sharing these lessons will facilitate the development of the new sites and that the infusion of an expanded group of investigators will invigorate and develop new directions and best practices for use by all. The CC and new Clinical Sites are anticipated to bring new ideas and alternative approaches to refine and improve upon current IRP-UDP practices and adapt them for use outside the unique setting of the NIH Clinical Center.
It is the intent of the NIH to establish a Network CC several months prior to the selection of the new CS. This will permit a careful study and codification of the processes used and refined by the IRP-UDP since 2008 for consideration for Network-wide adoption and refinement by the Network Steering Committee once the new sites are awarded. Although every undiagnosed patient is unique and requires some individualized investigation, certain core components are expected to be relevant to all patients. All CS (including the IRP-UDP) will thus be expected to utilize common investigative and data collection protocols, to the degree possible, to facilitate pooling of data to enhance the scientific and diagnostic value of the resulting information. All data from UDN patients will be submitted as soon as they are collected to the CC for cleaning, quality control, and compilation in a Network-wide dataset to be distributed periodically to all CS (including the IRP-UDP) as agreed upon by the Network Steering Committee.
The awards funded under this FOA will be cooperative agreements (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award). Close interactions among awardees and NIH will be required to develop this complex Network. Shortly after the award, CS Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) and key co-investigators will meet with CC representatives, IRP-UDP investigators and NIH program staff to plan approaches, identify barriers, and propose solutions for creating and maintaining the UDN.
The UDN governance will rest with the Network Steering Committee in collaboration with NIH program officials, with advice from an External Scientific Panel, and subject to oversight by a UDP Working Group of the NIH Common Fund. The Steering Committee may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific Network functions such as patient recruitment, patient selection and assignment to specific CS, clinical evaluation, final diagnosis, and access to Core Laboratories, as needed.
A Steering Committee composed of PD(s)/PI(s) from all sites (including the Clinical Sites, CC and the IRP-UDP) and the NIH Project Scientist(s) will be responsible for the scientific direction of the Network. The Steering Committee will meet quarterly during the first year and two to three times per year or as needed subsequently.
The UDN Steering Committee will be the operational group through which the NIH UDP Working Group interacts with the UDN. The UDN Steering Committee will identify scientific and policy issues that need to be addressed at the Network level and develop recommendations to the NIH UDP Working Group for addressing such issues. Working through the CC, the Steering Committee will develop and implement an approach for network-wide patient selection and assignment to Clinical Site, as well as evaluation, imaging and laboratory investigation, final diagnosis, and follow-up. It will also ensure dissemination of program data, clinical protocols, training schedules and other materials to the wider scientific community.
An External Scientific Panel (ESP) will be named by NIH program officials and will be responsible for monitoring Network activities and making recommendations to the UDP Working Group and NIH regarding process and substantive issues that arise during Network operations.
An Interim Executive Committee composed of the IRP-UDP PD/PI, the CC PD/PI, and the NIH Project Scientist(s) will collaborate and communicate on a regular (likely weekly) basis to prepare draft protocols and preliminary materials prior to award of the new Clinical Sites. Once the new sites are added to the Network, the Chair of the Steering Committee, the PD/PI of the CC, the NIH Project Scientist(s), and the PD/PI of the IRP-UDP will continue to engage in regular (again, likely weekly) phone conferences to facilitate the program's maturation from 6-8 individual sites to a functional, integrated and effective Network of investigators.
Core Laboratories for specialized technologies will be established by the IRP-UDP in FY13 and made available to new CS in FY14 and FY15 for investigation of genes implicated in their UDP patients, as described above. To facilitate data sharing and pooled analyses, Core Laboratories would typically provide these services Network-wide but depending on capabilities at the individual CS, such testing could be conducted locally according to agreed-upon standards, with resulting data submitted for Network-wide analyses and deposition. A competition for providers of Core Laboratory functions, to which the new CS may apply, will be conducted once the new CS are established and running smoothly. The Network SC will be tasked with developing an equitable process for prioritizing access to these resources, whether at the IRP-UDP, the new CS, or their contractors or collaborators, to be reviewed and approved by the Network's External Scientific Panel and the NIH Working Group. This process will likely involve a subcommittee or working group to define priorities for access, formats for requests, and expectations for turnaround and follow-up as needed.
Data from the UDN are expected to be handled so as to increase the value of the significant public investment in the creation and operation of the Network. Consistent with achieving the goals of the program, NIH expects that the project datasets (phenotypic, environmental, covariate, process, and other relevant data) and associated genotyping data from the Network will be widely shared with the scientific community for research, while carefully observing standards of patient privacy, confidentiality, and management of health information. Information such as study protocols, descriptions, bioinformatic tools, and publications are expected to be made available through an open access section of a database such as dbGaP, other public web sites, and publication in the scientific literature.
Applicants should describe their plans to participate with the CC in preparing yearly reports for the Network leadership, the External Scientific Panel, and the NIH UDP Working Group. The yearly report for FY17 will include a more detailed report which an external group will use to make recommendations on the continuation or shut-down of the UDN effort.
This review group will also be asked to make recommendations for orderly close-out of this project either in FY18/FY19 if the mid-year review determines that close-out is warranted, or for issuing a renewal solicitation to continue the project through final closeout in FY22.
The Network can be envisioned as beginning with a phase of network design prior to Clinical Site award; this Design phase will involve only the CC, IRP-UDP, and NIH program staff and not the new CS. Once the new CS are awarded, subsequent phases involving them will include: 1) start-up; 2) full network operation; and 3) mid-course review. Should the mid-course review be successful, a repeat solicitation for Network continuation and eventual close-out will be released; if unsuccessful, modest close-out funding may be provided.
Funding Instrument
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
The total amount of funds available for this award is approximately $4.8M for FY2014 contingent upon receiving scientifically meritorious applications. Five to seven awards are anticipated from the solicitation. In FY2015, a total of $11.0M is anticipated, and in FY2016 and FY2017, $14.0M per year is anticipated.
Award Budget
Application budgets should not exceed $800K total costs in FY14, $1.8M total costs in FY15, and $2.3M total costs per year for FY16 and FY17 and must reflect the actual needs of the proposed project.
Award Project Period
The total award period for this FOA is 4 years (FY14 through FY17).
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
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
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 must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.
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.
Applications for a clinical site grant may be submitted by individuals located at the same institution as an applicant for the CC submitted under FOA RFA-RM-12-020, but an individual may not be the PD/PI of RFA-RM-12-020 and the clinical site grant.
