75 FR 11574 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-11

... agency's ``Regulatory Guide'' series. This series was developed to describe and make available to the... protection during plant operation and maintenance activities. For plants that have a design basis that... coatings be qualified and capable of surviving a design-basis accident without adversely affecting safety...

Quality Management Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-10-01

According to {section} 35.32, Quality Management Program,'' of 10 CFR Part 35, Medical Use of Byproduct Material,'' applicants or licensees, as applicable, are required to establish a quality management (QM) program. This regulatory guide provides guidance to licensees and applicants for developing policies and procedures for the QM program. This guide does not restrict or limit the licensee from using other guidance that may be equally useful in developing a QM program, e.g., information available from the Joint Commission on Accreditation of Healthcare Organizations or the American College of Radiology. Any information collection activities mentioned in this regulatory guide aremore » contained as requirements in 10 CFR Part 35, which provides the regulatory basis for this guide. This information collection requirements in 10 CFR Part 35 have been cleared under OMB Clearance No. 3150-0010.« less

76 FR 10917 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

... in the agency's ``Regulatory Guide'' series. This series was developed to describe and make available... connection assemblies can perform their safety functions during and after a design-basis event. Title 10 of... Reprocessing Plants,'' Criterion III, ``Design Control,'' requires, in part, that test programs used to verify...

75 FR 16516 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

...: R.A. Jervey, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: (301) 251...'' series. This series was developed to describe and make available to the public such information as.... Although a time limit is given, comments and suggestions in connection with items for inclusion in guides...

75 FR 3760 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0018] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory...) is issuing for public comment a draft guide in the agency's ``Regulatory Guide'' series. This series...

76 FR 189 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

.../reading-rm/doc-collections/ . In addition, regulatory guides are available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0265] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3...

75 FR 79049 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

..., Division of Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission... INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to an existing... Development Branch, Division of Engineering, Office of Nuclear Regulatory Research. [FR Doc. 2010-31731 Filed...

77 FR 8902 - Draft Regulatory Guide: Issuance, Availability Decommissioning of Nuclear Power Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... Decommissioning of Nuclear Power Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide... draft regulatory guide (DG) DG-1271 ``Decommissioning of Nuclear Power Reactors.'' This guide describes... Regulatory Guide 1.184, ``Decommissioning of Nuclear Power Reactors,'' dated July 2000. This proposed...

Model competencies in regulatory therapeutic product assessment: Health Canada's good review guiding principles as a reviewing community's code of intellectual conduct.

PubMed

Lim, Robyn R

2007-08-01

This article describes some work from the Therapeutic Products Directorate of Health Canada regarding Good Review Practices (GRP). Background information is provided on the Therapeutic Products Directorate (TPD) and its regulatory activities regarding drug and medical device assessment in both the pre- and post-market setting. The TPD Good Review Guiding Principles (GRGP) are described which include a Definition of a Good Therapeutic Product Regulatory Review, Ten Hallmarks of a Good Therapeutic Product Regulatory Review and Ten Precepts. Analysis of the guiding principles discusses possible linkages between the guiding principles and intellectual virtues. Through this analysis an hypothesis is developed that the guiding principles outline a code of intellectual conduct for Health Canada's reviewers of evidence for efficacy, safety, manufacturing quality and benefit-risk regarding therapeutic products. Opportunities to advance therapeutic product regulatory review as a scientific discipline in its own right and to acknowledge that these reviewers constitute a specific community of practice are discussed. Integration of intellectual and ethical approaches across therapeutic product review sectors is also suggested.

76 FR 6085 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

...-2011-0014] RIN 3150-AI49 Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice Availability of Draft Regulatory Guide. SUMMARY: The U.S. Nuclear Regulatory Commission (Commission or NRC) is issuing for public comment Draft Regulatory Guide, DG-5019, ``Reporting and...

75 FR 18241 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0148] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory.... Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment a draft guide in the...

75 FR 45166 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0265] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory.... Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment a draft guide in the...

75 FR 52996 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0287] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Draft Regulatory Guide, DG-8035, ``Administrative Practices in Radiation Surveys and Monitoring.'' FOR FURTHER...

76 FR 38212 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0275] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Revision 1 of Regulatory Guide (RG) 1.179, ``Standard Format [[Page 38213

75 FR 1830 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... review of applications for permits and licenses. RG 5.71, ``Cyber Security Programs for Nuclear... NUCLEAR REGULATORY COMMISSION [NRC-2010-0009] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

76 FR 31382 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0287] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.2, Revision 1, ``Administrative Practices in Radiation Surveys and Monitoring.'' FOR FURTHER INFORMATION...

76 FR 6086 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... NUCLEAR REGULATORY COMMISSION 10 CFR Part 73 [NRC-2011-0015] RIN 3150-AI49 Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Availability of Draft... comment Draft Regulatory Guide, DG-5020, ``Applying for Enhanced Weapons Authority, Applying for...

75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0275] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1228, ``Standard Format and Content of License Termination Plans for Nuclear Power Reactors.'' FOR FURTHER INFORMATION CONTACT: James C....

78 FR 47012 - Developing Software Life Cycle Processes Used in Safety Systems of Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Developing Software Life Cycle Processes Used in... revised regulatory guide (RG), revision 1 of RG 1.173, ``Developing Software Life Cycle Processes for... Developing a Software Project Life Cycle Process,'' issued 2006, with the clarifications and exceptions as...

77 FR 33253 - Regulatory Guide 8.33, Quality Management Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0126] Regulatory Guide 8.33, Quality Management Program... Regulatory Commission (NRC or Commission) is withdrawing Regulatory Guide (RG) 8.33, ``Quality Management... Quality Management Program was deleted from the regulations as part of an overall revision in 2002 of the...

75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-3039, ``Standard Format and Content for Emergency Plans for Fuel Cycle and Materials Facilities.'' FOR FURTHER INFORMATION CONTACT: Kevin M....

76 FR 2726 - Withdrawal of Regulatory Guide 1.154

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0010] Withdrawal of Regulatory Guide 1.154 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.154, ``Format and Content of Plant-Specific Pressurized Thermal Shock Safety Analysis Reports for Pressurized Water Reactors.'' FOR FURTHER INFORMATION CONTACT: Mekonen M. Bayssie,...

76 FR 24539 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide (RG) 3.67, ``Standard Format and Content for Emergency Plans for Fuel Cycle and Materials Facilities.'' FOR FURTHER INFORMATION CONTACT: Kevin M. Ramse...

Impact of guided exploration and enactive exploration on self-regulatory mechanisms and information acquisition through electronic search.

PubMed

Debowski, S; Wood, R E; Bandura, A

2001-12-01

Following instruction in basic skills for electronic search, participants who practiced in a guided exploration mode developed stronger self-efficacy and greater satisfaction than those who practiced in a self-guided exploratory mode. Intrinsic motivation was not affected by exploration mode. On 2 post-training tasks, guided exploration participants produced more effective search strategies. expended less effort, made fewer errors, rejected fewer lines of search, and achieved higher performance. Relative lack of support for self-regulatory factors as mediators of exploration mode impacts was attributed to the uninformative feedback from electronic search, which causes most people to remain at a novice level and to require external guidance for development of self-efficacy and skills. Self-guided learning will be more effective on structured tasks with more informative feedback and for individuals with greater expertise on dynamic tasks.

76 FR 32878 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-07

...-0129] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1253, ``Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors''. FOR FURTHER INFORMATION CONTACT: Mekonen M...

75 FR 20868 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

...: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.68.2... Water-Cooled Nuclear Power Plants.'' FOR FURTHER INFORMATION CONTACT: Mark P. Orr, Regulatory Guide... Shutdown Capability for Water-Cooled Nuclear Power Plants,'' was issued with a temporary identification as...

75 FR 33361 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... staff needs in its review of applications for permits and licenses. Revision 4 of Regulatory Guide 1.28... (Design and Construction).'' Proposed RG 1.28, Revision 4, extends the scope of the NRC's endorsement to...: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

[Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis].

PubMed

Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin

2015-11-01

Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.

75 FR 45677 - Draft Regulatory Guide, DG-1216,”Plant-Specific Applicability of Transition Break Size Specified...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0229] Draft Regulatory Guide, DG-1216,''Plant-Specific... Commission (NRC) is extending the public comment period for DG-1216 from August 25, 2010 to November 8, 2010... [email protected] . The Draft Regulatory Guide, DG-1216, ``Plant- Specific Applicability of...

75 FR 12804 - Withdrawal of Regulatory Guide 8.6

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear...[uuml]ller Counters.'' FOR FURTHER INFORMATION CONTACT: Harriet Karagiannis, U.S. Nuclear Regulatory... . SUPPLEMENTARY INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC) is withdrawing...

KWOC (Key-Word-Out-of-Context) Index of US Nuclear Regulatory Commission Regulatory Guide Series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jennings, S.D.

1990-04-01

To meet the objectives of the program funded by the Department of Energy (DOE)-Nuclear Energy (NE) Technology Support Programs, the Performance Assurance Project Office (PAPO) administers a Performance Assurance Information Program that collects, compiles, and distributes program-related information, reports, and publications for the benefit of the DOE-NE program participants. THE KWOC Index of US Nuclear Regulatory Commission Regulatory Guide Series'' is prepared as an aid in searching for specific topics in the US Nuclear Regulatory Commission, Regulatory Guide Series.

76 FR 50275 - Guidance for the Assessment of Beyond-Design-Basis Aircraft Impacts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

...: Mekonen M. Bayssie, Regulatory Guide Development Branch, Division of Engineering, Office of Nuclear... e-mail to [email protected] . SUPPLEMENTARY INFORMATION: I. Introduction The Nuclear..., Division of Engineering, Office of Nuclear Regulatory Research. [FR Doc. 2011-20513 Filed 8-11-11; 8:45 am...

77 FR 48177 - Fuel Oil Systems for Emergency Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0159] Fuel Oil Systems for Emergency Power Supplies AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide; extension of comment period. SUMMARY: On... Regulatory Guide, DG- 1282, ``Fuel Oil Systems for Emergency Power Supplies,'' in the Federal Register for a...

78 FR 58574 - Maintenance, Testing, and Replacement of Vented Lead-Acid Storage Batteries for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... time that a document is referenced. Revision 3 of Regulatory Guide 1.129 is available in ADAMS under...-251-7455; email: [email protected] . Both of the Office of Nuclear Regulatory Research, U.S... NRC is issuing a revision to an existing guide in the NRC's ``Regulatory Guide'' series. This series...

76 FR 26320 - Draft Regulatory Guide: Reissuance and Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

... Guide, DG-1217 ``Protection Against Turbine Missiles.'' SUMMARY: On November 2, 2009 (74 FR 56672), the... availability of Draft Regulatory Guide (DG)--1217, ``Protection Against Turbine Missiles.'' The guide is being... appropriately protected against the effects of missiles that might result from equipment failures. Failures that...

Social Possible Selves, Self-Regulation, and Social Goal Progress in Older Adulthood

ERIC Educational Resources Information Center

Ko, Han-Jung; Mejía, Shannon; Hooker, Karen

2014-01-01

Lifespan development involves setting and pursuing self-guided goals. This study examines how in the social domain, possible selves, a future-oriented self-concept, and self-regulation, including self-regulatory beliefs and intraindividual variability in self-regulatory behavior, relate to differences in overall daily social goal progress. An…

Development and testing of the VITAMIN-B7/BUGLE-B7 coupled neutron-gamma multigroup cross-section libraries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Risner, J.M.; Wiarda, D.; Miller, T.M.

2011-07-01

The U.S. Nuclear Regulatory Commission's Regulatory Guide 1.190 states that calculational methods used to estimate reactor pressure vessel (RPV) fluence should use the latest version of the evaluated nuclear data file (ENDF). The VITAMIN-B6 fine-group library and BUGLE-96 broad-group library, which are widely used for RPV fluence calculations, were generated using ENDF/B-VI.3 data, which was the most current data when Regulatory Guide 1.190 was issued. We have developed new fine-group (VITAMIN-B7) and broad-group (BUGLE-B7) libraries based on ENDF/B-VII.0. These new libraries, which were processed using the AMPX code system, maintain the same group structures as the VITAMIN-B6 and BUGLE-96 libraries.more » Verification and validation of the new libraries were accomplished using diagnostic checks in AMPX, 'unit tests' for each element in VITAMIN-B7, and a diverse set of benchmark experiments including critical evaluations for fast and thermal systems, a set of experimental benchmarks that are used for SCALE regression tests, and three RPV fluence benchmarks. The benchmark evaluation results demonstrate that VITAMIN-B7 and BUGLE-B7 are appropriate for use in RPV fluence calculations and meet the calculational uncertainty criterion in Regulatory Guide 1.190. (authors)« less

Development and Testing of the VITAMIN-B7/BUGLE-B7 Coupled Neutron-Gamma Multigroup Cross-Section Libraries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Risner, Joel M; Wiarda, Dorothea; Miller, Thomas Martin

2011-01-01

The U.S. Nuclear Regulatory Commission s Regulatory Guide 1.190 states that calculational methods used to estimate reactor pressure vessel (RPV) fluence should use the latest version of the Evaluated Nuclear Data File (ENDF). The VITAMIN-B6 fine-group library and BUGLE-96 broad-group library, which are widely used for RPV fluence calculations, were generated using ENDF/B-VI data, which was the most current data when Regulatory Guide 1.190 was issued. We have developed new fine-group (VITAMIN-B7) and broad-group (BUGLE-B7) libraries based on ENDF/B-VII. These new libraries, which were processed using the AMPX code system, maintain the same group structures as the VITAMIN-B6 and BUGLE-96more » libraries. Verification and validation of the new libraries was accomplished using diagnostic checks in AMPX, unit tests for each element in VITAMIN-B7, and a diverse set of benchmark experiments including critical evaluations for fast and thermal systems, a set of experimental benchmarks that are used for SCALE regression tests, and three RPV fluence benchmarks. The benchmark evaluation results demonstrate that VITAMIN-B7 and BUGLE-B7 are appropriate for use in LWR shielding applications, and meet the calculational uncertainty criterion in Regulatory Guide 1.190.« less

78 FR 57916 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... Relating to Amendments to the Discovery Guide Used in Customer Arbitration Proceedings, as Modified by... update the Discovery Guide (``Guide'') used in customer arbitration proceedings.\\1\\ According to FINRA, the Guide supplements the discovery rules contained in the FINRA Code of Arbitration Procedure for...

77 FR 36017 - Regulatory Guide 7.3, Procedures for Picking Up and Receiving Packages of Radioactive Material

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... Receiving Packages of Radioactive Material AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... Guide (RG) 7.3, ``Procedures for Picking Up and Receiving Packages of Radioactive Material.'' The guide..., ``Administrative Guide for Verifying Compliance with Packaging Requirements for Shipment and Receipt of Radioactive...

Drug interactions evaluation: An integrated part of risk assessment of therapeutics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping

2010-03-01

Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industrymore » and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.« less

78 FR 73566 - Standard Format and Content for a License Application for an Independent Spent Fuel Storage...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-06

...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-3042, ``Standard Format and Content for a License Application for an Independent Spent Fuel Storage Installation or a Monitored Retrievable Storage Facility.'' This draft regulatory guide is proposed revision 2 of Regulatory Guide 3.50, which provides a format that the NRC considers acceptable for submitting the information for license applications to store spent nuclear fuel, high-level radioactive waste, and/or reactor-related Greater than Class C waste.

Verification and Validation Strategy for LWRS Tools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carl M. Stoots; Richard R. Schultz; Hans D. Gougar

2012-09-01

One intension of the Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program is to create advanced computational tools for safety assessment that enable more accurate representation of a nuclear power plant safety margin. These tools are to be used to study the unique issues posed by lifetime extension and relicensing of the existing operating fleet of nuclear power plants well beyond their first license extension period. The extent to which new computational models / codes such as RELAP-7 can be used for reactor licensing / relicensing activities depends mainly upon the thoroughness with which they have been verifiedmore » and validated (V&V). This document outlines the LWRS program strategy by which RELAP-7 code V&V planning is to be accomplished. From the perspective of developing and applying thermal-hydraulic and reactivity-specific models to reactor systems, the US Nuclear Regulatory Commission (NRC) Regulatory Guide 1.203 gives key guidance to numeric model developers and those tasked with the validation of numeric models. By creating Regulatory Guide 1.203 the NRC defined a framework for development, assessment, and approval of transient and accident analysis methods. As a result, this methodology is very relevant and is recommended as the path forward for RELAP-7 V&V. However, the unique issues posed by lifetime extension will require considerations in addition to those addressed in Regulatory Guide 1.203. Some of these include prioritization of which plants / designs should be studied first, coupling modern supporting experiments to the stringent needs of new high fidelity models / codes, and scaling of aging effects.« less

76 FR 11288 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... Guide, DG-7008, ``Leakage Tests on Packages for Shipment of Radioactive Materials.'' FOR FURTHER... regulatory guide (DG), entitled, ``Leakage Tests on Packages for Shipment of Radioactive Materials'' is... Radioactive and Nonnuclear Hazardous Materials, N14, Subcommittee of the American National Standards Institute...

75 FR 45171 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555...-3040. This guide describes some engineering practices and methods generally considered by the NRC to be... they reflect the latest general engineering approaches that are acceptable to the NRC staff. If future...

76 FR 14108 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

..., Revision 1, ``Control of Preheat Temperature for Welding of Low-Alloy Steel.'' FOR FURTHER INFORMATION... for Welding of Low-Alloy Steel,'' was issued with a temporary identification as Draft Regulatory Guide... implementing regulatory requirements related to the control of welding for low-alloy steel components during...

78 FR 15753 - Maintenance, Testing, and Replacement of Vented Lead-Acid Storage Batteries for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

.... Although a time limit is given, comments and suggestions in connection with items for inclusion in guides currently being developed or improvements in all published guides are encouraged at any time. ADDRESSES: You...: 301-251-7455, or by email: [email protected] . Both of the Office of Nuclear Regulatory Research...

77 FR 55877 - Initial Test Program of Condensate and Feedwater Systems for Light-Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

...-492- 3668; email: [email protected] . NRC's Agencywide Documents Access and Management System... Systems for Light-Water Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide; issuance... Systems for Boiling Water Reactor Power Plants.'' This regulatory guide is being revised to: (1) Expand...

77 FR 64564 - Implementation of Regulatory Guide 1.221 on Design-Basis Hurricane and Hurricane Missiles

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

...-Basis Hurricane and Hurricane Missiles AGENCY: Nuclear Regulatory Commission. ACTION: Proposed interim...-ISG-024, ``Implementation of Regulatory Guide 1.221 on Design-Basis Hurricane and Hurricane Missiles....221, ``Design-Basis Hurricane and Hurricane Missiles for Nuclear Power Plants.'' DATES: Submit...

78 FR 36278 - Fuel Oil Systems for Emergency Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... this notice (if that document is available in ADAMS) is provided the first time that a document is..., Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001... issuing a revision to an existing guide in the NRC's ``Regulatory Guide'' series. This series was...

The VTAC Committee: developing guidance for an alternative regulatory pathway to the anadromous salmonid protection rules

Treesearch

Michael Liquori; Peter Cafferata; Kevin Boston; Richard Gienger; David Hope

2012-01-01

In recent decades, riparian protection standards have been guided by generalized prescriptive rules. With the passage of the Anadromous Salmonid Protection rules in 2009, the Board of Forestry and Fire Protection (Board) established a regulatory pathway that provides an alternative approach for riparian protection based on site-specific criteria (14 CCR § 916....

78 FR 37261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Change Relating to Amendments to the Discovery Guide Used in Customer Arbitration Proceedings June 13... Discovery Guide (``Guide'') used in customer arbitration proceedings to provide general guidance on electronic discovery (``e-discovery'') issues and product cases and to clarify the existing provision...

76 FR 46330 - NUREG-1934, Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG); Second Draft...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0568] NUREG-1934, Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG); Second Draft Report for Comment AGENCY: Nuclear Regulatory Commission... 1023259), ``Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG), Second Draft Report for...

75 FR 16202 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

..., Revision 2, ``An Acceptable Model and Related Statistical Methods for the Analysis of Fuel Densification.... Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to an existing guide in the... nuclear power reactors. To meet these objectives, the guide describes statistical methods related to...

77 FR 33253 - Regulatory Guide 8.24, Revision 2, Health Physics Surveys During Enriched Uranium-235 Processing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0115] Regulatory Guide 8.24, Revision 2, Health Physics..., ``Health Physics Surveys During Enriched Uranium-235 Processing and Fuel Fabrication'' was issued with a... specifically with the following aspects of an acceptable occupational health physics program that are closely...

78 FR 37848 - ASME Code Cases Not Approved for Use

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1233, ``ASME Code Cases not Approved for Use.'' This regulatory guide lists the American Society of Mechanical Engineers (ASME) Code Cases that the NRC has determined not to be acceptable for use on a generic basis.

76 FR 63541 - Design-Basis Hurricane and Hurricane Missiles for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

... Hurricane Missiles for Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide... regulatory guide, (RG) 1.221, ``Design-Basis Hurricane and Hurricane Missiles for Nuclear Power Plants... missiles that a nuclear power plant should be designed to withstand to prevent undue risk to the health and...

75 FR 45172 - Withdrawal of Regulatory Guides 3.44 and 3.49

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... Format and Content for the Safety Analysis Report for an Independent Spent Fuel Storage Installation... on the format and content of the safety analysis report that is required as part of an application to...: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 3.44, ``Standard Format and Content...

Thermal overload protection for electric motors on safety-related motor-operated valves: Generic Issue II. E. 6. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothberg, O.

1988-06-01

NRC regulatory positions, as stated in Regulatory Guide 1.106, Revision 1, have been identified by the Office for Analysis and Evaluation of Operational Data (AEOD) as potential contributors to valve motor burnout. AEOD is particularly concerned about the allowed policy of bypassing thermal overload devices during normal or accident conditions. Regulatory Guide 1.106 favors compromising the function of thermal overload devices in favor of completing the safety-related action of valves. The purpose of this study was to determine if the guidance contained in Regulatory Guide 1.106 is appropriate and, if not, to recommend the necessary changes. This report describes thermalmore » overload devices commonly used to protect safety-related valve operator motors. The regulatory guidelines stated in Regulatory Guide 1.106 along with the limitations of thermal overload protection are discussed. Supplements and alternatives to thermal overload protection are also described. Findings and conclusions of several AEOD reports are discussed. Information obtained from the standard review plan, standard technical specifications, technical specifications from representative plants, and several papers are cited.« less

Identifying p53 Transactivation Domain 1-Specific Inhibitors to Alleviate the Side Effects of Prostate Cancer Therapy

DTIC Science & Technology

2013-09-01

further expanded with the exciting   7   development of Tal-effector and CRISPR guided nucleases. Transcription activator-like effector nucleases...also be achieved by the recently developed CRISPR -Cas9 system. CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats) is widely believed...to be the most efficient method to engineer mammalian genomes. CRISPR RNAs (crRNA) that hybridize to a specific target DNA can be utilized to guide a

Scientific, statistical, practical, and regulatory considerations in design space development.

PubMed

Debevec, Veronika; Srčič, Stanko; Horvat, Matej

2018-03-01

The quality by design (QbD) paradigm guides the pharmaceutical industry towards improved understanding of products and processes, and at the same time facilitates a high degree of manufacturing and regulatory flexibility throughout the establishment of the design space. This review article presents scientific, statistical and regulatory considerations in design space development. All key development milestones, starting with planning, selection of factors, experimental execution, data analysis, model development and assessment, verification, and validation, and ending with design space submission, are presented and discussed. The focus is especially on frequently ignored topics, like management of factors and CQAs that will not be included in experimental design, evaluation of risk of failure on design space edges, or modeling scale-up strategy. Moreover, development of a design space that is independent of manufacturing scale is proposed as the preferred approach.

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, E.L.; Sullivan, E.J.

1997-02-01

In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule asmore » a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with.« less

77 FR 40921 - Communication With Transport Vehicles

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-11

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0163] Communication With Transport Vehicles AGENCY... Transport Vehicles,'' published in May 1975. The guide is being withdrawn because it is outdated due to... withdrawing Regulatory Guide 5.32, revision 1, ``Communication with Transport Vehicles,'' published in May...

76 FR 24538 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

... Guide, DG-1264, ``Thermal Overload Protection for Electric Motors On Motor- Operated Valves.'' FOR FURTHER INFORMATION CONTACT: Darrell Murdock, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: 301-251- 7629 or e-mail [email protected] . SUPPLEMENTARY INFORMATION: I...

State planning in New Jersey

DOT National Transportation Integrated Search

1998-12-31

In trying to develop a state plan for to guide regulatory and spending decision-making on land use and spending on transportation facilities and other forms of infrastructure, New Jersey has rejected mandatory compliance in favor of seeking voluntary...

78 FR 663 - Decommissioning Planning During Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

...] Decommissioning Planning During Operations AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide..., ``Decommissioning Planning During Operations.'' The guide describes a method that the NRC staff considers acceptable for use by holders of licenses in complying with the NRC's Decommissioning Planning Rule (DPR) (76 FR...

75 FR 81675 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... Fuel Cycle Facilities.'' FOR FURTHER INFORMATION CONTACT: Mekonen M. Bayssie, Regulatory Guide... Materials in Liquid and Gaseous Effluents from Nuclear Fuel Cycle Facilities,'' was published as Draft... guidance is applicable to nuclear fuel cycle facilities, with the exception of uranium milling facilities...

76 FR 2725 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

.... The draft regulatory guide, entitled, ``Inspection of Water-Control Structures Associated with Nuclear... and surveillance program for dams, slopes, canals, and other water-control structures associated with emergency cooling water systems or flood protection of nuclear power plants. II. Further Information The NRC...

75 FR 79049 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... (RG) 5.80, ``Pressure-Sensitive and Tamper-Indicating Device Seals for Material Control and Accounting... and licenses. Regulatory Guide 5.80, ``Pressure-Sensitive and Tamper-Indicating Device Seals for... and Use of Pressure-Sensitive Seals on Containers for Onsite Storage of Special Nuclear Material...

75 FR 62436 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-08

... Power Plants,'' includes in its scope safety- related structures, systems, and components (SSCs) that... monitor the effectiveness of maintenance for protective coatings within its scope (as discrete systems or... and Management System (ADAMS) under Accession No. ML102230359. Electronic copies of Regulatory Guide 1...

75 FR 54921 - Withdrawal of Regulatory Guides 1.38, 1.94, and 1.116

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

....116, ``Quality Assurance Requirements for Installation, Inspection, and Testing of Mechanical....116, ``Quality Assurance Requirements for Installation, Inspection, and Testing of Mechanical Equipment and Systems,'' dated May 1977. Regulatory Guide 1.38 endorses the American Society of Mechanical...

77 FR 18871 - Administrative Guide for Verifying Compliance With Packaging Requirements for Shipment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... Packaging Requirements for Shipment and Receipt of Radioactive Material AGENCY: Nuclear Regulatory... with Packaging Requirements for Shipment and Receipt of Radioactive Material.'' This regulatory guide... for transporting licensed material under 10 CFR part 71, ``Packaging and Transportation of Radioactive...

Adverse outcome pathway (AOP) development: Guiding principles and best practices

EPA Science Inventory

Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

78 FR 64030 - Monitoring Criteria and Methods To Calculate Occupational Radiation Doses

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0234] Monitoring Criteria and Methods To Calculate... regulatory guide (DG), DG-8031, ``Monitoring Criteria and Methods to Calculate Occupational Radiation Doses.'' This guide describes methods that the NRC staff considers acceptable for licensees to use to determine...

76 FR 55137 - Monitoring the Effectiveness of Maintenance at Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0212] Monitoring the Effectiveness of Maintenance at... comment draft regulatory guide (DG) DG-1278, ``Monitoring the Effectiveness of Maintenance at Nuclear Power Plants.'' This guide endorses Revision 4A to Nuclear Management and Resources Council (NUMARC) 93...

76 FR 46856 - Qualification of Connection Assemblies for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

... Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide; issuance. SUMMARY: The U.S..., ``Qualification of Connection Assemblies for Nuclear Power Plants.'' This guide describes a method that the NRC... in nuclear power plants. The environmental qualification helps ensure that connection assemblies can...

76 FR 65541 - Assuring the Availability of Funds for Decommissioning Nuclear Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0263] Assuring the Availability of Funds for Decommissioning Nuclear Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide; issuance. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision to Regulatory...

Implementing Ethics Policies in Developing Countries: Ploughing on Parched Ground?

ERIC Educational Resources Information Center

Mazonde, Isaac N.; Jackson-Malete, Jose; Sugarman, Jeremy

2007-01-01

It is globally expected that universities will ensure that policies guiding researchers' conduct are in place and adhered to. This expectation is not waived in developing countries. Successful implementation of an ethics policy is facilitated by an appropriate national regulatory framework on which to base the argument for compliance. However, it…

78 FR 63517 - Control of Ferrite Content in Stainless Steel Weld Metal

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

...The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to Regulatory Guide (RG) 1.31, ``Control of Ferrite Content in Stainless Steel Weld Metal.'' This guide (Revision 4) describes a method that the NRC staff considers acceptable for controlling ferrite content in stainless steel weld metal. It updates the guide to remove references to outdated standards and to remove an appendix that has been incorporated into relevant specifications.

76 FR 82323 - Design, Inspection, and Testing Criteria for Air Filtration and Adsorption Units

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0296] Design, Inspection, and Testing Criteria for Air... for public comment draft regulatory guide (DG), DG-1274, ``Design, Inspection, and Testing Criteria... Systems in Light-Water-Cooled Nuclear Power Plants.'' This guide applies to the design, inspection, and...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oland, CB

Boiler owners and operators who need additional generating capacity face a number of legal, political, environmental, economic, and technical challenges. Their key to success requires selection of an adequately sized low-emission boiler and combustion equipment that can be operated in compliance with emission standards established by state and federal regulatory agencies. Recognizing that many issues are involved in making informed selection decisions, the U.S. Department of Energy (DOE), Office of Industrial Technologies (OIT) sponsored efforts at the Oak Ridge National Laboratory (ORNL) to develop a guide for use in choosing low-emission boilers and combustion equipment. To ensure that the guidemore » covers a broad range of technical and regulatory issues of particular interest to the commercial boiler industry, the guide was developed in cooperation with the American Boiler Manufacturers Association (ABMA), the Council of Industrial Boiler Owners (CIBO), and the U.S. Environmental Protection Agency (EPA). The guide presents topics pertaining to industrial, commercial, and institutional (ICI) boilers. Background information about various types of commercially available boilers is provided along with discussions about the fuels that they burn and the emissions that they produce. Also included are discussions about emissions standards and compliance issues, technical details related to emissions control techniques, and other important selection considerations. Although information in the guide is primarily applicable to new ICI boilers, it may also apply to existing boiler installations.« less

77 FR 60478 - Control of Ferrite Content in Stainless Steel Weld Metal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

...The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing for public comment draft regulatory guide (DG), DG-1279, ``Control of Ferrite Content in Stainless Steel Weld Metal.'' This guide describes a method that the NRC staff considers acceptable for controlling ferrite content in stainless steel weld metal. Revision 4 updates the guide to remove references to outdated standards and to remove an appendix that has been incorporated into relevant specifications.

Regulatory aspects of total product life cycle.

PubMed

Hausman, Ethan D; Altaie, Sousan S

2004-12-01

Total Product Life Cycle (TPLC) is a conceptual framework for assessing any product or service (medical or otherwise). This article will address how the Center for Devices and Radiological Health of the U.S. Food and Drug Administration utilizes TPLC in a regulatory paradigm. TPLC will help guide the regulation of market-driven evolution of medical devices and radiation-emitting products from conception, through pre-market development, to widespread market use, and finally to obsolescence and replacement by subsequent generations of products.

77 FR 24228 - Condition Monitoring Techniques for Electric Cables Used in Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

... Used in Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide; issuance... guide, (RG) 1.218, ``Condition Monitoring Techniques for Electric Cables Used in Nuclear Power Plants... of electric cables for nuclear power plants. RG 1.218 is not intended to be prescriptive, instead it...

77 FR 40385 - Withdrawal of Regulatory Guide 7.3; Procedures for Picking Up and Receiving Packages of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... Picking Up and Receiving Packages of Radioactive Material AGENCY: Nuclear Regulatory Commission. ACTION... Receiving Packages of Radioactive Material.'' The RG is being withdrawn because it is outdated and the..., ``Administrative Guide for Verifying Compliance with Packaging Requirements for Shipment and Receipt of Radioactive...

75 FR 36445 - Draft Regulatory Guide, DG-4018, “Constraint on Releases of Airborne Radioactive Materials To the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... Releases of Airborne Radioactive Materials To the Environment for Licensees Other Than Power Reactors... Regulatory Guide (DG)-4018, ``Constraint on Releases of Airborne Radioactive Materials to the Environment for..., ``Constraint on Releases of Airborne Radioactive Materials to the Environment for Licensees Other than Power...

NEW APPROACHES IN RISK ANALYSIS OF ENVIRONMENTAL STRESSORS TO HUMAN AND ECOLOGICAL SYSTEMS

EPA Science Inventory

We explore the application of novel techniques for improving and integrating risk analysis of environmental stressors to human and ecological systems. Environmental protection decisions are guided by risk assessments serving as tools to develop regulatory policy and other relate...

Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

PubMed Central

Kang, Joonsoo; Malhotra, Nidhi

2015-01-01

Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

78 FR 40776 - Issuance of Regulatory Guide 1.124 and Regulatory Guide 1.130

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... Limits and Loading Combinations for Class 1 Plate-and- Shell-Type Supports.'' There are no substantive... 1 linear-type component and piping supports, and Class 1 plate-and-shell-type component and piping... Rulemaking Web site: Go to http://www.regulations.gov and search for Docket ID NRC-2013-0141. Address...

76 FR 14107 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision... Branch, Division of Engineering, Office of Nuclear Regulatory Research. [FR Doc. 2011-5967 Filed 3-14-11...

Regulatory Guidance for Lightning Protection in Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kisner, Roger A; Wilgen, John B; Ewing, Paul D

2006-01-01

Abstract - Oak Ridge National Laboratory (ORNL) was engaged by the U.S. Nuclear Regulatory Commission (NRC) Office of Nuclear Regulatory Research (RES) to develop the technical basis for regulatory guidance to address design and implementation practices for lightning protection systems in nuclear power plants (NPPs). Lightning protection is becoming increasingly important with the advent of digital and low-voltage analog systems in NPPs. These systems have the potential to be more vulnerable than older analog systems to the resulting power surges and electromagnetic interference (EMI) when lightning strikes facilities or power lines. This paper discusses the technical basis for guidance tomore » licensees and applicants covered in Regulatory Guide (RG) 1.204, Guidelines for Lightning Protection of Nuclear Power Plants, issued August 2005. RG 1.204 describes guidance for practices that are acceptable to the NRC staff for protecting nuclear power structures and systems from direct lightning strikes and the resulting secondary effects.« less

Regulatory guidance for lightning protection in nuclear power plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kisner, R. A.; Wilgen, J. B.; Ewing, P. D.

2006-07-01

Oak Ridge National Laboratory (ORNL) was engaged by the U.S. Nuclear Regulatory Commission (NRC) Office of Nuclear Regulatory Research (RES) to develop the technical basis for regulatory guidance to address design and implementation practices for lightning protection systems in nuclear power plants (NPPs). Lightning protection is becoming increasingly important with the advent of digital and low-voltage analog systems in NPPs. These systems have the potential to be more vulnerable than older analog systems to the resulting power surges and electromagnetic interference (EMI) when lightning strikes facilities or power lines. This paper discusses the technical basis for guidance to licensees andmore » applicants covered in Regulatory Guide (RG) 1.204, Guidelines for Lightning Protection of Nuclear Power Plants, issued August 2005. RG 1.204 describes guidance for practices that are acceptable to the NRC staff for protecting nuclear power structures and systems from direct lightning strikes and the resulting secondary effects. (authors)« less

Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

PubMed Central

Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2015-01-01

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

78 FR 38739 - Standard Format and Content for Post-Shutdown Decommissioning Activities Report

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-27

...The U.S. Nuclear Regulatory Commission (NRC) is issuing Revision 1 of Regulatory Guide (RG) 1.185, ``Standard Format and Content for Post-shutdown Decommissioning Activities Report.'' This guide describes a method that the NRC staff considers acceptable for use in complying with the Commission's requirements regarding the submission of a post-shutdown decommissioning activities report (PSDAR).

