RFQ_Section_J_-_Attachments_I_-_V.docx

ATTACHMENT I – STATEMENT OF WORK

ENVIRONMENTAL HEALTH PERSPECTIVES LANGUAGE TRANSLATION SCIENTIFIC SERVICES

NATIONAL INSTITUTES OF ENVIRONMENTAL HEALTH SCIENCES

RESEARCH TRIANGLE PARK, NC

1.0. BACKGROUND: The National Institute of Environmental Health Sciences (NIEHS), located in Research Triangle Park, North Carolina, is one (1) of 27 research institutes and centers that comprise the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). The mission of the NIEHS is to discover how the environment affects people in order to promote healthier lives. The Branches & Laboratories at NIEHS fall under the Intramural Research and the National Toxicology Program (NTP) Divisions. The NIEHS publishes the monthly scientific journal Environmental Health Perspectives (EHP), a world-renowned monthly online-only journal of peer-reviewed research and news, and one of the top journals in Toxicology, Environmental Sciences, and Public, Environmental, and Occupational Health. Although the EHP falls under the Office of the Deputy Director and is published with support from the NIEHS, it maintains editorial independence. Since the publication is supported by the Federal government, content published in EHP is completely open access, and is free of any author publication charges or page fees. The journal also prides itself on distributing and disseminating cutting-edge research throughout the scientific community, helping the NIEHS to implement its strategic plan of advancing science and improving health, while keeping the journal at the forefront of the publishing landscape.

EHP publishes 12 issues per year, in a continuous publication format. Each issue consists of both Research and original News content. This diversity of content helps EHP to reach a broad audience, from both researchers and clinicians to policymakers and citizen scientists. EHP also publishes a Chinese Edition for international readers, on a quarterly release schedule. The Chinese Edition consists solely of content translated from the English edition. The Chinese Edition is published online, and is distributed in print in limited quantities within China. Currently, articles for the Chinese Edition are selected for translation by EHP’s editorial staff, led by the International Program Manager, and in conjunction with the News Editor and Editor-in-Chief. Content for the Chinese edition is translated with assistance from partner organizations in China. EHP staff handles the licensing and acquisition of all graphics that accompany the translated articles. These partners also currently handle the typesetting of the Chinese content. Under the current process, publication-ready Portable Data Files (PDFs) and manuscript-quality Microsoft Word files containing translated Chinese text, are delivered to EHP. Typesetting and publication of content is not included in the scope of work nor is it requested under this requirement.

2.0. OBJECTIVES: The basic service objective is to provide support for the EHP to control the translation of its content, and to translate scientific journal content into multiple languages for worldwide distribution. The contractor shall provide translators who are specifically trained and technically capable of accurately translating content that is scientific and highly technical in nature. Translation of the journal’s scientific content is needed throughout the performance period; however, Simplified Chinese and Spanish will be the focus in year one (1) and two (2) of the contract while years three (3) through five (5) will be expanded to include Portuguese, Russian, Japanese, French, and Hindi. The Contractor shall translate content in a continuous-publication format to match the English content. The Contractor shall accept a continuous stream of content at various volumes and shall provide translated content in JATS XML format to complement the English version. This will allow for EHP’s online platform to deliver a seamless reading experience to the user no matter what language they prefer. Prior to final delivery of the content to the public, EHP’s International Program Manager will have the opportunity to review all translated content for accuracy. It is anticipated that there will be 100–120 articles per year; the length and complexity of each article varies, but at least 50% are expected to be short-form (approximately 800 words) per year during year one (1) and year two (2). The output is expected to increase in year three (3) to between 150–200 articles per year.

3.0. SCOPE: This Statement of Work (SOW) will be used to execute a broad range of language translation scientific services under the resultant single award requirements contract. During the contract period, the Government will identify tasks required to complete each specific project. Task orders with more specific details will be placed as needed by the NIEHS. Specific performance dates and quantities will be specified on each individual task order.

3.1. This is a non-personal services contract. The Government will not exercise any supervision or control over the contract service providers performing the services herein. Such contract service providers shall be accountable solely to the contractor who, in turn is responsible to the Government. The Contractor, in turn, shall be accountable to the Government for contractor personnel, subcontractors, or contract service providers.

4.0 TASKS: The Contractor shall provide services to manage and execute a broad range of scientific translation task orders awarded under this contract:

4.1. TRANSLATION SUPPORT SERVICES: The contractor shall provide scientific translation services for select published content. The Contractor shall translate provided articles into the language specified on task orders and shall tag that translation in XML according to the Document Type Definition (DTD) and EHP’s tagging guidelines, meeting the guidelines specified herein. Translations shall be performed according to EHP’s specified style guidelines and Production Schedule. The contractor shall maintain high standards of quality at all times, use robust software to automate routine processes when practical, and adapt to the varying volume of content that is commonplace in any journal publishing workflow as timeliness and quality are of the utmost importance to EHP.