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.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the 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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
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:
The letter of intent should be sent to:
Anastasia L. Wise, PhD
National Human Genome Research Institute
Telephone: 301-443-0585
Email: firstname.lastname@example.com
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate "optional" components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Please include the following information in the "Facilities and Other Resources" attachment:
Applicants should describe the relevant institutional environments which would facilitate the effective implementation of the proposed program. Applicants should also describe existing or planned resources that would be available to the CS, such as clinical and laboratory facilities, participating and affiliated institutions and units, geographic distribution of space and personnel, and consultative and statistical resources.
Institutional commitments to providing a comprehensive clinical evaluation within one week of initiation should be clearly documented.
Other Attachments: Please include the following information as an "Other Attachment."
The Responsibilities of the UDN Clinical Sites (CS) are described in Section VI.2, "Administrative and National Policy Requirements." Applicants should indicate their willingness to cooperate with other awardees in the development and design of research approaches, procedures, policies and strategies to be applied to this program.
Applicants should describe how they will work with the other members of the Network Steering Committee (SC) to define a mode of operation that best matches the capabilities of the selected sites, within broad guidelines of parity, openness, cost-effectiveness, timeliness, and optimal patient care, as defined by the SC, the NIH, and its advisors.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
The PD/PI should be well-established in clinical research and must devote at least 2.4 person months (20% of full-time professional effort) to this Program.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
In this FOA, as in all FOAs related to the UDN, applicants are encouraged to creatively engage the scientific and operational problems that need to be addressed for the Network to be a success. NIH recognizes that the approach to diagnosis and investigation developed by the IRP-UDP is only one model, albeit a successful one, that may be challenging to adapt outside the unique setting of the NIH Clinical Center. New ideas and alternative approaches proposed by the CC and eventually all Clinical Sites are likely to refine and enhance the care of patients and the science generated from careful study of their cases. Within the framework of this FOA, there are a variety of approaches to Network creation and subsequent function that may ultimately be adopted by the Steering Committee and NIH. Applicants should discuss alternatives, defend the approaches they favor, and describe their willingness to implement approaches agreed upon by the Network as a whole.
Specific Aims
List each aim for the CS and how it supports the Objectives of this Research Program as described in Section I. Funding Opportunity Description.
Research Strategy
Describe how the PD(s)/PI(s) will provide the following responsibilities in the development of this UDN CS:
The creation of an integrated and collaborative Network is an essential task for all investigators who are chosen to participate. The following recommendations should be considered when describing the concept of a UDN CS:
Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project.
Applicants should discuss their plans to collect data on environment, genotype and phenotype and describe plans to work with the CC to optimize data collection and analysis strategies and facilitate public access to the UDN data through the CC and organizations such as the National Center for Biotechnology Information (NCBI), which maintains NIH databases such as dbGaP, to optimize data analysis and public access to the data.
Network Start-up (July 2014 - December 2015)
Within the Research Strategy, applicants should describe how they will collaborate with each other, the CC, IRP-UDP, and program officials to design Network operations and implement protocols. This includes reviewing and modifying draft protocols and operating guidelines developed in the Design phase for handling patient inquiries, reviewing prior diagnostic efforts, accepting patients for and conducting detailed evaluation, collecting and submitting data, discussing results with patients, their families, and their clinicians, and conducting follow-up.
Applicants should describe plans to create their proposed new Clinical Sites and the Network as a whole, including collaboration in central collection and distribution of inquiries across sites, sharing of chart review, potential use of special patient evaluations at specific Clinical Sites to take advantage of local expertise, creation of sites with specific disease-area interests and skills, and transfer of patients among clinical sites based upon expertise,interest and geographic proximity to the patient.
Each site will be expected to recruit 10 UDN patients in FY14, 25 in FY15, and 50 per year in FY16 and FY17. Plans to meet these recruitment milestones should be described, as should plans for analyzing 35 whole exomes or whole genomes per site in FY15, increasing to 140 whole exomes or whole genomes per site per year in FY16 and FY17.
Full Operation (January 2016 - June 2017)
Within the research strategy, applicants should describe plans for identifying and solving operational problems involving recruitment, data collection, quality assurance and refinement of protocols and manual of operations. Applicants should suggest plans that will assist in developing collaborations between clinical and laboratory scientists both within and outside the Network.
Applicants should describe plans for maintaining a throughput of roughly one UDN patient per week while pursuing outcome follow-up, gene function studies, and specialized technologic investigations of patients previously seen.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via Grants.gov, 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.
Applicants are responsible for viewing their application before the deadline 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.
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.
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 (SAM). 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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at email@example.com when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
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.
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? 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? How will this project improve the approach to patients who suffer from rare diseases or yet to be described diseases? How will this project improve the understanding of the etiology of these diseases and lead to their mitigation?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Have the PD(s)/PI(s) participated in evaluation and management of difficult-to-diagnose patients and are they recognized within and outside their institutions as expert diagnosticians? Have the PD(s)/PI(s) participated in a clinical site in any collaborative, multi-center networks? Do the PD(s)/PI(s) have experience collecting, analyzing, and publishing phenotypic and genomic data?
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? Will this research advance the use of genomics, related technologies and the use of common data elements/protocols in clinical care of patients with rare or as-yet-undescribed diseases?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
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?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion 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? Are institutional resources and infrastructure being committed or leveraged? Are adequate plans for investigation and referral for care of uninsured or under-insured patients? Are there plans for sustaining the new Clinical Site once Common Fund support ends, presented and substantiated by clear institutional commitments?
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.
Protections for Human Subjects
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 Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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.
Not Applicable
Not Applicable
Not Applicable
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.
Applications from Foreign Organizations
Not Applicable
Select Agent Research
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).
Resource Sharing Plans
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) Genome Wide Association Studies (GWAS).
Budget and Period of Support
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 NHGRI, 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:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:
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.
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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for the UDN will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the UDN and that NIH staff will be given the opportunity to offer input to this process. The Project Scientist(s) will participate as members of the Steering Committee and will have one vote. The Project Scientist(s) will have the following substantial involvement:
Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Official may also serve as an NIH Working Group Project Scientist(s).
Collaborative Responsibilities
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop the UDN. The awardee and the Project Scientist(s) will meet in person with the program Steering Committee on a quarterly schedule during the first year of Network operation and subsequently three times per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.