77 FR 75198 - Standard Format and Content for Post-Shutdown Decommissioning Activities Report

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1272, ``Standard Format and Content for Post-shutdown Decommissioning Activities Report.'' This guide describes a method that the NRC staff considers acceptable for use in complying with the Commission's requirements regarding the submission of a post-shutdown decommissioning activities report (PSDAR).

A health app developer's guide to law and policy: a multi-sector policy analysis.

PubMed

Parker, Lisa; Karliychuk, Tanya; Gillies, Donna; Mintzes, Barbara; Raven, Melissa; Grundy, Quinn

2017-10-02

Apps targeted at health and wellbeing sit in a rapidly growing industry associated with widespread optimism about their potential to deliver accessible and cost-effective healthcare. App developers might not be aware of all the regulatory requirements and best practice principles are emergent. Health apps are regulated in order to minimise their potential for harm due to, for example, loss of personal health privacy, financial costs, and health harms from delayed or unnecessary diagnosis, monitoring and treatment. We aimed to produce a comprehensive guide to assist app developers in producing health apps that are legally compliant and in keeping with high professional standards of user protection. We conducted a case study analysis of the Australian and related international policy environment for mental health apps to identify relevant sectors, policy actors, and policy solutions. We identified 29 policies produced by governments and non-government organisations that provide oversight of health apps. In consultation with stakeholders, we developed an interactive tool targeted at app developers, summarising key features of the policy environment and highlighting legislative, industry and professional standards around seven relevant domains: privacy, security, content, promotion and advertising, consumer finances, medical device efficacy and safety, and professional ethics. We annotated this developer guidance tool with information about: the relevance of each domain; existing legislative and non-legislative guidance; critiques of existing policy; recommendations for developers; and suggestions for other key stakeholders. We anticipate that mental health apps developed in accordance with this tool will be more likely to conform to regulatory requirements, protect consumer privacy, protect consumer finances, and deliver health benefit; and less likely to attract regulatory penalties, offend consumers and communities, mislead consumers, or deliver health harms. We encourage government, industry and consumer organisations to use and publicise the tool.

77 FR 69508 - Inservice Inspection of Prestressed Concrete Containment Structures With Grouted Tendons

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-19

... real-time, multiple-strategy approach (i.e., appropriate grout design and installation, installed... is available in ADAMS) is provided the first time that a document is referenced. Revision 2 of... ``Regulatory Guide'' series. This series was developed to describe and make available to the public information...

A guide to federal-aid programs and projects

DOT National Transportation Integrated Search

1999-05-01

This guide provides basic information about Federal-aid programs, projects, and other program characteristics. The information sheets contained in the guide provide fiscal information, statutory and regulatory references, general eligibility and back...

Financial constraints in capacity planning: a national utility regulatory model (NUREG). Volume III of III: software description. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1981-10-29

This volume is the software description for the National Utility Regulatory Model (NUREG). This is the third of three volumes provided by ICF under contract number DEAC-01-79EI-10579. These three volumes are: a manual describing the NUREG methodology; a users guide; and a description of the software. This manual describes the software which has been developed for NUREG. This includes a listing of the source modules. All computer code has been written in FORTRAN.

77 FR 14047 - Guidance for Decommissioning Planning During Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

...)-4014, ``Decommissioning Planning During Operations.'' This action is necessary to correct the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2011-0286] Guidance for Decommissioning Planning During Operations AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide; correction. SUMMARY: The U...

Guidelines for spaceborne microwave remote sensors

NASA Technical Reports Server (NTRS)

Litman, V.; Nicholas, J.

1982-01-01

A handbook was developed to provide information and support to the spaceborne remote sensing and frequency management communities: to guide sensor developers in the choice of frequencies; to advise regulators on sensor technology needs and sharing potential; to present sharing analysis models and, through example, methods for determining sensor sharing feasibility; to introduce developers to the regulatory process; to create awareness of proper assignment procedures; to present sensor allocations; and to provide guidelines on the use and limitations of allocated bands. Controlling physical factors and user requirements and the regulatory environment are discussed. Sensor frequency allocation achievable performance and usefulness are reviewed. Procedures for national and international registration, the use of non-allocated bands and steps for obtaining new frequency allocations, and procedures for reporting interference are also discussed.

Application of USNRC NUREG/CR-6661 and draft DG-1108 to evolutionary and advanced reactor designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang 'Apollo', Chen

2006-07-01

For the seismic design of evolutionary and advanced nuclear reactor power plants, there are definite financial advantages in the application of USNRC NUREG/CR-6661 and draft Regulatory Guide DG-1108. NUREG/CR-6661, 'Benchmark Program for the Evaluation of Methods to Analyze Non-Classically Damped Coupled Systems', was by Brookhaven National Laboratory (BNL) for the USNRC, and Draft Regulatory Guide DG-1108 is the proposed revision to the current Regulatory Guide (RG) 1.92, Revision 1, 'Combining Modal Responses and Spatial Components in Seismic Response Analysis'. The draft Regulatory Guide DG-1108 is available at http://members.cox.net/apolloconsulting, which also provides a link to the USNRC ADAMS site to searchmore » for NUREG/CR-6661 in text file or image file. The draft Regulatory Guide DG-1108 removes unnecessary conservatism in the modal combinations for closely spaced modes in seismic response spectrum analysis. Its application will be very helpful in coupled seismic analysis for structures and heavy equipment to reduce seismic responses and in piping system seismic design. In the NUREG/CR-6661 benchmark program, which investigated coupled seismic analysis of structures and equipment or piping systems with different damping values, three of the four participants applied the complex mode solution method to handle different damping values for structures, equipment, and piping systems. The fourth participant applied the classical normal mode method with equivalent weighted damping values to handle differences in structural, equipment, and piping system damping values. Coupled analysis will reduce the equipment responses when equipment, or piping system and structure are in or close to resonance. However, this reduction in responses occurs only if the realistic DG-1108 modal response combination method is applied, because closely spaced modes will be produced when structure and equipment or piping systems are in or close to resonance. Otherwise, the conservatism in the current Regulatory Guide 1.92, Revision 1, will overshadow the advantage of coupled analysis. All four participants applied the realistic modal combination method of DG-1108. Consequently, more realistic and reduced responses were obtained. (authors)« less

78 FR 37850 - Quality Assurance Program Requirements (Operations)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0021] Quality Assurance Program Requirements (Operations... Regulatory Commission (NRC) is issuing a revision to Regulatory Guide (RG) 1.33, ``Quality Assurance Program... managerial and administrative Quality Assurance (QA) controls for nuclear power plants during operations...

Template protocol for clinical trials investigating vaccines--focus on safety elements.

PubMed

Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2013-11-12

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Promoting Adoption of the 3Rs through Regulatory Qualification.

PubMed

Walker, Elizabeth Gribble; Baker, Amanda F; Sauer, John-Michael

2016-12-01

One mechanism to advance the application of novel safety assessment methodologies in drug development, including in silico or in vitro approaches that reduce the use of animals in toxicology studies, is regulatory qualification. Regulatory qualification, a formal process defined at the the U. S. Food and Drug Administration and the European Medicines Agency, hinges on a central concept of stating an appropriate "context of use" for a novel drug development tool (DDT) that precisely defines how that DDT can be used to support decision making in a regulated drug development setting. When accumulating the data to support a particular "context-of-use," the concept of "fit-for-purpose" often guides assay validation, as well as the type and amount of data or evidence required to evaluate the tool. This paper will review pathways for regulatory acceptance of novel DDTs and discuss examples of safety projects considered for regulatory qualification. Key concepts to be considered when defining the evidence required to formally adopt and potentially replace animal-intensive traditional safety assessment methods using qualified DDTs are proposed. Presently, the use of qualified translational kidney safety biomarkers can refine and reduce the total numbers of animals used in drug development. We propose that the same conceptual regulatory framework will be appropriate to assess readiness of new technologies that may eventually replace whole animal models. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Sociocognitive Correlates of Gender-Linked Conduct.

ERIC Educational Resources Information Center

Bussey, Kay

This study of the processes guiding children's gender-linked conduct focused on ages prior to the development of self-regulatory control through the exercise of self-evaluative reactions. The study sample consisted of 29 boys and 33 girls in Australia between 17 and 48 months old. Measures included: (1) a videotaped toy play session in which…

77 FR 75462 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... Amending Section 102(a) of the NYSE MKT Company Guide To Eliminate an Erroneous Reference December 14, 2012... MKT Company Guide (the ``Company Guide'') to eliminate an erroneous reference. The text of the... Company Guide (to eliminate an erroneous reference. Section 102(a) of the Company Guide provides that a...

FEDERAL RULEMAKING: Procedural and Analytical Requirements at OSHA and Other Agencies

DTIC Science & Technology

2001-06-14

informal rulemaking. Formal rulemaking is used in ratemaking proceedings and in certain other cases when rules are required by statute to be made “on...crosscutting statutory requirements that I have just listed are by no means the only statutory requirements that guide agency rulemaking. Regulations generally...directives designed to guide the federal rulemaking process, often with the goal of reducing regulatory burden. Although independent regulatory agencies are

Evolution of robustness to damage in artificial 3-dimensional development.

PubMed

Joachimczak, Michał; Wróbel, Borys

2012-09-01

GReaNs is an Artificial Life platform we have built to investigate the general principles that guide evolution of multicellular development and evolution of artificial gene regulatory networks. The embryos develop in GReaNs in a continuous 3-dimensional (3D) space with simple physics. The developmental trajectories are indirectly encoded in linear genomes. The genomes are not limited in size and determine the topology of gene regulatory networks that are not limited in the number of nodes. The expression of the genes is continuous and can be modified by adding environmental noise. In this paper we evolved development of structures with a specific shape (an ellipsoid) and asymmetrical pattering (a 3D pattern inspired by the French flag problem), and investigated emergence of the robustness to damage in development and the emergence of the robustness to noise. Our results indicate that both types of robustness are related, and that including noise during evolution promotes higher robustness to damage. Interestingly, we have observed that some evolved gene regulatory networks rely on noise for proper behaviour. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Assessment of Individual Differences in Regulatory Focus among Cigarette Smokers

PubMed Central

Haaga, David A. F.; Friedman-Wheeler, Dara G.; McIntosh, Elizabeth; Ahrens, Anthony H.

2008-01-01

Smoking cessation programs might benefit from tailoring messages to individual differences in regulatory focus (see Higgins, 1997), but there is little evidence on the stability or convergent validity of regulatory focus measures. In two studies, smokers completed four measures of regulatory focus: (a) Regulatory Focus Questionnaire (RFQ); (b) actual-ideal and actual-ought self-discrepancies; (c) response duration in naming name ideal or ought self-guides; and (d) reaction time for lexical decisions about one’s ideal or ought self-guides. Study 1 included a one-month retest. Retest reliability was adequate, but convergent validity was poor. Questionnaire and self-discrepancy measures were unrelated to each other or to the reaction time measures. To facilitate future studies of tailored health behavior change interventions, research is needed to determine whether weak convergent validity resulted from (a) invalidity of some or all of the regulatory focus measures or (b) validity of each for measuring a different aspect of the construct. PMID:18958291

International STakeholder NETwork (ISTNET): Creating a ...

EPA Pesticide Factsheets

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test sys-tems and methods on the other hand. Alignment of academically and industrially-driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISNET) in DNT testing. The first meeting of ISTNET was held in Zur-ich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems develop-ment according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a roadmap towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and address-ing the transit

Regulating transgenic crops sensibly: lessons from plant breeding, biotechnology and genomics.

PubMed

Bradford, Kent J; Van Deynze, Allen; Gutterson, Neal; Parrott, Wayne; Strauss, Steven H

2005-04-01

The costs of meeting regulatory requirements and market restrictions guided by regulatory criteria are substantial impediments to the commercialization of transgenic crops. Although a cautious approach may have been prudent initially, we argue that some regulatory requirements can now be modified to reduce costs and uncertainty without compromising safety. Long-accepted plant breeding methods for incorporating new diversity into crop varieties, experience from two decades of research on and commercialization of transgenic crops, and expanding knowledge of plant genome structure and dynamics all indicate that if a gene or trait is safe, the genetic engineering process itself presents little potential for unexpected consequences that would not be identified or eliminated in the variety development process before commercialization. We propose that as in conventional breeding, regulatory emphasis should be on phenotypic rather than genomic characteristics once a gene or trait has been shown to be safe.

76 FR 54739 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the guided sport...

78 FR 18323 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... the guided sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the...

78 FR 47015 - Software Requirement Specifications for Digital Computer Software Used in Safety Systems of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Requirement Specifications for Digital Computer Software Used in Safety Systems of Nuclear Power Plants AGENCY: Nuclear Regulatory Commission... issuing a revised regulatory guide (RG), revision 1 of RG 1.172, ``Software Requirement Specifications for...

78 FR 25488 - Qualification Tests for Safety-Related Actuators in Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0079] Qualification Tests for Safety-Related Actuators in... regulatory guide (DG), DG-1235, ``Qualification Tests for Safety-Related Actuators in Nuclear Power Plants...-251- 7495, email: [email protected] . Both of the Office of Nuclear Regulatory Research, U.S. Nuclear...

Regulatory Facility Guide for Tennessee

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, S.S.; Bock, R.E.; Francis, M.W.

1994-02-28

This guide provides detailed compilations of international, federal, and state transportation related regulations applicable to shipments originating at or destined to Tennessee facilities. Information on preferred routes is also given.

ENERGY STAR® Retail Products Platform (RPP): Conditions and Considerations in Evaluating Market Transformation Programs and Evaluation Guidance for RPP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Michael; Banwell, Peter

2018-01-09

The purpose of this guide is to provide a resource for state utility regulators, utilities, the evaluation community and regulatory stakeholders on methods to measure energy savings from the ENERGY STAR Retail Products Platform (link is external). The guidelines outlined in this document were developed by evaluation experts.

Federal guide for a radiological response: Supporting the Nuclear Regulatory Commission during the initial hours of a serious accident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, R.T.

1993-11-01

This document is a planning guide for those Federal agencies that work with the Nuclear Regulatory commission (NRC) during the initial hours of response to a serious radiological emergency in which the NRC is the Lead Federal Agency (LFA). These Federal agencies are: DOE, EPA, USDA, HHS, NOAA, and FEMA. This guide is intended to help these agencies prepare for a prompt response. Instructions are provided on receiving the initial notification, the type of person to send to the scene, the facility at which people are needed, how to get them to that facility, and what they should do whenmore » they arrive. Federal agencies not specifically mentioned in this guide may also be asked to support the NRC.« less

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

PubMed

Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

2015-02-01

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

The development of regulatory expectations for computer-based safety systems for the UK nuclear programme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, P. J.; Westwood, R.N; Mark, R. T.

2006-07-01

The Nuclear Installations Inspectorate (NII) of the UK's Health and Safety Executive (HSE) has completed a review of their Safety Assessment Principles (SAPs) for Nuclear Installations recently. During the period of the SAPs review in 2004-2005 the designers of future UK naval reactor plant were optioneering the control and protection systems that might be implemented. Because there was insufficient regulatory guidance available in the naval sector to support this activity the Defence Nuclear Safety Regulator (DNSR) invited the NII to collaborate with the production of a guidance document that provides clarity of regulatory expectations for the production of safety casesmore » for computer based safety systems. A key part of producing regulatory expectations was identifying the relevant extant standards and sector guidance that reflect good practice. The three principal sources of such good practice were: IAEA Safety Guide NS-G-1.1 (Software for Computer Based Systems Important to Safety in Nuclear Power Plants), European Commission consensus document (Common Position of European Nuclear Regulators for the Licensing of Safety Critical Software for Nuclear Reactors) and IEC nuclear sector standards such as IEC60880. A common understanding has been achieved between the NII and DNSR and regulatory guidance developed which will be used by both NII and DNSR in the assessment of computer-based safety systems and in the further development of more detailed joint technical assessment guidance for both regulatory organisations. (authors)« less

76 FR 16017 - Withdrawal of Regulatory Guide 8.5

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

...) Standard N2.3-1979 ``Immediate Evacuation Signal for Use in Industrial Installations,'' published September... Branch, Division of Engineering, Office of Nuclear Regulatory Research. [FR Doc. 2011-6665 Filed 3-21-11...

Reformation of Regulatory Technical Standards for Nuclear Power Generation Equipments in Japan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikio Kurihara; Masahiro Aoki; Yu Maruyama

2006-07-01

Comprehensive reformation of the regulatory system has been introduced in Japan in order to apply recent technical progress in a timely manner. 'The Technical Standards for Nuclear Power Generation Equipments', known as the Ordinance No.622) of the Ministry of International Trade and Industry, which is used for detailed design, construction and operating stage of Nuclear Power Plants, was being modified to performance specifications with the consensus codes and standards being used as prescriptive specifications, in order to facilitate prompt review of the Ordinance with response to technological innovation. The activities on modification were performed by the Nuclear and Industrial Safetymore » Agency (NISA), the regulatory body in Japan, with support of the Japan Nuclear Energy Safety Organization (JNES), a technical support organization. The revised Ordinance No.62 was issued on July 1, 2005 and is enforced from January 1 2006. During the period from the issuance to the enforcement, JNES carried out to prepare enforceable regulatory guide which complies with each provisions of the Ordinance No.62, and also made technical assessment to endorse the applicability of consensus codes and standards, in response to NISA's request. Some consensus codes and standards were re-assessed since they were already used in regulatory review of the construction plan submitted by licensee. Other consensus codes and standards were newly assessed for endorsement. In case that proper consensus code or standards were not prepared, details of regulatory requirements were described in the regulatory guide as immediate measures. At the same time, appropriate standards developing bodies were requested to prepare those consensus code or standards. Supplementary note which provides background information on the modification, applicable examples etc. was prepared for convenience to the users of the Ordinance No. 62. This paper shows the activities on modification and the results, following the NISA's presentation at ICONE-13 that introduced the framework of the performance specifications and the modification process of the Ordinance NO. 62. (authors)« less

Geothermal : A Regulatory Guide to Leasing, Permitting, and Licensing in Idaho, Montana, Oregon, and Washington.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloomquist, R.Gordon

1991-10-01

The actual geothermal exploration and development may appear to be a simple and straightforward process in comparison to the legal and institutional maze which the developer must navigate in order to obtain all of the federal, state, and local leases, permits, licenses, and approvals necessary at each step in the process. Finally, and often most difficult, is obtaining a contract for the sale of thermal energy, brine, steam, or electricity. This guide is designed to help developers interested in developing geothermal resource sites in the Bonneville Power Administration Service Territory in the state of Idaho, Montana, Oregon, and Washington bettermore » understand the federal, state, and local institutional process, the roles and responsibilities of each agency, and how and when to make contact in order to obtain the necessary documents.« less

76 FR 52715 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... review Draft Final Regulatory Guide (RG) 1.93, ``Availability of Electric Power Sources,'' Revision 1 and new Draft Final RG 1.218, ``Condition Monitoring Techniques for Electric Cables Used in Nuclear Power... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS...

77 FR 60481 - Design, Inspection, and Testing Criteria for Air Filtration and Adsorption Units of Post-Accident...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

...The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing a revision to Regulatory Guide (RG) 1.52, ``Design, Inspection, and Testing Criteria for Air Filtration and Adsorption Units of Post-accident Engineered-Safety-Feature Atmosphere Cleanup Systems in Light-Water-Cooled Nuclear Power Plants.'' This guide applies to the design, inspection, and testing of air filtration and iodine adsorption units of engineered-safety-feature (ESF) atmosphere cleanup systems in light-water-cooled nuclear power plants.

1 CFR 6.5 - Indexes, digests, and guides.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ANCILLARIES § 6.5 Indexes, digests, and guides. (a) The Director of the Federal Register may order the..., regulatory documents, and notice materials published by the Office, which will serve users of the Federal Register. Indexes, digests, and similar guides will be published yearly or at other intervals as necessary...

A MODIS direct broadcast algorithm for mapping wildfire burned area in the western United States

Treesearch

S. P. Urbanski; J. M. Salmon; B. L. Nordgren; W. M. Hao

2009-01-01

Improved wildland fire emission inventory methods are needed to support air quality forecasting and guide the development of air shed management strategies. Air quality forecasting requires dynamic fire emission estimates that are generated in a timely manner to support real-time operations. In the regulatory and planning realm, emission inventories are essential for...

Overview of FDA approval paths optical surgical navigation

NASA Astrophysics Data System (ADS)

Jacobs, Paula M.

2017-02-01

The development of drugs and devices to guide surgical resection of tumors in the United States requires the approval of the US Food and Drug Administration. Because these combine a drug and a device, the regulatory pathways can be confusing, particularly to academics or small companies. This paper discusses some of the issues and provides some guidance in this area.

76 FR 18262 - Notice of issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... application and processing of stainless steel to avoid severe sensitization that could lead to stress-corrosion cracking. This guide applies to light-water-cooled reactors. II. Further Information In June 2009...

Evidence for Deep Regulatory Similarities in Early Developmental Programs across Highly Diverged Insects

PubMed Central

Zhang, Yinan; Samee, Md. Abul Hassan; Halfon, Marc S.; Sinha, Saurabh

2014-01-01

Many genes familiar from Drosophila development, such as the so-called gap, pair-rule, and segment polarity genes, play important roles in the development of other insects and in many cases appear to be deployed in a similar fashion, despite the fact that Drosophila-like “long germband” development is highly derived and confined to a subset of insect families. Whether or not these similarities extend to the regulatory level is unknown. Identification of regulatory regions beyond the well-studied Drosophila has been challenging as even within the Diptera (flies, including mosquitoes) regulatory sequences have diverged past the point of recognition by standard alignment methods. Here, we demonstrate that methods we previously developed for computational cis-regulatory module (CRM) discovery in Drosophila can be used effectively in highly diverged (250–350 Myr) insect species including Anopheles gambiae, Tribolium castaneum, Apis mellifera, and Nasonia vitripennis. In Drosophila, we have successfully used small sets of known CRMs as “training data” to guide the search for other CRMs with related function. We show here that although species-specific CRM training data do not exist, training sets from Drosophila can facilitate CRM discovery in diverged insects. We validate in vivo over a dozen new CRMs, roughly doubling the number of known CRMs in the four non-Drosophila species. Given the growing wealth of Drosophila CRM annotation, these results suggest that extensive regulatory sequence annotation will be possible in newly sequenced insects without recourse to costly and labor-intensive genome-scale experiments. We develop a new method, Regulus, which computes a probabilistic score of similarity based on binding site composition (despite the absence of nucleotide-level sequence alignment), and demonstrate similarity between functionally related CRMs from orthologous loci. Our work represents an important step toward being able to trace the evolutionary history of gene regulatory networks and defining the mechanisms underlying insect evolution. PMID:25173756

Evidence for deep regulatory similarities in early developmental programs across highly diverged insects.

PubMed

Kazemian, Majid; Suryamohan, Kushal; Chen, Jia-Yu; Zhang, Yinan; Samee, Md Abul Hassan; Halfon, Marc S; Sinha, Saurabh

2014-09-01

Many genes familiar from Drosophila development, such as the so-called gap, pair-rule, and segment polarity genes, play important roles in the development of other insects and in many cases appear to be deployed in a similar fashion, despite the fact that Drosophila-like "long germband" development is highly derived and confined to a subset of insect families. Whether or not these similarities extend to the regulatory level is unknown. Identification of regulatory regions beyond the well-studied Drosophila has been challenging as even within the Diptera (flies, including mosquitoes) regulatory sequences have diverged past the point of recognition by standard alignment methods. Here, we demonstrate that methods we previously developed for computational cis-regulatory module (CRM) discovery in Drosophila can be used effectively in highly diverged (250-350 Myr) insect species including Anopheles gambiae, Tribolium castaneum, Apis mellifera, and Nasonia vitripennis. In Drosophila, we have successfully used small sets of known CRMs as "training data" to guide the search for other CRMs with related function. We show here that although species-specific CRM training data do not exist, training sets from Drosophila can facilitate CRM discovery in diverged insects. We validate in vivo over a dozen new CRMs, roughly doubling the number of known CRMs in the four non-Drosophila species. Given the growing wealth of Drosophila CRM annotation, these results suggest that extensive regulatory sequence annotation will be possible in newly sequenced insects without recourse to costly and labor-intensive genome-scale experiments. We develop a new method, Regulus, which computes a probabilistic score of similarity based on binding site composition (despite the absence of nucleotide-level sequence alignment), and demonstrate similarity between functionally related CRMs from orthologous loci. Our work represents an important step toward being able to trace the evolutionary history of gene regulatory networks and defining the mechanisms underlying insect evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

76 FR 59173 - Standard Format and Content of License Applications for Conventional Uranium Mills

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

...On May 30, 2008 (73 FR 31152), the U.S. Nuclear Regulatory Commission (NRC) published for public comment a notice of issuance and availability of Draft Regulatory Guide (DG)-3024, ``Standard Format and Content of License Applications for Conventional Uranium Mills.'' DG- 3024 was a proposed Revision 2 of Regulatory Guide (RG) 3.5. However, upon further consideration the NRC has decided not to revise RG 3.5 at this time. For this reason, DG-3024 will be withdrawn. The comment period closed on August 4, 2008, and 6 comments were received. The comments received will be considered and incorporated as appropriate if the NRC decides to revise RG 3.5 in the future.

76 FR 65544 - Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

...The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision to regulatory guide (RG) 3.39, ``Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities.'' This guide endorses the standard format and content for license applications and integrated safety analysis (ISA) summaries described in the current version of NUREG-1718, ``Standard Review Plan for the Review of an Application for a Mixed Oxide (MOX) Fuel Fabrication Facility,'' as a method that the NRC staff finds acceptable for meeting the regulatory requirements of Title 10 of the Code of Federal Regulations (10 CFR) part 70, ``Domestic Licensing of Special Nuclear Material'' for mixed oxide fuel fabrication facilities.

Regulatory Concerns on the In-Containment Water Storage System of the Korean Next Generation Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Hyung-Joon; Lee, Jae-Hun; Bang, Young-Seok

2002-07-15

The in-containment water storage system (IWSS) is a newly adopted system in the design of the Korean Next Generation Reactor (KNGR). It consists of the in-containment refueling water storage tank, holdup volume tank, and cavity flooding system (CFS). The IWSS has the function of steam condensation and heat sink for the steam release from the pressurizer and provides cooling water to the safety injection system and containment spray system in an accident condition and to the CFS in a severe accident condition. With the progress of the KNGR design, the Korea Institute of Nuclear Safety has been developing Safety andmore » Regulatory Requirements and Guidances for safety review of the KNGR. In this paper, regarding the IWSS of the KNGR, the major contents of the General Safety Criteria, Specific Safety Requirements, Safety Regulatory Guides, and Safety Review Procedures were introduced, and the safety review items that have to be reviewed in-depth from the regulatory viewpoint were also identified.« less

Carpet Specifiers Guide. Ultron, Advanced Generation Nylon Carpet Fiber.

ERIC Educational Resources Information Center

Monsanto Textiles Co., Atlanta, GA.

The purpose of this guide is to assist specifiers in properly specifying carpet made of Monsanto Ultron advanced generation nylon fiber. The guide describes a variety of conditions that should be considered in arriving at the proper selection and provides reference information and data, ranging from varying regulatory requirements, performance and…

77 FR 3514 - Protection Against Turbine Missiles

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0481] Protection Against Turbine Missiles AGENCY: Nuclear... (NRC or Commission) is issuing a revision to Regulatory Guide 1.115, ``Protection Against Turbine... structures, systems, and components against missiles resulting from turbine failure by the appropriate...

77 FR 56239 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... Draft Final Revision 1 to Regulatory Guide 1.163, ``Performance-Based Containment Leak-Test Program... inconvenience. If attending this meeting, please enter through the One White Flint North building, 11555...

77 FR 68162 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... Water Reactors,'' Revision 2, and Regulatory Guide 1.79.1, ``Initial Test Program of Emergency Core... White Flint North building, 11555 Rockville Pike, Rockville, MD. After registering with security, please...

Adverse Outcome Pathways: From Research to Regulation ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop co-sponsored by NICEATM and PCRM considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. This manuscript provides a

77 FR 64148 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-18

... Regulatory Guides (RG) RG 1.79, ````Preoperational Testing of Emergency Core Cooling Systems for Pressurized Water Reactors,'' Revision 2 and RG 1.79.1, ``Initial Test Program of Emergency Core Cooling Systems for...

76 FR 50274 - Terrestrial Environmental Studies for Nuclear Power Stations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0182] Terrestrial Environmental Studies for Nuclear Power... draft regulatory guide (DG), DG-4016, ``Terrestrial Environmental Studies for Nuclear Power Stations... environmental studies and analyses supporting licensing decisions for nuclear power reactors. DATES: Submit...

Smart Grid Legislative and Regulatory Policies and Case Studies

EIA Publications

2011-01-01

In recent years, a number of U.S. states have adopted or are considering smart grid related laws, regulations, and voluntary or mandatory requirements. At the same time, the number of smart grid pilot projects has been increasing rapidly. The Energy Information Administration (EIA) commissioned SAIC to research the development of smart grid in the United States and abroad. The research produced several documents that will help guide EIA as it considers how best to track smart grid developments.

77 FR 15812 - Initial Test Program of Condensate and Feedwater Systems for Light-Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... comments received on or before this date. Although a time limit is given, comments and suggestions in... guides are encouraged at any time. ADDRESSES: You may access information and comment submissions related... Information The NRC is issuing for public comment a draft guide in the NRC's ``Regulatory Guide'' series. This...

10 CFR 2.1001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., magnetic, graphic matter, or other documentary material, regardless of form or characteristic. Documentary... documentary material shall be guided by the topical guidelines in the applicable NRC Regulatory Guide. DOE... Network means the combined system that makes documentary material available electronically to parties...

Parallel evolution of chordate cis-regulatory code for development.

PubMed

Doglio, Laura; Goode, Debbie K; Pelleri, Maria C; Pauls, Stefan; Frabetti, Flavia; Shimeld, Sebastian M; Vavouri, Tanya; Elgar, Greg

2013-11-01

Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs), yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and Ciona embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of cis-regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations.

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

75 FR 22868 - Withdrawal of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Characterization of Seismic Sources and Determination of Safe Shutdown Earthquake Ground Motion.'' FOR FURTHER.... Nuclear Regulatory Commission (NRC) is withdrawing RG 1.165, ``Identification and Characterization of... alter the licensing basis of any currently operating reactor or any of the currently issued early site...

78 FR 64028 - Decommissioning of Nuclear Power Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0035] Decommissioning of Nuclear Power Reactors AGENCY... Commission (NRC) is issuing Revision 1 of regulatory guide (RG) 1.184 ``Decommissioning of Nuclear Power... the NRC's regulations relating to the decommissioning process for nuclear power reactors. The revision...

The future of yogurt: scientific and regulatory needs1234

PubMed Central

German, J Bruce

2014-01-01

Lactation biology, microbial selection, and human diversity are central themes that could guide investment in scientific research, industrial innovation, and regulatory policy oversight to propel yogurt into the central role for health-promoting food products. The ability of yogurt to provide the nourishing properties of milk together with the live microorganisms from fermentation provides a unique combination of food assets. Academic research must now define the various targets on which these biological assets act to improve health and develop the metrics that can quantitatively document their benefits. The food industry must reconcile that yogurt and its microorganisms cannot be expected to provide measurable benefits for all consumers, at all doses, and at all times. A supportive regulatory oversight must demand safety and yet encourage innovations that support a value proposition for yogurt in health. Health valuation in the marketplace will be driven by parallel innovations, including accurate assessment technologies, validated microbial ingredients, and health-aware consumers. PMID:24695899

The future of yogurt: scientific and regulatory needs.

PubMed

German, J Bruce

2014-05-01

Lactation biology, microbial selection, and human diversity are central themes that could guide investment in scientific research, industrial innovation, and regulatory policy oversight to propel yogurt into the central role for health-promoting food products. The ability of yogurt to provide the nourishing properties of milk together with the live microorganisms from fermentation provides a unique combination of food assets. Academic research must now define the various targets on which these biological assets act to improve health and develop the metrics that can quantitatively document their benefits. The food industry must reconcile that yogurt and its microorganisms cannot be expected to provide measurable benefits for all consumers, at all doses, and at all times. A supportive regulatory oversight must demand safety and yet encourage innovations that support a value proposition for yogurt in health. Health valuation in the marketplace will be driven by parallel innovations, including accurate assessment technologies, validated microbial ingredients, and health-aware consumers.

Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice.

PubMed

Smita, Shuchi; Katiyar, Amit; Chinnusamy, Viswanathan; Pandey, Dev M; Bansal, Kailash C

2015-01-01

MYB transcription factor (TF) is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by "top-down" and "guide-gene" approaches. More than 50% of OsMYBs were strongly correlated under 50 experimental conditions with 51 hub genes via "top-down" approach. Further, clusters were identified using Markov Clustering (MCL). To maximize the clustering performance, parameter evaluation of the MCL inflation score (I) was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by "guide-gene" approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought response in rice. Thus, the co-regulatory network analysis facilitated the identification of complex OsMYB regulatory networks, and candidate target regulon genes of selected guide MYB genes. The results contribute to the candidate gene screening, and experimentally testable hypotheses for potential regulatory MYB TFs, and their targets under stress conditions.

Guide for the preparation of applications for Nuclear Pharmacy Licenses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1985-08-01

The purpose of this regulatory guide is to provide assistance to applicants and licensees in preparing applications for new licenses, license amendments, and license renewals for the possession, use, and distribution of by-product material in nuclear pharmacy operations.

78 FR 58575 - Review of Experiments for Research Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0219] Review of Experiments for Research Reactors AGENCY... Commission (NRC) is withdrawing Regulatory Guide (RG) 2.4, ``Review of Experiments for Research Reactors... withdrawing RG 2.4, ``Review of Experiments for Research Reactors,'' (ADAMS Accession No. ML003740131) because...

76 FR 28102 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

..., Probabilistic Risk Assessment Branch, Division of Risk Analysis, Office of Nuclear Regulatory Research, U.S... approaches and methods (whether quantitative or qualitative, deterministic or probabilistic), data, and... uses in evaluating specific problems or postulated accidents, and data that the staff needs in its...

76 FR 2425 - Draft Regulatory Guide: Reissuance and Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-13

... posted on the NRC website and on the Federal rulemaking website Regulations.gov . Because your comments... publicly disclosed. Federal Rulemaking Website: Go to http://www.regulations.gov and search for [email protected] . The Regulatory Analysis is available electronically under ADAMS Accession Number...

Stepping Stones To Using "Caring for Our Children": National Health and Safety Performance Standards for Out-of-Home Child Care Programs. Protecting Children from Harm.

ERIC Educational Resources Information Center

Colorado Univ. Health Sciences Center, Denver.

Developed in support of state licensing and regulatory agencies as well as state child care, health, and resource and referral agencies, and a variety of other public and private organizations, parents, and advocacy groups, this guide identifies those standards most needed for the prevention of injury, morbidity, and mortality in child care…

76 FR 20052 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... Guide 1.149, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License..., ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License Examinations, and... simulation facility for use in operator and senior operator training, license examination operating tests...

75 FR 29785 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... Guide, DG-1248, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License..., ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License Examinations, and... or acceptance of a nuclear power plant simulation facility for use in operator and senior operator...