4.1.1. The contractor shall:

· The contractor shall translate electronic format English article files, including article XML, graphics, and PDF (for reference) into specified scientific language. The contractor shall receive and confirm receipt of delivered files from EHP:

· All confirmations shall be received within 1 business day of receipt of files. When using ftp delivery, it is expected that the contractor shall automate the confirmation email, so that these are received by EHP in near-real time.

· The contractor shall tag the translation in XML, using the appropriate elements built into the DTD specified (the appropriate @xml:lang attribute shall be added to the document, depending on the language the document is being translated into; additional guidance will be provided by EHP). The XML file shall not contain any parsing errors upon its return to EHP. Further, the contractor shall develop a Schematron to ensure consistency in content tagging and adherence to EHP and publishing platform tagging guidelines.

· The contractor shall develop a plan to tag the translated text programmatically; responses to the solicitation that simply include hand-tagging of all translated elements (this includes manual copy/paste operations) will not be considered, due to the high risk of introducing errors that this plan causes.

· The contractor shall adhere to the EHP style guide. The Contractor shall provide feedback to EHP on the overall usability of the manual, as well as specific style points.

· The Contractor shall provide translations free of grammatical, spelling, and punctuation errors.

· The contractor shall assign a unique DOI to each translated file. The DOI for each translation will be based on the DOI of the original English file, and will follow the convention of the @xml:lang attribute in the translated article XML. (For example, if the English article has the DOI 10.1289/EHP1234, and the article is being translated into Simplified Chinese, the contractor should assign a DOI of 10.1289/EHP1234-zh to the translated article.) Additional guidance will be provided by EHP.

· The contractor shall preserve all MathML tagging in the final deliverable (EHP currently follows the MathML 2.0 Presentation specification). If changes are needed in the display of the math to conform with certain grammatical rules in the translated language, the contractor shall provide correct MathML for the new equation in the XML deliverable.

· “Math” is defined as any construct containing an operator, variable, sub/superscript, or Greek character. The contractor shall ensure that appropriate fonts and symbols are used. Note that all equations shall be tagged in their entirety; for example, in the expression x2 = 5, it is not sufficient to only tag the left-hand portion of the equation. Some general mathematical guidelines include:

· Do not capture spaces between operators or characters, unless the space conveys mathematical meaning (there is no instance where extra space around an operator conveys meaning). When space is appropriately captured, always use the <mspace> tagging.

· Blank or empty tags are not allowed.

· Certain characters (such as the degree symbol, when paired with a temperature) are not considered operators, and shall not be captured in math unless they are part of a larger equation.

· Fences (parentheses, brackets, braces) are considered operators when used in mathematical expressions. Do not capture fences in MathML when used as part of text – this includes when the fences surround a mathematical expression in its entirety, and have no mathematical influence on the expression.

· Variables shall be tagged consistently throughout the manuscript – all variables shall be tagged as “math”, not just italic text.

· Correct symbols shall be used for all characters, and these shall map to the appropriate Unicode character. For instance, hyphens or dashes cannot be used in place of a minus sign. SGML/HTML entities shall not be used.

· The contractor shall ensure that all companion papers (parts 1 and 2, letter and response combinations, news articles associated with a research paper) are translated by the same translator, in consecutive sessions, when provided by EHP at the same time. If companion papers are assigned to the translation contractor at different times, the contractor will make every effort possible to assign the work to the same translator, so long as the translation schedule can be accommodated. The contractor shall ensure consistency of the translation throughout these papers no matter which translator is assigned.

· The contractor shall accept timely feedback from EHP staff regarding incorrect translations or updated style guidelines, and have a policy in place for how that feedback will be distributed to the staff, and how staff will be monitored to ensure the same error is not repeated. The policy should specify how long it will take to distribute feedback to the staff. Priority shall be given to correction of the errors.

· The contractor shall ensure that figures and images are translated along with the paper and shall ensure that changes are not made to the figures themselves. Any figures or images containing English text shall have translated text added to the figure caption. This may take the form of a verbatim translation, or simply a summary of what the English text means. Specific instructions for the scope of such translations will be provided with each paper.

· The contractor shall ensure that tables are translated along with the paper. Tables shall follow EHP style with regard to headings and layout, and shall meet 508 accessibility guidelines.