The Steering Committee will serve as the main scientific body of the program. The Steering Committee will be responsible for coordinating the activities being conducted by the program. The Steering Committee membership will include the PD(s)/PI(s) of each CS and CC award, other CC and CS staff as needed (ex-officio) and the NIH Project Scientist(s). The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired. Each CS (including the IRP-UDP), the CC, will have one vote and the NIH Program Scientist(s) together will have one vote.
The Steering Committee may establish working groups as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The UDN SC will have the overall responsibility of assessing and prioritizing the progress of the various working groups and other needed subcommittees.
The Clinical Site Awardees agree to work collaboratively to:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.
A final progress report, 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.
We encourage inquiries concerning this funding opportunity and
welcome the opportunity to answer questions from potential applicants.
Customer Support (Questions regarding Grants.gov registration and
submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: email@example.com
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
Email: email@example.com
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Email: firstname.lastname@example.com
Anastasia L. Wise, Ph.D.
National Human Genome Research Institute
Telephone: (301) 443-0585
Email: firstname.lastname@example.com
Rudy O. Pozzatti, Ph. D.
National Human Genome Research Institute
Telephone: (301) 402-0838
Email: email@example.com
Lisa Oken
National Human Genome Research Institute
Telephone: (301) 594-5250
Email: email@example.com
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 Parts 74 and 92.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
Department of Health
and Human Services (HHS)
NIH... Turning Discovery Into Health®
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.


text:
Career Coach Online Office Hours for Engineering Master's Students
Career Services and Professional Development
All engineering Master's students are invited to use this weekday service to have an individual conversation with a career coach about any topic. No appointment is needed and the conversation length will vary based on the number of students waiting. Login directions are available at: https://waitwhile.com/welcome/officehours The CSPD Events calendar lists schedule updates and cancellations: http://calendar.duke.edu/index?gf%5B%5D=Engineering+Master%E2%80%99s+Career+Services+and+Professional+Development/ The EMP Career Coach Alerts channel has an active post alerting you whether office hours are open for business: https://teams.microsoft.com/l/channel/19%3aJ8Z343okAfaDgExPkqbo-TE52499Va2l7kB1DVtd5cc1%40thread.tacv2/General?groupId=375bcbdc-f0fb-41dc-a39a-47595f7c4613&tenantId=cb72c54e-4a31-4d9e-b14a-1ea36dfac94c Also, check out the CSPD website. There's lots to help you if office hours aren't currently open: https://careerhub.students.duke.edu/channels/engineering-masters/
Engineering, Training, Meeting, Information Session, Open House

subset: commoncrawl


text:
8871 W. Flamingo Rd. Ste 202
Las Vegas, NV 89147
Phone: (888) 778-7403
Information Privacy Notice
This Information Privacy Policy has been adopted in order to maintain clear standards of privacy and security with the information we are provided by customers for confidentiality. It states:
(1) We will not sell or provide secure proprietary information input by customers to any outside parties except as expressly authorized or implied by specific request for services that requires the disclosure of your information in order to provide said services requested; and
(2) No customer information is kept on a publicly available server.
By accessing this web site, users agree to be bound by all of the terms and conditions of the guidelines set out in this Disclaimer. Do not consult this web site unless you agree not to hold NPPN liable for any errors or omissions.
We offer our services as prescribed by a duly authorized and licensed medical practitioner or other healthcare provider. The services or products found listed on our web site are intended for use by duly authorized and licensed medical practitioners or other healthcare providers in the delivery of appropriate medical care to assist practitioners diagnose and treat disease. We give no warranty that any of our services will prevent disease. All material is provided for educational purposes only and is not intended to be a substitute for a physician's consultation. Although NPPN encourages increased self-awareness and self-care, all readers are strongly encouraged to consult and work with an experienced healthcare practitioner. Individuals with health disorders, medical conditions, or any condition needing medical supervision assume full responsibility for obtaining such professional medical assistance. Consult your physician regarding any symptoms or medical condition. We specifically disclaim any expressed or implied warranties or merchantability of fitness for any particular usage, application or purpose. NPPN does not recommend self-diagnosis or self-medication, and no information within this web site or presented by NPPN or its associates may be construed or interpreted as recommending self-diagnosis or self-medication.
If a laboratory test result is outside normal range, you should immediately see your prescribing physician. Many tests, to be validated, will need to be repeated at the discretion of a physician. Laboratory test results may vary depending upon age, sex, time of day blood sample is taken, diet, medications, and the limits of modern technology. A single laboratory test or group of tests cannot guarantee good health. False positive and false negative test results are possible. There are various medical diseases that cannot be uncovered by these tests alone. Testing by the medical laboratory staff to whom your medical specimen is delivered by us, only constitutes a partial evaluation of your state of health and does not represent a diagnosis or treatment of disease.
NPPN shall not be liable to you or anyone else for any loss or injury caused in whole or in part by procuring, compiling, interpreting, delivering or reporting information through this web site. In no event shall NPPN be liable to you or anyone else for any decisions made or action taken or not taken by you in reliance on such information. Material placed online by users does not represent medical advice of NPPN and we make no representations with respect to the accuracy, reliability, completeness, timeliness or usefulness of the contents.
Privacy Policy
The general position of The National Phlebotomy Provider Network on implementation and compliance with HIPAA and other privacy laws is as follows:
A. Protect and enhance consumer's rights of access to information.
B. Improve healthcare quality by restoring trust in the system.
C. Improve efficiency of delivery with national framework.
D. NPPN will not use or disclose an individual's protected health information (PHI) except as otherwise permitted and/or required by HIPAA.
E. PHI may be used only for treatment, payment, or healthcare operations. All other uses and disclosures will be by authorization only and Patient may revoke authorization.
F. All NPPN Patients will receive and acknowledge the Privacy Notice. It is also available for the asking by mail or email. It is also carried by each field service technician and available upon request.
G. Privacy Notice will describe how medical information about Patients may be used and disclosed and how they may access said information.
H. NPPN will make reasonable efforts to limit disclosure of PHI as much as possible.
I. Continuing compliance with HIPAA will be achieved through ongoing assessment, oversight and informational training, as coordinated through the privacy officer.
J. NPPN shall address all complaints received from patients, clients, employees or third parties in an expeditious and meaningful manner.
K. NPPN respects the rights of individuals, including employees, to make complaints, ask questions or inquire as to NPPN's compliance with HIPAA and other privacy laws.
L. No adverse action or retaliation shall be taken against any such individual or employee based on any legitimate complaint, question, or inquiry.