76 FR 77431 - Decommissioning Planning During Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... (DG) DG-4014, ``Decommissioning Planning During Operations.'' This guide describes a method that the.... The draft regulatory guide entitled, ``Decommissioning Planning During Operations,'' is temporarily..., 40, 50, 70, and 72 RIN 3150-AI55 [NRC-2011-0286; NRC-2008-0030] Decommissioning Planning During...

Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence

PubMed Central

Gordon, Kacy L.; Arthur, Robert K.; Ruvinsky, Ilya

2015-01-01

Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2) from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements. PMID:26020930

Air Force Third Party Financing Management Guide.

DTIC Science & Technology

1984-05-01

lhe Public Utility Regulatory Policies Act of 1978 ( PURPA ) a l,s qualifying cogenerators to sell their power back to the utilities al the utilities...Conditions favorable to the sale of cogenerated or independrt~y produced power created by the Public Utility Regulatory Policies Act ( PURPA ) of 1978; o...electrical energy. The Public Utility Regulatory Policies Act of 1978 ( PURPA ) allows qualifying cogenerators to sell their powcr back to the

THE CLEAN ENERGY-ENVIRONMENT GUIDE TO ACTION ...

EPA Pesticide Factsheets

The Guide to Action identifies and describes sixteen clean energy policies and strategies that are delivering economic and environmental results for states. For each policy, the Guide describes: Objectives and benefits of the policy; Examples of states that have implemented the policy; Responsibilities of key players at the state level, including typical roles of the main stakeholders; Opportunities to coordinate implementation with other federal and state policies, partnerships and technical assistance resources; Best practices for policy design, implementation, and evaluation, including state examples; Action steps for states to take when adopting or modifying their clean energy policies, based on existing state experiences; Resources for additional information on individual state policies, legislative and regulatory language, and analytical tools and methods. States participating in the Clean Energy-Environment State Partnership Program will use the Guide to Action to: Develop their own Clean Energy-Environment Action Plan that is appropriate to their state; Identify the roles and responsibilities of key decision-makers, such as environmental regulators, state legislatures, public utility commissioners, and state energy offices; Access and apply technical assistance resources, models, and tools available for state-specific analyses and program implementation; and Learn from each other as they develop their own clean energy programs and policies.

76 FR 65753 - Monitoring the Effectiveness of Maintenance at Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0212] Monitoring the Effectiveness of Maintenance at...) re-issued Draft Regulatory Guide, DG-1278, ``Monitoring the Effectiveness of Maintenance at Nuclear... Revision 4A to Nuclear Management and Resources Council (NUMARC) 93-01, ``Industry Guideline for Monitoring...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Quality assurance program change. 63.144 Section 63.144 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN A GEOLOGIC... assurance program information that duplicates language in quality assurance regulatory guides and quality...

77 FR 823 - Guidance for Fuel Cycle Facility Change Processes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-06

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0262] Guidance for Fuel Cycle Facility Change Processes... Fuel Cycle Facility Change Processes.'' This regulatory guide describes the types of changes for which fuel cycle facility licensees should seek prior approval from the NRC and discusses how licensees can...

Gene network analysis: from heart development to cardiac therapy.

PubMed

Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B

2015-03-01

Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.

Masters Thesis- Criticality Alarm System Design Guide with Accompanying Alarm System Development for the Radioisotope Production Laboratory in Richland, Washington

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenfield, Bryce A.

2009-12-01

A detailed instructional manual was created to guide criticality safety engineers through the process of designing a criticality alarm system (CAS) for Department of Energy (DOE) hazard class 1 and 2 facilities. Regulatory and technical requirements were both addressed. A list of design tasks and technical subtasks are thoroughly analyzed to provide concise direction for how to complete the analysis. An example of the application of the design methodology, the Criticality Alarm System developed for the Radioisotope Production Laboratory (RPL) of Richland, Washington is also included. The analysis for RPL utilizes the Monte Carlo code MCNP5 for establishing detector coveragemore » in the facility. Significant improvements to the existing CAS were made that increase the reliability, transparency, and coverage of the system.« less

75 FR 13599 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... Guide, DG-8040, ``Health Physics Surveys During Enriched Uranium-235 Processing and Fuel Fabrication... it deal specifically with the following aspects of an acceptable occupational health physics program that are closely related to surveys: (1) The number and qualification of the health physics staff, (2...

75 FR 58444 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... Guide, DG-1244, ``Availability of Electric Power Sources.'' FOR FURTHER INFORMATION CONTACT: Satish..., ``Availability of Electric Power Sources'' temporarily identified by its task number, DG- 1244, which should be... Commission (NRC) considers acceptable when the available electric power sources are less than the number of...

75 FR 62610 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Plant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

...: Draft Regulatory Guide DG-1237, ``Guidance on Making Changes to Emergency Plans for Nuclear Power Reactors,'' Interim Staff Guidance (ISG) NSIR/DPR-ISG-01, ``Emergency Planning for Nuclear Power Plants... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS...

78 FR 39284 - Technical Guidance for Assessing Environmental Justice in Regulatory Analysis

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... environmental justice assessments of its regulatory actions for years. This experience and body of work... set of questions to guide analysts in evaluating potential environmental justice concerns in EPA rules.... This guidance takes into account EPA's past experience in integrating EJ into the rulemaking process...

77 FR 59023 - Preoperational Testing of Instrument and Control Air Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-25

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0065] Preoperational Testing of Instrument and Control Air..., ``Preoperational Testing of Instrument and Control Air Systems.'' This regulatory guide is being revised to address... instrument and control air systems (ICAS) to meet seismic requirement, ICAS air- dryer testing to meet dew...

77 FR 50720 - Test Documentation for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Test Documentation for Digital Computer Software...) is issuing for public comment draft regulatory guide (DG), DG-1207, ``Test Documentation for Digital... practices for test documentation for software and computer systems as described in the Institute of...

78 FR 28896 - Design Limits and Loading Combinations for Metal Primary Reactor Containment System Components

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0095] Design Limits and Loading Combinations for Metal... Regulatory Guide (RG) 1.57, ``Design Limits and Loading Combinations for Metal Primary Reactor Containment... the NRC staff considers acceptable for design limits and loading combinations for metal primary...

76 FR 74630 - Making Changes to Emergency Plans for Nuclear Power Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... NUCLEAR REGULATORY COMMISSION 10 CFR Parts 50 and 52 RIN 3150-AI10 [NRC-2008-0122] Making Changes to Emergency Plans for Nuclear Power Reactors AGENCY: Nuclear Regulatory Commission. ACTION... guide (RG) 1.219, ``Guidance on Making Changes to Emergency Plans for Nuclear Power Reactors.'' This...

78 FR 24438 - Evaluations of Explosions Postulated To Occur at Nearby Facilities and on Transportation Routes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... Nearby Facilities and on Transportation Routes Near Nuclear Power Plants AGENCY: Nuclear Regulatory... Nearby Facilities and on Transportation Routes Near Nuclear Power Plants.'' This regulatory guide describes for applicants seeking nuclear power reactor licenses and licensees of nuclear power reactors...

76 FR 44049 - Guidance for Fuel Cycle Facility Change Processes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0262] Guidance for Fuel Cycle Facility Change Processes...-issued Draft Regulatory Guide, DG- 3037, ``Guidance for Fuel Cycle Facility Change Processes'' in the...-3037 from August 12, 2011 to September 16, 2011. DG-3037 describes the types of changes for fuel cycle...

77 FR 36014 - Initial Test Program of Emergency Core Cooling Systems for Boiling-Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0134] Initial Test Program of Emergency Core Cooling... for public comment draft regulatory guide (DG), DG-1277, ``Initial Test Program of Emergency Core... acceptable to implement with regard to initial testing features of emergency core cooling systems (ECCSs) for...

Groundwater quality, age, and susceptibility and vulnerability to nitrate contamination with linkages to land use and groundwater flow, Upper Black Squirrel Creek Basin, Colorado, 2013

USGS Publications Warehouse

Wellman, Tristan P.; Rupert, Michael G.

2016-03-03

The results of this investigation offer the foundational information needed for developing best management practices to mitigate nitrate contamination, basic concepts on water quality to aid public education, and information to guide regulatory measures if policy makers determine this is warranted. Science-based decision making will require continued monitoring and analysis of water quality in the future.

76 FR 31467 - Guide Concerning Fuel Economy Advertising for New Automobiles

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

...The Federal Trade Commission (``FTC'' or ``Commission'') gives notice that it is postponing any amendments to its Guide Concerning Fuel Economy Advertising for New Automobiles (``Fuel Economy Guide'' or ``Guide'') pending completion of ongoing review by the Environmental Protection Agency (``EPA'') and the National Highway Traffic Safety Administration (``NHTSA'') of current fuel economy labeling requirements and the Commission's accelerated regulatory review of its own Labeling Requirements for Alternative Fuels and Alternative Fueled Vehicles Rule (``Alternative Fuels Rule'').

Advanced Tools Webinar Series Presents: Regulatory Issues and Case Studies of Advanced Tools

EPA Science Inventory

U.S. EPA has released A Guide for Assessing Biodegradation and Source Identification of Organic Ground Water Contaminants using Compound Specific Isotope Analysis (CSIA) [EPA 600/R-08/148 | December 2008 | www.epa.gov/ada]. The Guide provides recommendations for sample collecti...

Guiding principles of safety as a basis for developing a pharmaceutical safety culture.

PubMed

Edwards, Brian; Olsen, Axel K; Whalen, Matthew D; Gold, Marla J

2007-05-01

Despite the best efforts of industry and regulatory authorities, the trust of society in the process of medicine development and communication of pharmaceutical risk has ebbed away. In response the US government has called for a culture of compliance while the EU regulators talk of a 'culture of scientific excellence'. However, one of the fundamental problems hindering progress to rebuilding trust based on a pharmaceutical safety culture is the lack of agreement and transparency between all stakeholders as to what is meant by a 'Safety of Medicines'. For that reason, we propose 'Guiding Principles of Safety for Pharmaceuticals' are developed analogous to the way that Chemical Safety has been tackled. A logical starting point would be to examine the Principles outlined by the US Institute of Medicine although we acknowledge that these Principles require further extensive debate and definition. Nevertheless, the Principles should take centre stage in the reform of pharmaceutical development required to restore society's trust.

Expert opinion vs. empirical evidence

PubMed Central

Herman, Rod A; Raybould, Alan

2014-01-01

Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops. PMID:24637724

Expert opinion vs. empirical evidence: the precautionary principle applied to GM crops.

PubMed

Herman, Rod A; Raybould, Alan

2014-01-01

Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops.

Independent data monitoring committees: Preparing a path for the future

PubMed Central

Hess, Connie N.; Roe, Matthew T.; Gibson, C. Michael; Temple, Robert J.; Pencina, Michael J.; Zarin, Deborah A.; Anstrom, Kevin J.; Alexander, John H.; Sherman, Rachel E.; Fiedorek, Fred T.; Mahaffey, Kenneth W.; Lee, Kerry L.; Chow, Shein-Chung; Armstrong, Paul W.; Califf, Robert M.

2014-01-01

Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs. PMID:25066551

Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United States Food and Drug Administration.

PubMed

Zineh, Issam; Pacanowski, Michael A

2011-08-01

Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities.

Product Development and Commercialization of Diagnostic or Life Science Products for Scientists and Researchers.

PubMed

Alonso, Meghan M

2017-01-01

Commercializing a diagnostic or life science product often encompasses different goals than that of research and grant funding. There are several necessary steps, and a strategy needs to be well defined in order to be successful. Product development requires input from and between various groups within a company and, for academia, outside entities. The product development stakeholder groups/entities are research, marketing, development, regulatory, manufacturing, clinical, safety/efficacy, and quality. After initial research and development, much of the work in product development can be outsourced or jointly created using public-private partnerships. This chapter serves as an overview of the product development process and provides a guide to best define a product strategy.

Acrilan Contract Carpet Specification Guide.

ERIC Educational Resources Information Center

Monsanto Textiles Co., Atlanta, GA.

The purpose of this guide is to assist specifiers in properly specifying carpet made of Monsanto Acrilan acrylic fiber. As carpet is used in an expanding range of applications, it must meet increasing and varying regulatory requirements. Performance needs vary with the type of environment in which the carpet is installed. Carpet construction must…

76 FR 59448 - Draft Regulatory Guide; Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... consideration only for comments received on or before this date. Although a time limit is given, comments and... published guides are encouraged at any time. ADDRESSES: Please include Docket ID NRC-2011-0224 in the... document using the following methods: NRC's Public Document Room (PDR): The public may examine and have...

78 FR 38739 - Special Nuclear Material Control and Accounting Systems for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-27

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0109] Special Nuclear Material Control and Accounting... Guide (RG) 5.29, ``Special Nuclear Material Control and Accounting Systems for Nuclear Power Plants... material control and accounting. This guide applies to all nuclear power plants. ADDRESSES: Please refer to...

77 FR 19740 - Water Sources for Long-Term Recirculation Cooling Following a Loss-of-Coolant Accident

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0249] Water Sources for Long-Term Recirculation Cooling... Regulatory Guide (RG) 1.82, ``Water Sources for Long-Term Recirculation Cooling Following a Loss-of-Coolant... regarding the sumps and suppression pools that provide water sources for emergency core cooling, containment...

75 FR 54918 - Draft Regulatory Guide, DG-1247, “Design-Basis Hurricane and Hurricane Missiles for Nuclear Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... that the staff uses in evaluating specific problems or postulated accidents, and data that the staff... turbine missiles. NUREG/CR 7004 is the technical basis for regulatory guidance on design-basis hurricane... hurricane wind speeds for new nuclear power plants. [[Page 54919

Evaluation of Modified Risk Claim Advertising Formats for Camel Snus

ERIC Educational Resources Information Center

Fix, Brian V.; Adkison, Sarah E.; O'Connor, Richard J.; Bansal-Travers, Maansi; Cummings, K. Michael; Rees, Vaughan W.; Hatsukami, Dorothy K.

2017-01-01

Objectives: The US Food and Drug Administration (FDA) has regulatory authority for modified risk tobacco product advertising claims. To guide future regulatory efforts, we investigated how variations in modified risk claim advertisements influence consumer perceptions of product risk claims for Camel Snus. Methods: Young people and adults (15-65),…

77 FR 50722 - Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Unit Testing for Digital Computer Software...) is issuing for public comment draft regulatory guide (DG), DG-1208, ``Software Unit Testing for Digital Computer Software used in Safety Systems of Nuclear Power Plants.'' The DG-1208 is proposed...

78 FR 47011 - Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Unit Testing for Digital Computer Software... revised regulatory guide (RG), revision 1 of RG 1.171, ``Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants.'' This RG endorses American National Standards...

77 FR 70846 - Regulatory Guide 1.182, “Assessing and Managing Risk Before Maintenance Activities at Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... Risk Before Maintenance Activities at Nuclear Power Plants'' AGENCY: Nuclear Regulatory Commission... Activities at Nuclear Power Plants,'' published in May 2000. The document is redundant due to the inclusion... Risk Before Maintenance Activities at Nuclear Power Plants,'' published in May 2000. The requirements...

Voices from the Other Side of the Fence: Early Childhood Teachers' Experiences with Mandatory Regulatory Requirements

ERIC Educational Resources Information Center

Bown, Kathryn; Sumsion, Jennifer

2007-01-01

Guided by feminist research principles, the study reported in this article contributes to the growing research dialogue on early childhood teachers' experiences with, and perceptions of, the impact of regulatory requirements on their teaching and on their perceptions of themselves as professionals. Specifically, three teachers from metropolitan…

78 FR 64027 - Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

...The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to regulatory guide (RG), 1.79, ``Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors.'' This RG is being revised to incorporate guidance for preoperational testing of new pressurized water reactor (PWR) designs.

76 FR 53979 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Thermal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Thermal Hydraulics Phenomena; Notice of Meeting The ACRS Subcommittee on Thermal Hydraulics... Revision 4 to Regulatory Guide 1.82, ``Water Sources for Long-Term Recirculation Cooling Following a Loss...

76 FR 43356 - Evaluations of Explosions Postulated To Occur at Nearby Facilities and on Transportation Routes...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... the ``Regulatory Guides'' collection of the NRC's Library at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2011-0152] Evaluations of Explosions Postulated To Occur at..., ``Evaluations of Explosions Postulated to Occur at Nearby Facilities and on Transportation Routes Near Nuclear...

77 FR 38856 - An Approach for Probabilistic Risk Assessment in Risk-Informed Decisions on Plant-Specific...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... discussion on defense-in-depth. Specifically, the SRM stated, Because the statements in Regulatory Guide 1... language to assure that the defense-in-depth philosophy is interpreted and implemented consistently. To the extent that other regulatory guidance refers to defense in depth, the relevant documents should be...

[Task sharing with radiotherapy technicians in image-guided radiotherapy].

PubMed

Diaz, O; Lorchel, F; Revault, C; Mornex, F

2013-10-01

The development of accelerators with on-board imaging systems now allows better target volumes reset at the time of irradiation (image-guided radiotherapy [IGRT]). However, these technological advances in the control of repositioning led to a multiplication of tasks for each actor in radiotherapy and increase the time available for the treatment, whether for radiotherapy technicians or radiation oncologists. As there is currently no explicit regulatory framework governing the use of IGRT, some institutional experiments show that a transfer is possible between radiation oncologists and radiotherapy technicians for on-line verification of image positioning. Initial training for every technical and drafting procedures within institutions will improve audit quality by reducing interindividual variability. Copyright © 2013. Published by Elsevier SAS.

Assessing the Benefit-Risk Profile for Pediatric Implantable Auditory Prostheses.

PubMed

Fisher, Laurel M; Martinez, Amy S; Richmond, Frances J; Krieger, Mark D; Wilkinson, Eric P; Eisenberg, Laurie S

2017-01-01

Children with congenital cochleovestibular abnormalities associated with profound hearing loss have few treatment options if cochlear implantation does not yield benefit. An alternative is the auditory brainstem implant (ABI). Regulatory authority device approvals currently include a structured benefit-risk assessment. Such an assessment, for regulatory purposes or to guide clinical decision making, has not been published, to our knowledge, for the ABI and may lead to the design of a research program that incorporates regulatory authority, family, and professional input. Much structured benefit-risk research has been conducted in the context of drug trials; here we apply this approach to device studies. A qualitative framework organized benefit (speech recognition, parent self-report measures) and risk (surgery- and device-related) information to guide the selection of candidates thought to have potential benefit from ABI. Children with cochleovestibular anatomical abnormalities are challenging for appropriate assessment of candidacy for a cochlear implant or an ABI. While the research is still preliminary, children with an ABI appear to slowly obtain benefit over time. A team of professionals, including audiological, occupational, and educational therapy, affords maximum opportunity for benefit. Pediatric patients who have abnormal anatomy and are candidates for an implantable auditory prosthetic require an individualized, multisystems review. The qualitative benefit-risk assessment used here to characterize the condition, the medical need, potential benefits, risks, and risk management strategies has revealed the complex factors involved. After implantation, continued team support for the family during extensive postimplant therapy is needed to develop maximum auditory skill benefit.

An analysis of the early-warning system in emerging markets for reducing the financial crisis

NASA Astrophysics Data System (ADS)

Shen, Xiangguang; Song, Xiaozhong

2009-07-01

The large number of financial crises in emerging markets over the past ten years has left many observers, both from academia and financial institutions, puzzled by an apparent lack of homogenous causal relations between endogenous economic variables and the bursting of large financial shocks. The frequency of financial crises in the last 20 years can be attributed to the lack of a comprehensive theory of financial regulation to guide policy makers. Existing theories fail to define the range of regulatory models, the causes of regulatory failure, and how to measure and prevent it. Faulty design of regulatory models, and the lack of ongoing performance monitoring incorporating early warning systems, is disrupting economic and social development. The main aim of this article is to propose an early warning system (EWS) which purposes issuing warning signal against the possible financial crisis in the emerging market, and makes the emerging market survived the first wave of the crisis be able to continue their operation in the following years.

SCANS (Shipping Cask ANalysis System) a microcomputer-based analysis system for shipping cask design review: User`s manual to Version 3a. Volume 1, Revision 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mok, G.C.; Thomas, G.R.; Gerhard, M.A.

SCANS (Shipping Cask ANalysis System) is a microcomputer-based system of computer programs and databases developed at the Lawrence Livermore National Laboratory (LLNL) for evaluating safety analysis reports on spent fuel shipping casks. SCANS is an easy-to-use system that calculates the global response to impact loads, pressure loads and thermal conditions, providing reviewers with an independent check on analyses submitted by licensees. SCANS is based on microcomputers compatible with the IBM-PC family of computers. The system is composed of a series of menus, input programs, cask analysis programs, and output display programs. All data is entered through fill-in-the-blank input screens thatmore » contain descriptive data requests. Analysis options are based on regulatory cases described in the Code of Federal Regulations 10 CFR 71 and Regulatory Guides published by the US Nuclear Regulatory Commission in 1977 and 1978.« less

[Genome-editing: focus on the off-target effects].

PubMed

He, Xiubin; Gu, Feng

2017-10-25

Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

The U. S. Department of Energy SARP review training program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauck, C.J.

1988-01-01

In support of its radioactive material packaging certification program, the U.S. Department of Energy (DOE) has established a special training workshop. The purpose of the two-week workshop is to develop skills in reviewing Safety Analysis Reports for Packagings (SARPs) and performing confirmatory analyses. The workshop, conducted by the Lawrence Livermore National Laboratory (LLNL) for DOE, is divided into two parts: methods of review and methods of analysis. The sessions covering methods of review are based on the DOE document, ''Packaging Review Guide for Reviewing Safety Analysis Reports for Packagings'' (PRG). The sessions cover relevant DOE Orders and all areas ofmore » review in the applicable Nuclear Regulatory Commission (NRC) Regulatory Guides. The technical areas addressed include structural and thermal behavior, materials, shielding, criticality, and containment. The course sessions on methods of analysis provide hands-on experience in the use of calculational methods and codes for reviewing SARPs. Analytical techniques and computer codes are discussed and sample problems are worked. Homework is assigned each night and over the included weekend; at the conclusion, a comprehensive take-home examination is given requiring six to ten hours to complete.« less

Advancing the Adverse Outcome Pathway Framework - an ...

EPA Pesticide Factsheets

The ability of scientists to conduct whole organism toxicity tests to understand chemical safety has been significantly outpaced by the rapid synthesis of new chemicals. Therefore, to increase efficiencies in chemical risk assessment, scientists are turning to mechanistic-based studies, making greater use of in vitro and in silico methods, to screen for potential environmental and human health hazards. A framework that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP). A number of international activities have focused on AOP development and plausible applications to regulatory decision-making. These interactions have prompted dialog between research scientists and regulatory communities to consider how best to use the AOP framework in risk assessment. While expert-facilitated discussions have been instrumental in moving the science of AOPs forward, it was recognized that a survey of the broader scientific community would aid in identifying shortcomings and guiding future initiatives for the AOP framework. To that end, a ?‘Horizon Scanning’ exercise was conducted to solicit questions from the global scientific and regulatory communities concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. The m

Molecular mechanisms of system responses to novel stimuli are predictable from public data

PubMed Central

Danziger, Samuel A.; Ratushny, Alexander V.; Smith, Jennifer J.; Saleem, Ramsey A.; Wan, Yakun; Arens, Christina E.; Armstrong, Abraham M.; Sitko, Katherine; Chen, Wei-Ming; Chiang, Jung-Hsien; Reiss, David J.; Baliga, Nitin S.; Aitchison, John D.

2014-01-01

Systems scale models provide the foundation for an effective iterative cycle between hypothesis generation, experiment and model refinement. Such models also enable predictions facilitating the understanding of biological complexity and the control of biological systems. Here, we demonstrate the reconstruction of a globally predictive gene regulatory model from public data: a model that can drive rational experiment design and reveal new regulatory mechanisms underlying responses to novel environments. Specifically, using ∼1500 publically available genome-wide transcriptome data sets from Saccharomyces cerevisiae, we have reconstructed an environment and gene regulatory influence network that accurately predicts regulatory mechanisms and gene expression changes on exposure of cells to completely novel environments. Focusing on transcriptional networks that induce peroxisomes biogenesis, the model-guided experiments allow us to expand a core regulatory network to include novel transcriptional influences and linkage across signaling and transcription. Thus, the approach and model provides a multi-scalar picture of gene dynamics and are powerful resources for exploiting extant data to rationally guide experimentation. The techniques outlined here are generally applicable to any biological system, which is especially important when experimental systems are challenging and samples are difficult and expensive to obtain—a common problem in laboratory animal and human studies. PMID:24185701

Rationales for regulatory activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perhac, R.M.

1997-02-01

The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

Increasing Student Achievement: Educators' Guide to Secondary Career & Technical Education Assessment

ERIC Educational Resources Information Center

National Occupational Competency Testing Institute, 2012

2012-01-01

This guide attempts to address an aspect of secondary CTE (Career and Technical Education) that has received little attention; the assessment literacy of educators. School leaders need to go beyond ensuring routine compliance with external and internal regulatory forces to identify ways in which CTE program teachers might better understand…

76 FR 51308 - Retail Food Store Advertising and Marketing Practices Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... FTC rules and guides, the Commission requests public comment on the overall costs, benefits, necessity..., after a comment period and public hearings, the Commission concluded that the costs of complying with... about the costs and benefits of the rules and guides as well as their regulatory and economic impact...

75 FR 66411 - Small Entity Compliance Guide: Women-Owned Small Business Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

...-Owned Small Business (WOSB) Program. This guide sets forth in plain language the requirements for... effective February 4, 2011 because the agency is in the process of working with the Federal Acquisition Regulatory Council to implement this program in the Federal Acquisition Regulations. In addition, the SBA is...

78 FR 70482 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-71; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

...: Small Entity Compliance Guide. SUMMARY: This document is issued under the joint authority of DOD, GSA... the FAR case number. For information pertaining to status or publication schedules, contact the Regulatory Secretariat at 202- 501-4755. Rules Listed in FAC 2005-71 Item Subject FAR Case Analyst *I...

76 FR 41150 - Notice Announcing Ten-Year Regulatory Review Schedule and Request for Public Comment on the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... in the face of changing marketplace conditions, evolving consumer behavior, and technological...) 326-2984, Attorney, Division of Enforcement, Bureau of Consumer Protection, Federal Trade Commission... continuing need for the rule or guide as well as the rule's or guide's costs and benefits to consumers and...

76 FR 72738 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

...-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Correcting an Error by Renumbering the Subsections of Section 101 of the Company Guide November 18, 2011... thereunder,\\3\\ notice is hereby given that on November 16, 2011, NYSE Amex LLC (the ``Exchange'' or...

Regulatory Services and Records. A Major Occupational Group in the Public Service Cluster. Teacher's Manual.

ERIC Educational Resources Information Center

Gwinnett County Schools, GA.

Part of a course designed to acquaint high school students with basic information concerning careers in public service, this teacher's manual is one of nine (each with accompanying student guide) which constitute a course entitled "Orientation to Public Service." Focus in the units covered by the manual is on regulatory services and…

76 FR 19155 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-06

... stated that it would offer training on the revised Discovery Guide in a workshop that FINRA would post as... Procedure for Customer Disputes April 1, 2011. I. Introduction On July 12, 2010, the Financial Industry... Arbitration Procedure for Customer Disputes (``Customer Code''). The proposed rule change was published for...

77 FR 75453 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 68443; File No. SR-DTC-2012-09] Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Make Ministerial Changes to the Existing Reorganization Service Guide December 14, 2012. Pursuant to Section 19(b)(1) of the Securitie...

End-of-life decisions in Malaysia: Adequacies of ethical codes and developing legal standards.

PubMed

Kassim, Puteri Nemie Jahn; Alias, Fadhlina

2015-06-01

End-of-life decision-making is an area of medical practice in which ethical dilemmas and legal interventions have become increasingly prevalent. Decisions are no longer confined to clinical assessments; rather, they involve wider considerations such as a patient's religious and cultural beliefs, financial constraints, and the wishes and needs of family members. These decisions affect everyone concerned, including members of the community as a whole. Therefore it is imperative that clear ethical codes and legal standards are developed to help guide the medical profession on the best possible course of action for patients. This article considers the relevant ethical, codes and legal provisions in Malaysia governing certain aspects of end-of-life decision-making. It highlights the lack of judicial decisions in this area as well as the limitations with the Malaysian regulatory system. The article recommends the development of comprehensive ethical codes and legal standards to guide end-of-life decision-making in Malaysia.

Regulatory incentives to ensure better medicines for older people: From ICH E7 to the EMA reflection paper on quality aspects.

PubMed

van Riet-Nales, Diana A; Hussain, Nasir; Sundberg, Katarina A E; Eggenschwyler, Doris; Ferris, Cristina; Robert, Jean-Louis; Cerreta, Francesca

2016-10-30

Ageing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline "Studies in support of special populations, geriatrics", the ICH Q8 guideline "Pharmaceutical development", the EMA good practice guide on "Risk minimisation and prevention of medication errors" and the forthcoming EMA CHMP QWP reflection paper on the "Quality aspects (pharmaceutical development) of medicines for older people". In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Cell-Specific Actions of a Human LHX3 Gene Enhancer During Pituitary and Spinal Cord Development

PubMed Central

Park, Soyoung; Mullen, Rachel D.

2013-01-01

The LIM class of homeodomain protein 3 (LHX3) transcription factor is essential for pituitary gland and nervous system development in mammals. In humans, mutations in the LHX3 gene underlie complex pediatric syndromes featuring deficits in anterior pituitary hormones and defects in the nervous system. The mechanisms that control temporal and spatial expression of the LHX3 gene are poorly understood. The proximal promoters of the human LHX3 gene are insufficient to guide expression in vivo and downstream elements including a conserved enhancer region appear to play a role in tissue-specific expression in the pituitary and nervous system. Here we characterized the activity of this downstream enhancer region in regulating gene expression at the cellular level during development. Human LHX3 enhancer-driven Cre reporter transgenic mice were generated to facilitate studies of enhancer actions. The downstream LHX3 enhancer primarily guides gene transcription in α-glycoprotein subunit -expressing cells secreting the TSHβ, LHβ, or FSHβ hormones and expressing the GATA2 and steroidogenic factor 1 transcription factors. In the developing nervous system, the enhancer serves as a targeting module active in V2a interneurons. These results demonstrate that the downstream LHX3 enhancer is important in specific endocrine and neural cell types but also indicate that additional regulatory elements are likely involved in LHX3 gene expression. Furthermore, these studies revealed significant gonadotrope cell heterogeneity during pituitary development, providing insights into the cellular physiology of this key reproductive regulatory cell. The human LHX3 enhancer-driven Cre reporter transgenic mice also provide a valuable tool for further developmental studies of cell determination and differentiation in the pituitary and nervous system. PMID:24100213

Brownfield to Brightfield Initiative in Oak Ridge, TN - 12346

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hough, Gil; Fairless, Chad

Experience characterizing, permitting, and restoring 'Brownfield' sites-government or industrial sites with restricted future use due to the presence or potential presence of hazardous substances, pollutants, or contaminants-is being leveraged to identify opportunities for redevelopment into solar power generating facilities which, in this context, are called 'Brightfields'. Brownfield sites offer the expansive land necessary for large photovoltaic (PV) solar farms, but require an in-depth working knowledge of complicated regulatory restrictions and environmental constraints to develop them. As a part of the effort to identify opportunities for redevelopment of Brownfield sites for solar applications, a technical guide, was composed specifically for themore » development of solar generation on restricted use sites. The basis of the technical guide gives specific consideration to environmental requirements and installation methods breaking that into three areas for assessing: 1) levels of contamination, 2) ground penetration requirements, and 3) the requirements for aesthetics and maintenance. Brightfield projects are underway to support the technical guide and expand re-industrialization efforts for the former DOE Gaseous Diffusion Plant in Oak Ridge, TN. There are exciting opportunities to turn Brownfields into Brightfield solar energy solutions for meeting the future renewable energy needs of our country. Brownfields that offer the large surface area required for solar PV farms coupled with the technical guide for the installation of solar farms on restricted use sites supports efforts to develop the solar capacities and expertise to tap this future market. The initial projects designed following the technical guide will provide verification of the installation requirements and beneficial reuse of restricted use sites. (authors)« less

76 FR 52596 - Request for Comment Concerning Interpretations of the Magnuson-Moss Warranty Act; Rule Governing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... requests public comment on the overall costs, benefits, necessity and regulatory and economic impact of... of the Interpretations, Rules and Guides? Why or why not? 2. What benefits and costs have the... benefits and costs have the Interpretations, Rules and Guides had on consumers who purchase the warranted...

Urban Stormwater Runoff. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Simko, Robert A.

Urban stormwater runoff collects pollutants from many parts of a city and is an important consideration in water quality planning. Presented is an instructor's guide for a learning session covering various aspects of urban runoff including pollutant sources, management practices, and regulatory programs. Intended for citizen advisory groups, this…

78 FR 55117 - Ultimate Heat Sink for Nuclear Power Plants; Draft Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... applicants may use to implement general design criteria (GDC) that are applicable to the ultimate heat sink... only for comments received on or before this date. Although a time limit is given, comments and... published guides are encouraged at any time. ADDRESSES: You may submit comment by any of the following...

Occupational Safety and Health in Vocational Education: A Guide for Administrators, Faculty, and Staff.

ERIC Educational Resources Information Center

Godbey, Frank W.

This guide is intended to help administrators at schools having vocational education programs assess their occupational safety and health needs and establish a program to ensure a safer and more healthful work environment. It consists of three sections: (1) administrative guidelines, (2) technical-regulatory guidelines, and (3) a self-evaluation…

77 FR 12086 - Final Staff Guidance, Revision 4 to Standard Review Plan; Section 8.1 on Electric Power-Introduction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... incorporate Revision 4 of SRP Section 8.1 into the next revisions of the Regulatory Guide 1.206, ``Combined..., 2011 (76 FR 31381), the NRC published for public comment the proposed Revision 4 on Section 8.1 on... NUCLEAR REGULATORY COMMISSION [NRC-2011-0119] Final Staff Guidance, Revision 4 to Standard Review...

Clinical and regulatory considerations in pharmacogenetic testing.

PubMed

Schuck, Robert N; Marek, Elizabeth; Rogers, Hobart; Pacanowski, Michael

2016-12-01

Both regulatory science and clinical practice rely on best available scientific data to guide decision-making. However, changes in clinical practice may be driven by numerous other factors such as cost. In this review, we reexamine noteworthy examples where pharmacogenetic testing information was added to drug labeling to explore how the available evidence, potential public health impact, and predictive utility of each pharmacogenetic biomarker impacts clinical uptake. Advances in the field of pharmacogenetics have led to new discoveries about the genetic basis for variability in drug response. The Food and Drug Administration recognizes the value of pharmacogenetic testing strategies and has been proactive about incorporating pharmacogenetic information into the labeling of both new drugs and drugs already on the market. Although some examples have readily translated to routine clinical practice, clinical uptake of genetic testing for many drugs has been limited. Both regulatory science and clinical practice rely on data-driven approaches to guide decision making; however, additional factors are also important in clinical practice that do not impact regulatory decision making, and these considerations may result in heterogeneity in clinical uptake of pharmacogenetic testing. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

A guide to large-scale RNA sample preparation.

PubMed

Baronti, Lorenzo; Karlsson, Hampus; Marušič, Maja; Petzold, Katja

2018-05-01

RNA is becoming more important as an increasing number of functions, both regulatory and enzymatic, are being discovered on a daily basis. As the RNA boom has just begun, most techniques are still in development and changes occur frequently. To understand RNA functions, revealing the structure of RNA is of utmost importance, which requires sample preparation. We review the latest methods to produce and purify a variation of RNA molecules for different purposes with the main focus on structural biology and biophysics. We present a guide aimed at identifying the most suitable method for your RNA and your biological question and highlighting the advantages of different methods. Graphical abstract In this review we present different methods for large-scale production and purification of RNAs for structural and biophysical studies.