· The contractor shall ensure that translators translate the alternative text that is provided for figures, equations, or any graphical elements as needed to conform with 508 accessibility guidelines.

· The contractor shall ensure that Translators query EHP for any problems they are unable to resolve, or to confirm any translations that may change the meaning of the text.

· The contractor shall ensure that all translations are proofread for accuracy prior to delivery.

· The contractor shall ensure that they deliver all final publication files (including but not limited to XML, figures, and lists of queries) to EHP or one of its contractors.

· The contractor shall ensure that if ftp delivery is being used, an electronic “reverse feed” shall be supplied to EHP’s tracking system (in XML format via ftp) when translation of a paper is complete. This feed shall not only confirm the end date of the work, but shall include any relevant metadata updates as directed by EHP.

· The contractor shall ensure that some type of version-control system on their server is maintain for all working files generated during the translation process.

· The contractor shall archive all working files and correspondence off their system after an agreed-upon period (for instance, 6 months after final publication). These archives shall be maintained for the life of the contract (and any follow-on contracts), and shall be turned over to EHP in the event a follow-on contract is not issued, or the contract has ended or is terminated for any reason.

· The contractor shall ensure that management, training, and review of all translators is performed. EHP will provide appropriate guidelines and feedback to the contractor as needed to facilitate the successful training of these individuals in the expectations of the journal.

· The contractor shall ensure that all translators are fluent in both English and the language they are translating the text into, and have experience translating scientific content.

· The contractor shall complete work within the timeframe specified.

· The contractor shall bill for translations on a per-word basis, with the number of words for each article determined by the reference English PDF provided. The unit cost for each translated word shall be fixed per language, and the price specified in the contractor’s price proposal. Contractors shall include a separate line item for the translation of figures; this shall also have a fixed unit price that is specified in the price proposal.

4.2. PUBLISHER PORTAL SUPPORT SERVICES: The contractor shall provide a Publisher Portal to allow EHP to view the progress of work on all assigned papers, as well as the correspondence history for each job. The contractor shall provide an online publisher portal for EHP staff to monitor and review the progress of work. The portal shall be customizable to supply EHP with the information we need, and to suit the workflow that we specify.

· The portal shall provide real-time online access and monitoring of all papers throughout the translation process.

· The portal shall provide access to all files provided by EHP, and shall contain a record of all correspondence related to each paper.

· The portal shall be secured via username/password, with credentials provided to EHP staff upon request.

· The portal shall specify both total working days for all papers with the contractor, as well as working days spent in each work queue. These data must be available even after the assignment is complete, and data should be available for export from the portal.

· The portal shall include a search feature.

· The contractor shall track manuscripts according to EHP’s manuscript numbers. The portal shall also track manuscripts in this manner.

· The portal shall display relevant metadata for each paper, as directed by EHP during setup.

· No materials containing PII will be provided to the contractor.

· The portal will have no direct connection to the Federal government network, and will not be hosted using any government resources. The portal will be hosted and maintained exclusively by the contractor.

· The cost to maintain the portal should be integrated into the unit cost of the translations; separate funds will not be made available for the creation, maintenance, or customization of the portal.

· The phase-in period (Sec. 13.1) is provided, in part, for the customization of the publisher portal. It is expected that the contractor will already be in possession of this technology at the time they issue their response to the SOW, as time to build or develop the portal is not provided under this contract.

· All data provided to the contractor for inclusion on the portal remains the property of the government, and cannot be used for any purpose beyond what is specified in this SOW. At the conclusion of the contract, all copies of the data must be either returned to the government, or destroyed, as directed.

4.3. DELIVERABLES AND OTHER PROCEDURAL REQUIREMENTS: In addition to the required reports set forth elsewhere in the contract and under attachment II - Deliverable Schedule, the Contractor shall provide the following:

· The contractor shall meet all timelines for delivering content to EHP, and all internal deadlines, as specified in the Timelines section and shall abide by all customer service guidelines, as detailed in the Customer Service section.

· The contractor shall complete each translation (the day of delivery will be day 0; the job shall be complete by day 5) within five (5) working days, including translation, proofreading, tagging the translated text in XML, and providing the deliverables to EHP or its contractor, as specified. In the event that EHP provides incorrect or incomplete files for translation or incorrect instructions, the time spent to resolve that query will not count against the contractor, and the deadline will be extended for those papers.

· The Contractor shall provide a single customer support representative (with a backup) at the contractor, to act as a single point of contact for all inquiries from the journal. Direct email and phone contact information shall be provided for both individuals. EHP will not utilize a ticketing system or phone queue for this support.