M.NPPN must identify those members of its workforce that require access to protected health information to perform their duties, specify the protected health information to which they require access and make reasonable efforts to limit their access accordingly.
N. All employees will be trained in order that NPPN will be HIPAA compliant. New employees will be trained on a regular basis to ensure continued compliance with new personnel. Personnel will be retrained if significant changes occur which affect HIPAA or privacy laws. Employees, who fail to follow HIPAA requirements and/or the policies of NPPN with respect to privacy rules, shall be sanctioned appropriately. Such sanctions may range from verbal reprimand to termination. Any intentional breach of patient confidentiality, not permitted by law, shall be severely punished. All such sanctions shall be documented, in writing, by NPPN.
O. To the extent practicable, NPPN will mitigate the harmful effects of any known use or disclosure, by itself or its business associates that is in violation of the privacy rule and/or NPPN's policies and procedures.
For more information on our information privacy practices, or to file an information privacy concern, please contact The National Phlebotomy Provider Network's Information Privacy Officer at: The National Phlebotomy Provider Network, Inc. 8871 W. Flamingo Rd. Ste 202 Las Vegas, NV 89147.


text:
Exactly three months after their very first live performance at the Wilson Center in D.C., Fugazi returns to this venue to deliver some more. And as tentative as their first gig might have been, the band (now joined by Guy on vocals) is quickly shaping up to become the outspoken outfit that is known and remembered to this day; as would often be the case, Ian basically doesn't pass up an opportunity to try and engage his listeners.
I quite enjoyed this recording, for a number of reasons. For one, it is Joe Lally's birthday show and fortunately his bass overall sounds tremendously thick and buttery in the mix for the occasion.
Early comers were in for a treat as well on this particular night, as the band plays through the arrangements that would make up the songs Lockdown and Suggestion, released as part of the Margin Walker EP (1989) and 7 Songs EP (1988) respectively.
Mark Andersen provides some opening remarks after which KYEO lights this sucker up; note that the early live versions of this song include a fast part before the breakdown riff and chorus, and as such differ distinctly from the eventual official studio take.
The band then decides to "break some voodoo" catapulting the (up until then) usual set closer The Word toward the beginning of the set. An intermezzo about overthrowing school is up next, followed by Song #1 which Ian dedicates to his sister Amanda who is being thrown out of school.
During Interlude 2 Ian states that "the PA man fucked up and put an extra mic up here" insisting "anyone who wants to sing or something to come on up and use it because otherwise it goes to waste, what the fuck". It seems someone actually picks up on this during And The Same, laying down some "ooooooooooooh" singalong vocals if you listen closely.
Since the band does not have an official release under its belt at this point, lyric sheets are still being distributed to familiarise listeners with the topics at hand. Ian refers to these sheets repeatedly during this gig, to introduce songs and to try and get attendees to participate.
As mentioned in the previous comment, Furniture is introduced as "a song we did yesterday, 8:30 am Fugazi live at BCC High School for a video" (according to the side-notes of that show, only about 10 people attended the event; unfortunately, the tape of that performance has been lost since).
As to the rest of the set list, both Break-in and Waiting Room stand out for me personally. Break-in because of Guy's fierce leading vocals and Ian's aggressive guitar play that provides for a tailored setting; Waiting Room because of the prolonged bass intro, allowing Joe to shine as Ian literally talks the listeners through the song arrangements.
All in all, I would say the mix of this recording is definitely enjoyable, although some of the acoustics seem to suffer slight volume drops, especially during some of the more energetic outbursts.
During interlude 3, Ian says that they played Furniture at the high school show the day before (at 8:30am!). He kind of made it sound like they only played that song, or at least not a full set.
Also, an emocore reference before Turn Off Your Guns.
|Lockdown Instrumental
|Suggestion Instrumental
|Opening Remarks
|The Word
|Interlude 1
|Song #1
|Interlude 2
|And The Same
|Interlude 3
|Interlude 4
|Bad Mouth
|Interlude 5
|In Defense of Humans
|Turn Off Your Guns
|Waiting Room
Please Note: Available recordings have been mastered to correct for volume shifts, drop outs, etc. but some sonic anomalies will still exist, especially early in the set when the mix is being settled. The band has rated each show for sound quality and set the general price of a download at $5 per show. If you have a different price in mind feel free to utilize the alternative pricing option.


text:
This one is non-fiction, but caught my eye today. Looks like an interesting biography…her life would make an intriguing novel!
Emily Post: Daughter of the Gilded Age, Mistress of American Manners
by Laura Claridge
"What would Emily Post do?" Even today, Americans cite the author of the perennial bestseller Etiquette as a touchstone for proper behavior. But who was the woman behind the myth, the authority on good manners who has outlasted all comers? Award-winning author Laura Claridge presents the first authoritative biography of the unforgettable woman who changed the mindset of millions of Americans, an engaging book that sweeps from the Gilded Age to the 1960s.
Born shortly after the Civil War, Emily Post was a daughter of high society, the only child of an ambitious Baltimore architect, Bruce Price, and his wellborn wife. Within a few years of his daughter's birth, Price moved his family to New York City, where they mingled with the Roosevelts and the Astors as well as with the new crowd in town–J. P. Morgan and the Vanderbilt clan. Blossoming into one of Manhattan's most sought-after debutantes, Emily went on to marry Edwin Post, planning to re-create in her own home the happiness she'd observed between her parents. Instead, she would find herself in the middle of a scandalous divorce, its humiliating details splashed across the front pages of New York newspapers for months.
Traumatic though it was, the end of her marriage forced Emily Post to become her own person. She would spend the next fifteen years writing novels and attending high-powered literary events alongside the likes of Mark Twain and Edith Wharton, but in middle age she decided she would try something different.
When it debuted in 1922 with a tiny first print run, Etiquette represented a fifty-year-old woman at her wisest–and a country at its wildest. Claridge addresses the secret of Etiquette's tremendous success and gives us a panoramic view of the culture from which Etiquette took its shape, as its author meticulously updated her book twice a decade to keep it consistent with America's constantly changing social landscape.
A tireless advocate for middle-class and immigrant Americans, Emily Post became the emblem of a new kind of manners in which etiquette and ethics were forever entwined. Now, nearly fifty years after her death, we still feel her enormous influence on how we think Best Society should behave.


text:
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|This page is no longer active. It is being kept for historical interest.
|No discussion is needed to revive this page; simply remove the
{{inactive}} tag and bring it up to date.