Strategies to overcome clinical, regulatory, and financial challenges in the implementation of personalized medicine.

PubMed

Tsimberidou, Apostolia M; Ringborg, Ulrik; Schilsky, Richard L

2013-01-01

This article highlights major developments over the last decade in personalized medicine in cancer. Emerging data from clinical studies demonstrate that the use of targeted agents in patients with targetable molecular aberrations improves clinical outcomes. Despite a surge of studies, however, significant gaps in knowledge remain, especially in identifying driver molecular aberrations in patients with multiple aberrations, understanding molecular networks that control carcinogenesis and metastasis, and most importantly, discovering effective targeted agents. Implementation of personalized medicine requires continued scientific and technological breakthroughs; standardization of tumor tissue acquisition and molecular testing; changes in oncology practice and regulatory standards for drug and device access and approval; modification of reimbursement policies by health care payers; and innovative ways to collect and analyze electronic patient information that are linked to prospective clinical registries and rapid learning systems. Informatics systems that integrate clinical, laboratory, radiologic, molecular, and economic data will improve clinical care and will provide infrastructure to enable clinical research. The initiative of the EurocanPlatform aims to overcome the challenges of implementing personalized medicine in Europe by sharing patients, biologic materials, and technological resources across borders. The EurocanPlatform establishes a complete translational cancer research program covering the drug development process and strengthening collaborations among academic centers, pharmaceutical companies, regulatory authorities, health technology assessment organizations, and health care systems. The CancerLinQ rapid learning system being developed by ASCO has the potential to revolutionize how all stakeholders in the cancer community assemble and use information obtained from patients treated in real-world settings to guide clinical practice, regulatory decisions, and health care payment policy.

Defining Tobacco Regulatory Science Competencies.

PubMed

Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

2017-02-01

In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Quality Assurance Framework Implementation Guide for Isolated Community Power Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esterly, Sean R.; Baring-Gould, Edward I.; Burman, Kari A.

This implementation guide is a companion document to the 'Quality Assurance Framework for Mini-Grids' technical report. This document is intended to be used by one of the many stakeholder groups that take part in the implementation of isolated power systems. Although the QAF could be applied to a single system, it was designed primarily to be used within the context of a larger national or regional rural electrification program in which many individual systems are being installed. This guide includes a detailed overview of the Quality Assurance Framework and provides guidance focused on the implementation of the Framework from themore » perspective of the different stakeholders that are commonly involved in expanding energy development within specific communities or regions. For the successful long-term implementation of a specific rural electrification program using mini-grid systems, six key stakeholders have been identified that are typically engaged, each with a different set of priorities 1. Regulatory agency 2. Governmental ministry 3. System developers 4. Mini-utility 5. Investors 6. Customers/consumers. This document is broken into two distinct sections. The first focuses on the administrative processes in the development and operation of community-based mini-grid programs, while the second focuses on the process around the installation of the mini-grid project itself.« less

DEVELOPMENT OF HFE SECTIONS OF DG-1145.

DOE Office of Scientific and Technical Information (OSTI.GOV)

HIGGINS,J.C.; OHARA, J.M.; BONGARRA, J.

2007-03-26

For the licensing of the current fleet of commercial nuclear power plants (NPPs), the Nuclear Regulatory Commission (NRC) used two key documents, NUREG-0800 and Regulatory Guide (RG) 1.70. RG 1.70 provided guidance to applicants on the contents needed in their Safety Analysis Reports (SARs) submitted as part of their application to construct or operate an NPP. NUREG-0800, the NRC Standard Review Plan (SRP), provides guidance to the NRR staff reviewers on performing their safety reviews of these applications. As part of the preparation for a new wave of improved NPP designs the NRC is in the process of updating themore » SRP and is also developing a new RG designated as draft RG or DG-1145, ''Combined License Applications for Nuclear Power Plants (LWR Edition).'' This will eventually become RG 1.206 and will take the place of RG 1.70. This will provide guidance for combined license (COL) applicants, as well as for other 10CFR Part 52 variations that are permitted.« less

75 FR 16216 - Self-Regulatory Organizations; the Depository Trust Company; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... Change To Update Its Settlement Service Guide as It Relates to the ID Net Service March 25, 2010... change amends DTC's rules in order to update its Settlement Service Guide as it relates to the ID Net... the purpose of and basis for the proposed rule change and discussed any comments it received on the...

An Exploration of the Legal and Regulatory Environment of Privacy and Security through Active Research, Guided Study, Blog Creation, and Discussion

ERIC Educational Resources Information Center

Peslak, Alan R.

2010-01-01

One of the most important topics for today's information technology professional is the study of legal and regulatory issues as they relate to privacy and security of personal and business data and identification. This manuscript describes the topics and approach taken by the instructors that focuses on independent research of source documents and…

Development by Design in Colombia: Making Mitigation Decisions Consistent with Conservation Outcomes

PubMed Central

Saenz, Shirley; Walschburger, Tomas; González, Juan Carlos; León, Jorge; McKenney, Bruce; Kiesecker, Joseph

2013-01-01

Mitigation policy and regulatory frameworks are consistent in their strong support for the mitigation hierarchy of: (1) avoiding impacts, (2) minimizing impacts, and then (3) offsetting/compensating for residual impacts. While mitigation frameworks require developers to avoid, minimize and restore biodiversity on-site before considering an offset for residual impacts, there is a lack of quantitative guidance for this decision-making process. What are the criteria for requiring impacts be avoided altogether? Here we examine how conservation planning can guide the application of the mitigation hierarchy to address this issue. In support of the Colombian government's aim to improve siting and mitigation practices for planned development, we examined five pilot projects in landscapes expected to experience significant increases in mining, petroleum and/or infrastructure development. By blending landscape-level conservation planning with application of the mitigation hierarchy, we can proactively identify where proposed development and conservation priorities would be in conflict and where impacts should be avoided. The approach we outline here has been adopted by the Colombian Ministry of Environment and Sustainable Development to guide licensing decisions, avoid piecemeal licensing, and promote mitigation decisions that maintain landscape condition. PMID:24339972

Development by design in Colombia: making mitigation decisions consistent with conservation outcomes.

PubMed

Saenz, Shirley; Walschburger, Tomas; González, Juan Carlos; León, Jorge; McKenney, Bruce; Kiesecker, Joseph

2013-01-01

Mitigation policy and regulatory frameworks are consistent in their strong support for the mitigation hierarchy of: (1) avoiding impacts, (2) minimizing impacts, and then (3) offsetting/compensating for residual impacts. While mitigation frameworks require developers to avoid, minimize and restore biodiversity on-site before considering an offset for residual impacts, there is a lack of quantitative guidance for this decision-making process. What are the criteria for requiring impacts be avoided altogether? Here we examine how conservation planning can guide the application of the mitigation hierarchy to address this issue. In support of the Colombian government's aim to improve siting and mitigation practices for planned development, we examined five pilot projects in landscapes expected to experience significant increases in mining, petroleum and/or infrastructure development. By blending landscape-level conservation planning with application of the mitigation hierarchy, we can proactively identify where proposed development and conservation priorities would be in conflict and where impacts should be avoided. The approach we outline here has been adopted by the Colombian Ministry of Environment and Sustainable Development to guide licensing decisions, avoid piecemeal licensing, and promote mitigation decisions that maintain landscape condition.

Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blasing, T.J.; Brown, R.A.; Cada, G.F.

1992-02-01

The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production ofmore » medical and industrial isotopes such as {sup 252}Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2.« less

Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language

PubMed Central

Scharff, Constance; Petri, Jana

2011-01-01

The evolution of novel morphological features, such as feathers, involves the modification of developmental processes regulated by gene networks. The fact that genetic novelty operates within developmental constraints is the central tenet of the ‘evo-devo’ conceptual framework. It is supported by findings that certain molecular regulatory pathways act in a similar manner in the development of morphological adaptations, which are not directly related by common ancestry but evolved convergently. The Pax6 gene, important for vision in molluscs, insects and vertebrates, and Hox genes, important for tetrapod limbs and fish fins, exemplify this ‘deep homology’. Recently, ‘evo-devo’ has expanded to the molecular analysis of behavioural traits, including social behaviour, learning and memory. Here, we apply this approach to the evolution of human language. Human speech is a form of auditory-guided, learned vocal motor behaviour that also evolved in certain species of birds, bats and ocean mammals. Genes relevant for language, including the transcription factor FOXP2, have been identified. We review evidence that FoxP2 and its regulatory gene network shapes neural plasticity in cortico-basal ganglia circuits underlying the sensory-guided motor learning in animal models. The emerging picture can help us understand how complex cognitive traits can ‘descend with modification’. PMID:21690130

Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language.

PubMed

Scharff, Constance; Petri, Jana

2011-07-27

The evolution of novel morphological features, such as feathers, involves the modification of developmental processes regulated by gene networks. The fact that genetic novelty operates within developmental constraints is the central tenet of the 'evo-devo' conceptual framework. It is supported by findings that certain molecular regulatory pathways act in a similar manner in the development of morphological adaptations, which are not directly related by common ancestry but evolved convergently. The Pax6 gene, important for vision in molluscs, insects and vertebrates, and Hox genes, important for tetrapod limbs and fish fins, exemplify this 'deep homology'. Recently, 'evo-devo' has expanded to the molecular analysis of behavioural traits, including social behaviour, learning and memory. Here, we apply this approach to the evolution of human language. Human speech is a form of auditory-guided, learned vocal motor behaviour that also evolved in certain species of birds, bats and ocean mammals. Genes relevant for language, including the transcription factor FOXP2, have been identified. We review evidence that FoxP2 and its regulatory gene network shapes neural plasticity in cortico-basal ganglia circuits underlying the sensory-guided motor learning in animal models. The emerging picture can help us understand how complex cognitive traits can 'descend with modification'.

NRC safety research in support of regulation - FY 1994. Volume 9

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

This report, the tenth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1994. The goal of the Office of Nuclear Regulatory Research (RES) is to ensure the availability of sound technical bases for timely rulemaking and related decisions in support of NRC regulatory/licensing/inspection activities. RES also has responsibilities related to the resolution of generic safety issues and to the review of licensee submittals regarding individual plant examinations. It is the responsibility of RES to conductmore » the NRC`s rulemaking process, including the issuance of regulatory guides and rules that govern NRC licensed activities.« less

Challenges in Developing Competency-based Training Curriculum for Food Safety Regulators in India.

PubMed

Thippaiah, Anitha; Allagh, Komal Preet; Murthy, G V

2014-07-01

The Food Safety and Standards Act have redefined the roles and responsibilities of food regulatory workforce and calls for highly skilled human resources as it involves complex management procedures. 1) Identify the competencies needed among the food regulatory workforce in India. 2) Develop a competency-based training curriculum for food safety regulators in the country. 3) Develop training materials for use to train the food regulatory workforce. The Indian Institute of Public Health, Hyderabad, led the development of training curriculum on food safety with technical assistance from the Royal Society for Public Health, UK and the National Institute of Nutrition, India. The exercise was to facilitate the implementation of new Act by undertaking capacity building through a comprehensive training program. A competency-based training needs assessment was conducted before undertaking the development of the training materials. THE TRAINING PROGRAM FOR FOOD SAFETY OFFICERS WAS DESIGNED TO COMPRISE OF FIVE MODULES TO INCLUDE: Food science and technology, Food safety management systems, Food safety legislation, Enforcement of food safety regulations, and Administrative functions. Each module has a facilitator guide for the tutor and a handbook for the participant. Essentials of Food Hygiene-I (Basic level), II and III (Retail/ Catering/ Manufacturing) were primarily designed for training of food handlers and are part of essential reading for food safety regulators. The Food Safety and Standards Act calls for highly skilled human resources as it involves complex management procedures. Despite having developed a comprehensive competency-based training curriculum by joint efforts by the local, national, and international agencies, implementation remains a challenge in resource-limited setting.

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

PubMed Central

Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

2017-01-01

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24–25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. PMID:27994170

Print Me an Organ? Ethical and Regulatory Issues Emerging from 3D Bioprinting in Medicine.

PubMed

Gilbert, Frederic; O'Connell, Cathal D; Mladenovska, Tajanka; Dodds, Susan

2018-02-01

Recent developments of three-dimensional printing of biomaterials (3D bioprinting) in medicine have been portrayed as demonstrating the potential to transform some medical treatments, including providing new responses to organ damage or organ failure. However, beyond the hype and before 3D bioprinted organs are ready to be transplanted into humans, several important ethical concerns and regulatory questions need to be addressed. This article starts by raising general ethical concerns associated with the use of bioprinting in medicine, then it focuses on more particular ethical issues related to experimental testing on humans, and the lack of current international regulatory directives to guide these experiments. Accordingly, this article (1) considers whether there is a limit as to what should be bioprinted in medicine; (2) examines key risks of significant harm associated with testing 3D bioprinting for humans; (3) investigates the clinical trial paradigm used to test 3D bioprinting; (4) analyses ethical questions of irreversibility, loss of treatment opportunity and replicability; (5) explores the current lack of a specific framework for the regulation and testing of 3D bioprinting treatments.

75 FR 19665 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-15

... processes, including welding, heat treating, and nondestructive testing, are controlled and accomplished by... that when stressed under operating, maintenance, testing, and postulated accident conditions (1) the...

75 FR 48381 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

..., (2) demonstrating containment structural integrity related to combustible gas control, and (3... pertain to the containment structural capacity above design-basis pressures, to combustible gas control...

A drug's life: the pathway to drug approval.

PubMed

Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Lessons from innovation in drug-device combination products.

PubMed

Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

2012-01-01

Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon. Copyright © 2011 Elsevier B.V. All rights reserved.

Genome and epigenome engineering CRISPR toolkit for in vivo modulation of cis-regulatory interactions and gene expression in the chicken embryo.

PubMed

Williams, Ruth M; Senanayake, Upeka; Artibani, Mara; Taylor, Gunes; Wells, Daniel; Ahmed, Ahmed Ashour; Sauka-Spengler, Tatjana

2018-02-23

CRISPR/Cas9 genome engineering has revolutionised all aspects of biological research, with epigenome engineering transforming gene regulation studies. Here, we present an optimised, adaptable toolkit enabling genome and epigenome engineering in the chicken embryo, and demonstrate its utility by probing gene regulatory interactions mediated by neural crest enhancers. First, we optimise novel efficient guide-RNA mini expression vectors utilising chick U6 promoters, provide a strategy for rapid somatic gene knockout and establish a protocol for evaluation of mutational penetrance by targeted next-generation sequencing. We show that CRISPR/Cas9-mediated disruption of transcription factors causes a reduction in their cognate enhancer-driven reporter activity. Next, we assess endogenous enhancer function using both enhancer deletion and nuclease-deficient Cas9 (dCas9) effector fusions to modulate enhancer chromatin landscape, thus providing the first report of epigenome engineering in a developing embryo. Finally, we use the synergistic activation mediator (SAM) system to activate an endogenous target promoter. The novel genome and epigenome engineering toolkit developed here enables manipulation of endogenous gene expression and enhancer activity in chicken embryos, facilitating high-resolution analysis of gene regulatory interactions in vivo . © 2018. Published by The Company of Biologists Ltd.

NRC ARDC Guidance Support Status Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holbrook, Mark R.

This report provides a summary that reflects the progress and status of proposed regulatory design criteria for advanced non-light water reactor (LWR) designs in accordance with the Level 3 milestone M3AT-17IN2001013 in work package AT-17IN200101. These criteria have been designated as advanced reactor design criteria (ARDC) and they provide guidance to future applicants for addressing the general design criteria (GDC) that are currently applied specifically to LWR designs. This report provides a summary of Phase 2 activities related to the various tasks associated with ARDC development and the subsequent development of ARDC regulatory guidance for sodium fast reactor (SFR) andmore » modular high-temperature gas-cooled reactor (HTGR) designs. Status Report Organization: Section 2 discusses the origin of the GDC and their application to LWRs. Section 3 addresses the objective of this initiative and how it benefits the advanced non-LWR reactor vendors. Section 4 discusses the scope and structure of the initiative. Section 5 provides background on the U.S. Department of Energy (DOE) ARDC team’s original development of the proposed ARDC that were submitted to the NRC for consideration. Section 6 provides a summary of recent ARDC Phase 2 activities. Appendices A through E document the DOE ARDC team’s public comments on various sections of the NRC’s draft regulatory guide DG–1330, “Guidance for Developing Principal Design Criteria for Non-Light Water Reactors.”« less

Interpreting labels of abuse-deterrent opioid analgesics.

PubMed

Webster, Lynn R

To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. A nonsystematic review of ADO literature and regulatory documents guiding their development. A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels. The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

NASA Astrophysics Data System (ADS)

Elliott, Kevin C.; Volz, David C.

2012-01-01

Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

Acid-base homeostasis in the human system

NASA Technical Reports Server (NTRS)

White, R. J.

1974-01-01

Acid-base regulation is a cooperative phenomena in vivo with body fluids, extracellular and intracellular buffers, lungs, and kidneys all playing important roles. The present account is much too brief to be considered a review of present knowledge of these regulatory systems, and should be viewed, instead, as a guide to the elements necessary to construct a simple model of the mutual interactions of the acid-base regulatory systems of the body.

Implementation of 10 CFR 20.1406 Through Life Cycle Planning for Decommissioning

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Donnell, E.; Ott, W.R.

2008-01-15

The focus of this paper is on a regulatory guide (draft guide DG-4012) being developed by the Office of Nuclear Regulatory Research for the implementation of 10 CFR 20.1406. The draft guide was published in the Federal Register on July 31, 2007 for a 90 day public comment period. Besides being available in the Federal Register, it is also available electronically in NRC's agency data management system (ADAMS). The accession number is ML0712100110. 10 CFR 20.1406 requires license applicants, other than renewals, after August 20, 1997, '..to describe in the application how facility design and procedures for operation will minimize,more » to the extent practicable, contamination of the facility and the environment, facilitate eventual decommissioning, and minimize to the extent practicable, the generation of radioactive waste'. The intent of the regulation is to diminish the occurrence and severity of 'legacy sites' by taking measures that will reduce and control contamination and facilitate eventual decommissioning. 10 CFR 20.1406 is significant because it applies to all new facilities and in the very near future (perhaps as soon as the fall of 2007), the U.S. Nuclear Regulatory Commission (NRC) anticipates receiving one or more license applications for new nuclear power plants. The regulatory guide is intended to facilitate that licensing by providing suggestions of things an applicant can do to minimize contamination of the facility and the environment, minimize generation of waste, and to facilitate decommissioning. Over 100 different kinds of activities are covered by license applications submitted to the NRC. They do not all reflect the same potential for contamination of a facility and the environment, or for the generation of radioactive waste. Therefore, an applicant should use sound judgment to evaluate the potential for contamination and the consequences of such contamination in deciding on the extent to which this guide applies to any given facility or activity. Factors which may enter into this decision include form (e.g., dry solids, liquids, gases), inventory, and environmental mobility of unintended releases. The bulk of the guidance presented in the guide will consist of specific design considerations drawn from nuclear industry experience and lessons learned from decommissioning. These design suggestions provide examples of measures which can be combined to support a contaminant management philosophy for a new facility. The principles embodied in this philosophy are threefold: (1) prevention of unintended release, (2) early detection if there is unintended release of radioactive contamination, and (3) prompt and aggressive clean-up should there be an unintended release of radioactive contamination. If the guiding principles are followed through the use of 'good' engineering and science, as well as careful attention to operational practices, it should result in meeting the requirements of 10 CFR 20.1406. All this should be considered in the context of the life cycle of the facility from the early planning stages through the final plans for decommissioning and waste disposal. Some of the mechanisms which can be employed for life cycle planning are described further in the Discussion section. In summary: The principles of the guide are threefold: prevention, early detection, and prompt response. If these guiding principles are followed through the use of 'good' engineering and science, as well as careful attention to operational practices, it should result in meeting the requirements of 10 CFR 20 In summary, the thrust of this guide is for an applicant to use technically sound engineering judgment and a practical risk-informed approach to achieve the objectives of 10 CFR 20.1406. This approach should consider the materials and processes involved (e.g., solids, liquids, gases) and focus on: (1) the relative significance of potential contamination; (2) areas most susceptible to leaks; and (3) the appropriate level of consideration to prevention and control of contamination that should be incorporated in facility design. Since the applicability of the guidance is a facility-by-facility decision, early consultation with the NRC is strongly suggested.« less

Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions.

PubMed

Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long

By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

Connecting pre-marketing clinical research and medical practice: opinion-based study of core issues and possible changes in drug regulation.

PubMed

Wieringa, Nicolien F; Peschar, Jules L; Denig, Petra; de Graeff, Pieter A; Vos, Rein

2003-01-01

To identify core issues that contribute to the gap between pre-marketing clinical research and practice as seen from the perspective of medical practice, as well as possible changes and potential barriers for dosing this gap. Interviews with 47 physicians and pharmacists who were liaised to drug regulation through their role in the pre- and post-marketing shaping of new cardiovascular drugs. Data were analyzed using methods of grounded theory and analytical evaluations. Six core issues were identified that referred to the standards in drug regulation, the organization of the regulatory system, and conflicting interests. Pre-marketing trials should focus more on populations and research questions relevant to medical practice. In particular, variability in drug responses between subgroups of patients and demonstration of effectiveness should become major principles in drug regulation. An interactive post-marketing process in which public interests are represented was considered necessary to further guide research and development according to the needs in daily practice. Strategies for change could be applied within the present system of drug regulation, or affect its basic principles. Regulatory authorities were primarily identified to initiate changes, but many other parties should be involved. Barriers for change were identified regarding differences in interests between parties, organizational matters, and with respect to broader healthcare policies. Based on the respondents' opinions, there is a need to focus regulatory standards more on the needs in medical practice. Therefore, regulatory authorities should further develop their influence in the pre- and post-marketing drug development process, together with other parties involved, in order to bridge the gap between clinical research and medical practice.

Comparisons of ANS, ASME, AWS, and NFPA standards cited in the NRC standard review plan, NUREG-0800, and related documents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ankrum, A.R.; Bohlander, K.L.; Gilbert, E.R.

This report provides the results of comparisons of the cited and latest versions of ANS, ASME, AWS and NFPA standards cited in the NRC Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants (NUREG 0800) and related documents. The comparisons were performed by Battelle Pacific Northwest Laboratories in support of the NRC`s Standard Review Plan Update and Development Program. Significant changes to the standards, from the cited version to the latest version, are described and discussed in a tabular format for each standard. Recommendations for updating each citation in the Standard Review Plan are presented.more » Technical considerations and suggested changes are included for related regulatory documents (i.e., Regulatory Guides and the Code of Federal Regulations) citing the standard. The results and recommendations presented in this document have not been subjected to NRC staff review.« less

A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

PubMed

Smith, Robin P; Riesenfeld, Samantha J; Holloway, Alisha K; Li, Qiang; Murphy, Karl K; Feliciano, Natalie M; Orecchia, Lorenzo; Oksenberg, Nir; Pollard, Katherine S; Ahituv, Nadav

2013-07-18

Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment.more » Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.« less

A Field Experiment Testing the Utility of Regulatory Fit Messages for Promoting Physical Activity.

PubMed

Latimer, Amy E; Rivers, Susan E; Rench, Tara A; Katulak, Nicole A; Hicks, Althea; Hodorowski, Julie Keany; Higgins, E Tory; Salovey, Peter

2008-05-01

Guided by regulatory focus theory, we examined whether messages tailored to individuals' promotion- or prevention-goal orientation (regulatory focus) elicit positive thoughts and feelings about physical activity and increase participation in physical activity. Inactive participants (N = 206) were assigned randomly to receive either promotion-focused or prevention-focused messages encouraging physical activity. Two weeks after message exposure, we assessed participants' thoughts and feelings about physical activity and physical activity behavior. Tailored messages that fit individuals' regulatory focus led to greater physical activity participation and more positive feelings than non-fit messages, particularly in the promotion-focused condition. Furthermore, positive retrospective feelings about physical activity mediated the effects of the tailored messages on behavior. These findings provide support for regulatory focus theory and direction for enhancing the effectiveness of messages encouraging physical activity and other health behaviors.

Tube structural integrity evaluation of Palo Verde Unit 1 steam generators for axial upper-bundle cracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodman, B.W.; Begley, J.A.; Brown, S.D.

1995-12-01

The analysis of the issue of upper bundle axial ODSCC as it apples to steam generator tube structural integrity in Unit 1 at the Palo Verde Nuclear generating Station is presented in this study. Based on past inspection results for Units 2 and 3 at Palo Verde, the detection of secondary side stress corrosion cracks in the upper bundle region of Unit 1 may occur at some future date. The following discussion provides a description and analysis of the probability of axial ODSCC in Unit 1 leading to the exceedance of Regulatory Guide 1.121 structural limits. The probabilities of structuralmore » limit exceedance are estimated as function of run time using a conservative approach. The chosen approach models the historical development of cracks, crack growth, detection of cracks and subsequent removal from service and the initiation and growth of new cracks during a given cycle of operation. Past performance of all Palo Verde Units as well as the historical performance of other steam generators was considered in the development of cracking statistics for application to Unit 1. Data in the literature and Unit 2 pulled tube examination results were used to construct probability of detection curves for the detection of axial IGSCC/IGA using an MRPC (multi-frequency rotating panake coil) eddy current probe. Crack growth rates were estimated from Unit 2 eddy current inspection data combined with pulled tube examination results and data in the literature. A Monte-Carlo probabilistic model is developed to provide an overall assessment of the risk of Regulatory Guide exceedance during plant operation.« less

Review of various approaches for assessing public health risks in regulatory decision making: choosing the right approach for the problem.

PubMed

Dearfield, Kerry L; Hoelzer, Karin; Kause, Janell R

2014-08-01

Stakeholders in the public health risk analysis community can possess differing opinions about what is meant by "conduct a risk assessment." In reality, there is no one-size-fits-all risk assessment that can address all public health issues, problems, and regulatory needs. Although several international and national organizations (e.g., Codex Alimentarius Commission, Office International des Epizooties, Food and Agricultural Organization, World Health Organization, National Research Council, and European Food Safety Authority) have addressed this issue, confusion remains. The type and complexity of a risk assessment must reflect the risk management needs to appropriately inform a regulatory or nonregulatory decision, i.e., a risk assessment is ideally "fit for purpose" and directly applicable to risk management issues of concern. Frequently however, there is a lack of understanding by those not completely familiar with risk assessment regarding the specific utility of different approaches for assessing public health risks. This unfamiliarity can unduly hamper the acceptance of risk assessment results by risk managers and may reduce the usefulness of such results for guiding public health policies, practices, and operations. Differences in interpretation of risk assessment terminology further complicate effective communication among risk assessors, risk managers, and stakeholders. This article provides an overview of the types of risk assessments commonly conducted, with examples primarily from the food and agricultural sectors, and a discussion of the utility and limitations of these specific approaches for assessing public health risks. Clarification of the risk management issues and corresponding risk assessment design needs during the formative stages of the risk analysis process is a key step for ensuring that the most appropriate assessment of risk is developed and used to guide risk management decisions.

Communication Regulatory Science: Mapping a New Field.

PubMed

Noar, Seth M; Cappella, Joseph N; Price, Simani

2017-12-13

Communication regulatory science is an emerging field that uses validated techniques, tools, and models to inform regulatory actions that promote optimal communication outcomes and benefit the public. In the opening article to this special issue on communication and tobacco regulatory science, we 1) describe Food and Drug Administration (FDA) regulation of tobacco products in the US; 2) introduce communication regulatory science and provide examples in the tobacco regulatory science realm; and 3) describe the special issue process and final set of articles. Communication research on tobacco regulatory science is a burgeoning area of inquiry, and this work advances communication science, informs and potentially guides the FDA, and may help to withstand legal challenges brought by the tobacco industry. This research has the potential to have a major impact on the tobacco epidemic and population health by helping implement the most effective communications to prevent tobacco initiation and increase cessation. This special issue provides an example of 10 studies that exemplify tobacco regulatory science and demonstrate how the health communication field can affect regulation and benefit public health.

Towards a successful clinical implementation of fluorescence-guided surgery.

PubMed

Snoeks, T J A; van Driel, P B A A; Keereweer, S; Aime, S; Brindle, K M; van Dam, G M; Löwik, C W G M; Ntziachristos, V; Vahrmeijer, A L

2014-04-01

During the European Molecular Imaging Meeting (EMIM) 2013, the fluorescence-guided surgery study group held its inaugural session to discuss the clinical implementation of fluorescence-guided surgery. The general aim of this study group is to discuss and identify the steps required to successfully and safely bring intraoperative fluorescence imaging to the clinics. The focus group intends to use synergies between interested groups as a tool to address regulatory and implementation hurdles in Europe and operates within the intraoperative focus group of the World Molecular Imaging Society (WMIS) that promotes the same interests at the WMIS level. The major topics on the critical path of implementation identified within the study group were quality controls and standards for ensuring accurate imaging and the ability to compare results from different studies, regulatory affairs, and strategies to increase awareness among physicians, regulators, insurance companies, and a broader audience. These hurdles, and the possible actions discussed to overcome them, are summarized in this report. Furthermore, a number of recommendations for the future shape of the fluorescence-guided study group are discussed. A main driving conclusion remains that intraoperative imaging has great clinical potential and that many of the solutions required are best addressed with the community working together to optimally promote and accelerate the clinical implementation of fluorescence imaging towards improving surgical procedures.

Mixed reality ultrasound guidance system: a case study in system development and a cautionary tale.

PubMed

Ameri, Golafsoun; Baxter, John S H; Bainbridge, Daniel; Peters, Terry M; Chen, Elvis C S

2018-04-01

Real-time ultrasound has become a crucial aspect of several image-guided interventions. One of the main constraints of such an approach is the difficulty in interpretability of the limited field of view of the image, a problem that has recently been addressed using mixed reality, such as augmented reality and augmented virtuality. The growing popularity and maturity of mixed reality has led to a series of informal guidelines to direct development of new systems and to facilitate regulatory approval. However, the goals of mixed reality image guidance systems and the guidelines for their development have not been thoroughly discussed. The purpose of this paper is to identify and critically examine development guidelines in the context of a mixed reality ultrasound guidance system through a case study. A mixed reality ultrasound guidance system tailored to central line insertions was developed in close collaboration with an expert user. This system outperformed ultrasound-only guidance in a novice user study and has obtained clearance for clinical use in humans. A phantom study with 25 experienced physicians was carried out to compare the performance of the mixed reality ultrasound system against conventional ultrasound-only guidance. Despite the previous promising results, there was no statistically significant difference between the two systems. Guidelines for developing mixed reality image guidance systems cannot be applied indiscriminately. Each design decision, no matter how well justified, should be the subject of scientific and technical investigation. Iterative and small-scale evaluation can readily unearth issues and previously unknown or implicit system requirements. We recommend a wary eye in development of mixed reality ultrasound image guidance systems emphasizing small-scale iterative evaluation alongside system development. Ultimately, we recommend that the image-guided intervention community furthers and deepens this discussion into best practices in developing image-guided interventions.

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

PubMed

Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M E Bette; Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M; Whelan, Maurice

2017-02-01

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Challenges in Developing Competency-based Training Curriculum for Food Safety Regulators in India

PubMed Central

Thippaiah, Anitha; Allagh, Komal Preet; Murthy, G. V.

2014-01-01

Context: The Food Safety and Standards Act have redefined the roles and responsibilities of food regulatory workforce and calls for highly skilled human resources as it involves complex management procedures. Aims: 1) Identify the competencies needed among the food regulatory workforce in India. 2) Develop a competency-based training curriculum for food safety regulators in the country. 3) Develop training materials for use to train the food regulatory workforce. Settings and Design: The Indian Institute of Public Health, Hyderabad, led the development of training curriculum on food safety with technical assistance from the Royal Society for Public Health, UK and the National Institute of Nutrition, India. The exercise was to facilitate the implementation of new Act by undertaking capacity building through a comprehensive training program. Materials and Methods: A competency-based training needs assessment was conducted before undertaking the development of the training materials. Results: The training program for Food Safety Officers was designed to comprise of five modules to include: Food science and technology, Food safety management systems, Food safety legislation, Enforcement of food safety regulations, and Administrative functions. Each module has a facilitator guide for the tutor and a handbook for the participant. Essentials of Food Hygiene-I (Basic level), II and III (Retail/ Catering/ Manufacturing) were primarily designed for training of food handlers and are part of essential reading for food safety regulators. Conclusion: The Food Safety and Standards Act calls for highly skilled human resources as it involves complex management procedures. Despite having developed a comprehensive competency-based training curriculum by joint efforts by the local, national, and international agencies, implementation remains a challenge in resource-limited setting. PMID:25136155

Printing and Related Support Activities Sector (NAICS 323)

EPA Pesticide Factsheets

Find environmental regulatory and compliance information for the printing sector, including NESHAPs for paper surface coating, RCRA hazardous waste guide for small business, and a pollution prevention guidance for lithographic and screen printing

75 FR 42170 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

..., techniques that the staff uses in evaluating specific problems or postulated accidents, and data that the... (EDEX) radiation exposures. These methods provide a conservative estimate of the EDEX and may be used to...

Integrating Data Clustering and Visualization for the Analysis of 3D Gene Expression Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Data Analysis and Visualization; nternational Research Training Group ``Visualization of Large and Unstructured Data Sets,'' University of Kaiserslautern, Germany; Computational Research Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA

2008-05-12

The recent development of methods for extracting precise measurements of spatial gene expression patterns from three-dimensional (3D) image data opens the way for new analyses of the complex gene regulatory networks controlling animal development. We present an integrated visualization and analysis framework that supports user-guided data clustering to aid exploration of these new complex datasets. The interplay of data visualization and clustering-based data classification leads to improved visualization and enables a more detailed analysis than previously possible. We discuss (i) integration of data clustering and visualization into one framework; (ii) application of data clustering to 3D gene expression data; (iii)more » evaluation of the number of clusters k in the context of 3D gene expression clustering; and (iv) improvement of overall analysis quality via dedicated post-processing of clustering results based on visualization. We discuss the use of this framework to objectively define spatial pattern boundaries and temporal profiles of genes and to analyze how mRNA patterns are controlled by their regulatory transcription factors.« less

Netting Novel Regulators of Hematopoiesis and Hematologic Malignancies in Zebrafish.

PubMed

Kwan, Wanda; North, Trista E

2017-01-01

Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis. Significantly, perturbations in many of the key developmental signals controlling hematopoiesis are associated with hematological disorders and disease, including anemia, bone marrow failure syndromes, and leukemia. Thus, understanding the regulatory pathways controlling HSPC production and function has important clinical implications. In this review, we describe how the blood system forms and is maintained in zebrafish, with particular focus on new insights into vertebrate hematological regulation gained using this model. The interplay of factors controlling development and disease in the hematopoietic system combined with the unique attributes of the zebrafish make this a powerful platform to discover novel targets for the treatment of hematological disease. © 2017 Elsevier Inc. All rights reserved.

Regulation of naturally occurring radioactive materials in Australia.

PubMed

Jeffries, Cameron; Akber, Riaz; Johnston, Andrew; Cassels, Brad

2011-07-01

In order to promote uniformity between jurisdictions, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has developed the National Directory for Radiation Protection, which is a regulatory framework that all Australian governments have agreed to adopt. There is a large and diverse range of industries involved in mining or mineral processing, and the production of fossil fuels in Australia. Enhanced levels of naturally occurring radionuclides can be associated with mineral extraction and processing, other industries (e.g. metal recycling) and some products (e.g. plasterboard). ARPANSA, in conjunction with industry and State regulators, has undertaken a review and assessment of naturally occurring radioactive material (NORM) management in Australian industries. This review has resulted in guidance on the management of NORM that will be included in the National Directory for Radiation Protection. The first NORM safety guide provides the framework for NORM management and addresses specific NORM issues in oil and gas production, bauxite, aluminium and phosphate industries. Over time further guidance material for other NORM-related industries will be developed. This presentation will provide an overview of the regulatory approach to managing NORM industries in Australia.

xLPR Sim Editor 1.0 User's Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariner, Paul E.