· The Contractor shall provide support to host regular conference calls with EHP and the account manager, and with any other members of the contractor’s team that are required based on current projects or problems. The frequency for these calls is expected to be once a week at the start of the contract, moving to once every two weeks or once a month under normal operations. A regular meeting schedule will be established to ensure consistency in these conference calls. When materials need to be shared in real time, a WebEx (or similar) meeting can be initiated by the contractor.

· The contractor shall have frequent contact and interaction with individuals who work closely with EHP. The contractor shall contact individuals on behalf of the journal. The contractor shall maintain exceptional service standards in all these interactions, and shall always present the journal in a positive manner.

5.0. COMPLIANCE: The contractor shall comply with NIEHS guidelines for websites and other communications materials (see Attachments). See Section 508 accessibility guidelines as defined by the federal government. Please see the following URLs for details:

· Section 508 Information: http://www.section508.gov/

· Guide to the Section 508 Standards: https://www.access-board.gov/guidelines-and-standards/communications-and-it/about-the-section-508-standards/guide-to-the-section-508-standards

· Making Files Accessible: http://www.hhs.gov/web/section-508/making-files-accessible/index.html

5.1. The following Section 508 accessibility standards apply to the tasks identified in this SOW:

· 36 CFR Part 1194-Subpart B—“Technical Standards”

· 1194.21—Software Applications and Operating Systems

· 1194.22—Web-based Intranet and Internet Information & Applications

· 1194.24—Video and Multimedia Products

· 36 CFR Part 1194-Subpart C—“Functional Performance Criteria”

· 1194.31 --- Functional Performance Criteria are intended to ensure that the individual accessible components work together to create an accessible product.

· 36 CFR Part 1194-Subpart D—“Information, Documentation, and Support”

· 1194.41 --- In order for EIT to be fully usable by people with disabilities, the information about the EIT and EIT support services shall also be usable by people with disabilities.

· Other Requirements

· The anticipated information content deliverable may include topics that address EIT products or EIT-related services. Delivered information content shall include data and/or knowledge appropriate and responsive to the functional performance criteria detailed in 36 CFR part 1194 Subpart C, as well as any technical provisions of 36 CFR part 1194 Subpart B applicable to the specific type of EIT addressed in the delivered information content.

· The anticipated information content deliverable is intended to be posted a website. Delivered information content shall consider the specific Section 508 accessibility requirements detailed in 36 CFR part 1194.22 and the functional performance criteria detailed in 36 CFR 1194 Subpart C.

· The anticipated information content deliverable is intended to be made available in a multimedia format. Delivered information content shall consider the specific Section 508 accessibility requirements detailed in 36 CFR part 1194.24 and the functional performance criteria detailed in 36 CFR 1194 Subpart C.

· The work outlined in the SOW is expected to involve tasks that relate to or require the use of EIT. Delivered effort shall include knowledge and capabilities in the functional performance criteria detailed in 36 CFR part 1194 Subpart C, as well as any technical provisions of 36 CFR part 1194 Subpart B applicable to the specific type of EIT involved in the expected tasks.

5.2. EHP-Specific Section 508 Requirements: The EHP website shall meet all accessibility standards outlined in Section 1194.22 of the Section 508 Product Evaluation Template and described in detail at https://www.access-board.gov/sec508/guide/1194.22.htm. EHP content often includes complex figures, tables, and equations published in HTML format. EHP content published in video or multimedia formats shall comply with standards outlined in Section 1194.24 of the Section 508 Evaluation Template. In addition, some EHP content may be published in PDF, Word, PowerPoint, or Excel formats only. These documents and files, which may include text, tables, figures, equations, and hyperlinks, also shall meet Section 508 accessibility requirements before publication. PDF files shall pass Adobe Accessibility Full Check scans, including both the ‘Adobe PDF’ and ‘Section 508 web-based intranet and internet information and applications’ (1194.22) options. Microsoft Office products (Word, Excel, and PowerPoint files) shall pass Microsoft Accessibility Checker scans or comply with Word, Excel, or PowerPoint Document 508 Checklists available at http://www.hhs.gov/web/508/accessiblefiles/index.html.

NOTE: If the deliverable includes features and functions in addition to those identified as requirements, these features and functions also need to conform to relevant Section 508 technical provisions, functional performance criteria, and information, documentation and support.

6.0. OTHER CONSIDERATIONS:

· Restriction on contractor’s use of or dissemination of databases: Mailing lists either furnished to the contractor by the COR or prepared by the contractor as part of its continuing efforts to support the journal are protected by the Privacy Act, and shall not be used by the contractor or any other third party for any purposes other than for the expressed purpose of this contract. Mailing lists provided as part of this contract shall not be disseminated to other persons or entities, except the COR, and shall not be used by the contractor, its subcontractors, or any other organization of persons for any purpose other than the services specifically described by the SOW and contract document. The contractor shall ensure that all subcontracts and consultant agreements in support of this contract include this restriction.