This page lists all the announcements that are of value to the Wiktionary Community. New announcements go at the top of the list.
See also Wiktionary:Milestones and Wiktionary:News for editors
|June 24, 2010
|Wiktionary:Votes/pl-2010-10/Treatment_of_toneless_pinyin_other_than_syllables passes with the result of 9 support, 1 oppose and 4 abstain.
|June 24, 2010
|HotCat can now be enabled in the Gadgets tab of Special:Preferences.
|June 18, 2010
|The Names of specific entities section in CFI has been replaced, per Wiktionary:Votes/pl-2010-05/Names of specific entities.
|June 11, 2010
|The Flood Flag has been enabled.
|May 25, 2010
|A new voting policy has been added to Wiktionary:Votes.
|May 17, 2010
|The LiquidThreads extension is enabled per Wiktionary:Votes/2010-02/Installing LiquidThreads.
|March 3, 2010
{{Wikisaurus-link}} template has been deprecated.
|February 18, 2010
|"Modern English possessive forms" section of CFI is removed and replaced with "Language-specific issues" as the results of this vote.
|February 17, 2010
|"Prepositional phrase" is now allowed as a standard POS header as the results of this vote.
|February 13, 2010
|A new blocking policy has been approved as the results of this vote.
|February 9, 2010
|Given name appendices have been renamed as the results of this vote.
|January 24, 2010
|CFI section entitled "What Wiktionary is not with respect to names" is renamed "Genealogic content". See this vote.
|January 19, 2010
|Two namespace aliases are set, to redirect WT: and WS: to Wiktionary: and Wikisaurus:, respectively, as the results of this vote.
|January 16, 2010
|Anagrams section of ELE is modified per this vote.
|January 13, 2010
|Unidiomatic terms made up of multiple words officially meet WT:CFI when significantly more common than a single-word spelling that already meets CFI. See vote.
|October 20th, 2009
|An RSS feed for the daily dumps on devtionary is now available at http://www.devtionary.org/cgi-bin/feed.pl
|July 14th, 2009
|Daily dumps are being produced again at 126.96.36.199. None had been since the site crashed even after it was brought back online until a couple of days ago.
|June 12th, 2009
|A new version of nearbypages is available for testing. See the Beer Parlour for how to try it out.
|June 8th, 2009
|Our daily dump site is now reachable again at 188.8.131.52.
|June 3rd, 2009
|Our daily dump site, www.devtionary.info which had already lost its DNS is no longer reachable even by its IP address 188.8.131.52. Fortunately new official dumps are now arriving at fairly regular 5 day intervals from download.wikipedia.org/enwiktionary.
|March 1st, 2008
|Experimenting with the efficacy of the XFF-forwarded headers, AOL has now been tentatively unblocked.
|February 16th 2008
|Additions refine the Criteria for Inclusion as they pertain to terms from fictional universes, and previously to brand names.
|February 13th 2008
|Italian overtakes English as having the most entries on English Wiktionary.
|February 5th 2008
|Two thirds of the way to a million entries
|December 3rd
|"100 random pages" shows continued increase in percentage of foreign words
|November 18th
|Citations namespace created
|October 12th
|The Wiktionary community officially adopts Assume Good Faith as a guideline.
|October 9th
|As of yesterday, according to Alexa's ranking, we are in the top 2000 web sites.
|September 21st
|We have a new 'crat.
|August 16th
|English Wiktionary reaches 500,000 entries (Well done everybody!).
|August 4th
|Simple English Wiktionary reaches 2,000 entries.
|July 14th
|Daily Article mailing list now includes en.wikt's WOTD.
|July 9th
|Jyril's Finnish noun rohto became entry 450,000!
|June 28th
|Uncompressed XML dump over 504MB now.
|June 9th
|SemperBlotto's noun reflectin became entry 400,000!
|March 10th
|At long last, Wiktionary:Statistics#Detail shows inflected forms broken out.
|February 12th
|Two new sysops appointed, Atelaes and Dmcdevit.
|January 30th
|Carl Daniels' Japanese noun 雷雨 became entry 325,000!
|January 16th
|Special:Log/patrol new log added - log of all patrol markings (Mainly for nl.wiki, where all users patrol edits.)
|December 31st
|WT:VOTE Reaches a new milestone, with eight active votes.
|December 11th
|The Wiktionary:Christmas Competition 2006 is now open to all contributors.
|November 4th
|TheCheatBot's English plural electroplatings became entry 300,000!
|October 12-13
|DAVilla resurrects the Collaboration of the week.
|October 8-15
|A batch of fresh nominations and votes started at WT:VOTES.
|October 3rd
|Dvortygirl's English noun escapist became entry 250,000!
|September 28th
|Dijan's word आवश्यक became the 200,000th entry!
|September 11th
|Dvortygirl's word holdover became the 175,000th entry!
|September 3
|Two new sysops appointed, BD2412 and Pathoschild.
|August 31
|The vote for our first local CheckUsers begins. Please vote because we need at least two people to get at least 25 votes for anything to happen at all.
|August 25
|Wiktionary becomes the second project (after de.wiki) with sampled usage statistics, showing the top 1,000 pages viewed by anonymous IPs. http://tools.wikimedia.de/~leon/stats/wikicharts/?wiki=enwiktionary
|August 21
|Congratulations to our latest bureaucrat, Vildricianus.
|August 21
|The severe decline in AOL vandalism coincides with the IP change of the Wikimedia servers; the secure server(s) have not rolled to the new IP addresses properly yet. Everything else seems to be OK, with the new IP addresses (i.e. 18.104.22.168-112.)
|August 18
|Wikimedia.org (wik*.org) is planning to move from 188.8.131.52/26 to 18.104.22.168/24 this weekend retaining the last octets in the number switching. Do your nslookup/dig checks now and break out your binary calculators, as DNS disruptions are very likely, for the next five days.
|August 18
|Wikimedia.org down for 2 hours, 29 minutes, due to a routing problem with Cogent. See mailing list for info.
|July 31
|Wikimania in full swing. Live and archived audio/video feeds at http://wikimania2006.wikimedia.org/wiki/Archives.
|July 2006
|French Wikiquote taken down for systemic copyright questions. http://fr.wikiquote.org/wiki/Accueil
|July 31
|Wikimania starting tomorrow. Extra sysop attention needed at WT:LWM and other WT:DW tasks, all week long.