2017-03-01

The United States Nuclear Regulatory Commission in cooperation with the Electric Power Research Institute contracted Sandia National Laboratories to develop the framework of a probabilistic fracture mechanics assessment code called xLPR ( Extremely Low Probability of Rupture) Version 2.0 . The purpose of xLPR is to evaluate degradation mechanisms in piping systems at nuclear power plants and to predict the probability of rupture. This report is a user's guide for xLPR Sim Editor 1.0 , a graphical user interface for creating and editing the xLPR Version 2.0 input file and for creating, editing, and using the xLPR Version 2.0 databasemore » files . The xLPR Sim Editor, provides a user - friendly way for users to change simulation options and input values, s elect input datasets from xLPR data bases, identify inputs needed for a simulation, and create and modify an input file for xLPR.« less

Land and Water Use Characteristics and Human Health Input Parameters for use in Environmental Dosimetry and Risk Assessments at the Savannah River Site. 2016 Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jannik, G. Tim; Hartman, Larry; Stagich, Brooke

Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) regulatory guides. Within the regulatory guides, default values are provided for many of the dose model parameters, but the use of applicant site-specific values is encouraged. Detailed surveys of land-use and water-use parameters were conducted in 1991 and 2010. They are being updated in this report. These parameters include local characteristics of meat, milk andmore » vegetable production; river recreational activities; and meat, milk and vegetable consumption rates, as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors (to be used in human health exposure calculations at SRS) are documented. The intent of this report is to establish a standardized source for these parameters that is up to date with existing data, and that is maintained via review of future-issued national references (to evaluate the need for changes as new information is released). These reviews will continue to be added to this document by revision.« less

Land and Water Use Characteristics and Human Health Input Parameters for use in Environmental Dosimetry and Risk Assessments at the Savannah River Site 2017 Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jannik, T.; Stagich, B.

Operations at the Savannah River Site (SRS) result in releases of relatively small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) regulatory guides. Within the regulatory guides, default values are provided for many of the dose model parameters, but the use of site-specific values is encouraged. Detailed surveys of land-use and water-use parameters were conducted in 1991, 2008, 2010, and 2016 and are being concurred with or updated in this report. These parameters include localmore » characteristics of meat, milk, and vegetable production; river recreational activities; and meat, milk, and vegetable consumption rates, as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors (to be used in human health exposure calculations at SRS) are documented. The intent of this report is to establish a standardized source for these parameters that is up to date with existing data, and that is maintained via review of future-issued national references (to evaluate the need for changes as new information is released). These reviews will continue to be added to this document by revision.« less

Tiered Approach to Resilience Assessment.

PubMed

Linkov, Igor; Fox-Lent, Cate; Read, Laura; Allen, Craig R; Arnott, James C; Bellini, Emanuele; Coaffee, Jon; Florin, Marie-Valentine; Hatfield, Kirk; Hyde, Iain; Hynes, William; Jovanovic, Aleksandar; Kasperson, Roger; Katzenberger, John; Keys, Patrick W; Lambert, James H; Moss, Richard; Murdoch, Peter S; Palma-Oliveira, Jose; Pulwarty, Roger S; Sands, Dale; Thomas, Edward A; Tye, Mari R; Woods, David

2018-04-25

Regulatory agencies have long adopted a three-tier framework for risk assessment. We build on this structure to propose a tiered approach for resilience assessment that can be integrated into the existing regulatory processes. Comprehensive approaches to assessing resilience at appropriate and operational scales, reconciling analytical complexity as needed with stakeholder needs and resources available, and ultimately creating actionable recommendations to enhance resilience are still lacking. Our proposed framework consists of tiers by which analysts can select resilience assessment and decision support tools to inform associated management actions relative to the scope and urgency of the risk and the capacity of resource managers to improve system resilience. The resilience management framework proposed is not intended to supplant either risk management or the many existing efforts of resilience quantification method development, but instead provide a guide to selecting tools that are appropriate for the given analytic need. The goal of this tiered approach is to intentionally parallel the tiered approach used in regulatory contexts so that resilience assessment might be more easily and quickly integrated into existing structures and with existing policies. Published 2018. This article is a U.S. government work and is in the public domain in the USA.

76 FR 66090 - Facility Operating License Amendment From Virginia Electric and Power Company, Surry Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... operating pressures, leakage from primary water stress corrosion cracking below the proposed limited... discussed in Regulatory Guide (RG) 1.121, ``Bases for Plugging Degraded PWR [Pressurized-Water Reactor...

Guide for FOIA Requests for Pesticide Information

EPA Pesticide Factsheets

Much scientific and regulatory information concerning pesticides is available to the public without submitting a FOIA request. Review pesticide information resources that may include the information you are seeking. Learn how to submit a FOIA request.

75 FR 9627 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-03

... staff uses in evaluating specific problems or postulated accidents, and data that the staff needs in its... qualification testing of a prototype unit under the most adverse design conditions. II. Further Information In...

Self-regulation of motor vehicle advertising: is it working in Australia?

PubMed

Donovan, Robert J; Fielder, Lynda J; Ouschan, Robyn; Ewing, Michael

2011-05-01

There is growing concern that certain content within motor vehicle advertising may have a negative influence on driving attitudes and behaviours of viewers, particularly young people, and hence a negative impact on road safety. In response, many developed countries have adopted a self-regulatory approach to motor vehicle advertising. However, it appears that many motor vehicle advertisements in Australia and elsewhere are not compliant with self-regulatory codes. Using standard commercial advertising methods, we exposed three motor vehicle ads that had been the subject of complaints to the Australian Advertising Standards Board (ASB) to, N = 463, 14-55 year olds to assess the extent to which their perceptions of the content of the ads communicated themes that were contrary to the Australian self-regulatory code. All three ads were found to communicate messages contrary to the code (such as the vehicle's speed and acceleration capabilities). However, the ASB had upheld complaints about only one of the ads. Where motor vehicle advertising regulatory frameworks exist to guide motor vehicle advertisers as to what is and what is not acceptable in their advertising, greater efforts are needed to ensure compliance with these codes. One way may be to make it mandatory for advertisers to report consumer pre-testing of their advertising to ensure that undesirable messages are not being communicated to viewers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Structural responses to the obesity and non-communicable diseases epidemic: the Chilean Law of Food Labeling and Advertising.

PubMed

Corvalán, C; Reyes, M; Garmendia, M L; Uauy, R

2013-11-01

In 12 July 2012, the Chilean Senate approved the Law of Food Labeling and Advertising, resulting from the joint efforts of a group of health professionals, researchers and legislators who proposed a regulatory framework in support of healthy diets and active living. Its goal was to curb the ongoing epidemic increase of obesity and non-communicable diseases. Two actions included: (i) improving point of food purchase consumer information by incorporating easy-to-understand front-of-packages labeling and specific messages addressing critical nutrients, and (ii) decreasing children's exposure to unhealthy foods by restricting marketing, advertising and sales. We summarize the work related to the law's release and discuss the conclusions reached by the various expert committees that were convened by the Ministry of Health to guide the development of the regulatory norms. Throughout the process, the food industry has overtly expressed its disagreement with the regulatory effort. The final content of the regulatory norms is still pending; however there are suggestions that its implementation will be delayed and might be modified based on the industry lobbying actions. These lessons should contribute to show the need of anticipating and addressing potential barriers to obesity-prevention policy implementation, particularly with respect to the role of the private sector. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.

Is there a need for a universal benefit-risk assessment framework for medicines? Regulatory and industry perspectives.

PubMed

Leong, James; McAuslane, Neil; Walker, Stuart; Salek, Sam

2013-09-01

To explore the current status and need for a universal benefit-risk framework for medicines in regulatory agencies and pharmaceutical companies. A questionnaire was developed and sent to 14 mature regulatory agencies and 24 major companies. The data were analysed using descriptive statistics, for a minority of questions preceded by manual grouping of the responses. Overall response rate was 82%, and study participants included key decision makers from agencies and companies. None used a fully quantitative system, most companies preferring a qualitative method. The major reasons for this group not using semi-quantitative or quantitative systems were lack of a universal and scientifically validated framework. The main advantages of a benefit-risk framework were that it provided a systematic standardised approach to decision-making and that it acted as a tool to enhance quality of communication. It was also reported that a framework should be of value to both agencies and companies throughout the life cycle of a product. They believed that it is possible to develop an overarching benefit-risk framework that should involve relevant stakeholders in the development, validation and application of a universal framework. The entire cohort indicated common barriers to implementing a framework were resource limitations, a lack of knowledge and a scientifically validated and acceptable framework. Stakeholders prefer a semi-quantitative, overarching framework that incorporates a toolbox of different methodologies. A coordinating committee of relevant stakeholders should be formed to guide its development and implementation. Through engaging the stakeholders, these outcomes confirm sentiments and need for developing a universal benefit-risk assessment framework. Copyright © 2013 John Wiley & Sons, Ltd.

COL Application Content Guide for HTGRs: Revision to RG 1.206, Part 1 - Status Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wayne Moe

2012-08-01

A combined license (COL) application is required by the Nuclear Regulatory Commission (NRC) for all proposed nuclear plants. The information requirements for a COL application are set forth in 10 CFR 52.79, “Contents of Applications; Technical Information in Final Safety Analysis Report.” An applicant for a modular high temperature gas-cooled reactor (HTGR) must develop and submit for NRC review and approval a COL application which conforms to these requirements. The technical information necessary to allow NRC staff to evaluate a COL application and resolve all safety issues related to a proposed nuclear plant is detailed and comprehensive. To this, Regulatorymore » Guide (RG) 1.206, “Combined License Applications for Nuclear Power Plants” (LWR Edition), was developed to assist light water reactor (LWR) applicants in incorporating and effectively formatting required information for COL application review (Ref. 1). However, the guidance prescribed in RG 1.206 presumes a LWR design proposal consistent with the systems and functions associated with large LWR power plants currently operating under NRC license.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, H. P.; Basso, T. S.; Kroposki, B.

The Department of Energy (DOE) Distributed Power Program (DPP) is conducting work to complete, validate in the field, and support the development of a national interconnection standard for distributed energy resources (DER), and to address the institutional and regulatory barriers slowing the commercial adoption of DER systems. This work includes support for the IEEE standards, including P1547 Standard for Interconnecting Distributed Resources with Electric Power Systems, P1589 Standard for Conformance Test Procedures for Equipment Interconnecting Distributed Resources with Electric Power Systems, and the P1608 Application Guide. Work is also in progress on system integration research and development (R&D) on themore » interface and control of DER with local energy systems. Additional efforts are supporting high-reliability power for industry, evaluating innovative concepts for DER applications, and exploring plug-and-play interface and control technologies for intelligent autonomous interconnection systems. This paper summarizes (1) the current status of the IEEE interconnection standards and application guides in support of DER, and (2) the R&D in progress at the National Renewable Energy Laboratory (NREL) for interconnection and system integration and application of distributed energy resources.« less

Development and validation of the ASPIRE-VA coaching fidelity checklist (ACFC): a tool to help ensure delivery of high-quality weight management interventions.

PubMed

Damschroder, Laura J; Goodrich, David E; Kim, Hyungjin Myra; Holleman, Robert; Gillon, Leah; Kirsh, Susan; Richardson, Caroline R; Lutes, Lesley D

2016-09-01

Practical and valid instruments are needed to assess fidelity of coaching for weight loss. The purpose of this study was to develop and validate the ASPIRE Coaching Fidelity Checklist (ACFC). Classical test theory guided ACFC development. Principal component analyses were used to determine item groupings. Psychometric properties, internal consistency, and inter-rater reliability were evaluated for each subscale. Criterion validity was tested by predicting weight loss as a function of coaching fidelity. The final 19-item ACFC consists of two domains (session process and session structure) and five subscales (sets goals and monitor progress, assess and personalize self-regulatory content, manages the session, creates a supportive and empathetic climate, and stays on track). Four of five subscales showed high internal consistency (Cronbach alphas > 0.70) for group-based coaching; only two of five subscales had high internal reliability for phone-based coaching. All five sub-scales were positively and significantly associated with weight loss for group- but not for phone-based coaching. The ACFC is a reliable and valid instrument that can be used to assess fidelity and guide skill-building for weight management interventionists.

76 FR 44155 - Pacific Halibut Fisheries; Catch Sharing Plan for Guided Sport and Commercial Fisheries in Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

...NMFS proposes regulations that would implement a catch sharing plan for the guided sport and commercial fisheries for Pacific halibut in waters of International Pacific Halibut Commission (IPHC) Regulatory Areas 2C (Southeast Alaska) and 3A (Central Gulf of Alaska). If approved, this catch sharing plan will change the annual process of allocating halibut between the guided sport and commercial fisheries in Area 2C and Area 3A, establish allocations for each sector, and specify harvest restrictions for guided sport anglers that are intended to limit harvest to the annual guided sport fishery catch limit. In order to provide flexibility for individual commercial and guided sport fishery participants, the proposed catch sharing plan also will authorize annual transfers of commercial halibut quota to charter halibut permit holders for harvest in the guided sport fishery. This action is necessary to achieve the halibut fishery management goals of the North Pacific Fishery Management Council.

76 FR 31424 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-52; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... Business Regulatory Enforcement Fairness Act of 1996. It consists of a summary of rules appearing in... implement Executive Order 13514, Federal Leadership in Environmental, Energy, and Economic Performance, and...

T Cell Receptor Signaling in the Control of Regulatory T Cell Differentiation and Function

PubMed Central

Li, Ming O.; Rudensky, Alexander Y.

2016-01-01

Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self-tolerance and inflammatory responses. Recent studies have revealed a discrete mode of TCR signaling that regulates Treg cell differentiation, maintenance and function and that impacts on gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of Treg cells in the context of their function in health and disease. PMID:27026074

Performance testing of the environmental TLD system for the Three Mile Island Nuclear Station.

PubMed

Toke, L F; Carson, B H; Baker, G G; McBride, M H; Plato, P A; Miklos, J A

1984-05-01

Panasonic UD-801 thermoluminescent dosimeters ( TLDs ) containing two calcium sulfate phosphors were tested under Performance Specification 3.1 established by the American National Standard Institute ( ANSI75 ) and in the U.S. Nuclear Regulatory Commission's Regulatory Guide 4.13 ( NRC77 ). The specific qualifying tests included TLD uniformity, reproducibility, energy dependence and directional dependence. The overall measurement uncertainties and associated confidence levels are within the prescribed guidelines defined in the qualifying requirements for environmental TLDs .

MMV in partnership: the Eurartesim® experience

PubMed Central

2013-01-01

Background This case study describes how a public-private partnership between Medicines for Malaria Venture (MMV) and Sigma-Tau Industrie Farmaceutiche Riunite SpA achieved international regulatory approval for use of the fixed-dose artemisinin-based combination therapy dihydroartemisinin-piperaquine (Eurartesim®) for the treatment of malaria, enabling more widespread access to the medicine in malaria-endemic countries. Case description The combination of dihydroartemisinin and piperaquine demonstrated success in clinical trials for the treatment of malaria in Asia and Africa in the 2000s. However, as it had not been developed to international regulatory standards it was out of the reach of the majority of patients in disease-endemic countries, particularly those reliant on public healthcare systems supported by international donor funding. To overcome this, as of 2004 MMV worked in partnership with Sigma-Tau, Holleykin, Oxford University, the Institute of Tropical Medicine Antwerp, and the National Institute of Malaria Research India to develop the dihydroartemisinin-piperaquine combination to international standards. In 2011, the European Commission granted full marketing authorization to Sigma-Tau for Eurartesim. Discussion and evaluation The partnership between MMV, Sigma-Tau, and numerous other academic and industrial partners across the world, led to the successful development to EMA regulatory standards of a high-quality and highly efficacious anti-malarial treatment that otherwise would not have been possible. The dossier has also been submitted to the WHO for prequalification, and a safety statement to guide correct use of Eurartesim has been produced. In July 2012, the first delivery to a disease-endemic country was made to Cambodia, where the medicine is being used to treat patients and help counter the emergence of artemisinin resistance in the area. A paediatric dispersible formulation of Eurartesim is being developed, with the objective to submit the dossier to the EMA by the end of 2014. Conclusions The development of Eurartesim to international regulatory standards exemplifies the strengths of the product development partnership model in utilising the individual skills and expertise of partners with differing objectives to achieve a common goal. Successful uptake of Eurartesim by public health systems in malaria-endemic countries poses new challenges, which may require additional partnerships as we move forward. PMID:23782869

The role of stakeholders in developing an international regulatory framework for carbon capture and storage

NASA Astrophysics Data System (ADS)

Augustin, C. M.; Broad, K.; Swart, P. K.

2011-12-01

It is estimated that carbon capture and storage (CCS) could be used to achieve between 15% and 55% of the carbon emission reductions necessary to avoid dangerous levels of climate change. It is also believed that achieving emission reduction goals will be less costly with CCS than without it. The expansion of active CCS sites over the past decade, from three to 53 demonstrates the value that industry sees in CCS as a transition technology for governments seeking to reduce their CO2 emissions. However, to continue developing CCS for industry scale implementation, it is essential to provide the regulatory certainty needed to foster energy industry wide adoption of CCS. Existing CCS regulatory regimes are inadequate, fragmented and contradictory. There is a need for comprehensive, unifying regulations for CCS that are flexible enough to adapt as the technology develops. Governments are limited by the fact that carbon capture and storage is a multidisciplinary issue that touches on the fields of oil drilling, groundwater quality, greenhouse gas management, air quality, and risk management. Though it is in part a technological, environmental and management issue there is also a complex political element to tackling the CCS problem. Due to its cross-cutting nature, CCS regulations should be based off the best practices and standards developed by industry stakeholders. Industry standards are stakeholder developed and consensus based, created through a democratic and collaborative process by bodies such as the International Standards Organization, the National Institutes of Standards and Testing (USA), ASTM International, and the Canadian Standards Organization. Standards can typically be broken down into six general categories: test methods, specifications, classifications, practices, guides, and terminology. These standards are created by stakeholders across the industry and across geographic boundaries to create an trade-wide, rather than nationwide, consensus and ensuring that the standards are international in scope. This paper examines regulatory issues post-capture, particularly the transport and geological storage of carbon dioxide and seeks to identify areas where relevant stakeholders should collaborate to develop a comprehensive list of industry standards and provides several case study examples.

Integrating non-coding RNAs in JAK-STAT regulatory networks

PubMed Central

Witte, Steven; Muljo, Stefan A

2014-01-01

Being a well-characterized pathway, JAK-STAT signaling serves as a valuable paradigm for studying the architecture of gene regulatory networks. The discovery of untranslated or non-coding RNAs, namely microRNAs and long non-coding RNAs, provides an opportunity to elucidate their roles in such networks. In principle, these regulatory RNAs can act as downstream effectors of the JAK-STAT pathway and/or affect signaling by regulating the expression of JAK-STAT components. Examples of interactions between signaling pathways and non-coding RNAs have already emerged in basic cell biology and human diseases such as cancer, and can potentially guide the identification of novel biomarkers or drug targets for medicine. PMID:24778925

7 CFR 400.162 - Qualification ratios.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulatory Information System” distributed by NAIC, 120 West 12th St., Kansas City, MO 64105-1925; (b) Three... Key Rating Guide, A.M. Best, Ambest Road, Oldwick, N.J. 08858-0700; (c) One ratio found in § 400.170(d...

7 CFR 400.162 - Qualification ratios.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulatory Information System” distributed by NAIC, 120 West 12th St., Kansas City, MO 64105-1925; (b) Three... Key Rating Guide, A.M. Best, Ambest Road, Oldwick, N.J. 08858-0700; (c) One ratio found in § 400.170(d...

7 CFR 400.162 - Qualification ratios.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Regulatory Information System” distributed by NAIC, 120 West 12th St., Kansas City, MO 64105-1925; (b) Three... Key Rating Guide, A.M. Best, Ambest Road, Oldwick, N.J. 08858-0700; (c) One ratio found in § 400.170(d...

7 CFR 400.162 - Qualification ratios.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulatory Information System” distributed by NAIC, 120 West 12th St., Kansas City, MO 64105-1925; (b) Three... Key Rating Guide, A.M. Best, Ambest Road, Oldwick, N.J. 08858-0700; (c) One ratio found in § 400.170(d...

7 CFR 400.162 - Qualification ratios.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulatory Information System” distributed by NAIC, 120 West 12th St., Kansas City, MO 64105-1925; (b) Three... Key Rating Guide, A.M. Best, Ambest Road, Oldwick, N.J. 08858-0700; (c) One ratio found in § 400.170(d...

Quick Tips for Buying Medicines Over the Internet: A Consumer Safety Guide

MedlinePlus

... Laser Products Other Resources State Pharmacy Boards Federal Trade Commission U.S. Customs and Border Protection Spotlight A ... Products Advisory Committees Regulatory Information Safety Emergency Preparedness International Programs News & Events Training & Continuing Education Inspections & Compliance ...

77 FR 75780 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-64; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... asterisk (*) next to a rule indicates that a regulatory flexibility analysis has been prepared. Interested... for performance by service employees of the same or similar work at the same location. It requires...

Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system.

PubMed

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L

2015-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early, which were not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system.

A quantitative framework for the forward design of synthetic miRNA circuits.

PubMed

Bloom, Ryan J; Winkler, Sally M; Smolke, Christina D

2014-11-01

Synthetic genetic circuits incorporating regulatory components based on RNA interference (RNAi) have been used in a variety of systems. A comprehensive understanding of the parameters that determine the relationship between microRNA (miRNA) and target expression levels is lacking. We describe a quantitative framework supporting the forward engineering of gene circuits that incorporate RNAi-based regulatory components in mammalian cells. We developed a model that captures the quantitative relationship between miRNA and target gene expression levels as a function of parameters, including mRNA half-life and miRNA target-site number. We extended the model to synthetic circuits that incorporate protein-responsive miRNA switches and designed an optimized miRNA-based protein concentration detector circuit that noninvasively measures small changes in the nuclear concentration of β-catenin owing to induction of the Wnt signaling pathway. Our results highlight the importance of methods for guiding the quantitative design of genetic circuits to achieve robust, reliable and predictable behaviors in mammalian cells.

Precision Cardiovascular Medicine: State of Genetic Testing.

PubMed

Giudicessi, John R; Kullo, Iftikhar J; Ackerman, Michael J

2017-04-01

In the 15 years following the release of the first complete human genome sequences, our understanding of rare and common genetic variation as determinants of cardiovascular disease susceptibility, prognosis, and therapeutic response has grown exponentially. As such, the use of genomics to enhance the care of patients with cardiovascular diseases has garnered increased attention from clinicians, researchers, and regulatory agencies eager to realize the promise of precision genomic medicine. However, owing to a large burden of "complex" common diseases, emphasis on evidence-based practice, and a degree of unfamiliarity/discomfort with the language of genomic medicine, the development and implementation of genomics-guided approaches designed to further individualize the clinical management of a variety of cardiovascular disorders remains a challenge. In this review, we detail a practical approach to genetic testing initiation and interpretation as well as review the current state of cardiovascular genetic and pharmacogenomic testing in the context of relevant society and regulatory agency recommendations/guidelines. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Clinical pharmacology review of escitalopram for the treatment of depression.

PubMed

Pastoor, Devin; Gobburu, Joga

2014-01-01

Depression is a serious and debilitating psychiatric condition with serious societal health and economic implications. Escitalopram , the S-enantiomer of racemic citalopram, is an effective treatment for major depressive disorder. This review covers the clinical pharmacology of escitalopram, with emphasis on regulatory approval. Its pharmacokinetics, pharmacodynamics and clinical efficacy for major depressive disorder are evaluated, along with data regarding safety and tolerability. Drug development of escitalopram was heavily guided by prior approval of citalopram. Select safety and efficacy studies for escitalopram in combination with supportive evidence from the results of prior citalopram studies allowed for regulatory approval for acute and maintenance claims in both adults and adolescents, while minimizing burden on the sponsor. Escitalopram has been shown to have better efficacy and safety profile than other selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs, including racemic citalopram. The first generic escitalopram was approved in 2012, along with Abbreviated New Drug Applications. The associated cost savings have helped reduce the burden of weighing the benefits of escitalopram over less-expensive alternatives.

Implantation of an ergonomics administration system in a company: report of an occupational therapist specialist in ergonomics.

PubMed

Moraes, Berla; Andrade, Valéria Sousa

2012-01-01

This article aims to describe step-by-step the implementation of an ergonomics administration system in a company from March 2009 till March 2011 by an occupational therapist specialist in ergonomics based on the OSHAS 18001 guidelines and the Regulatory Norms 17 manual. The process began with the definition of five requisites with bases on the manual of application of the Regulatory Norms 17: survey; materials individual transportation and discharge; workplace furniture; workplace equipments; work environment and organization of the work to be managed with bases on the OSHAS 18001 guidelines. The following steps were established: sensitization of the company high administration, elaboration and institution of an ergonomics politics, development of ergonomics committees, ergonomics analysis of the work with recommendation of ergonomic improvements, implantation of improvements and evaluation or the results. This research experiment suggests the importance not only of a guiding axle but also of a professional qualification and participation of the company on the implementation of an ergonomics management system.

The European Medicines Agency's approval of new medicines for type 2 diabetes.

PubMed

Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

2018-05-08

Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

Toward a Personalized Science of Emotion Regulation

PubMed Central

Doré, Bruce P.; Silvers, Jennifer A.; Ochsner, Kevin N.

2018-01-01

The ability to successfully regulate emotion plays a key role in healthy development and the maintenance of psychological well-being. Although great strides have been made in understanding the nature of regulatory processes and the consequences of deploying them, a comprehensive understanding of emotion regulation that can specify what strategies are most beneficial for a given person in a given situation is still a far-off goal. In this review, we argue that moving toward this goal represents a central challenge for the future of the field. As an initial step, we propose a concrete framework that (i) explicitly considers emotion regulation as an interaction of person, situation, and strategy, (ii) assumes that regulatory effects vary according to these factors, and (iii) sets as a primary scientific goal the identification of person-, situation-, and strategy-based contingencies for successful emotion regulation. Guided by this framework, we review current questions facing the field, discuss examples of contextual variation in emotion regulation success, and offer practical suggestions for continued progress in this area. PMID:29750085

Recent developments in aircraft protection systems for laser guide star operations

NASA Astrophysics Data System (ADS)

Stomski, Paul J.; Murphy, Thomas W.; Campbell, Randy

2012-07-01

The astronomical community's use of high power laser guide star adaptive optics (LGS-AO) systems presents a potential hazard to aviation. Historically, the most common and trusted means of protecting aircraft and their occupants has been the use of safety observers (aka spotters) armed with shut-off switches. These safety observers watch for aircraft at risk and terminate laser propagation before the aircraft can be adversely affected by the laser. Efforts to develop safer and more cost-effective automated aircraft protection systems for use by the astronomical community have been inhibited by both technological and regulatory challenges. This paper discusses recent developments in these two areas. Specifically, with regard to regulation and guidance we discuss the 2011 release of AS-6029 by the SAE as well as the potential impact of RTCA DO-278A. With regard to the recent developments in the technology used to protect aircraft from laser illumination, we discuss the novel Transponder Based Aircraft Detection (TBAD) system being installed at W. M. Keck Observatory (WMKO). Finally, we discuss our strategy for evaluating TBAD compliance with the regulations and for seeking appropriate approvals for LGS operations at WMKO using a fully automated, flexibly configured, multi-tier aircraft protection system incorporating this new technology.

Augmenting endogenous repair of soft tissues with nanofibre scaffolds

PubMed Central

Snelling, Sarah; Dakin, Stephanie; Carr, Andrew

2018-01-01

As our ability to engineer nanoscale materials has developed we can now influence endogenous cellular processes with increasing precision. Consequently, the use of biomaterials to induce and guide the repair and regeneration of tissues is a rapidly developing area. This review focuses on soft tissue engineering, it will discuss the types of biomaterial scaffolds available before exploring physical, chemical and biological modifications to synthetic scaffolds. We will consider how these properties, in combination, can provide a precise design process, with the potential to meet the requirements of the injured and diseased soft tissue niche. Finally, we frame our discussions within clinical trial design and the regulatory framework, the consideration of which is fundamental to the successful translation of new biomaterials. PMID:29695606

Informational ergonomics and design: signage design for Monte Sião Camp.

PubMed

Marques, Luiz Guilherme Oliveira; Cardoso, Vânia Maria Batalha

2012-01-01

This paper refers to the development of a signage system, driven by the vector of Signage Design and Informational Ergonomics associated with Regulatory Standards. The methodology of the Ergonomic Intervention of Moraes and Mont'Alvão (2003), in its early stages, and the Method of the Signage Pyramid of Calori (2007) were used to develop the research, data collection and analysis and to guide the design by a signaling system. The system contemplated by this job is called Mount Zion, a site of 19 hectares, which has signs of disturbance. As a result, we obtained a signaling system, with graphic features that refer to formal-site, capable of meeting the needs of orientation and displacement inherent to the site.

Implementation Guide for Minimum Retroreflectivity Requirements for Traffic Signs

DOT National Transportation Integrated Search

1998-04-01

Although the "Manual on Uniform Traffic Control Devices" (MUTCD) stipulates that all warning and regulatory signs be illuminated or reflectorized to show the same color and shape by day or night, there are no specific guidelines for required retroref...

76 FR 5215 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... Compliance with Packaging Requirements for Shipment and Receipt of Radioactive Material,'' is temporarily... Code of Federal Regulations, Part 71, ``Packaging and Transportation of Radioactive Material'' (10 CFR... Compliance with Packaging Requirements for Shipments of Radioactive Materials,'' as an acceptable process for...

Sublethal exposure, insecticide resistance, and community stress

USDA-ARS?s Scientific Manuscript database

Although a prevalent pest management tool and anthropogenic stressors of widespread occurrence, insecticides are subject to biased perceptions and research demands largely guided by their use, market value, and regulatory requirements. As a result, short-term and simplistic efforts focusing on letha...

Adapting Pharmacoeconomics to Shape Efficient Health Systems en Route to UHC - Lessons from Two Continents.

PubMed

Miot, Jacqui; Thiede, Michael

2017-01-01

Background: Pharmacoeconomics is receiving increasing attention globally as a set of tools ensuring efficient use of resources in health systems, albeit with different applications depending on the contextual, cultural and development stages of each country. The factors guiding design, implementation and optimisation of pharmacoeconomics as a steering tool under the universal health coverage paradigm are explored using case studies of Germany and South Africa. Findings: German social health insurance is subject to the efficiency precept. Pharmaco-regulatory tools reflect the respective framework conditions under which they developed at particular points in time. The institutionalization and integration of pharmacoeconomics into the remit of the Institute for Quality and Efficiency in Health Care occurred only rather recently. The road has not been smooth, requiring political discourse and complex processes of negotiation. Although enshrined in the National Drug Policy, South Africa has had a more fragmented approach to medicine selection and pricing with different policies in private and public sectors. The regulatory reform for use of pharmacoeconomic tools is ongoing and will be further shaped by the introduction of National Health Insurance. Conclusion: A clear vision or framework is essential as the regulatory introduction of pharmacoeconomics is not a single event but rather a growing momentum. The path will always be subject to influences of politics, economics and market forces beyond the healthcare system so delays and modifications to pharmacoeconomic tools are to be expected. Health systems are dynamic and pharmacoeconomic reforms need to be sufficiently flexible to evolve alongside.

Engineering and control of biological systems: A new way to tackle complex diseases.

PubMed

Menolascina, Filippo; Siciliano, Velia; di Bernardo, Diego

2012-07-16

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Regulatory-Science: Biphasic Cancer Models or the LNT—Not Just a Matter of Biology!

PubMed Central

Ricci, Paolo F.; Sammis, Ian R.

2012-01-01

There is no doubt that prudence and risk aversion must guide public decisions when the associated adverse outcomes are either serious or irreversible. With any carcinogen, the levels of risk and needed protection before and after an event occurs, are determined by dose-response models. Regulatory law should not crowd out the actual beneficial effects from low dose exposures—when demonstrable—that are inevitably lost when it adopts the linear non-threshold (LNT) as its causal model. Because regulating exposures requires planning and developing protective measures for future acute and chronic exposures, public management decisions should be based on minimizing costs and harmful exposures. We address the direct and indirect effects of causation when the danger consists of exposure to very low levels of carcinogens and toxicants. The societal consequences of a policy can be deleterious when that policy is based on a risk assumed by the LNT, in cases where low exposures are actually beneficial. Our work develops the science and the law of causal risk modeling: both are interwoven. We suggest how their relevant characteristics differ, but do not attempt to keep them separated; as we demonstrate, this union, however unsatisfactory, cannot be severed. PMID:22740778

Considerations regarding the unintended radiation exposure of the embryo, fetus or nursing child. NCRP commentary No. 9

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

NCRP Commentary No. 9 was developed in response to a request by the Nuclear Regulatory Commission (NRC) to address issues specific to the exposure of a nursing child or the exposure of an embryo or fetus subsequent to a medical misadministration or radioactive material. Thirteen pages of text, consisting of 5 chapters and 5 tables, comprise the document. The NRC requested this commentary be used as a guide in developing regulations on the unintended irradiation of an embryo, fetus or nursing child. The NCRP clearly implies that intentional irradiation is fully within the purview of medical judgement. Although it ismore » clear that appropriate medical procedures must be implemented to avoid unintended irradiation of a conceptus of nursing child, the NCRP provides no guidance on the division between medical and regulatory responsibilities for either preadministration or postadministration management of the pregnant patient or the nursing child. The important issue to address at this juncture regards the specific regulations, if any, that should be inaugurated for unintended exposures, and whether such regulations would represent a responsible protection of the public.« less

Inference and interrogation of a coregulatory network in the context of lipid accumulation in Yarrowia lipolytica.

PubMed

Trébulle, Pauline; Nicaud, Jean-Marc; Leplat, Christophe; Elati, Mohamed

2017-01-01

Complex phenotypes, such as lipid accumulation, result from cooperativity between regulators and the integration of multiscale information. However, the elucidation of such regulatory programs by experimental approaches may be challenging, particularly in context-specific conditions. In particular, we know very little about the regulators of lipid accumulation in the oleaginous yeast of industrial interest Yarrowia lipolytica . This lack of knowledge limits the development of this yeast as an industrial platform, due to the time-consuming and costly laboratory efforts required to design strains with the desired phenotypes. In this study, we aimed to identify context-specific regulators and mechanisms, to guide explorations of the regulation of lipid accumulation in Y. lipolytica . Using gene regulatory network inference, and considering the expression of 6539 genes over 26 time points from GSE35447 for biolipid production and a list of 151 transcription factors, we reconstructed a gene regulatory network comprising 111 transcription factors, 4451 target genes and 17048 regulatory interactions (YL-GRN-1) supported by evidence of protein-protein interactions. This study, based on network interrogation and wet laboratory validation (a) highlights the relevance of our proposed measure, the transcription factors influence, for identifying phases corresponding to changes in physiological state without prior knowledge (b) suggests new potential regulators and drivers of lipid accumulation and (c) experimentally validates the impact of six of the nine regulators identified on lipid accumulation, with variations in lipid content from +43.2% to -31.2% on glucose or glycerol.

MINER: exploratory analysis of gene interaction networks by machine learning from expression data.