· Privacy Act Notice: This SOW requires the Parties to do one or more of the following: design, develop, or operate a system of records on individuals to accomplish an agency function in accordance with the Privacy Act of 1974, Public Law 93-579, December 31, 1974 (5 USC 552a) and applicable agency regulations. Violation of the Act may involve the imposition of criminal penalties. The Privacy Act System of Records applicable to this project is Number 09-90-0024.

· Public Affairs Clearances: Any printing product produced under this contract for public distribution shall be submitted by the COR to the Assistant Secretary for Public Affairs (ASPA) office for clearance using form HHS-615 (to be completed by contractor).

7.0. CONTRACTOR PERSONNEL: The Contractor(s)’ personnel shall perform in a professional and courteous manner and shall abide by applicable NIEHS policies, rules, and procedures while on site.

7.1. KEY PERSONNEL: Qualified personnel shall be provided by the Contractor for performance of work listed herein to assure that requests for services are responded to in a prompt and safe manner. The following will be considered key personnel by the Government:

7.1.1. Project Manager: The Contractor shall provide a Project Manager who shall be responsible for overseeing all aspects of the work including under the contract and task orders.

· Qualifications: The Project Manager shall have a Bachelor’s degree at minimum. This individual shall have a minimum of 5 years of work related experience in coordinating the electronic publishing activities of a scientific publisher or scientific publishing services provider, with prior experience in scientific journals content.

7.1.2. Scientific Language Translators: The Contractor shall provide Scientific Language Translators who shall be responsible for translations into Simplified Chinese, Portuguese, Russian, Japanese, Spanish, French, and Hindi languages.

· Qualifications: The translators shall have the following:

· Demonstrate existing experience of translating articles from English to those languages specified in Section 2, for a scientific publication.

· Demonstrate an understanding of 508 and WCAG compliance principles, and shall have existing experience analyzing content and applying 508-specific alternatives to technical content.

· Demonstrate the ability to handle varying amounts of input on a week-to-week basis (shall indicate how translation assignments are made to staff or freelance contractors).

· Demonstrate the use of an existing publisher portal, its capabilities, flexibility, and the ability for the contractor to tailor it to the needs of EHP.

· Achieve at least 90% accuracy on the translation test file provided.

· Demonstrate strong customer service abilities.

· Demonstrate expertise of XML journal publishing principles, MathML publishing principles, and participation in the scholarly XML publishing community. The contractor shall have demonstrated experience working with and modifying XML content for a scholarly client.

· Familiarity with and experience implementing AMA style.

· Fluency in both English and the language they are translating the text into.

7.1.3. Central Customer Support Representative: The representative shall act as a single point of contact for all inquiries from the journal.

· Qualifications: A minimum of a High school diploma and a minimum of 2 years of customer service experience. Shall demonstrate strong customer service abilities and experience working with scholarly authors, researchers, translators, and reviewers.

8.0. QUALITY CONTROL: The Government is committed to a highly interactive relationship between quality control by the contractor and quality assurance by the government. This relationship shall be achieved through an effective prevention based quality control program dedicated to ensuring the best possible products and services to end users. As part of quality control, the Contractor shall submit a Quality Control Plan (QCP) which at a minimum shall include a self-inspection plan, an internal staffing plan, and an outline of the procedures that the contractor shall use to maintain quality, timeliness, responsiveness, customer satisfaction, and any other requirements set forth in this SOW. The QCP shall be updated five (5) days after contract award. The QCP shall document how the contractor intends on meeting and complying with the quality standards established in this SOW. The contractor’s QCP shall be maintained throughout the life of the contract and shall include the contractor’s procedures to routinely evaluate the effectiveness of the plan to ensure the contractor is meeting the performance standards and requirements of the contract. An updated copy shall be provided to the COR no later than five (5) days after any updates.

9.0. GOVERNMENT FURNISHED PROPERTY, EQUIPMENT, AND SERVICES: This section identifies those items such as property, information and/or services that will be provided for the contractor’s use (without cost to the contractor): N/A

10.0. CONTRACTOR FURNISHED ITEMS AND RESPONSIBILITIES: The Contractor shall furnish all supplies, equipment, and services required to perform work under this contract that are not listed under section 9 of this SOW.

· Items: The contractor shall provide all required hardware, software, licenses, internet access, etc., along with all necessary support, to perform this work. The Government shall not provide any equipment, materials, or technical support. The contractor will not have access to the NIEHS network or email accounts.