|July 20
|Two new bureaucrats: Dvortygirl and Hippietrail. One new nominee in the running... Vildricianus
|July 14
|New bureaucrats are called for! Vote for Dvortygirl.
|July 14
|A vote is already being called for at meta (and being opposed.)
|July 01
|Half of en.Wiktionary entries are English words - see here for details
|June 28
|14 new namespaces have been introduced. See WT:BP
|June 18
|A new logo is being discussed at meta.
|June 14
|Two new admins are elected: Davilla and Kappa
|June 5
|Connel's word natures became the 150,000th entry!
|May 30
|de:w:User:Duesentrieb activates CommonsTicker for the English Wiktionary!
|May 28
|Two new discussion rooms are made official: the Grease pit, for technical debate, and the Information desk, for minor or specific assistance/questions.
|May 28
|For the first time since January 11, 2005 there are no new admin candidates running!
|May 25
|User:Dvortygirl's entry greener pastures became entry 145,000.
|May 23
|Four new admins: Celestianpower, Widsith, Andrew massyn and Rodasmith.
|May 20
|Latest XML dump available at http://download.wikimedia.org/.
|May 5
|Widsith, nominated for admin status.
|May 4
|Jusjih, Psy guy and Aulis Eskola granted admin status.
|May 3
|EncycloPetey and Kipmaster granted admin status.
|April 24
|A new concordance of Bible words
|April 24
|WikiSaurus has 16,700 Google Hits beyond wiktionary.org [1]
|April 23
|Latest XML download of current pages on en.wiktionary generated on 4/21/2006 at http://download.wikimedia.org/ is corrupt.
|April 22
|Yorktown1776 starts the 500,000th article pool.
|April 19
|More downtime caused by a colo power outage.
|April 17
|A new Weekly Collaboration is set up.
|April 14
|A new upload of the complete Shakespeare word list is added.
|April 10
|Extended downtime caused an edge routing problem.
|April 9
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text:
The Marble Faun
by Nathaniel Hawthorne
Chapter XI: "Fragmentary Sentences"
Additional Information
- Year Published: 1860
- Language: English
- Country of Origin: United States of America
- Source: Hawthorne, N. (1860). The Marble Faun. Boston: Ticknor and Fields.
- Flesch–Kincaid Level: 11.5
- Word Count: 2,208
- Genre: Gothic
- Keywords: 19th century literature, american literature, nathaniel hawthorne, the marble faun
- ✎ Cite This
Share |
Hawthorne, N. (1860). Chapter XI: "Fragmentary Sentences". The Marble Faun (Lit2Go Edition). Retrieved October 01, 2023, from https://etc.usf.edu/lit2go/39/the-marble-faun/532/chapter-xi-fragmentary-sentences/
Hawthorne, Nathaniel. "Chapter XI: "Fragmentary Sentences"." The Marble Faun. Lit2Go Edition. 1860. Web. <https://etc.usf.edu/lit2go/39/the-marble-faun/532/chapter-xi-fragmentary-sentences/>. October 01, 2023.
Nathaniel Hawthorne, "Chapter XI: "Fragmentary Sentences"," The Marble Faun, Lit2Go Edition, (1860), accessed October 01, 2023, https://etc.usf.edu/lit2go/39/the-marble-faun/532/chapter-xi-fragmentary-sentences/.
In the Borghese Grove, so recently uproarious with merriment and music, there remained only Miriam and her strange follower.
A solitude had suddenly spread itself around them. It perhaps symbolized a peculiar character in the relation of these two, insulating them, and building up an insuperable barrier between their life-streams and other currents, which might seem to flow in close vicinity. For it is one of the chief earthly incommodities of some species of misfortune, or of a great crime, that it makes the actor in the one, or the sufferer of the other, an alien in the world, by interposing a wholly unsympathetic medium betwixt himself and those whom he yearns to meet.
Owing, it may be, to this moral estrangement,—this chill remoteness of their position,—there have come to us but a few vague whisperings of what passed in Miriam's interview that afternoon with the sinister personage who had dogged her footsteps ever since the visit to the catacomb. In weaving these mystic utterances into a continuous scene, we undertake a task resembling in its perplexity that of gathering up and piecing together the fragments of a letter which has been torn and scattered to the winds. Many words of deep significance, many entire sentences, and those possibly the most important ones, have flown too far on the winged breeze to be recovered. If we insert our own conjectural amendments, we perhaps give a purport utterly at variance with the true one. Yet unless we attempt something in this way, there must remain an unsightly gap, and a lack of continuousness and dependence in our narrative; so that it would arrive at certain inevitable catastrophes without due warning of their imminence.
Of so much we are sure, that there seemed to be a sadly mysterious fascination in the influence of this ill-omened person over Miriam; it was such as beasts and reptiles of subtle and evil nature sometimes exercise upon their victims. Marvellous it was to see the hopelessness with which being naturally of so courageous a spirit she resigned herself to the thraldom in which he held her. That iron chain, of which some of the massive links were round her feminine waist, and the others in his ruthless hand,—or which, perhaps, bound the pair together by a bond equally torturing to each,—must have been forged in some such unhallowed furnace as is only kindled by evil passions, and fed by evil deeds.
Yet, let us trust, there may have been no crime in Miriam, but only one of those fatalities which are among the most insoluble riddles propounded to mortal comprehension; the fatal decree by which every crime is made to be the agony of many innocent persons, as well as of the single guilty one.
It was, at any rate, but a feeble and despairing kind of remonstrance which she had now the energy to oppose against his persecution.
"You follow me too closely," she said, in low, faltering accents; "you allow me too scanty room to draw my breath. Do you know what will be the end of this?"
"I know well what must be the end," he replied.
"Tell me, then," said Miriam, "that I may compare your foreboding with my own. Mine is a very dark one."
"There can be but one result, and that soon," answered the model. "You must throw off your present mask and assume another. You must vanish out of the scene: quit Rome with me, and leave no trace whereby to follow you. It is in my power, as you well know, to compel your acquiescence in my bidding. You are aware of the penalty of a refusal."
"Not that penalty with which you would terrify me," said Miriam; "another there may be, but not so grievous."
"What is that other?" he inquired.
"Death! simply death!" she answered.
"Death," said her persecutor, "is not so simple and opportune a thing as you imagine. You are strong and warm with life. Sensitive and irritable as your spirit is, these many months of trouble, this latter thraldom in which I hold you, have scarcely made your cheek paler than I saw it in your girlhood. Miriam,—for I forbear to speak another name, at which these leaves would shiver above our heads,—Miriam, you cannot die!"