PubMed

Kadupitige, Sidath Randeni; Leung, Kin Chun; Sellmeier, Julia; Sivieng, Jane; Catchpoole, Daniel R; Bain, Michael E; Gaëta, Bruno A

2009-12-03

The reconstruction of gene regulatory networks from high-throughput "omics" data has become a major goal in the modelling of living systems. Numerous approaches have been proposed, most of which attempt only "one-shot" reconstruction of the whole network with no intervention from the user, or offer only simple correlation analysis to infer gene dependencies. We have developed MINER (Microarray Interactive Network Exploration and Representation), an application that combines multivariate non-linear tree learning of individual gene regulatory dependencies, visualisation of these dependencies as both trees and networks, and representation of known biological relationships based on common Gene Ontology annotations. MINER allows biologists to explore the dependencies influencing the expression of individual genes in a gene expression data set in the form of decision, model or regression trees, using their domain knowledge to guide the exploration and formulate hypotheses. Multiple trees can then be summarised in the form of a gene network diagram. MINER is being adopted by several of our collaborators and has already led to the discovery of a new significant regulatory relationship with subsequent experimental validation. Unlike most gene regulatory network inference methods, MINER allows the user to start from genes of interest and build the network gene-by-gene, incorporating domain expertise in the process. This approach has been used successfully with RNA microarray data but is applicable to other quantitative data produced by high-throughput technologies such as proteomics and "next generation" DNA sequencing.

Atlas Toolkit: Fast registration of 3D morphological datasets in the absence of landmarks

PubMed Central

Grocott, Timothy; Thomas, Paul; Münsterberg, Andrea E.

2016-01-01

Image registration is a gateway technology for Developmental Systems Biology, enabling computational analysis of related datasets within a shared coordinate system. Many registration tools rely on landmarks to ensure that datasets are correctly aligned; yet suitable landmarks are not present in many datasets. Atlas Toolkit is a Fiji/ImageJ plugin collection offering elastic group-wise registration of 3D morphological datasets, guided by segmentation of the interesting morphology. We demonstrate the method by combinatorial mapping of cell signalling events in the developing eyes of chick embryos, and use the integrated datasets to predictively enumerate Gene Regulatory Network states. PMID:26864723

Atlas Toolkit: Fast registration of 3D morphological datasets in the absence of landmarks.

PubMed

Grocott, Timothy; Thomas, Paul; Münsterberg, Andrea E

2016-02-11

Image registration is a gateway technology for Developmental Systems Biology, enabling computational analysis of related datasets within a shared coordinate system. Many registration tools rely on landmarks to ensure that datasets are correctly aligned; yet suitable landmarks are not present in many datasets. Atlas Toolkit is a Fiji/ImageJ plugin collection offering elastic group-wise registration of 3D morphological datasets, guided by segmentation of the interesting morphology. We demonstrate the method by combinatorial mapping of cell signalling events in the developing eyes of chick embryos, and use the integrated datasets to predictively enumerate Gene Regulatory Network states.

75 FR 62893 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... for using portland cement grout to protect prestressing steel from corrosion. The prestressing tendon system of a prestressed concrete containment structure is a principal strength element of the structure... of the structure depends on the functional reliability of the structure's principal strength elements...

75 FR 7526 - Withdrawal of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

... water chemistry program. For example, the 2004 revision of the Electric Power Research Institute report... Pressure Boundary'' of Appendix A, ``General Design Criteria for Nuclear Power Plants,'' in Title 10, Part..., which are controlled by regulations and plant technical specifications. For example, in-service...

75 FR 33853 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... performance or condition of structures, systems, or components * * * in a manner sufficient to provide reasonable assurance that these structures, systems, and components * * * are capable of fulfilling their... Management System (ADAMS). Comments would be most helpful if received by August 13, 2010. Comments received...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, James; Goins, Monty; Paul, Pran

This safety analysis report for packaging (SARP) presents the results of the safety analysis prepared in support of the Consolidated Nuclear Security, LLC (CNS) request for licensing of the Model ES-3100 package with bulk highly enriched uranium (HEU) contents and issuance of a Type B(U) Fissile Material Certificate of Compliance. This SARP, published in the format specified in the Nuclear Regulatory Commission (NRC) Regulatory Guide 7.9 and using information provided in UCID-21218 and NRC Regulatory Guide 7.10, demonstrates that the Y-12 National Security Complex (Y-12) ES-3100 package with bulk HEU contents meets the established NRC regulations for packaging, preparation formore » shipment, and transportation of radioactive materials given in Title 10, Part 71, of the Code of Federal Regulations (CFR) [10 CFR 71] as well as U.S. Department of Transportation (DOT) regulations for packaging and shipment of hazardous materials given in Title 49 CFR. To protect the health and safety of the public, shipments of adioactive materials are made in packaging that is designed, fabricated, assembled, tested, procured, used, maintained, and repaired in accordance with the provisions cited above. Safety requirements addressed by the regulations that must be met when transporting radioactive materials are containment of radioactive materials, radiation shielding, and assurance of nuclear subcriticality.« less

Development and implementation of clinical algorithms in occupational health practice.

PubMed

Ghafur, Imran; Lalloo, Drushca; Macdonald, Ewan B; Menon, Manju

2013-12-01

Occupational health (OH) practice is framed by legal, ethical, and regulatory requirements. Integrating this information into daily practice can be a difficult task. We devised evidence-based framework standards of good practice that would aid clinical management, and assessed their impact. The clinical algorithm was the method deemed most appropriate to our needs. Using "the first OH consultation" as an example, the development, implementation, and evaluation of an algorithm is described. The first OH consultation algorithm was developed. Evaluation demonstrated an overall improvement in recording of information, specifically consent, recreational drug history, function, and review arrangements. Clinical algorithms can be a method for assimilating and succinctly presenting the various facets of OH practice, for use by all OH clinicians as a practical guide and as a way of improving quality in clinical record-keeping.

Determining Epigenetic Targets: A Beginner's Guide to Identifying Genome Functionality Through Database Analysis.

PubMed

Hay, Elizabeth A; Cowie, Philip; MacKenzie, Alasdair

2017-01-01

There can now be little doubt that the cis-regulatory genome represents the largest information source within the human genome essential for health. In addition to containing up to five times more information than the coding genome, the cis-regulatory genome also acts as a major reservoir of disease-associated polymorphic variation. The cis-regulatory genome, which is comprised of enhancers, silencers, promoters, and insulators, also acts as a major functional target for epigenetic modification including DNA methylation and chromatin modifications. These epigenetic modifications impact the ability of cis-regulatory sequences to maintain tissue-specific and inducible expression of genes that preserve health. There has been limited ability to identify and characterize the functional components of this huge and largely misunderstood part of the human genome that, for decades, was ignored as "Junk" DNA. In an attempt to address this deficit, the current chapter will first describe methods of identifying and characterizing functional elements of the cis-regulatory genome at a genome-wide level using databases such as ENCODE, the UCSC browser, and NCBI. We will then explore the databases on the UCSC genome browser, which provides access to DNA methylation and chromatin modification datasets. Finally, we will describe how we can superimpose the huge volume of study data contained in the NCBI archives onto that contained within the UCSC browser in order to glean relevant in vivo study data for any locus within the genome. An ability to access and utilize these information sources will become essential to informing the future design of experiments and subsequent determination of the role of epigenetics in health and disease and will form a critical step in our development of personalized medicine.

Proliferation of CD4CD25Foxp3 regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma.

PubMed

Lee, Shin Wha; Kim, Yong-Man; Lee, Ha-Young; Kim, Dae-Yeon; Kim, Jong-Hyeok; Nam, Joo-Hyun; Kim, Young-Tak

2010-03-01

Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4(+)CD25(high+)Foxp3(+) T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2). Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry. Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4(+) T lymphocytes increased, CD8(+) T lymphocytes decreased, and the proportion of CD3(-)CD16(+)56(+) NK cells was unchanged. The proportion of CD4(+)CD25(high+)Foxp3(+) regulatory T lymphocytes in CD4(+) T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group. This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.

76 FR 38213 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... quality standards for using Portland Cement grout to protect prestressing steel from corrosion. The prestressing tendon system of a prestressed concrete containment structure is a principal strength element of... strength elements. Thus, any significant deterioration of the prestressing elements caused by corrosion may...

75 FR 20399 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

..., Revision 1, ``Establishing Quality Assurance Programs for the Manufacture and Distribution of Sealed... Manufacture and Distribution of Sealed Sources and Devices Containing Byproduct Material,'' was issued with a... during the review of an application to manufacture or distribute sealed sources and devices containing...

10 CFR 50.55a - Codes and standards.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., standard design approval, and standard design certification application under part 52 of this chapter is..., and components must be designed, fabricated, erected, constructed, tested, and inspected to quality... Operation and Maintenance of Nuclear Power Plants; NRC Regulatory Guide (RG) 1.84, Revision 35, “Design...

76 FR 66089 - Access Authorization Program for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0245] Access Authorization Program for Nuclear Power... Program for Nuclear Power Plants.'' This guide describes a method that NRC staff considers acceptable to... Regulations (10 CFR), section 73.56, ``Personnel Access Authorization Requirements for Nuclear Power Plants...

75 FR 61530 - Issuance of Regulatory Guides

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... Materials Code Case Acceptability, ASME Section III,'' and RG 1.147, Rev. 16, ``Inservice Inspection Code Case Acceptability, ASME Section XI, Division 1.'' FOR FURTHER INFORMATION CONTACT: Wallace E. Norris... specific problems or postulated accidents, and data the staff needs in its review of applications for...

Regulatory Reform: Compliance Guide Requirement Has Had Little Effect on Agency Practices

DTIC Science & Technology

2001-12-01

United States General Accounting Office GAO Report to the Ranking Minority Member Committee on Small Business and Entrepreneurship , U.S. Senate...20548 December 28, 2001 The Honorable Christopher S. Bond Ranking Minority Member Committee on Small Business and Entrepreneurship United States

76 FR 25725 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

....18, Revision 2, ``Information Relevant to Ensuring that Occupational Radiation Exposures at Medical..., techniques that the staff uses in evaluating specific problems or postulated accidents, and data that the..., ``Information Relevant to Ensuring that Occupational Radiation Exposures at Medical Institutions will be As Low...

A new age in functional genomics using CRISPR/Cas9 in arrayed library screening.

PubMed

Agrotis, Alexander; Ketteler, Robin

2015-01-01

CRISPR technology has rapidly changed the face of biological research, such that precise genome editing has now become routine for many labs within several years of its initial development. What makes CRISPR/Cas9 so revolutionary is the ability to target a protein (Cas9) to an exact genomic locus, through designing a specific short complementary nucleotide sequence, that together with a common scaffold sequence, constitute the guide RNA bridging the protein and the DNA. Wild-type Cas9 cleaves both DNA strands at its target sequence, but this protein can also be modified to exert many other functions. For instance, by attaching an activation domain to catalytically inactive Cas9 and targeting a promoter region, it is possible to stimulate the expression of a specific endogenous gene. In principle, any genomic region can be targeted, and recent efforts have successfully generated pooled guide RNA libraries for coding and regulatory regions of human, mouse and Drosophila genomes with high coverage, thus facilitating functional phenotypic screening. In this review, we will highlight recent developments in the area of CRISPR-based functional genomics and discuss potential future directions, with a special focus on mammalian cell systems and arrayed library screening.

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

PubMed

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Development of CRISPR/Cas9 mediated virus resistance in agriculturally important crops.

PubMed

Khatodia, Surender; Bhatotia, Kirti; Tuteja, Narendra

2017-05-04

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) system of targeted genome editing has already revolutionized the plant science research. This is a RNA guided programmable endonuclease based system composed of 2 components, the Cas9 nuclease and an engineered guide RNA targeting any DNA sequence of the form N20-NGG for novel genome editing applications. The CRISPR/Cas9 technology of targeted genome editing has been recently applied for imparting virus resistance in plants. The robustness, wide adaptability, and easy engineering of this system has proved its potential as an antiviral tool for plants. Novel DNA free genome editing by using the preassembled Cas9/gRNA ribonucleoprotein complex for development of virus resistance in any plant species have been prospected for the future. Also, in this review we have discussed the reports of CRISPR/Cas9 mediated virus resistance strategy against geminiviruses by targeting the viral genome and transgene free strategy against RNA viruses by targeting the host plant factors. In conclusion, CRISPR/Cas9 technology will provide a more durable and broad spectrum viral resistance in agriculturally important crops which will eventually lead to public acceptance and commercialization in the near future.

The Environmental Protection Agency's Safety Standards for Disposal of Spent Nuclear Fuel: Potential Path Forward in Response to the Report of the Blue Ribbon Commission on America's Nuclear Future - 13388

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forinash, Betsy; Schultheisz, Daniel; Peake, Tom

2013-07-01

Following the decision to withdraw the Yucca Mountain license application, the Department of Energy created a Blue Ribbon Commission (BRC) on America's Nuclear Future, tasked with recommending a national strategy to manage the back end of the nuclear fuel cycle. The BRC issued its final report in January 2012, with recommendations covering transportation, storage and disposal of spent nuclear fuel (SNF); potential reprocessing; and supporting institutional measures. The BRC recommendations on disposal of SNF and high-level waste (HLW) are relevant to the U.S. Environmental Protection Agency (EPA), which shares regulatory responsibility with the Nuclear Regulatory Commission (NRC): EPA issues 'generallymore » applicable' performance standards for disposal repositories, which are then implemented in licensing. For disposal, the BRC endorses developing one or more geological repositories, with siting based on an approach that is adaptive, staged and consent-based. The BRC recommends that EPA and NRC work cooperatively to issue generic disposal standards-applying equally to all sites-early in any siting process. EPA previously issued generic disposal standards that apply to all sites other than Yucca Mountain. However, the BRC concluded that the existing regulations should be revisited and revised. The BRC proposes a number of general principles to guide the development of future regulations. EPA continues to review the BRC report and to assess the implications for Agency action, including potential regulatory issues and considerations if EPA develops new or revised generic disposal standards. This review also involves preparatory activities to define potential process and public engagement approaches. (authors)« less

Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN.

PubMed

Ul Ain, Qurrat; Chung, Jee Young; Kim, Yong-Hee

2015-05-10

Gene therapy by engineered nucleases is a genetic intervention being investigated for curing the hereditary disorders by targeting selected genes with specific nucleotides for establishment, suppression, abolishment of a function or correction of mutation. Here, we review the fast developing technology of targeted genome engineering using site specific programmable nucleases zinc finger nucleases (ZFNs), transcription activator like nucleases (TALENs) and cluster regulatory interspaced short palindromic repeat/CRISPR associated proteins (CRISPR/Cas) based RNA-guided DNA endonucleases (RGENs) and their different characteristics including pros and cons of genome modifications by these nucleases. We have further discussed different types of delivery methods to induce gene editing, novel development in genetic engineering other than nucleases and future prospects. Copyright © 2014 Elsevier B.V. All rights reserved.

A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs)

PubMed Central

Jones, David R; McBlane, James W; McNaughton, Graham; Rajakumaraswamy, Nishanthan; Wydenbach, Kirsty

2013-01-01

The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines. PMID:23216470

Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell

PubMed Central

Lim, Wendell A.; Lee, Connie M.; Tang, Chao

2013-01-01

A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks. PMID:23352241

10 CFR 36.35 - Source rack protection.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Source rack protection. 36.35 Section 36.35 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Design and Performance... guides to prevent products and product carriers from hitting or touching the rack or mechanism. ...

77 FR 30030 - Monitoring the Effectiveness of Maintenance at Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0212] Monitoring the Effectiveness of Maintenance at... (RG) 1.160, ``Monitoring the Effectiveness of Maintenance at Nuclear Power Plants.'' This guide endorses Revision 4A to Nuclear Management and Resources Council (NUMARC) 93-01, ``Industry Guideline for...

77 FR 18271 - Terrestrial Environmental Studies for Nuclear Power Stations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0182] Terrestrial Environmental Studies for Nuclear Power... Environmental Studies for Nuclear Power Stations.'' This guide provides technical guidance that the NRC staff... nuclear power reactors. ADDRESSES: Please refer to Docket ID NRC-2011-0182 when contacting the NRC about...

RNA-Seq Atlas of Glycine max: a guide to the soybean transcriptome

USDA-ARS?s Scientific Manuscript database

A first analysis of the Glycine max (L.) Merr. (soybean) transcriptome using next generation sequencing technology and RNA-Sequencing (RNA-Seq) is presented. This analysis will provide an important resource for understanding transcription and gene co-regulatory networks in soybean, the most economic...

75 FR 45173 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... coolant system for measuring process variables (e.g., pressure, level, and flow). The term ``safety- related'' refers to those structures, systems, and components necessary to ensure (1) the integrity of the... are located in the NRC's Agencywide Documents Access and Management System (ADAMS) under Accession No...

Considerations that will determine if competency-based assessment is a sustainable innovation.

PubMed

Dauphinee, W Dale; Boulet, John R; Norcini, John J

2018-05-18

Educational assessment for the health professions has seen a major attempt to introduce competency based frameworks. As high level policy developments, the changes were intended to improve outcomes by supporting learning and skills development. However, we argue that previous experiences with major innovations in assessment offer an important road map for developing and refining assessment innovations, including careful piloting and analyses of their measurement qualities and impacts. Based on the literature, numerous assessment workshops, personal interactions with potential users, and our 40 years of experience in implementing assessment change, we lament the lack of a coordinated approach to clarify and improve measurement qualities and functionality of competency based assessment (CBA). To address this worrisome situation, we offer two roadmaps to guide CBA's further development. Initially, reframe and address CBA as a measurement development opportunity. Secondly, using a roadmap adapted from the management literature on sustainable innovation, the medical assessment community needs to initiate an integrated plan to implement CBA as a sustainable innovation within existing educational programs and self-regulatory enterprises. Further examples of down-stream opportunities to refocus CBA at the implementation level within faculties and within the regulatory framework of the profession are offered. In closing, we challenge the broader assessment community in medicine to step forward and own the challenge and opportunities to reframe CBA as an innovation to improve the quality of the clinical educational experience. The goal is to optimize assessment in health education and ultimately improve the public's health.

Tools and Models for Integrating Multiple Cellular Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerstein, Mark

2015-11-06

In this grant, we have systematically investigated the integrated networks, which are responsible for the coordination of activity between metabolic pathways in prokaryotes. We have developed several computational tools to analyze the topology of the integrated networks consisting of metabolic, regulatory, and physical interaction networks. The tools are all open-source, and they are available to download from Github, and can be incorporated in the Knowledgebase. Here, we summarize our work as follow. Understanding the topology of the integrated networks is the first step toward understanding its dynamics and evolution. For Aim 1 of this grant, we have developed a novelmore » algorithm to determine and measure the hierarchical structure of transcriptional regulatory networks [1]. The hierarchy captures the direction of information flow in the network. The algorithm is generally applicable to regulatory networks in prokaryotes, yeast and higher organisms. Integrated datasets are extremely beneficial in understanding the biology of a system in a compact manner due to the conflation of multiple layers of information. Therefore for Aim 2 of this grant, we have developed several tools and carried out analysis for integrating system-wide genomic information. To make use of the structural data, we have developed DynaSIN for protein-protein interactions networks with various dynamical interfaces [2]. We then examined the association between network topology with phenotypic effects such as gene essentiality. In particular, we have organized E. coli and S. cerevisiae transcriptional regulatory networks into hierarchies. We then correlated gene phenotypic effects by tinkering with different layers to elucidate which layers were more tolerant to perturbations [3]. In the context of evolution, we also developed a workflow to guide the comparison between different types of biological networks across various species using the concept of rewiring [4], and Furthermore, we have developed CRIT for correlation analysis in systems biology [5]. For Aim 3, we have further investigated the scaling relationship that the number of Transcription Factors (TFs) in a genome is proportional to the square of the total number of genes. We have extended the analysis from transcription factors to various classes of functional categories, and from individual categories to joint distribution [6]. By introducing a new analytical framework, we have generalized the original toolbox model to take into account of metabolic network with arbitrary network topology [7].« less

miRNA*: a passenger stranded in RNA-induced silencing complex?

PubMed

Mah, S M; Buske, C; Humphries, R K; Kuchenbauer, F

2010-01-01

Processing of the pre-microRNA (pre-miRNA) through Dicer1 generates a miRNA duplex, consisting of a miRNA and miRNA* strand (also termed guide strand and passenger strand, respectively). Despite the general consensus that miRNA*s have no regulatory activity, recent publications have provided evidence that the abundance, possible function, and physiological relevance of miRNA*s have been underestimated. This review provides an account of our current understanding of miRNA* origination and activity, mounting evidence for their unique functions and regulatory mechanisms, and examples of specific miRNA*s from the literature.

Audio visual summary: Implementing PURPA in Mid-America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The audio-visual presentation, Implementing PURPA in Mid-America, is a slide presentation designed to complement deliverable W-101-2, a booklet entitled Implementing PURPA in Mid-America: A Guide to the Public Utility Regulatory Policies Act. The presentation lasts 10 to 12 min and explains the major sections of PURPA, the rules promulgated by the Federal Energy Regulatory Commission to implement PURPA, and the implications of PURPA and its rules. It delineates the rights and responsibilities of citizens who want to sell electricity to utilities, explains the certification process, and discusses the rights and responsibilities of the utilities.

Characterization of microRNAs Expressed during Secondary Wall Biosynthesis in Acacia mangium

PubMed Central

Ong, Seong Siang; Wickneswari, Ratnam

2012-01-01

MicroRNAs (miRNAs) play critical regulatory roles by acting as sequence specific guide during secondary wall formation in woody and non-woody species. Although thousands of plant miRNAs have been sequenced, there is no comprehensive view of miRNA mediated gene regulatory network to provide profound biological insights into the regulation of xylem development. Herein, we report the involvement of six highly conserved amg-miRNA families (amg-miR166, amg-miR172, amg-miR168, amg-miR159, amg-miR394, and amg-miR156) as the potential regulatory sequences of secondary cell wall biosynthesis. Within this highly conserved amg-miRNA family, only amg-miR166 exhibited strong differences in expression between phloem and xylem tissue. The functional characterization of amg-miR166 targets in various tissues revealed three groups of HD-ZIP III: ATHB8, ATHB15, and REVOLUTA which play pivotal roles in xylem development. Although these three groups vary in their functions, -psRNA target analysis indicated that miRNA target sequences of the nine different members of HD-ZIP III are always conserved. We found that precursor structures of amg-miR166 undergo exhaustive sequence variation even within members of the same family. Gene expression analysis showed three key lignin pathway genes: C4H, CAD, and CCoAOMT were upregulated in compression wood where a cascade of miRNAs was downregulated. This study offers a comprehensive analysis on the involvement of highly conserved miRNAs implicated in the secondary wall formation of woody plants. PMID:23251324

CAS-viewer: web-based tool for splicing-guided integrative analysis of multi-omics cancer data.

PubMed

Han, Seonggyun; Kim, Dongwook; Kim, Youngjun; Choi, Kanghoon; Miller, Jason E; Kim, Dokyoon; Lee, Younghee

2018-04-20

The Cancer Genome Atlas (TCGA) project is a public resource that provides transcriptomic, DNA sequence, methylation, and clinical data for 33 cancer types. Transforming the large size and high complexity of TCGA cancer genome data into integrated knowledge can be useful to promote cancer research. Alternative splicing (AS) is a key regulatory mechanism of genes in human cancer development and in the interaction with epigenetic factors. Therefore, AS-guided integration of existing TCGA data sets will make it easier to gain insight into the genetic architecture of cancer risk and related outcomes. There are already existing tools analyzing and visualizing alternative mRNA splicing patterns for large-scale RNA-seq experiments. However, these existing web-based tools are limited to the analysis of individual TCGA data sets at a time, such as only transcriptomic information. We implemented CAS-viewer (integrative analysis of Cancer genome data based on Alternative Splicing), a web-based tool leveraging multi-cancer omics data from TCGA. It illustrates alternative mRNA splicing patterns along with methylation, miRNAs, and SNPs, and then provides an analysis tool to link differential transcript expression ratio to methylation, miRNA, and splicing regulatory elements for 33 cancer types. Moreover, one can analyze AS patterns with clinical data to identify potential transcripts associated with different survival outcome for each cancer. CAS-viewer is a web-based application for transcript isoform-driven integration of multi-omics data in multiple cancer types and will aid in the visualization and possible discovery of biomarkers for cancer by integrating multi-omics data from TCGA.

Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control

PubMed Central

Rothenberg, Ellen V.; Ungerbäck, Jonas; Champhekar, Ameya

2016-01-01

T lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of Innate Lymphoid Cells (ILCs) that share transcriptional regulation programs extensively with T cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly-common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate. PMID:26791859

75 FR 36698 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... information based on the likelihood of pipe breaks of different sizes. The rule would divide all coolant... to and including a ``transition break size,'' and breaks larger than the transition size up to the largest pipe in the reactor coolant system. Selection of the transition size was based upon pipe break...

Business Management for Independent Schools. Fourth Edition.

ERIC Educational Resources Information Center

National Association of Independent Schools, Boston, MA.

This fourth edition of a guide for independent school business managers has been produced in looseleaf format so that changes may be made promptly as decisions of regulatory bodies require modifications in current practice. Fourteen chapters are organized under three broad topic headings. Chapters in part 1, Accounting and Financial Reporting,…

75 FR 28074 - Advisory Committee on Reactor Safeguards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

..., 2009, (74 FR 52829-52830). Wednesday, June 9, 2010, Conference Room T2-B1, Two White Flint North... Regulatory Guide (RG) 1.216, ``Containment Structural Integrity Evaluation for Internal Pressure Loadings... representatives of the NRC staff regarding draft final RG 1.216, ``Containment Structural Integrity Evaluation for...

Guide for Determining Compliance With the Clean Air Act Standards for Radionuclide Emissions From NRC-Licensed and Non-DOE Federal Facilities: Revision 2

EPA Pesticide Factsheets

The requirements described apply to certain facilities licensed by the Nuclear Regulatory Commission (NRC) or its Agreement States to handle radioactive materials. Federal facilities not part of the Department of Energy (DOE) are also covered.

75 FR 41241 - Draft Regulatory Guide; Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

...: (301) 251-7404 or e-mail [email protected] . SUPPLEMENTARY INFORMATION: I. Introduction The U.S... analysis and testing applicable to Emergency Core Cooling System (ECCS) strainer performance and debris... provides text and image files of NRC's public documents. If you do not have access to ADAMS or if there are...

Benchmarking Australian and New Zealand University Meta-Policy in an Increasingly Regulated Tertiary Environment

ERIC Educational Resources Information Center

Freeman, Brigid

2014-01-01

The agencies responsible for tertiary education quality assurance in Australia and New Zealand have established regulatory regimes that increasingly intersect with tertiary institution policy management. An examination of university meta-policies identified good practices guiding university policy and policy management. Most Australian and half of…

77 FR 73912 - Used Motor Vehicle Trade Regulation Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-12

...'') has completed its regulatory review of its Used Motor Vehicle Trade Regulation Rule (``Used Car Rule... revisions to the Spanish translation of the Used Car Buyers Guide and nonsubstantive technical changes to.... SUPPLEMENTARY INFORMATION: I. Background The Commission promulgated the Used Car Rule in 1984 and the Rule...

Risk, Reward, and Regulations: Reshaping the Financial Services Industry.

ERIC Educational Resources Information Center

Saul, Ralph S.

1984-01-01

Deregulation has had much to do with the competitive drive and vitality of financial services within the United States. The risks and rewards of deregulation for financial institutions are discussed, and principles which should serve as a guide in building any new regulatory structure are examined. (RM)

75 FR 2894 - Withdrawal of Regulatory Guide 1.148

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' FOR FURTHER INFORMATION... for Active Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' RG 1.148 was... qualifying active mechanical equipment used in nuclear power plants. The NRC is withdrawing RG 1.148 because...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2013-01-01 2013-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2014-01-01 2014-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2012-01-01 2012-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

Multiple species inventory and monitoring technical guide

Treesearch

P.N. Manley; B. Van Horne; J.K. Roth; W.J. Zielinski; M.M. McKenzie; T.J. Weller; F.W. Weckerly; C. Vojta

2006-01-01

The National Forest Management Act (1976) recognizes the importance of maintaining species and community diversity on National Forest System (NFS) lands as a critical component of our ecological and cultural heritage. Monitoring is required of land management to assess the success of management activities in meeting legal, regulatory, and policy objectives, including...

77 FR 73056 - Initial Test Programs for Water-Cooled Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0293] Initial Test Programs for Water-Cooled Nuclear Power... (DG), DG-1259, ``Initial Test Programs for Water-Cooled Nuclear Power Plants.'' This guide describes the general scope and depth that the staff of the NRC considers acceptable for Initial Test Programs...

Impact of poultry litter application and land use on E. coli runoff from small agricultural watersheds

USDA-ARS?s Scientific Manuscript database

Fecal bacteria contamination of surface waters continues to be a critical water quality concern with serious human health implications, but relatively few land use specific data sets are available to guide management, restoration, policy, and regulatory decisions. In regions with substantial poultr...

76 FR 4390 - Draft Regulatory Guide: Comment Period Extension and Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

....'' This Federal Register notice stated that electronic copies of DG-1229 were available in the NRC's Agencywide Documents Access and Management System (ADAMS) ( http://www.nrc.gov/reading-rm/adams.html ), under... Documents Access and Management System (ADAMS): Publicly available documents created or received at the NRC...

77 FR 60482 - Regulatory Guide 5.67, Material Control and Accounting for Uranium Enrichment Facilities...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... Accounting for Uranium Enrichment Facilities Authorized To Produce Special Nuclear Material of Low Strategic... Accounting for Uranium Enrichment Facilities Authorized to Produce Special Nuclear Material of Low Strategic... INFORMATION CONTACT: Glenn Tuttle, Office of Nuclear Material Safety and Safeguards, Division of Fuel Cycle...

A Guide to Disbursement, Refund, and Repayment.

ERIC Educational Resources Information Center

Guthrie, Marty; Rappaport, Renee

Guidelines are provided to assist in the interpretation of the regulatory requirements regarding disbursement of funds to students under Title IV student aid programs. Attention is also directed to the higher education community's self-regulation initiatives regarding refund and repayment, as well as the Department of Education's regulations in…

75 FR 1658 - Withdrawal of Regulatory Guide 7.5

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

..., Washington, DC 20555-0001, telephone: 301-251-7447 or e-mail [email protected] . SUPPLEMENTARY..., e.g., Federal, State, or local government radioactive material shipments transported by government... 301- 415-3548, and by e-mail to [email protected] . Dated at Rockville, Maryland, this 5th day of...

75 FR 5630 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

... specific parts of the NRC's regulations, techniques that the staff uses in evaluating specific problems or postulated accidents, and data that the staff needs in its review of applications for permits and licenses... in license applications and for monitoring and reporting effluent data by licensees. The guidance is...

77 FR 39745 - Fuel Oil Systems for Emergency Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... fuel oil systems for safety-related emergency diesel generators and oil-fueled gas turbine generators... emergency diesel generators and oil-fueled gas turbine generators, including assurance of adequate fuel oil.... The DG-1282 is proposed revision 2 of Regulatory Guide 1.137, ``Fuel Oil Systems for Standby Diesel...

Regulatory Guide on Conducting a Security Vulnerability Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ek, David R.

This document will provide guidelines on conducting a security vulnerability assessment at a facility regulated by the Radiation Protection Centre. The guidelines provide a performance approach assess security effectiveness. The guidelines provide guidance for a review following the objectives outlined in IAEA NSS#11 for Category 1, 2, & 3 sources.

75 FR 27599 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

..., Revision 2, ``Preparation of an Environmental Report To Support a Rulemaking Petition Seeking an Exemption... staff uses in evaluating specific problems or postulated accidents, and data that the staff needs in its... preparation of environmental reports (ERs), that are submitted to support a rulemaking petition for an...

77 FR 63343 - Biweekly Notice: Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... PWR [Pressurized-Water Reactor] Steam Generator Tubes'' (Reference 32) and [Nuclear Energy Institute... maintains the required structural margins of the SG tubes for both normal and accident conditions. Nuclear Energy Institute 97-06, ``Steam Generator Program Guidelines'' (Reference 8), and NRC Regulatory Guide 1...

77 FR 5063 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on Thermal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... Subcommittee on Thermal-Hydraulics Phenomena; Notice of Meeting The ACRS Subcommittee on Thermal-Hydraulics... Regulatory Guide (1.79), ``Preoperational Testing of Emergency Core Cooling Systems for Pressurized Water... Water Reactors.'' The Subcommittee will hear presentations by and hold discussions with the NRC staff...

CTIC Cablebooks. Volume 2: A Guide for Local Policy.

ERIC Educational Resources Information Center

Jesuale, Nancy, Ed.; And Others

The second in a two-part series, this volume presents 13 chapters discussing many of the most pressing cable policy issues facing local government, describing alternative policy options, and suggesting regulatory procedures successfully used by decision makers in the United States. Topics covered are (1) "The Rationale for Regulation,"…

75 FR 52999 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... or postulated accidents, and data that the staff needs in its review of applications for permits and... Regulations (10 CFR) Part 20, ``Standards for Protection Against Radiation,'' the associated specific... (i.e. radiation doses in addition to and accounted for separately from the doses received under the...

Social cognitive theory of gender development and differentiation.

PubMed

Bussey, K; Bandura, A

1999-10-01

Human differentiation on the basis of gender is a fundamental phenomenon that affects virtually every aspect of people's daily lives. This article presents the social cognitive theory of gender role development and functioning. It specifies how gender conceptions are constructed from the complex mix of experiences and how they operate in concert with motivational and self-regulatory mechanisms to guide gender-linked conduct throughout the life course. The theory integrates psychological and sociostructural determinants within a unified conceptual structure. In this theoretical perspective, gender conceptions and roles are the product of a broad network of social influences operating interdependently in a variety of societal subsystems. Human evolution provides bodily structures and biological potentialities that permit a range of possibilities rather than dictate a fixed type of gender differentiation. People contribute to their self-development and bring about social changes that define and structure gender relationships through their agentic actions within the interrelated systems of influence.

Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

PubMed

Han, Xinxin; Yin, Linlin; Xue, Hongwei

2012-07-01

Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

Guide to active vaccine safety surveillance: Report of CIOMS working group on vaccine safety - executive summary.

PubMed

Heininger, U; Holm, K; Caplanusi, I; Bailey, S R

2017-07-13

In 2013, the Council for International Organizations of Medical Sciences (CIOMS) created a Working Group on Vaccine Safety (WG) to address unmet needs in the area of vaccine pharmacovigilance. Generating reliable data about specific vaccine safety concerns is becoming a priority due to recent progress in the development and deployment of new vaccines of global importance, as well as novel vaccines targeting diseases specifically endemic to many resource-limited countries (RLCs), e.g. malaria, dengue. The WG created a Guide to Active Vaccine Safety Surveillance (AVSS) to assist national regulatory authorities and national immunization program officers in RLCs in determining the best course of action with regards to non-routine pharmacovigilance activities, when confronted with a launch of a new vaccine or a vaccine that is new to their country. Here we summarize the results of the WG, further detailed in the Guide, which for the first time provides a structured approach to identifying and analyzing specific vaccines safety knowledge gaps, while considering all available sources of information, in order to determine whether AVSS is an appropriate solution. If AVSS is confirmed as being the appropriate tool, the Guide provides additional essential information on AVSS, a detailed overview of common types of AVSS and practical implementation considerations. It also provides a framework for a well-constructed and informative AVSS when needed, thus aiming to ensure the best possible safety of immunization in this new landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

PromoterCAD: data-driven design of plant regulatory DNA

PubMed Central

Cox, Robert Sidney; Nishikata, Koro; Shimoyama, Sayoko; Yoshida, Yuko; Matsui, Minami; Makita, Yuko; Toyoda, Tetsuro

2013-01-01

Synthetic promoters can control the timing, location and amount of gene expression for any organism. PromoterCAD is a web application for designing synthetic promoters with altered transcriptional regulation. We use a data-first approach, using published high-throughput expression and motif data from for Arabidopsis thaliana to guide DNA design. We demonstrate data mining tools for finding motifs related to circadian oscillations and tissue-specific expression patterns. PromoterCAD is built on the LinkData open platform for data publication and rapid web application development, allowing new data to be easily added, and the source code modified to add new functionality. PromoterCAD URL: http://promotercad.org. LinkData URL: http://linkdata.org. PMID:23766287

FPGA implementation of current-sharing strategy for parallel-connected SEPICs

NASA Astrophysics Data System (ADS)

Ezhilarasi, A.; Ramaswamy, M.