· Security/Security Log: The contractor shall maintain the security and integrity of their systems at all times. This includes promptly installing updates to mitigate security threats, actively testing all software releases for potential security holes, and promptly informing customers of known or suspected data breaches.

11.0. HOURS OF OPERATION: Normal business hours are Monday-Friday, excluding Federal holidays. Core hours at NIEHS typically fall between: 8:00 am – 5:00 pm.

11.1. The National Institutes of Environmental Health Sciences observes the following holidays:

12.0. PLACE OF PERFORMANCE: The management office place of performance, and the place of performance for EHP’s customer support representative, shall be anywhere in the United States. Additionally, translators can be anywhere in the world, as these positions require high-level language skills due to the translation requirement. Any other personnel involved in the contract outside of these particular positions, can be anywhere in the world as long as they are available in the required times of operations so as not to delay any contract requirement to the Government.

13.0. ORDERING PERIOD: The requirement has a 5 year ordering period. Individual task orders issued cannot exceed a 12-month period from the date of award.

13.1. Phase-In/Phase-Out Period: To minimize any decreases in productivity and to prevent possible negative impacts on additional services, the contractor shall have personnel on board during the 30 day Phase-In, and for up to 6 months during Phase-Out. During the phase in period, the contractor shall become familiar with performance requirements in order to commence full performance of services on the contract start date. The contractor shall prepare to assume full responsibility for all areas of operation in accordance with the terms and conditions of this contract. The contractor shall take all actions necessary for a smooth transition of the contracted support operations. Transition requirements are as follows:

· Publication of EHP online shall proceed on schedule and without interruption.

· Live work will be assigned to the contractor during the phase-in period, but the deadlines specified in Sec. 4.3 will not be enforced during phase-in.

· In order to minimize the disruption of service for any follow-on contract, the incumbent shall participate with the successor contractor and the contract officer representative (COR) in an orderly transfer of services for any follow-on contract. It is anticipated that a 30 day transition period is set aside at the end of the routine performance period for the phase-out of the contractor’s performance. Any resulting contract from this SOW shall include the phase-out transition period in the established completion date. During the transition period, the incumbent shall prepare transition reports and documents which shall describe the status of translation efforts, as well as any outstanding issues that a new contractor shall need to know in order to continue service of the publication with minimal disruption.

· All electronic and print documentation and materials developed under the contract (including applications, databases, and intellectual property) shall be transferred, as directed by the COR, to the successor or the NIEHS.

14.0 SECURITY: The contractor shall maintain the security and integrity of their systems at all times. This includes promptly installing updates to mitigate security threats, actively testing all software releases for potential security holes, and promptly informing customers of known or suspected data breaches. A security plan shall be included with all proposals.

15.0. DATA RIGHTS: The Government has unlimited rights to all documents/material produced under this contract to the extent permitted by the data rights clauses. The parties mutually acknowledge their understanding that this is the government’s intent. All documents and materials produced under this task order shall be government owned and are the property of the government with all rights and privileges of ownership/copyright belonging exclusively to the government. These documents and materials may not be used or sold by the contractor without written permission from the contracting officer. All materials supplied to the Government will be the sole property of the government and may not be used for any other purpose. This right does not abrogate any other government rights.

RFQ Section J - Attachments I - V

ATTACHMENT II

DELIVERABLE SCHEDULE

SOW Ref

Deliverable

· Updated Five (5) days after contract award

· No later than five (5) days after any updates.

· Updated Five (5) days after contract award

· No later than five (5) days after any updates.

· Updated applicable security plans and forms as required under the section

ATTACHMENT III

QUALITY ASSURANCE REQUIREMENT SUMMARY

ATTACHMENT IV

CONTRACT PRICING MATRIX

Contract Price Rates { FOR FUTURE TASK ORDERS} – Do not add to or change the service items below

ATTACHMENT V – SAMPLE TASK ORDER STATEMENT OF WORK

ENVIRONMENTAL HEALTH PERSPECTIVES LANGUAGE TRANSLATION SCIENTIFIC SERVICES

NATIONAL INSTITUTES OF ENVIRONMENTAL HEALTH SCIENCES

RESEARCH TRIANGLE PARK, NC

1.0. INTRODUCTION: The Quoter shall translate the following into Simplified Chinese, adding the translation to the XML file according to the DTD called out in the file, and add any necessary translation of text in the figures/Graphics to the translated caption. Queries should also be supplied as a separate file.

image1.emf

EHP3127.alt.pdf

What Is Your Gut Telling You? Exploring the Role of the Microbiome in Gut–Brain Signaling Lindsey Konkel https://doi.org/10.1289/EHP3127

On 6 June 1822, French Canadian fur trade voyageur Alexis St.