"Might not a dagger find my heart?" said she, for the first time meeting his eyes. "Would not poison make an end of me? Will not the Tiber drown me?"
"It might," he answered; "for I allow that you are mortal. But, Miriam, believe me, it is not your fate to die while there remains so much to be sinned and suffered in the world. We have a destiny which we must needs fulfil together. I, too, have struggled to escape it. I was as anxious as yourself to break the tie between us,—to bury the past in a fathomless grave,—to make it impossible that we should ever meet, until you confront me at the bar of Judgment! You little can imagine what steps I took to render all this secure; and what was the result? Our strange interview in the bowels of the earth convinced me of the futility of my design."
"Ah, fatal chance!" cried Miriam, covering her face with her hands.
"Yes, your heart trembled with horror when you recognized me," rejoined he; "but you did not guess that there was an equal horror in my own!"
"Why would not the weight of earth above our heads have crumbled down upon us both, forcing us apart, but burying us equally?" cried Miriam, in a burst of vehement passion. "O, that we could have wandered in those dismal passages till we both perished, taking opposite paths in the darkness, so that when we lay down to die, our last breaths might not mingle!"
"It were vain to wish it," said the model. "In all that labyrinth of midnight paths, we should have found one another out to live or die together. Our fates cross and are entangled. The threads are twisted into a strong cord, which is dragging us to an evil doom. Could the knots be severed, we might escape. But neither can your slender fingers untie these knots, nor my masculine force break them. We must submit!"
"Pray for rescue, as I have," exclaimed Miriam. "Pray for deliverance from me, since I am your evil genius, as you mine. Dark as your life has been, I have known you to pray in times past!"
At these words of Miriam, a tremor and horror appeared to seize upon her persecutor, insomuch that he shook and grew ashy pale before her eyes. In this man's memory there was something that made it awful for him to think of prayer; nor would any torture be more intolerable than to be reminded of such divine comfort and succor as await pious souls merely for the asking; This torment was perhaps the token of a native temperament deeply susceptible of religious impressions, but which had been wronged, violated, and debased, until, at length, it was capable only of terror from the sources that were intended for our purest and loftiest consolation. He looked so fearfully at her, and with such intense pain struggling in his eyes, that Miriam felt pity.
And now, all at once, it struck her that he might be mad. It was an idea that had never before seriously occurred to her mind, although, as soon as suggested, it fitted marvellously into many circumstances that lay within her knowledge. But, alas! such was her evil fortune, that, whether mad or no, his power over her remained the same, and was likely to be used only the more tyrannously, if exercised by a lunatic.
"I would not give you pain," she said, soothingly; "your faith allows you the consolations of penance and absolution. Try what help there may be in these, and leave me to myself."
"Do not think it, Miriam," said he; "we are bound together, and can never part again."
"Why should it seem so impossible?" she rejoined. "Think how I had escaped from all the past! I had made for myself a new sphere, and found new friends, new occupations, new hopes and enjoyments. My heart, methinks, was almost as unburdened as if there had been no miserable life behind me. The human spirit does not perish of a single wound, nor exhaust itself in a single trial of life. Let us but keep asunder, and all may go well for both."
"We fancied ourselves forever sundered," he replied. "Yet we met once, in the bowels of the earth; and, were we to part now, our fates would fling us together again in a desert, on a mountain-top, or in whatever spot seemed safest. You speak in vain, therefore."
"You mistake your own will for an iron necessity," said Miriam; "otherwise, you might have suffered me to glide past you like a ghost, when we met among those ghosts of ancient days. Even now you might bid me pass as freely."
"Never!" said he, with unmitigable will; "your reappearance has destroyed the work of years. You know the power that I have over you. Obey my bidding; or, within a short time, it shall be exercised: nor will I cease to haunt you till the moment comes."
"Then," said Miriam more calmly, "I foresee the end, and have already warned you of it. It will be death!"
"Your own death, Miriam,—or mine?" he asked, looking fixedly at her.
"Do you imagine me a murderess?" said she, shuddering; "you, at least, have no right to think me so!"
"Yet," rejoined he, with a glance of dark meaning, "men have said that this white hand had once a crimson stain." He took her hand as he spoke, and held it in his own, in spite of the repugnance, amounting to nothing short of agony, with which she struggled to regain it. Holding it up to the fading light (for there was already dimness among the trees), he appeared to examine it closely, as if to discover the imaginary blood-stain with which he taunted her. He smiled as he let it go. "It looks very white," said he; "but I have known hands as white, which all the water in the ocean would not have washed clean."
"It had no stain," retorted Miriam bitterly, "until you grasped it in your own."
The wind has blown away whatever else they may have spoken.
They went together towards the town, and, on their way, continued to make reference, no doubt, to some strange and dreadful history of their former life, belonging equally to this dark man and to the fair and youthful woman whom he persecuted. In their words, or in the breath that uttered them, there seemed to be an odor of guilt, and a scent of blood. Yet, how can we imagine that a stain of ensanguined crime should attach to Miriam! Or how, on the other hand, should spotless innocence be subjected to a thraldom like that which she endured from the spectre, whom she herself had evoked out of the darkness! Be this as it might, Miriam, we have reason to believe, still continued to beseech him, humbly, passionately, wildly, only to go his way, and leave her free to follow her own sad path.
Thus they strayed onward through the green wilderness of the Borghese grounds, and soon came near the city wall, where, had Miriam raised her eyes, she might have seen Hilda and the sculptor leaning on the parapet. But she walked in a mist of trouble, and could distinguish little beyond its limits. As they came within public observation, her persecutor fell behind, throwing off the imperious manner which he had assumed during their solitary interview. The Porta del Popolo swarmed with life. The merry-makers, who had spent the feast-day outside the walls, were now thronging in; a party of horsemen were entering beneath the arch; a travelling carriage had been drawn up just within the verge, and was passing through the villainous ordeal of the papal custom-house. In the broad piazza, too, there was a motley crowd.
But the stream of Miriam's trouble kept its way through this flood of human life, and neither mingled with it nor was turned aside. With a sad kind of feminine ingenuity, she found a way to kneel before her tyrant undetected, though in full sight of all the people, still beseeching him for freedom, and in vain.


text:
DHEA, Testosterone and Age-Related Cognitive Health
This blog does not intend to provide diagnosis...
In this article:
- What Does the Research Have to say About DHEA and Cognitive Function?