2016-01-01

The attempt echoes to evolve an equal current-sharing algorithm over a number of single-ended primary inductance converters connected in parallel. The methodology involves the development of state-space model to predict the condition for the existence of a stable equilibrium portrait. It acquires the role of a variable structure controller to guide the trajectory, with a view to circumvent the circuit non-linearities and arrive at a stable performance through a preferred operating range. The design elicits an acceptable servo and regulatory characteristics, the desired time response and ensures regulation of the load voltage. The simulation results validated through a field programmable gate array-based prototype serves to illustrate its suitability for present-day applications.

Comparative Genomics as a Foundation for Evo-Devo Studies in Birds.

PubMed

Grayson, Phil; Sin, Simon Y W; Sackton, Timothy B; Edwards, Scott V

2017-01-01

Developmental genomics is a rapidly growing field, and high-quality genomes are a useful foundation for comparative developmental studies. A high-quality genome forms an essential reference onto which the data from numerous assays and experiments, including ChIP-seq, ATAC-seq, and RNA-seq, can be mapped. A genome also streamlines and simplifies the development of primers used to amplify putative regulatory regions for enhancer screens, cDNA probes for in situ hybridization, microRNAs (miRNAs) or short hairpin RNAs (shRNA) for RNA interference (RNAi) knockdowns, mRNAs for misexpression studies, and even guide RNAs (gRNAs) for CRISPR knockouts. Finally, much can be gleaned from comparative genomics alone, including the identification of highly conserved putative regulatory regions. This chapter provides an overview of laboratory and bioinformatics protocols for DNA extraction, library preparation, library quantification, and genome assembly, from fresh or frozen tissue to a draft avian genome. Generating a high-quality draft genome can provide a developmental research group with excellent resources for their study organism, opening the doors to many additional assays and experiments.

Diverse set of microRNAs are responsive to powdery mildew infection and heat stress in wheat (Triticum aestivum L.)

PubMed Central

2010-01-01

Background MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. MiRNAs can have large-scale regulatory effects on development and stress response in plants. Results To test whether miRNAs play roles in regulating response to powdery mildew infection and heat stress in wheat, by using Solexa high-throughput sequencing we cloned the small RNA from wheat leaves infected by preponderant physiological strain Erysiphe graminis f. sp. tritici (Egt) or by heat stress treatment. A total of 153 miRNAs were identified, which belong to 51 known and 81 novel miRNA families. We found that 24 and 12 miRNAs were responsive to powdery mildew infection and heat stress, respectively. We further predicted that 149 target genes were potentially regulated by the novel wheat miRNA. Conclusions Our results indicated that diverse set of wheat miRNAs were responsive to powdery mildew infection and heat stress and could function in wheat responses to both biotic and abiotic stresses. PMID:20573268

The control of foreigners as researchers in Thailand.

PubMed

Ditton, Mary J; Lehane, Leigh

2009-09-01

AN IMPORTANT ASPECT OF ETHICAL CONDUCT of field research is for the researcher to have an appropriate relationship with the legitimate gatekeepers of the field site. This paper describes our experiences of obtaining approval from regulatory authorities in Thailand for field research on Burmese migrants, and discusses the nature and rationale of such government control in Asia and Western countries. It is intended to guide future humanitarian researchers who are planning to study oppressed groups at politically sensitive research sites where regulatory authorities monitor both research sites and research performance. Thailand, like several other Southeast Asian countries, operates a permit system for foreign researchers. This permit system is designed to promote research activities in Thailand so that the results can be used to further the country's development, and to enhance the cooperation and collaboration between Thai and foreign researchers providing opportunities for the exchange of knowledge, technical expertise, and experience. This control of foreign researchers is not prohibitive; foreign humanitarian researchers can organize research and advance the welfare of targeted oppressed populations in cooperation with government agencies.

Maxdose-SR and popdose-SR routine release atmospheric dose models used at SRS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jannik, G. T.; Trimor, P. P.

MAXDOSE-SR and POPDOSE-SR are used to calculate dose to the offsite Reference Person and to the surrounding Savannah River Site (SRS) population respectively following routine releases of atmospheric radioactivity. These models are currently accessed through the Dose Model Version 2014 graphical user interface (GUI). MAXDOSE-SR and POPDOSE-SR are personal computer (PC) versions of MAXIGASP and POPGASP, which both resided on the SRS IBM Mainframe. These two codes follow U.S. Nuclear Regulatory Commission (USNRC) Regulatory Guides 1.109 and 1.111 (1977a, 1977b). The basis for MAXDOSE-SR and POPDOSE-SR are USNRC developed codes XOQDOQ (Sagendorf et. al 1982) and GASPAR (Eckerman et. almore » 1980). Both of these codes have previously been verified for use at SRS (Simpkins 1999 and 2000). The revisions incorporated into MAXDOSE-SR and POPDOSE-SR Version 2014 (hereafter referred to as MAXDOSE-SR and POPDOSE-SR unless otherwise noted) were made per Computer Program Modification Tracker (CPMT) number Q-CMT-A-00016 (Appendix D). Version 2014 was verified for use at SRS in Dixon (2014).« less

Parental supervision for their children's toothbrushing: Mediating effects of planning, self-efficacy, and action control.

PubMed

Hamilton, Kyra; Cornish, Stephen; Kirkpatrick, Aaron; Kroon, Jeroen; Schwarzer, Ralf

2018-05-01

With 60-90% of children worldwide reportedly experiencing dental caries, poor oral health in the younger years is a major public health issue. As parents are important to children's oral hygiene practices, we examined the key self-regulatory behaviours of parents for supervising their children's toothbrushing using the health action process approach. Participants (N = 281, 197 mothers) comprised Australian parents of 2- to 5-year-olds. A longitudinal design was used to investigate the sequential mediation chain for the effect of intention (Time 1) on parental supervision for their youngest child's toothbrushing (Time 3), via self-efficacy and planning (Time 2), and action control (Time 3). A latent-variable structural equation model, controlling for baseline behaviour and habit, revealed significant indirect effects from intention via self-efficacy and action control and intention via planning and action control, on parental supervision behaviour. The model was a good fit to the data, explaining 74% of the variance in parents' supervising behaviour for their children's toothbrushing. While national recommendations are provided to guide parents in promoting good oral hygiene practices with their children, current results show the importance of going beyond simple knowledge transmission to support parents' intentions to supervise their children's toothbrushing actually materialize. Current findings make a significant contribution to the cumulative empirical evidence regarding self-regulatory components in health behaviour change and can inform intervention development to increase parents' participation in childhood oral hygiene practices, thus helping to curb rising oral health conditions and diseases. Statement of contribution What is already known on this subject? Self-regulatory skills are important to translate intentions into behaviour. Self-efficacy, planning, and action control are key self-regulatory skills for behaviour change. What does this study add? Self-regulatory skills are needed for parents to supervise their children's toothbrushings. Self-efficacy, planning, and action control are important self-regulatory skills in this context. Future interventions should map these self-regulatory predictors onto behaviour change techniques. © 2018 The British Psychological Society.

The CRISPR/Cas Genome-Editing Tool: Application in Improvement of Crops

PubMed Central

Khatodia, Surender; Bhatotia, Kirti; Passricha, Nishat; Khurana, S. M. P.; Tuteja, Narendra

2016-01-01

The Clustered Regularly Interspaced Short Palindromic Repeats associated Cas9/sgRNA system is a novel targeted genome-editing technique derived from bacterial immune system. It is an inexpensive, easy, most user friendly and rapidly adopted genome editing tool transforming to revolutionary paradigm. This technique enables precise genomic modifications in many different organisms and tissues. Cas9 protein is an RNA guided endonuclease utilized for creating targeted double-stranded breaks with only a short RNA sequence to confer recognition of the target in animals and plants. Development of genetically edited (GE) crops similar to those developed by conventional or mutation breeding using this potential technique makes it a promising and extremely versatile tool for providing sustainable productive agriculture for better feeding of rapidly growing population in a changing climate. The emerging areas of research for the genome editing in plants include interrogating gene function, rewiring the regulatory signaling networks and sgRNA library for high-throughput loss-of-function screening. In this review, we have described the broad applicability of the Cas9 nuclease mediated targeted plant genome editing for development of designer crops. The regulatory uncertainty and social acceptance of plant breeding by Cas9 genome editing have also been described. With this powerful and innovative technique the designer GE non-GM plants could further advance climate resilient and sustainable agriculture in the future and maximizing yield by combating abiotic and biotic stresses. PMID:27148329

77 FR 74745 - Used Motor Vehicle Trade Regulation Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

...Except as specifically described below, the FTC has completed its regulatory review of its Used Motor Vehicle Trade Regulation Rule (``Used Car Rule'' or ``Rule'') as part of the FTC's systematic review of all current Commission regulations and guides. The Commission has decided to retain the Rule and, in a separate Federal Register document, to amend it by changing the Spanish translation of the Buyers Guide. In addition, the Commission also has decided to issue a notice of proposed rulemaking (``NPR'') soliciting comments on proposed changes to the Rule. In this NPR, the Commission addresses the comments received during its review and invites public comment on the following four proposed changes to the Buyers Guide: adding boxes to the back of the Buyers Guide where dealers would have the option to indicate manufacturers' and other third-party warranties; adding a statement to the Buyers Guide encouraging consumers to seek vehicle history information and directing consumers to an FTC Web site for more information about vehicle histories; adding catalytic converters and airbags to the List of Systems on the back of the Buyers Guide; and adding a statement in Spanish to the English Buyers Guide directing consumers who cannot read the Buyers Guide in English to ask for a copy of it in Spanish.

Critical role of developing national strategic plans as a guide to strengthen laboratory health systems in resource-poor settings.

PubMed

Nkengasong, John N; Mesele, Tsehaynesh; Orloff, Sherry; Kebede, Yenew; Fonjungo, Peter N; Timperi, Ralph; Birx, Deborah

2009-06-01

Medical laboratory services are an essential, yet often neglected, component of health systems in developing countries. Their central role in public health, disease control and surveillance, and patient management is often poorly recognized by governments and donors. However, medical laboratory services in developing countries can be strengthened by leveraging funding from other sources of HIV/AIDS prevention, care, surveillance, and treatment programs. Strengthening these services will require coordinated efforts by national governments and partners and can be achieved by establishing and implementing national laboratory strategic plans and policies that integrate laboratory systems to combat major infectious diseases. These plans should take into account policy, legal, and regulatory frameworks; the administrative and technical management structure of the laboratories; human resources and retention strategies; laboratory quality management systems; monitoring and evaluation systems; procurement and maintenance of equipment; and laboratory infrastructure enhancement. Several countries have developed or are in the process of developing their laboratory plans, and others, such as Ethiopia, have implemented and evaluated their plan.

2011 White paper on recent issues in bioanalysis and regulatory findings from audits and inspections.

PubMed

Garofolo, Fabio; Rocci, Mario L; Dumont, Isabelle; Martinez, Suzanne; Lowes, Steve; Woolf, Eric; van Amsterdam, Peter; Bansal, Surendra; Barra, Ariadna Cristina Gomes; Bauer, Ronald; Booth, Brian P; Carrasco-Triguero, Montserrat; DeSilva, Binodh; Dunn, John; Gallicano, Keith; Gouty, Dominique; Ho, Stacy; Hucker, Richard; Jemal, Mohammed; Katori, Noriko; Le Blaye, Olivier; Lee, Jean; Li, Wenkui; Michael, Steve; Nehls, Corey; Nicholson, Robert; Ormsby, Eric; Tang, Daniel; Viswanathan, C T; Weiner, Russell; Young, Graeme

2011-09-01

The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Validation Group as a 2-day full immersion workshop for pharmaceutical companies, CROs and regulatory agencies to discuss, review, share perspectives, provide potential solutions and agree upon a consistent approach to recent issues in the bioanalysis of both small and large molecules. High quality, better compliance to regulations and scientific excellence are the foundation of this workshop. As in the previous editions of this significant event, recommendations were made and a consensus was reached among panelists and attendees, including industry leaders and regulatory experts representing the global bioanalytical community, on many 'hot' topics in bioanalysis. This 2011 White Paper is based on the conclusions from this workshop, and aims to provide a practical reference guide on those topics.

A survey on IVIVC/IVIVR development in the pharmaceutical industry - Past experience and current perspectives.

PubMed

Nguyen, M A; Flanagan, T; Brewster, M; Kesisoglou, F; Beato, S; Biewenga, J; Crison, J; Holm, R; Li, R; Mannaert, E; McAllister, M; Mueller-Zsigmondy, M; Muenster, U; Ojala, K; Page, S; Parr, A; Rossenu, S; Timmins, P; Van Peer, A; Vermeulen, A; Langguth, P

2017-05-01

The present work aimed to describe the current status of IVIVC/IVIVR development in the pharmaceutical industry, focusing on the use and perception of specific approaches as well as successful and failed case studies. Two questionnaires have been distributed to 13 EFPIA partners of the Oral Biopharmaceutics Tools Initiative and to the Pharmacokinetics Working Party of the European Medicines Agency in order to capture the perspectives and experiences of industry scientists and agency members, respectively. Responses from ten companies and three European Agencies were received between May 21st 2014 and January 19th 2016. The majority of the companies acknowledged the importance of IVIVC/IVIVR throughout the drug development stages and a well-balanced rate of return on investment. However, the IVIVC/IVIVR approach seemed to be underutilized in regulatory submissions. Four of the ten companies stated to have an internal guidance related to IVIVC/IVIVR modelling, whereas three felt that an overall strategy is not necessary. Successful models mainly served to support formulation development and to provide a better mechanistic understanding. There was not yet much experience with safe-space IVIVRs as well as the use of physiologically based modelling in the field of IVIVC. At the same time, the responses from both industry and agencies indicated that there might be a need for a regulatory framework to guide the application of these novel approaches. The relevance of IVIVC/IVIVR for oral IR drug products was recognized by most of the companies. For IR formulations, relationships other than Level A correlation were more common outcomes among the provided case studies, such as multiple Level C correlation or safe-space IVIVR, which could be successfully used for requesting regulatory flexibility. Compared to the responses from industry scientists, there was a trend towards a higher appreciation of the BCS among the regulators, but a less positive attitude towards the utility of non-compendial dissolution methods for establishing a successful IVIVC/IVIVR. The lack of appropriate in vivo data and regulatory uncertainty were considered the major difficulties in IVIVC/IVIVR development. The results of this survey provide unique insights into current IVIVC/IVIVR practices in the pharmaceutical industry. Pursuing an IVIVC/IVIVR should be generally encouraged, considering its high value from both industry and regulators' perspective. Copyright © 2017 Elsevier B.V. All rights reserved.

NATURAL RESOURCE MANAGEMENT PLAN FOR BROOKHAVEN NATIONAL LABORATORY.

DOE Office of Scientific and Technical Information (OSTI.GOV)

GREEN,T.ET AL.

2003-12-31

Brookhaven National Laboratory (BNL) is located near the geographic center of Long Island, New York. The Laboratory is situated on 5,265 acres of land composed of Pine Barrens habitat with a central area developed for Laboratory work. In the mid-1990s BNL began developing a wildlife management program. This program was guided by the Wildlife Management Plan (WMP), which was reviewed and approved by various state and federal agencies in September 1999. The WMP primarily addressed concerns with the protection of New York State threatened, endangered, or species of concern, as well as deer populations, invasive species management, and the revegetationmore » of the area surrounding the Relativistic Heavy Ion Collider (RHIC). The WMP provided a strong and sound basis for wildlife management and established a basis for forward motion and the development of this document, the Natural Resource Management Plan (NRMP), which will guide the natural resource management program for BNL. The body of this plan establishes the management goals and actions necessary for managing the natural resources at BNL. The appendices provide specific management requirements for threatened and endangered amphibians and fish (Appendices A and B respectively), lists of actions in tabular format (Appendix C), and regulatory drivers for the Natural Resource Program (Appendix D). The purpose of the Natural Resource Management Plan is to provide management guidance, promote stewardship of the natural resources found at BNL, and to integrate their protection with pursuit of the Laboratory's mission. The philosophy or guiding principles of the NRMP are stewardship, adaptive ecosystem management, compliance, integration with other plans and requirements, and incorporation of community involvement, where applicable.« less

Discrepancy-based and anticipated emotions in behavioral self-regulation.

PubMed

Brown, Christina M; McConnell, Allen R

2011-10-01

Discrepancies between one's current and desired states evoke negative emotions, which presumably guide self-regulation. In the current work we evaluated the function of discrepancy-based emotions in behavioral self-regulation. Contrary to classic theories of self-regulation, discrepancy-based emotions did not predict the degree to which people engaged in self-regulatory behavior. Instead, expectations about how future self-discrepancies would make one feel (i.e., anticipated emotions) predicted self-regulation. However, anticipated emotions were influenced by previous discrepancy-based emotional experiences, suggesting that the latter do not directly motivate self-regulation but rather guide expectations. These findings are consistent with the perspective that emotions do not necessarily direct immediate behavior, but rather have an indirect effect by guiding expectations, which in turn predict goal-directed action.

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--Part I.

PubMed

Hubert, Ph; Nguyen-Huu, J-J; Boulanger, B; Chapuzet, E; Chiap, P; Cohen, N; Compagnon, P-A; Dewé, W; Feinberg, M; Lallier, M; Laurentie, M; Mercier, N; Muzard, G; Nivet, C; Valat, L

2004-11-15

This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, ...) and other documents of normative character (ISO, ICH, FDA, ...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

Implementation of a safe-by-design approach in the development of new open pilot lines for the manufacture of carbon nanotube-based nano-enabled products

NASA Astrophysics Data System (ADS)

López de Ipiña, Jesús M.; Hernan, Angel; Cenigaonaindia, Xabier; Insunza, Mario; Florez, Sonia; Seddon, Richard; Vavouliotis, Antonios; Kostopoulos, Vasilios; Latko, Paulina; Durałek, Paweł; Kchit, Nadir

2017-06-01

The project PLATFORM (H2020, GA 646307) aims to develop three new pilot lines (PPLs) for the manufacture of carbon nanotube-based nano-enabled products (buckypapers, treated prepregs, doped veils), for the European aeronautics and automotive industries (a Technology Readiness Level 6 - TRL6 - is expected at the end of the project). The Machinery Directive 2006/42/EC (MD) - transposed into the respective national legislations - is the European regulatory framework for the design and construction of new machinery, as the future PPLs. PPLs are not required to comply with the provisions of the MD until they are put into service - expected in 2020, after project completion - but then, the MD will be fully applicable. In this regulatory context, the project PLATFORM is aligning the design of the PPLs according to the MD requirements, in order to facilitate the CE marking in 2020 (TRL9) and avoid potential economic costs associated with future re-adaptations or modifications needed to ensure compliance with the MD. This paper discusses the methodological approach followed by the project PLATFORM to integrate all the nanosafety aspects in the design of the PPLs, in order to achieve safe designs in conformity with the relevant Essential Health and Safety Requirements (EHSRs) of the MD. Since machinery must be designed and constructed taking into account the results of the risk assessment (RA), this paper describes the systematic and iterative approach for RA and risk reduction followed to eliminate hazards as far practicable and to adequately reduce risks by the implementation of protective measures. This process has been guided by the harmonized standards EN ISO 12100 and EN ISO 14123, taking the relevant phases of life cycle, expected uses and operation modes of the PPLs into account. A specific tool to guide the safe design of the PPLs and facilitate the RA process has also been produced by the project (PLATFORM - SbD toolkit).

75 FR 53169 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-45; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... Contract Act, and trade agreements thresholds. The Councils have also used the same methodology to adjust... Business Regulatory Enforcement Fairness Act of 1996. It consists of a summary of rules appearing in...-008 Davis. and Reinvestment Act of 2009 (the Recovery Act)-- Buy American Requirements for...

Resource Guide: Accountability for English Learners under the ESEA. Non-Regulatory Guidance

ERIC Educational Resources Information Center

Office of Elementary and Secondary Education, US Department of Education, 2017

2017-01-01

English learners (ELs) are among the fastest-growing populations of students in our nation's public schools. This diverse subgroup of approximately 4.5 million students brings important cultural and linguistic assets to the public education system, but also faces a greater likelihood of lower graduation rates, academic achievement, and college…

76 FR 30280 - Public Meeting To Discuss the Proposed Rule on Enhanced Weapons, Firearms Background Checks, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-25

... Proposed Rule on Enhanced Weapons, Firearms Background Checks, and Security Event Notifications AGENCY... the proposed enhanced weapons rule, the two draft regulatory guides, and the draft weapons safety.... No formal comments on the proposed enhanced weapons rule or the draft guidance documents will be...

75 FR 61321 - Domestic Licensing of Production and Utilization Facilities; Updates to Incorporation by...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... electronic reading room at http://www.nrc.gov/reading-rm/adams.html . From this page, the public can gain... Regulatory Guides dated April 2009. The NRC's electronic reading room contains later versions of these Draft... in the training provided to examiners. Computer-based training, through the use of animations...

Self-Regulatory Efficacy and Mindset of At-Risk Students: An Exploratory Study

ERIC Educational Resources Information Center

Matheson, Ian A.

2015-01-01

There is a limited body of research examining how students' beliefs about intelligence and about their abilities relate to different learning environments. As reported here, I examined secondary school students' beliefs, goals, and expectations guided by Zimmerman's (2000) model of self-regulated learning. In this exploratory study, 230 secondary…

The Design of Technology-Rich Learning Environments as Metacognitive Tools in History Education

ERIC Educational Resources Information Center

Poitras, Eric; Lajoie, Susanne; Hong, Yuan-Jin

2012-01-01

Research has shown that learners do not always engage in appropriate metacognitive and self-regulatory processes while learning complex historical topics. However, little research exists to guide the design of technology-rich learning environments as metacognitive tools in history education. In order to address this issue, we designed a…

Federal Guidance Report No. 11: Limiting Values Of Radionuclide Intake And Air Concentration And Dose Conversion Factors For Inhalation, Submersion, And Ingestion

EPA Pesticide Factsheets

These guides were designed to be implemented by various Federal agencies having regulatory responsibilities for workers in the public sector, such as NRC and OSHA, and by Federal agencies with responsibilities for their own workers, such as DOE and DOD.

IT Legislative and Regulatory Issues Agenda. Higher Education Information Technology Alliance

ERIC Educational Resources Information Center

National Association of State Universities and Land-Grant Colleges, 2004

2004-01-01

This document represents the higher education and library community's guiding public policy agenda on information technology (IT) for the current year. The Higher Education Information Technology (HEIT) Alliance is a coalition of 11 national higher education and library associations, whose members represent a broad array of stakeholders on college…

76 FR 27924 - Draft Regulatory Guide, Guidance for ITAAC Closure

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... received on or before this date. Although a time limit is given, comments and suggestions in connection... are encouraged at any time. ADDRESSES: Please include Docket ID NRC-2011-0102 in the subject line of... comments to: RADB at 301-492-3446. You can access publicly available documents related to this notice using...

76 FR 40943 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

..., Revision 3, ``Criteria for Use of Computers in Safety Systems of Nuclear Power Plants.'' FOR FURTHER..., ``Criteria for Use of Computers in Safety Systems of Nuclear Power Plants,'' was issued with a temporary... Fuel Reprocessing Plants,'' to 10 CFR part 50 with regard to the use of computers in safety systems of...

77 FR 16868 - Quality Verification for Plate-Type Uranium-Aluminum Fuel Elements for Use in Research and Test...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

... Fuel Elements for Use in Research and Test Reactors AGENCY: Nuclear Regulatory Commission. ACTION... Plate-Type Uranium-Aluminum Fuel Elements for Use in Research and Test Reactors.'' This guide describes... plate-type uranium-aluminum fuel elements used in research and test reactors (RTRs). DATES: Submit...

78 FR 31614 - Implementation of Regulatory Guide 1.221 on Design-Basis Hurricane and Hurricane Missiles

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... for Nuclear Power Plants,'' in support of NRC reviews of early site permit (ESP), standard design... NUREG-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants... License Applications for Nuclear Power Plants, (LWR Edition)'' (ML070630003) In addition, this ISG...

Section 1--The Value of Psychology in Health Professional Education

ERIC Educational Resources Information Center

Upton, Dominic

2008-01-01

The education of nurses, midwives and allied health care professionals in the UK is guided by professional bodies and the over arching Health Professionals Council (HPC)/Nursing and Midwifery Council (NMC). Each of these professional bodies provides regulatory frameworks and guidance notes on the educational content of the degree level programmes…

Interfering with Inner Speech Selectively Disrupts Problem Solving and Is Linked with Real-World Executive Functioning

ERIC Educational Resources Information Center

Wallace, Gregory L.; Peng, Cynthia S.; Williams, David

2017-01-01

Purpose: According to Vygotskian theory, verbal thinking serves to guide our behavior and underpins critical self-regulatory functions. Indeed, numerous studies now link inner speech usage with performance on tests of executive function (EF). However, the selectivity of inner speech contributions to multifactorial executive planning performance…

76 FR 41527 - Draft Regulatory Guide: Re-Issuance and Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... and methods that are acceptable to the NRC staff for implementing specific parts of the NRC's..., and fabrication of mixed-oxide fuel or fuel assemblies. DG-3037 provides guidance on how to meet the... publicly disclosed. You may submit comments by any one of the following methods: Federal Rulemaking Web...

76 FR 24062 - Florida Power and Light Company, St. Lucie, Unit Nos. 1 and 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... (d) is again required. Regulatory Guide 5.73, Fatigue Management for Nuclear Power Plant Personnel, endorses the Nuclear Energy Institute (NEI) report NEI 06- 11, revision 1, ``Managing Personnel Fatigue at Nuclear Power Plants,'' with certain clarifications, additions and exceptions. The NRC staff has endorsed...

Mentoring for Success in Tobacco Regulatory Science: A Qualitative Study

PubMed Central

Russo, Abigail R.; Solis, Amy C.; Villanti, Andrea C.; Wipfli, Heather L.; Kern, Teresa T.; Lawley, Rachel K.; Collins, Lauren K.; Abudayyeh, Haneen S.; Chansky, Melanie C.; Glantz, Stanton A.; Samet, Jonathan M.; Benjamin, Emelia J.

2017-01-01

Objectives Our study explores the experiences of early career and senior scientists regarding mentorship and career trajectories in tobacco regulatory science (TRS). Methods We conducted 22 phone interviews with early career and senior tobacco regulatory scientists from July 2015 to January 2016. All interviews were conducted using a structured interview guide and analyzed using a thematic approach by 2 independent coders. Results TRS presents specific opportunities and challenges to scientists due to its focused goal of informing tobacco regulation. An understanding of US Food and Drug Administration (FDA) research priorities and how science can inform tobacco regulation are essential for effective mentorship in TRS. Careers in TRS can be pursued in various academic and non-academic professional roles; both offer the distinct ability to conduct science that impacts public policy. Early career and senior scientists identified the importance and challenge of providing broad training across the diverse disciplines of TRS. Conclusions Effective mentorship in TRS requires that mentors possess an in-depth understanding of the scientific, regulatory, and legislative processes inherent to tobacco regulatory policy-making. A training program for mentors specific to TRS has the potential to meet diverse professional needs of mentors and mentees aiming to impact tobacco policy. PMID:28758143

LWR pressure vessel surveillance dosimetry improvement program: LWR power reactor surveillance physics-dosimetry data base compendium

DOE Office of Scientific and Technical Information (OSTI.GOV)

McElroy, W.N.

1985-08-01

This NRC physics-dosimetry compendium is a collation of information and data developed from available research and commercial light water reactor vessel surveillance program (RVSP) documents and related surveillance capsule reports. The data represents the results of the HEDL least-squares FERRET-SAND II Code re-evaluation of exposure units and values for 47 PWR and BWR surveillance capsules for W, B and W, CE, and GE power plants. Using a consistent set of auxiliary data and dosimetry-adjusted reactor physics results, the revised fluence values for E > 1 MeV averaged 25% higher than the originally reported values. The range of fluence values (new/old)more » was from a low of 0.80 to a high of 2.38. These HEDL-derived FERRET-SAND II exposure parameter values are being used for NRC-supported HEDL and other PWR and BWR trend curve data development and testing studies. These studies are providing results to support Revision 2 of Regulatory Guide 1.99. As stated by Randall (Ra84), the Guide is being updated to reflect recent studies of the physical basis for neutron radiation damage and efforts to correlate damage to chemical composition and fluence.« less

Roadmap for creating an accelerated three-year medical education program

PubMed Central

Leong, Shou Ling; Cangiarella, Joan; Fancher, Tonya; Dodson, Lisa; Grochowski, Colleen; Harnik, Vicky; Hustedde, Carol; Jones, Betsy; Kelly, Christina; Macerollo, Allison; Reboli, Annette C.; Rosenfeld, Melvin; Rundell, Kristen; Thompson, Tina; Whyte, Robert; Pusic, Martin

2017-01-01

ABSTRACT Medical education is undergoing significant transformation. Many medical schools are moving away from the concept of seat time to competency-based education and introducing flexibility in the curriculum that allows individualization. In response to rising student debt and the anticipated physician shortage, 35% of US medical schools are considering the development of accelerated pathways. The roadmap described in this paper is grounded in the experiences of the Consortium of Accelerated Medical Pathway Programs (CAMPP) members in the development, implementation, and evaluation of one type of accelerated pathway: the three-year MD program. Strategies include developing a mission that guides curricular development – meeting regulatory requirements, attaining institutional buy-in and resources necessary to support the programs, including student assessment and mentoring – and program evaluation. Accelerated programs offer opportunities to innovate and integrate a mission benefitting students and the public. Abbreviations: CAMPP: Consortium of accelerated medical pathway programs; GME: Graduate medical education; LCME: Liaison committee on medical education; NRMP: National residency matching program; UME: Undergraduate medical education PMID:29117817

Translational Neuroscience as a Tool for Intervention Development in the Context of High-Adversity Families

PubMed Central

Fisher, Philip A.

2017-01-01

The use of theory-driven models to develop and evaluate family-based intervention programs has a long history in psychology. Some of the first evidence-based parenting programs to address child problem behavior, developed in the 1970s, were grounded in causal models derived from longitudinal developmental research. The same translational strategies can also be applied to designing programs that leverage emerging scientific knowledge about the effects of early adverse experiences on neurobiological systems to reduce risk and promote well-being. By specifying not only behavioral targets but also affected underlying neural systems, interventions can become more precise and efficient. This chapter describes the development of a program of research focusing on an intervention for young children in foster care. The intervention emerged from social learning theory research and employs a translational neuroscience approach. The conceptual model guiding the research, which incorporates behavioral domains as well as stress-regulatory neural systems, is described. Finally, future directions for translational neuroscience in family-based intervention research are considered. PMID:27589501

Roadmap for creating an accelerated three-year medical education program.

PubMed

Leong, Shou Ling; Cangiarella, Joan; Fancher, Tonya; Dodson, Lisa; Grochowski, Colleen; Harnik, Vicky; Hustedde, Carol; Jones, Betsy; Kelly, Christina; Macerollo, Allison; Reboli, Annette C; Rosenfeld, Melvin; Rundell, Kristen; Thompson, Tina; Whyte, Robert; Pusic, Martin

2017-01-01

Medical education is undergoing significant transformation. Many medical schools are moving away from the concept of seat time to competency-based education and introducing flexibility in the curriculum that allows individualization. In response to rising student debt and the anticipated physician shortage, 35% of US medical schools are considering the development of accelerated pathways. The roadmap described in this paper is grounded in the experiences of the Consortium of Accelerated Medical Pathway Programs (CAMPP) members in the development, implementation, and evaluation of one type of accelerated pathway: the three-year MD program. Strategies include developing a mission that guides curricular development - meeting regulatory requirements, attaining institutional buy-in and resources necessary to support the programs, including student assessment and mentoring - and program evaluation. Accelerated programs offer opportunities to innovate and integrate a mission benefitting students and the public. CAMPP: Consortium of accelerated medical pathway programs; GME: Graduate medical education; LCME: Liaison committee on medical education; NRMP: National residency matching program; UME: Undergraduate medical education.

Applying quantitative benefit-risk analysis to aid regulatory decision making in diagnostic imaging: methods, challenges, and opportunities.

PubMed

Agapova, Maria; Devine, Emily Beth; Bresnahan, Brian W; Higashi, Mitchell K; Garrison, Louis P

2014-09-01

Health agencies making regulatory marketing-authorization decisions use qualitative and quantitative approaches to assess expected benefits and expected risks associated with medical interventions. There is, however, no universal standard approach that regulatory agencies consistently use to conduct benefit-risk assessment (BRA) for pharmaceuticals or medical devices, including for imaging technologies. Economics, health services research, and health outcomes research use quantitative approaches to elicit preferences of stakeholders, identify priorities, and model health conditions and health intervention effects. Challenges to BRA in medical devices are outlined, highlighting additional barriers in radiology. Three quantitative methods--multi-criteria decision analysis, health outcomes modeling and stated-choice survey--are assessed using criteria that are important in balancing benefits and risks of medical devices and imaging technologies. To be useful in regulatory BRA, quantitative methods need to: aggregate multiple benefits and risks, incorporate qualitative considerations, account for uncertainty, and make clear whose preferences/priorities are being used. Each quantitative method performs differently across these criteria and little is known about how BRA estimates and conclusions vary by approach. While no specific quantitative method is likely to be the strongest in all of the important areas, quantitative methods may have a place in BRA of medical devices and radiology. Quantitative BRA approaches have been more widely applied in medicines, with fewer BRAs in devices. Despite substantial differences in characteristics of pharmaceuticals and devices, BRA methods may be as applicable to medical devices and imaging technologies as they are to pharmaceuticals. Further research to guide the development and selection of quantitative BRA methods for medical devices and imaging technologies is needed. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.

PubMed

Rothenberg, Ellen V; Ungerbäck, Jonas; Champhekar, Ameya

2016-01-01

T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of innate lymphoid cells (ILCs) that share transcriptional regulation programs extensively with T-cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate. © 2016 Elsevier Inc. All rights reserved.

Strengthening the regulatory system through the implementation and use of a quality management system.

PubMed

Eisner, Reinhold; Patel, Rakeshkumar

2017-04-20

Quality management systems (QMS), based on ISO 9001 requirements, are applicable to government service organizations such as Health Canada's Biologics and Genetic Therapies Directorate (BGTD). This communication presents the process that the BGTD followed since the early 2000s to implement a quality management system and describes how the regulatory system was improved as a result of this project. BGTD undertook the implementation of a quality management system based on ISO 9001 and containing aspects of ISO 17025 with the goal of strengthening the regulatory system through improvements in the people, processes, and services of the organization. We discuss the strategy used by BGTD to implement the QMS and the benefits that were realized from the various stages of implementation. The eight quality principals upon which the QMS standards of the ISO 9000 series are based were used by senior management as a framework to guide QMS implementation.

Spent fuel cask handling at an operating nuclear power plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pal, A.C.

1988-01-01

The importance of spent fuel handling at operating nuclear power plants cannot be overstated. Because of its highly radioactive nature, however, spent fuel must be handled in thick, lead-lined containers or casks. Thus, all casks for spent fuel handling are heavy loads by the US Nuclear Regulatory Commission's definition, and any load-drop must be evaluated for its potential to damage safety-related equipment. Nuclear Regulatory Guide NUREG-0612 prescribes the regulatory requirements of alternative heavy-load-handling methodologies such as (a) by providing cranes that meet the requirements of NUREG-0554, which shall be called the soft path, or (b) by providing protective devices atmore » all postulated load-drop areas to prevent any damage to safety-related equipment, which shall be called the hard path. The work reported in this paper relates to cask handling at New York Power Authority's James A. FitzPatrick (JAF) plant.« less

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

A Brief Review of RNA–Protein Interaction Database Resources

PubMed Central

Yi, Ying; Zhao, Yue; Huang, Yan; Wang, Dong

2017-01-01

RNA–Protein interactions play critical roles in various biological processes. By collecting and analyzing the RNA–Protein interactions and binding sites from experiments and predictions, RNA–Protein interaction databases have become an essential resource for the exploration of the transcriptional and post-transcriptional regulatory network. Here, we briefly review several widely used RNA–Protein interaction database resources developed in recent years to provide a guide of these databases. The content and major functions in databases are presented. The brief description of database helps users to quickly choose the database containing information they interested. In short, these RNA–Protein interaction database resources are continually updated, but the current state shows the efforts to identify and analyze the large amount of RNA–Protein interactions. PMID:29657278

Renin and aldosterone measurements in the management of arterial hypertension.