Martin was shot accidentally in the stomach at an American Fur Company store on Michigan’s Mackinac Island.1 The blast left a gaping wound in St. Martin’s abdomen. St. Martin eventually recov-ered from the gruesome accident, but the wound never closed com-pletely, leaving a small permanent opening in his stomach wall.1

His surgeon, William Beaumont, began monitoring gastric secre-tions through this opening in St. Martin’s body. Beaumont, who would later become known as the father of gastric physiology, would attach various types of food to a string and suspend them through the hole. Later he would pull out the string to see what portion of the food had been digested. During these experiments, Beaumont noticed that St. Martin’s mood seemed to affect how quickly he digested food. When St. Martin was irritable, for instance, food broke down more slowly.2

These early observations provided the first clues of crosstalk between the brain and the gut. Researchers later called this bidirec-tional communication system the gut–brain axis. Over the years, studies have revealed that the brain influences the gastrointestinal

(GI) tract through several mechanisms that involve the nervous and immune systems.2

Only recently have scientists recognized the importance of a third component to the gut–brain axis: the trillions of bacteria, viruses, archaea, and eukaryotes that make up the gut microbiome.

In little more than a decade, researchers have uncovered intriguing associations between gut bacteria and a host of neurological disor-ders and psychiatric conditions. These include depression, anxiety, autism spectrum disorders (ASDs), and Parkinson’s disease.2

Most of the early research on the microbiome–gut–brain axis has been conducted in rodents.3 Germ-free mice—which are born in sterile conditions and free of all microorganisms—are popular for gut flora research because scientists can inoculate the mice with specific microbes and watch what happens.

Now, additional researchers are beginning to probe the connection in humans. Outside neuroscience, gut microbiome research in labora-tory animals and humans is changing the way some environmental health scientists view the effects of environmental exposures on neurodevelopment and brain chemistry.

From the moment of birth—and possibly even earlier—our microbiomes begin to develop. There is evidence that a healthy gut microbiome is important for brain development, but as toxicologist Matt Rand explains, “the complexity of the microbiome, with many thousands of microbial species existing as a commu-nity, predicts that individual ‘superbugs’ are not likely to be found that single-handedly mediate a gut–brain benefit or detriment.” Image: © Andesign101/ iStockphoto.

Environmental Health Perspectives 062001-1 126(6) June 2018

A Section 508–conformant HTML version of this article is available at https://doi.org/10.1289/EHP3127. Focus

Developmental Links Microbes colonize the infant gut shortly after birth. Starting with delivery2—and possibly even earlier in the womb4,5—infants are inoculated with microorganisms from their mother’s body. These pioneering microbes play a critical role in shaping the development of the GI tract and immune system.2 They also set the basis for the adult microbiome. By the end of the first 3–5 years of life, a child’s gut flora closely resemble those of an adult.2 “The architecture of the gut microbiome, once established in the first few years, remains more or less stable for life,” says Emeran Mayer, a gastroenterolo-gist and neuroscientist at the University of California, Los Angeles.

This critical window for microbes to colonize the infant gut coin-cides with a period of rapid brain development. A study published in 2004 provided the first experimental evidence that the two domains could be related.6 A group of scientists led by Nobuyuki Sudo of Kyushu University in Japan showed that germ-free laboratory mice inoculated early in life with a probiotic (i.e., beneficial) gut bacterial strain were less likely than conventionally reared mice to exhibit anxiety-like behaviors in stressful environments, such as mazes, brightly lit boxes, and open spaces.7,8,9

Beyond the critical early life window, some studies have shown that germ-free mice colonized with probiotics during adulthood also are less likely to engage in some anxiety- and depression-like behaviors.10 In one study, germ-free mice did not join in normal social behaviors and engaged in more repetitive behaviors than their conventionally colonized counterparts.11

However, in another study using a rodent model of autism, researchers showed it was possible to reverse deficits in social interactions by colonizing the initially germ-free animals with the beneficial bacterium Bacteroides fragilis.12

Some of the microbiome’s influence on neurodevelopment might be sex-specific. In a 2013 study, researchers showed that manipulating the microbiome resulted in altered levels of the neurotransmitter serotonin in male germ-free mice but not in females.9

Overall, accumulating evidence from rodent studies suggests links among gut flora, brain biochemistry, and behavior.10 Many of the findings remain untested in humans, however, and although the germ-free mouse is a powerful tool for testing hypotheses about commensal bacteria, it is not always environmentally relevant,10 because humans are bathed in microbes from birth. “In humans, you are looking for subtle variations in what bugs are present and what they are doing,” says Rebecca Knickmeyer, a neuroscientist at the University of North Carolina at Chapel Hill.