- Side Effects and Safety Concerns of DHEA and Testosterone
- A Promising Start but More studies are Needed
Dehydroepiandrosterone (DHEA) is a precursor of testosterone and other androgenic hormones and has many important roles in physiology including modulation of cognition, appetite and sexual behavior. Serum levels of DHEA and its sulfate form DHEA-S gradually decline with aging and reach their lowest levels in the 7th decade. A gradual decline in serum DHEA levels results in reduced synthesis of testosterone, which is associated with a variety of physical, emotional and cognitive symptoms such as fatigue, weight loss, depressed mood, irritability and memory problems. These symptoms are caused by decreases in beneficial effects of testosterone on different parts of the brain that modulate cognitive and emotional function including the amygdala and hypothalamus.
Animal studies have established that exogenous DHEA and DHEA-S have beneficial effects on the immune and cardiovascular systems. Both prohormones also have neuroprotective, antioxidant and anti-inflammatory effects in the brain, promote neurogenesis and increase the synthesis and release of the catecholamine neurotransmitters norepinephrine and dopamine. DHEA is widely used in Western medicine to self-treat decline in cognitive functioning associated with normal aging.
What Does the Research Have to say About DHEA and Cognitive Function?
Many studies have reported improvements in working memory, visual awareness, visuomotor dexterity and attention in healthy adults in response to DHEA. These beneficial effects may be mediated by DHEA-induced cortical plasticity that enhances neural processes underlying visual attention. However, research findings on the effects of DHEA on memory in healthy and cognitively impaired adults are inconsistent. DHEA may improve memory in elderly patients who have low DHEA serum levels more than in younger adults with normal DHEA levels.
In a small human clinical trial (N=10) adult males administered DHEA 500mg experienced significant increases in rapid eye movement (REM) sleep soon following sleep onset. This finding suggests that neurosteroid changes in the brain induced by DHEA have effects on GABA (Gamma-aminobutyric acid). In fact, DHEA binds to both γ-aminobutyric acid (GABA) receptors and N-methyl-D-aspartate (NMDA) receptors, however, it is not clear whether these receptor affinities are related to its cognitive-enhancing effects.
A systematic review and meta-analysis found no support for DHEA as a cognitive enhancer in healthy older individuals. The significance of findings was limited by the fact that only three studies met inclusion criteria, all studies reviewed were 3 months in duration or shorter, and doses tested ranged between 25 and 50 mg only. A separate systematic review and meta-analysis found that individuals with Alzheimer's Disease had consistently low serum DHEA-S levels but normal DHEA levels. The authors argue that this finding is consistent with the role of DHEA as a substrate for DHEA-S synthesis and that activity of sulfatase or other molecular mechanisms of DHEA-S bioconversion may be impaired in individuals with Alzheimer's Disease. A decline in serum DHEA-S levels may be associated with different stages of progression or levels of severity of Alzheimer's Disease, such that lower DHEA-S levels predispose to more severe cognitive impairment. Further studies are needed to determine whether DHEA-S levels provide a reliable diagnostic tool for Alzheimer's Disease risk.
In a 6-month randomized placebo-controlled study unmedicated male patients with Alzheimer's Disease were randomized to DHEA alone (50 mg twice daily) vs placebo. At 3 months the DHEA group showed a trend toward superior cognitive performance compared to the placebo group which persisted until the end of the study. In a small 4-week open study, 7 individuals with multi-infarct dementia who received daily intravenous administration of 200 mg DHEA-S exhibited significant increases in serum and CSF levels of DHEA-S, improvements in activities of daily living and less frequent emotional disturbances. The significance of the findings of both studies is limited by their small size.
Lower circulating testosterone levels in older men are associated with an increased risk of developing Alzheimer's Disease. In a 6-month double-blind, placebo-controlled study, 16 males with Alzheimer's Disease and 22 healthy adult males were randomized to receive testosterone 75 mg (in the form of a dermal gel) versus placebo together with their usual medications. Global quality of life improved in both the demented group and healthy controls. No significant group differences were found at the end of the study however mildly demented patients who received testosterone experienced less decline in visuospatial abilities.
Side Effects and Safety Concerns of DHEA and Testosterone
Exogenous DHEA and testosterone are associated with safety concerns. Mild insomnia is an infrequent side effect of DHEA, which should be dosed in the morning. It is prudent to avoid DHEA when there is a history of benign prostatic hypertrophy or prostate cancer. Testosterone supplementation may increase the risk of cardiovascular disease, stroke, and prostate cancer. It is prudent to consult with your physician before starting DHEA or testosterone.
A Promising Start but More studies are Needed
Large prospective placebo-controlled studies are needed to further characterize the potential cognitive-enhancing effects of DHEA in both healthy individuals and individuals with Alzheimer's Disease or multi-infarct dementia to determine safe, optimal dosing strategies.
- Martínez-Mota, L., Relationship between androgen deficiency and memory impairment in aging and Alzheimer's disease. Actas Esp Psiquiatr, 2017. 45(5): p. 227-47.
- Friess, E., et al., DHEA administration increases rapid eye movement sleep and EEG power in the sigma frequency range. American Journal of Physiology-Endocrinology And Metabolism, 1995. 268(1): p. E107-E113.
- Nguyen, T.-V., et al., Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development. Psychoneuroendocrinology, 2017. 86: p. 110-121.
- Evans, J.G., et al., Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database of Systematic Reviews, 2006(4).
- Pan, X., et al., Dehydroepiandrosterone and dehydroepiandrosterone sulfate in Alzheimer's disease: a systematic review and meta-analysis. Frontiers in aging neuroscience, 2019. 11: p. 61.
- Wolkowitz, O.M., et al., DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study. Neurology, 2003. 60(7): p. 1071-1076.
- Azuma, T., et al., The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia. Journal of the neurological sciences, 1999. 162(1): p. 69-73.
- Lv, W., et al., Low testosterone level and risk of Alzheimer's disease in the elderly men: a systematic review and meta-analysis. Molecular neurobiology, 2016. 53(4): p. 2679-2684.
- Ford, A.H., et al., Sex hormones and incident dementia in older men: The health in men study. Psychoneuroendocrinology, 2018. 98: p. 139-147.
- Lu, P.H., et al., Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Archives of neurology, 2006. 63(2): p. 177-185.
- Sheridan, PJ. Androgen receptors in the brain: what are we measuring? Endocr Rev. 1983;4(2):171-8.