Researchers have suspected a relationship between microbial colonization after birth and brain development, but until recently, no empirical evidence in humans has been found that demonstrates the link.13 That’s starting to change as researchers take what they have learned in early studies of germ-free mice and begin testing hypotheses in people. “Ultimately, the goal would be to manipulate the microbiome to improve cognitive functioning and reduce the risk for developmental and later-life disorders,” says Knickmeyer.

Recently Knickmeyer et al. took the first steps toward translating animal data to the clinic by linking the composition of an infant’s

Germ-free mice are well suited for microbiome research because they can be selectively inoculated with microbes of interest. Experiments with germ-free mice have yielded intriguing clues about the possible influence of the gut microbiome on behavior and neurodevelopment. However, it is still unclear whether these findings are relevant to humans. Image: © muratsenel/iStockphoto.

Environmental Health Perspectives 062001-2 126(6) June 2018 intestinal flora to its cognitive development.13 The researchers col-lected fecal samples from 89 typically developing 1-year-olds. They compared the microbial composition of the stool—a technique used to identify gut bacteria—to cognitive outcomes on an early learning test and magnetic resonance imaging scans of the brain at ages 1 and 2 years.

Knickmeyer’s group found that children with the highest lev-els of gut microbial diversity scored lower on tests of expressive language (how a person communicates their needs and wants) and visual perceptual processing (how the brain makes sense of what the eyes see), in comparison with children who had a less diverse gut microbiome.

The findings, says Knickmeyer, were a bit unexpected, because having a diverse microbiome is typically seen as a benefit. The thinking is that having many different kinds of bacteria in the gut can help buffer against environmental perturbations that could shift gut microbial composition away from its equilibrium, she explains.

The researchers are not sure why having a more diverse micro-biome, with a more adultlike profile of constituent microorganisms, was associated with worse cognitive outcomes. One possibility is that children with more microbial diversity could be harboring harmful bacterial strains, says Knickmeyer.

The researchers also do not know whether the microbiome itself actually caused the differences in cognitive scores. Instead, it could be acting as a proxy for some other environmental or genetic factor that’s driving the association, or there could be some other explanation altogether. It will be important to confirm these findings in other populations.

Erika Claud is using animal research to test associations seen in her work as a neonatologist at the University of Chicago Medical Center. Her research focuses on necrotizing enterocolitis (NEC), an inflammatory bowel disorder that affects premature infants. In babies with NEC, disease-causing bacteria invade the intestinal wall, caus-ing perforations that can result in a life-threatening infection.14

Earlier comparisons of preterm babies with and without NEC found that babies with the condition were more likely to have poorer neurodevelopmental outcomes.15,16,17 Claud wondered whether the same microbes that caused intestinal inflammation could also be linked to abnormal brain development. She collected fecal samples from preterm infants and transplanted them into pregnant germ-free mice. Her initial study used growth as an indicator of overall health of the dams’ pups. When the pregnant mice received gut bacteria from infants who were struggling to gain weight, their pups grew more slowly than pups whose dams had received microbes from babies who were gaining weight normally.14 In a follow-up study, she showed that the poorly growing mice had more neuroinflamma-tion and slower neuron development than the faster-growing mice.18

The research, Claud says, could begin to help researchers under-stand what differentiates a healthy microbiome in the preterm infant from an unhealthy one—and what role a child’s microbial makeup may play in driving developmental delays. “Once we understand the difference, we can try to manipulate the microbiome to move toward a more healthy state,” she says.

The Elusive Promise of Interventions Over the past decade, researchers have used a number of experimen-tal approaches to study gut–brain interactions in experimental ani-mals. They have tinkered with gut microbes using treatments with antibiotics, probiotics, and fecal microbial transplants in hopes of identifying potential therapies for illnesses that may be mediated by the microbiome.

GI symptoms ranging from chronic constipation to inflammatory bowel disease are common in people with ASDs.19 The causes of these problems are unclear, but there is some evidence that altered in-testinal flora may be involved. For example, in January 2017, a small trial in children diagnosed with ASDs provided preliminary evidence that changes to the gut flora may affect autism symptoms.20 The study compared 18 children with ASD diagnoses and severe gastrointesti-nal GI problems with a control group of 20 children who had neither ASD diagnoses nor GI problems. At baseline, the neurotypical chil-dren had much more diverse gut microbiomes than the children with ASDs.

The study team, led…