PubMed

Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

2015-06-01

Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy. © Georg Thieme Verlag KG Stuttgart · New York.

HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

PubMed Central

Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

2013-01-01

Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

Practical Solutions for Pesticide Safety: A Farm and Research Team Participatory Model

PubMed Central

Galvin, Kit; Krenz, Jen; Harrington, Marcy; Palmández, Pablo; Fenske, Richard A.

2018-01-01

Development of the Practical Solutions for Pesticide Safety guide used participatory research strategies to identify and evaluate solutions that reduce pesticide exposures for workers and their families and to disseminate these solutions. Project principles were (1) workplace chemicals belong in the workplace, and (2) pesticide handlers and farm managers are experts, with direct knowledge of production practices. The project’s participatory methods were grounded in self-determination theory. Practical solutions were identified and evaluated based on five criteria: practicality, adaptability, health and safety, novelty, and regulatory compliance. Research activities that had more personal contact provided better outcomes. The Expert Working Group, composed of farm managers and pesticide handlers, was key to the identification of solutions, as were farm site visits. Audience participation, hands-on testing, and orchard field trials were particularly effective in the evaluation of potential solutions. Small work groups in a Regional Advisory Committee provided the best direction and guidance for a “user-friendly” translational document that provided evidence-based practical solutions. The “farmer to farmer” format of the guide was endorsed by both the Expert Working Group and the Regional Advisory Committee. Managers and pesticide handlers wanted to share their solutions in order to “help others stay safe,” and they appreciated attribution in the guide. The guide is now being used in educational programs across the region. The fundamental concept that farmers and farmworkers are innovators and experts in agricultural production was affirmed by this study. The success of this process demonstrates the value of participatory industrial hygiene in agriculture. PMID:26488540

Practical Solutions for Pesticide Safety: A Farm and Research Team Participatory Model.

PubMed

Galvin, Kit; Krenz, Jen; Harrington, Marcy; Palmández, Pablo; Fenske, Richard A

2016-01-01

Development of the Practical Solutions for Pesticide Safety guide used participatory research strategies to identify and evaluate solutions that reduce pesticide exposures for workers and their families and to disseminate these solutions. Project principles were (1) workplace chemicals belong in the workplace, and (2) pesticide handlers and farm managers are experts, with direct knowledge of production practices. The project's participatory methods were grounded in self-determination theory. Practical solutions were identified and evaluated based on five criteria: practicality, adaptability, health and safety, novelty, and regulatory compliance. Research activities that had more personal contact provided better outcomes. The Expert Working Group, composed of farm managers and pesticide handlers, was key to the identification of solutions, as were farm site visits. Audience participation, hands-on testing, and orchard field trials were particularly effective in the evaluation of potential solutions. Small work groups in a Regional Advisory Committee provided the best direction and guidance for a "user-friendly" translational document that provided evidence-based practical solutions. The "farmer to farmer" format of the guide was endorsed by both the Expert Working Group and the Regional Advisory Committee. Managers and pesticide handlers wanted to share their solutions in order to "help others stay safe," and they appreciated attribution in the guide. The guide is now being used in educational programs across the region. The fundamental concept that farmers and farmworkers are innovators and experts in agricultural production was affirmed by this study. The success of this process demonstrates the value of participatory industrial hygiene in agriculture.

Developing a business-practice model for pharmacy services in ambulatory settings.

PubMed

Harris, Ila M; Baker, Ed; Berry, Tricia M; Halloran, Mary Ann; Lindauer, Kathleen; Ragucci, Kelly R; McGivney, Melissa Somma; Taylor, A Thomas; Haines, Stuart T

2008-02-01

A business-practice model is a guide, or toolkit, to assist managers and clinical pharmacy practitioners in the exploration, proposal, development and implementation of new clinical pharmacy services and/or the enhancement of existing services. This document was developed by the American College of Clinical Pharmacy Task Force on Ambulatory Practice to assist clinical pharmacy practitioners and administrators in the development of business-practice models for new and existing clinical pharmacy services in ambulatory settings. This document provides detailed instructions, examples, and resources on conducting a market assessment and a needs assessment, types of clinical services, operations, legal and regulatory issues, marketing and promotion, service development and exit plan, evaluation of service outcomes, and financial considerations in the development of a clinical pharmacy service in the ambulatory environment. Available literature is summarized, and an appendix provides valuable citations and resources. As ambulatory care practices continue to evolve, there will be increased knowledge of how to initiate and expand the services. This document is intended to serve as an essential resource to assist in the growth and development of clinical pharmacy services in the ambulatory environment.

Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

PubMed

Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

2016-05-01

Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

Food Reformulation, Responsive Regulation, and “Regulatory Scaffolding”: Strengthening Performance of Salt Reduction Programs in Australia and the United Kingdom

PubMed Central

Magnusson, Roger; Reeve, Belinda

2015-01-01

Strategies to reduce excess salt consumption play an important role in preventing cardiovascular disease, which is the largest contributor to global mortality from non-communicable diseases. In many countries, voluntary food reformulation programs seek to reduce salt levels across selected product categories, guided by aspirational targets to be achieved progressively over time. This paper evaluates the industry-led salt reduction programs that operate in the United Kingdom and Australia. Drawing on theoretical concepts from the field of regulatory studies, we propose a step-wise or “responsive” approach that introduces regulatory “scaffolds” to progressively increase levels of government oversight and control in response to industry inaction or under-performance. Our model makes full use of the food industry’s willingness to reduce salt levels in products to meet reformulation targets, but recognizes that governments remain accountable for addressing major diet-related health risks. Creative regulatory strategies can assist governments to fulfill their public health obligations, including in circumstances where there are political barriers to direct, statutory regulation of the food industry. PMID:26133973

77 FR 4498 - Rules and Regulations Under the Wool Products Labeling Act of 1939

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... Commission requests public comment on the overall costs, benefits, necessity, and regulatory and economic... seeking public comment on the continuing need for the rule or guide as well as its costs and benefits to..., and on the costs and benefits of certain provisions of the Wool Products Labeling Act of 1939. DATES...

75 FR 51134 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... Wertpapierb[ouml]rse (Frankfurt Stock Exchange) and traded on the Xetra trading system operated by Deutsche B[ouml]rse AG (``DBAG''). DBAG is regulated by the German Federal Financial Supervisory Authority (``Ba.... \\7\\ See ``Guide to the Equity Indices of Deutsche B[ouml]rse,'' at http://www.deutsche-boerse.com for...

Self-Efficacy, Planning and Action Control in an Oral Self-Care Intervention

ERIC Educational Resources Information Center

Zhou, Guangyu; Sun, Caiyun; Knoll, Nina; Hamilton, Kyra; Schwarzer, Ralf

2015-01-01

To evaluate a theory-guided intervention on oral self-care and examine the possible mechanisms among self-regulatory factors, two brief intervention arms were compared, an information-based education treatment and a self-regulation treatment focusing on planning and action control. Young adults (N = 284; aged 18-29 years) were assessed at baseline…

77 FR 50727 - Configuration Management Plans for Digital Computer Software Used in Safety Systems of Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... comments received on or before this date. Although a time limit is given, comments and suggestions in... guides are encouraged at any time. ADDRESSES: You may access information and comment submissions related... Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001; telephone: 301-251-7494 or email...

78 FR 33132 - Quality Verification for Plate-Type Uranium-Aluminum Fuel Elements for Use in Research and Test...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-03

... Fuel Elements for Use in Research and Test Reactors AGENCY: Nuclear Regulatory Commission. ACTION... Research and Test Reactors.'' This guide describes a method that the staff of the NRC considers acceptable... assurance program for verifying the quality of plate-type uranium-aluminum fuel elements used in research...

77 FR 31655 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... controverted. In addition, the requestor/petitioner shall provide a brief explanation of the bases for the... against burst, as discussed in Regulatory Guide (RG) 1.121, ``Bases for Plugging Degraded PWR [Pressurized... Institute] 97-06, Revision 3, ``Steam Generator Program Guidelines'' (Reference 1) and RG 1.121, ``Bases for...

Infant Mental Health Assessment and Intervention Guidance for Service Providers and Families of Young Children. Service Guideline 4.

ERIC Educational Resources Information Center

Connecticut Birth to Three System, Hartford.

This guide offers assessment and intervention guidelines for the Connecticut Birth to Three system concerning the emotional and psychological well-being of infants and toddlers in the system. Emphasis is on infants and toddlers who exhibit symptoms of traumatic stress disorder, depression or other affective disorders, regulatory disorders, sleep…

75 FR 47307 - Center for Devices and Radiological Health 510(k) Working Group Preliminary Report and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... 510(k) program optimally achieves these goals. In September 2009, CDRH convened an internal 510(k...) program and explore actions CDRH could take to strengthen the program and improve the consistency of its... CDRH uses science to guide its regulatory decision making across the total product life cycle of...

Hydropower: A Regulatory Guide to Permitting and Licensing in Idaho, Montana, Oregon, and Washington.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCoy, Gilbert A.

1992-12-01

The design, construction and operation of a hydropower project can result in many potential impacts. These potential impacts are of concern to a host of federal, state, and local authorities. Early consultation with land and water management, fish and wildlife resource protection, and health and human safety-oriented agencies should occur to determine specific concerns and study requirements for each proposed project. This Guide to Permitting and Licensing outlines the characteristic features of attractive hydropower sites; summarizes an array of developmental constraints; illustrates potential environmental impacts and concerns; and summarizes all federal, state, and local permitting and licensing requirements.

Hydropower : A Regulatory Guide to Permitting and Licensing in Idaho, Montana, Oregon, and Washington.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCoy, Gilbert A.

1992-12-01

The design, construction and operation of a hydropower project can result in many potential impacts. These potential impacts are of concern to a host of federal, state, and local authorities. Early consultation with land and water management, fish and wildlife resource protection, and health and human safety-oriented agencies should occur to determine specific concerns and study requirements for each proposed project. This Guide to Permitting and Licensing outlines the characteristic features of attractive hydropower sites; summarizes an array of developmental constraints; illustrates potential environmental impacts and concerns; and summarizes all federal, state, and local permitting and licensing requirements.

Building quality mHealth for low resource settings.

PubMed

Ettinger, Kate Michi; Pharaoh, Hamilton; Buckman, Reymound Yaw; Conradie, Hoffie; Karlen, Walter

In low- and middle-income countries (LMIC), community health care workers (CHCW) are the primary point of care for millions of people. Mobile phone health applications (mHealth app) are the preferred technology platform to deliver clinical support to CHCW. In LMIC, limited regulatory oversight exists to guide quality and safety for medical devices, including mHealth. During the development of a mHealth app to assist CHCW with patient assessment and clinical diagnosis in rural South Africa, we applied human-centred design (HCD) and a bioethics consultation. The HCD approach enabled us to develop a mHealth app that responded to the needs and capacities of CHCW. The bioethics consultation prompted early consideration of safety concerns, social implications of our mHealth app and our technology's impact on the CHCW-patient relationship. In this study, we found that combining a HCD approach with bioethics consultation improved the design quality and reduced safety concerns for our mHealth app.

iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines.

PubMed

Moise, Leonard; Gutierrez, Andres; Kibria, Farzana; Martin, Rebecca; Tassone, Ryan; Liu, Rui; Terry, Frances; Martin, Bill; De Groot, Anne S

2015-01-01

Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets. Several iVAX vaccine design projects have had success in pre-clinical studies in animal models and are progressing toward clinical studies. The toolkit now incorporates a range of immunoinformatics tools for infectious disease and cancer immunotherapy vaccine design. This article will provide a guide to the iVAX approach to computational vaccinology.

A structured policy review of the principles of professional self-regulation.

PubMed

Benton, D C; González-Jurado, M A; Beneit-Montesinos, J V

2013-03-01

The International Council of Nurses (ICN) has, for many years, based its work on professional self-regulation on a set of 12 principles. These principles are research based and were identified nearly three decades ago. ICN has conducted a number of reviews of the principles; however, changes have been minimal. In the past 5-10 years, a number of authors and governments, often as part of the review of regulatory systems, have started to propose principles to guide the way regulatory frameworks are designed and implemented. These principles vary in number and content. This study examines the current policy literature on principle-based regulation and compares this with the set of principles advocated by the ICN. A systematic search of the literature on principle-based regulation is used as the basis for a qualitative thematic analysis to compare and contrast the 12 principles of self-regulation with more recently published work. A mapping of terms based on a detailed description of the principles used in the various research and policy documents was generated. This mapping forms the basis of a critique of the current ICN principles. A professional self-regulation advocated by the ICN were identified. A revised and extended set of 13 principles is needed if contemporary developments in the field of regulatory frameworks are to be accommodated. These revised principles should be considered for adoption by the ICN to underpin their advocacy work on professional self-regulation. © 2013 The Authors. International Nursing Review © 2013 International Council of Nurses.

A powerful approach reveals numerous expression quantitative trait haplotypes in multiple tissues.

PubMed

Ying, Dingge; Li, Mulin Jun; Sham, Pak Chung; Li, Miaoxin

2018-04-26

Recently many studies showed single nucleotide polymorphisms (SNPs) affect gene expression and contribute to development of complex traits/diseases in a tissue context-dependent manner. However, little is known about haplotype's influence on gene expression and complex traits, which reflects the interaction effect between SNPs. In the present study, we firstly proposed a regulatory region guided eQTL haplotype association analysis approach, and then systematically investigate the expression quantitative trait loci (eQTL) haplotypes in 20 different tissues by the approach. The approach has a powerful design of reducing computational burden by the utilization of regulatory predictions for candidate SNP selection and multiple testing corrections on non-independent haplotypes. The application results in multiple tissues showed that haplotype-based eQTLs not only increased the number of eQTL genes in a tissue specific manner, but were also enriched in loci that associated with complex traits in a tissue-matched manner. In addition, we found that tag SNPs of eQTL haplotypes from whole blood were selectively enriched in certain combination of regulatory elements (e.g. promoters and enhancers) according to predicted chromatin states. In summary, this eQTL haplotype detection approach, together with the application results, shed insights into synergistic effect of sequence variants on gene expression and their susceptibility to complex diseases. The executable application "eHaplo" is implemented in Java and is publicly available at http://grass.cgs.hku.hk/limx/ehaplo/. jonsonfox@gmail.com, limiaoxin@mail.sysu.edu.cn. Supplementary data are available at Bioinformatics online.

Environmentally induced epigenetic toxicity: potential public health concerns

PubMed Central

Marczylo, Emma L.; Jacobs, Miriam N.; Gant, Timothy W.

2016-01-01

Abstract Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection. PMID:27278298

Environmentally induced epigenetic toxicity: potential public health concerns.

PubMed

Marczylo, Emma L; Jacobs, Miriam N; Gant, Timothy W

2016-09-01

Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.

The molecular mechanism of plant gravitropism.

PubMed

Wu, Di; Huang, Lin-zhou; Gao, Jin; Wang, Yong-hong

2016-07-20

Gravity is an important environmental factor that regulates plant growth and morphogenesis. In response to gravity stimulus, plants can set the optimum angle between the organs and the gravity vector. Plant gravitropism is divided into four sequential steps, including gravity perception, signal transduction, asymmetrical distribution of auxin, and organ curvature. In recent years, large numbers of mutants with defective gravitropism have been identified and genes involved in the regulation of gravitropism have been functionally characterized. In particular, progress has been achieved on elucidating the molecular mechanisms of gravity perception and asymmetrical distribution of auxin. As one of the most important strategies for plant to adapt environmental changes, gravitropism is also involved in the regulation of rice plant architecture and grain yield through modulating rice tiller angle. Therefore, the investigation of plant gravitropism not only contributes to decipher the regulatory mechanisms of plant growth and development, but also helps to guide the genetic improvement of crop architecture. However, the molecular mechanisms and regulatory network of gravitropism remain to be elusive. In this review, we focus on recent progress on elucidating molecular mechanisms underlying gravitropism and its involvement in regulating rice tiller angle, which is an important agronomic trait that determines rice plant architecture and thus grain yields.

A periodic table for cancer.

PubMed

Epstein, Richard J

2015-01-01

Cancers exhibit differences in metastatic behavior and drug sensitivity that correlate with certain tumor-specific variables such as differentiation grade, growth rate/extent and molecular regulatory aberrations. In practice, patient management is based on the past results of clinical trials adjusted for these biomarkers. Here, it is proposed that treatment strategies could be fine-tuned upfront simply by quantifying tumorigenic spatial (cell growth) and temporal (genetic stability) control losses, as predicted by genetic defects of cell-cycle-regulatory gatekeeper and genome-stabilizing caretaker tumor suppressor genes, respectively. These differential quantifications of tumor dysfunction may in turn be used to create a tumor-specific 'periodic table' that guides rational formulation of survival-enhancing anticancer treatment strategies.

Characterization of complex systems using the design of experiments approach: transient protein expression in tobacco as a case study.

PubMed

Buyel, Johannes Felix; Fischer, Rainer

2014-01-31

Plants provide multiple benefits for the production of biopharmaceuticals including low costs, scalability, and safety. Transient expression offers the additional advantage of short development and production times, but expression levels can vary significantly between batches thus giving rise to regulatory concerns in the context of good manufacturing practice. We used a design of experiments (DoE) approach to determine the impact of major factors such as regulatory elements in the expression construct, plant growth and development parameters, and the incubation conditions during expression, on the variability of expression between batches. We tested plants expressing a model anti-HIV monoclonal antibody (2G12) and a fluorescent marker protein (DsRed). We discuss the rationale for selecting certain properties of the model and identify its potential limitations. The general approach can easily be transferred to other problems because the principles of the model are broadly applicable: knowledge-based parameter selection, complexity reduction by splitting the initial problem into smaller modules, software-guided setup of optimal experiment combinations and step-wise design augmentation. Therefore, the methodology is not only useful for characterizing protein expression in plants but also for the investigation of other complex systems lacking a mechanistic description. The predictive equations describing the interconnectivity between parameters can be used to establish mechanistic models for other complex systems.

Basic Science and Public Policy: Informed Regulation for Nicotine and Tobacco Products.

PubMed

Fowler, Christie D; Gipson, Cassandra D; Kleykamp, Bethea A; Rupprecht, Laura E; Harrell, Paul T; Rees, Vaughan W; Gould, Thomas J; Oliver, Jason; Bagdas, Deniz; Damaj, M Imad; Schmidt, Heath D; Duncan, Alexander; De Biasi, Mariella

2018-06-07

Scientific discoveries over the past few decades have provided significant insight into the abuse liability and negative health consequences associated with tobacco and nicotine-containing products. While many of these advances have led to the development of policies and laws that regulate access to and formulations of these products, further research is critical to guide future regulatory efforts, especially as novel nicotine-containing products are introduced and selectively marketed to vulnerable populations. In this narrative review, we provide an overview of the scientific findings that have impacted regulatory policy and discuss considerations for further translation of science into policy decisions. We propose that open, bidirectional communication between scientists and policy makers is essential to develop transformative preventive- and intervention-focused policies and programs to reduce appeal, abuse liability, and toxicity of the products. Through these types of interactions, collaborative efforts to inform and modify policy have the potential to significantly decrease the use of tobacco and alternative nicotine products and thus enhance health outcomes for individuals. This work addresses current topics in the nicotine and tobacco research field to emphasize the importance of basic science research and provide examples of how it can be utilized to inform public policy. In addition to relaying current thoughts on the topic from experts in the field, the article encourages continued efforts and communication between basic scientists and policy officials.

GREGOR: evaluating global enrichment of trait-associated variants in epigenomic features using a systematic, data-driven approach.

PubMed

Schmidt, Ellen M; Zhang, Ji; Zhou, Wei; Chen, Jin; Mohlke, Karen L; Chen, Y Eugene; Willer, Cristen J

2015-08-15

The majority of variation identified by genome wide association studies falls in non-coding genomic regions and is hypothesized to impact regulatory elements that modulate gene expression. Here we present a statistically rigorous software tool GREGOR (Genomic Regulatory Elements and Gwas Overlap algoRithm) for evaluating enrichment of any set of genetic variants with any set of regulatory features. Using variants from five phenotypes, we describe a data-driven approach to determine the tissue and cell types most relevant to a trait of interest and to identify the subset of regulatory features likely impacted by these variants. Last, we experimentally evaluate six predicted functional variants at six lipid-associated loci and demonstrate significant evidence for allele-specific impact on expression levels. GREGOR systematically evaluates enrichment of genetic variation with the vast collection of regulatory data available to explore novel biological mechanisms of disease and guide us toward the functional variant at trait-associated loci. GREGOR, including source code, documentation, examples, and executables, is available at http://genome.sph.umich.edu/wiki/GREGOR. cristen@umich.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

PubMed

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

2017-08-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies

PubMed Central

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A.

2017-01-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy. PMID:28817344

77 FR 30029 - Advisory Committee on Reactor Safeguards; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

..., Rockville, Maryland. Wednesday, June 6, 2012, Conference Room T2-B1, 11545 Rockville Pike, Rockville... evaluation of the Fukushima Dai-ichi accident. 12:45 p.m.-2:15 p.m.: Proposed Revision 1 to Regulatory Guide... proprietary, pursuant to 5 U.S.C. 552b(c)(4)]. Thursday, June 7, 2012, Conference Room T2-B1, 11545 Rockville...

78 FR 29629 - Special Local Regulations and Safety Zones; Recurring Marine Events and Fireworks Displays Within...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

... Entities Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L....lD, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969... along longitude 074[deg]37'00'' W. 2 May--3rd Sunday...... Annual Escape from Escape from Fort All...

76 FR 41148 - Care Labeling of Textile Wearing Apparel and Certain Piece Goods as Amended

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... the overall costs, benefits, necessity, and regulatory and economic impact of the FTC's Rule on Care... periodically. These reviews seek information about the costs and benefits of the rules and guides as well as... modifications, if any, should the Commission make to the Rule to increase its benefits or reduce its costs to...

Transforming of Educational Institutions after GATS--Consequences in Social Relations as Corporation, Competition and State Regulation

ERIC Educational Resources Information Center

Jensen, Knud; Michel-Schertges, Dirk

2010-01-01

This article presents aspects of the regulatory reform work in public sectors was guided by the OECD in the 1990's manifested in GATS ( 1995 ) strategically planned by and through the Bologna Process and eagerly elaborated by boards and power holders of universities and university colleges. The tendency is privatisation which has as a consequence…

78 FR 75423 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change To List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... the proposed rule change is available on the Exchange's Web site at www.nyse.com , at the principal... policies pursued by central banks and economic environments. The Investment Adviser will search for...) (stating that Guide 4 ``permit[s] a fund to invest up to 15% of its assets in illiquid securities''). The...

A Unique Model Platform for C4 Plant Systems and Synthetic Biology

DTIC Science & Technology

2015-12-10

International Conference in Bioinformatics , Sydney, Australia, July 31 - August 2, 2014.  Nielsen LK (2015) Genome scale metabolic and regulatory...the comparison of transcriptome proteome and central metabolome in mature and immature tissue. Preliminary data were obtained suggesting successful...guide the comparison of transcriptome, proteome and central metabolome in mature and immature tissue. Preliminary data were obtained suggesting

Coordination of Ocean Management: A Perspective on the Gulf of Maine,

DTIC Science & Technology

1982-11-01

transportation modes. The U.S. Coast Guard operates two OMEGA stations; the remaining six are operated by host countries under international agreement. The...42 Reasons for a Comprehensive Approach .......................... 43 Regulatory Reform .................................. 44...physical ocean, but that framework falls short in its efforts to guide and coordinate the activities of ocean users. Much of the remaining effort in this

77 FR 70484 - Preoperational Testing of Onsite Electric Power Systems To Verify Proper Load Group Assignments...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... publicly available documents online in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To... reproduce them. NRC's PDR: You may examine and purchase copies of public documents at the NRC's PDR, Room O1... that the staff needs in its review of applications for permits and licenses. The draft regulatory guide...

75 FR 5632 - Office of New Reactors; Interim Staff Guidance on the Review of Nuclear Power Plant Designs Using...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

....8 and Regulatory Guide 1.206, ``Combined License Applications for Nuclear Power Plants (LWR Edition... Management System (ADAMS) Accession No. ML092640035). This ISG provides new guidance information for... (SRP), Section 8.3.1 and Sections 9.5.4 through 9.5.8. The NRC staff issues DC/COL-ISGs to facilitate...

Cogeneration : A Regulatory Guide to Leasing, Permitting, and Licensing in Idaho, Montana, Oregon, and Washington.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deshaye, Joyce; Bloomquist, R.Gordon

1992-12-01

This guidebook focuses on cogeneration development. It is one of a series of four guidebooks recently prepared to introduce the energy developer to the federal, state and local agencies that regulate energy facilities in Idaho, Montana, Oregon, and Washington (the Bonneville Power Administration Service Territory). It was prepared specifically to help cogeneration developers obtain the permits, licenses and approvals necessary to construct and operate a cogeneration facility. The regulations, agencies and policies described herein are subject to change. Changes are likely to occur whenever energy or a project becomes a political issue, a state legislature meets, a preexisting popular ormore » valuable land use is thought threatened, elected and appointed officials change, and new directions are imposed on states and local governments by the federal government. Accordingly, cogeneration developers should verify and continuously monitor the status of laws and rules that might affect their plans. Developers are cautioned that the regulations described herein may only be a starting point on the road to obtaining all the necessary permits.« less

2012 Global Summit on Regulatory Science (GSRS-2012)--modernizing toxicology.

PubMed

Miller, Margaret A; Tong, Weida; Fan, Xiaohui; Slikker, William

2013-01-01

Regulatory science encompasses the tools, models, techniques, and studies needed to assess and evaluate product safety, efficacy, quality, and performance. Several recent publications have emphasized the role of regulatory science in improving global health, supporting economic development and fostering innovation. As for other scientific disciplines, research in regulatory science is the critical element underpinning the development and advancement of regulatory science as a modern scientific discipline. As a regulatory agency in the 21st century, the Food and Drug Administration (FDA) has an international component that underpins its domestic mission; foods, drugs, and devices are developed and imported to the United States from across the world. The Global Summit on Regulatory Science, an international conference for discussing innovative technologies, approaches, and partnerships that enhance the translation of basic science into regulatory applications, is providing leadership for the advancement of regulatory sciences within the global context. Held annually, this international conference provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as developing a harmonized strategy to improve global public health through global collaboration.

Development of Regulatory Documents for Creation (Upgrade) of Physical Protection Systems under the Russian/American MPC&A Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izmaylov, Alexandr V.; Babkin, Vladimir; Kurov, Valeriy

2009-10-07

The development of new or the upgrade of existing physical protection systems (PPS) for nuclear facilities involves a multi-step and multidimensional process. The process consists of conceptual design, design, and commissioning stages. The activities associated with each of these stages are governed by Russian government and agency regulations. To ensure a uniform approach to development or upgrading of PPS at Russian nuclear facilities, the development of a range of regulatory and methodological documents is necessary. Some issues of PPS development are covered by the regulatory documents developed by Rosatom, as well as other Russian agencies with nuclear facilities under theirmore » control. This regulatory development has been accomplished as part of the U.S.-Russian MPC&A cooperation or independently by the Russian Federation. While regulatory coverage is extensive, there are a number of issues such as vulnerability analysis, effectiveness assessment, upgrading PPS, and protection of information systems for PPS that require additional regulations be developed. This paper reports on the status of regulatory coverage for PPS development or upgrade, and outlines a new approach to regulatory document development. It describes the evolutionary process of regulatory development through experience gained in the design, development and implementation of PPS as well as experience gained through the cooperative efforts of Russian and U.S. experts involved the development of MPC&A regulations.« less

Midwifery participatory curriculum development: Transformation through active partnership.

PubMed

Sidebotham, Mary; Walters, Caroline; Chipperfield, Janine; Gamble, Jenny

2017-07-01

Evolving knowledge and professional practice combined with advances in pedagogy and learning technology create challenges for accredited professional programs. Internationally a sparsity of literature exists around curriculum development for professional programs responsive to regulatory and societal drivers. This paper evaluates a participatory curriculum development framework, adapted from the community development sector, to determine its applicability to promote engagement and ownership during the development of a Bachelor of Midwifery curriculum at an Australian University. The structures, processes and resulting curriculum development framework are described. A representative sample of key curriculum development team members were interviewed in relation to their participation. Qualitative analysis of transcribed interviews occurred through inductive, essentialist thematic analysis. Two main themes emerged: (1) 'it is a transformative journey' and (2) focused 'partnership in action'. Results confirmed the participatory curriculum development process provides symbiotic benefits to participants leading to individual and organisational growth and the perception of a shared curriculum. A final operational model using a participatory curriculum development process to guide the development of accredited health programs emerged. The model provides an appropriate structure to create meaningful collaboration with multiple stakeholders to produce a curriculum that is contemporary, underpinned by evidence and reflective of 'real world' practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unraveling gene regulatory networks from time-resolved gene expression data -- a measures comparison study

PubMed Central

2011-01-01

Background Inferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance to systems biology and bioinformatics studies. Accurate methods to address this problem can ultimately provide a deeper insight into the complexity, behavior, and functions of the underlying biological systems. However, the large number of interacting genes coupled with short and often noisy time-resolved read-outs of the system renders the reverse engineering a challenging task. Therefore, the development and assessment of methods which are computationally efficient, robust against noise, applicable to short time series data, and preferably capable of reconstructing the directionality of the regulatory interactions remains a pressing research problem with valuable applications. Results Here we perform the largest systematic analysis of a set of similarity measures and scoring schemes within the scope of the relevance network approach which are commonly used for gene regulatory network reconstruction from time series data. In addition, we define and analyze several novel measures and schemes which are particularly suitable for short transcriptomics time series. We also compare the considered 21 measures and 6 scoring schemes according to their ability to correctly reconstruct such networks from short time series data by calculating summary statistics based on the corresponding specificity and sensitivity. Our results demonstrate that rank and symbol based measures have the highest performance in inferring regulatory interactions. In addition, the proposed scoring scheme by asymmetric weighting has shown to be valuable in reducing the number of false positive interactions. On the other hand, Granger causality as well as information-theoretic measures, frequently used in inference of regulatory networks, show low performance on the short time series analyzed in this study. Conclusions Our study is intended to serve as a guide for choosing a particular combination of similarity measures and scoring schemes suitable for reconstruction of gene regulatory networks from short time series data. We show that further improvement of algorithms for reverse engineering can be obtained if one considers measures that are rooted in the study of symbolic dynamics or ranks, in contrast to the application of common similarity measures which do not consider the temporal character of the employed data. Moreover, we establish that the asymmetric weighting scoring scheme together with symbol based measures (for low noise level) and rank based measures (for high noise level) are the most suitable choices. PMID:21771321

Turning Towards or Turning Away: A Comparison of Mindfulness Meditation and Guided Imagery Relaxation in Patients with Acute Depression.

PubMed

Costa, Ana; Barnhofer, Thorsten

2016-07-01

Disengaging from maladaptive thinking is an important imperative in the treatment of depression. Mindfulness training is aimed at helping patients acquire relevant skills for this purpose. It remains unclear, however, whether this practice is helpful when patients are acutely depressed. In order to investigate effects of mindfulness on symptoms and self-regulatory capacities in this group, the current study compared a brief training in mindfulness (n = 19) to guided imagery relaxation (n = 18). Participants were introduced to the respective techniques in a single session, and practised daily over one week. Self-reported severity of symptoms, difficulties in emotion-regulation, attentional control, the ability to decentre, and mindfulness were assessed pre and postintervention, and at a one-week follow-up. Symptoms of depression significantly decreased and self-regulatory functioning significantly increased in both groups, with changes being maintained during follow-up. When controlling for change in depressive symptoms, results showed significantly higher improvements in emotion regulation at follow-up in the mindfulness group. The ability to decentre predicted changes in symptoms from pre to postintervention, while mindfulness skills predicted changes in symptoms during the maintenance phase. The findings suggest that both practices can help to instigate reductions in symptoms and enhance self-regulatory functioning in depression. However, in order to improve emotion regulation above levels explained by reductions in symptoms more intentional mental training seems necessary. Furthermore, while the ability to disengage from negative patterns of thinking seems crucial for initial reduction of symptoms, maintenance of gains might require broader skills in mindfulness.

A model for mHealth skills training for clinicians: meeting the future now

PubMed Central

Malvey, Donna M.; Neigel, Alexis R.

2017-01-01

We describe the current state of mHealth skills acquisition, education, and training available to clinical professionals in educational programs. We discuss how telemedicine experienced exponential growth due in large part to the ubiquity of the mobile phone. An outcome of this unprecedented growth has been the emergence of the need for technology skills training programs for clinicians that address extant curricula gaps. We propose a model to guide the development of future training programs that incorporate effective training strategies across five domains: (I) digital communication skills; (II) technology literacy and usage skills; (III) deploying telehealth products and services; (VI) regulatory and compliance issues; and (V) telehealth business case. These domains are discussed within the context of interprofessional teams and broader organizational factors. PMID:28736733

A model for mHealth skills training for clinicians: meeting the future now.

PubMed

Slovensky, Donna J; Malvey, Donna M; Neigel, Alexis R

2017-01-01

We describe the current state of mHealth skills acquisition, education, and training available to clinical professionals in educational programs. We discuss how telemedicine experienced exponential growth due in large part to the ubiquity of the mobile phone. An outcome of this unprecedented growth has been the emergence of the need for technology skills training programs for clinicians that address extant curricula gaps. We propose a model to guide the development of future training programs that incorporate effective training strategies across five domains: (I) digital communication skills; (II) technology literacy and usage skills; (III) deploying telehealth products and services; (VI) regulatory and compliance issues; and (V) telehealth business case. These domains are discussed within the context of interprofessional teams and broader organizational factors.

Establishment of a public docket for medical device/radiological health policy statements and operating procedure guides--FDA. Notice.

PubMed

1993-07-27

The Food and Drug Administration (FDA) is announcing that it is establishing a public docket for policy speeches, policy statements, and standard operating procedure guides pertaining to product evaluation and regulatory enforcement for its medical device and radiological health programs. The docket will operate on a 1-year trial basis and will serve both as a repository for critical policy documents generated by the Center for Devices and Radiological Health (CDRH) and as a public display mechanism for access by representatives of the industry and other interested persons. This action is one element of an overall communications initiative to ensure uniform and timely access to important information.

Rad Toolbox User's Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eckerman, Keith F.; Sjoreen, Andrea L.

2013-05-01

The Radiological Toolbox software developed by Oak Ridge National Laboratory (ORNL) for U. S. Nuclear Regulatory Commission (NRC) is designed to provide electronic access to the vast and varied data that underlies the field of radiation protection. These data represent physical, chemical, anatomical, physiological, and mathematical parameters detailed in various handbooks which a health physicist might consult while in his office. The initial motivation for the software was to serve the needs of the health physicist away from his office and without access to his handbooks; e.g., NRC inspectors. The earlier releases of the software were widely used and acceptedmore » around the world by not only practicing health physicist but also those within educational programs. This release updates the software to accommodate changes in Windows operating systems and, in some aspects, radiation protection. This release has been tested on Windows 7 and 8 and on 32- and 64-bit machines. The nuclear decay data has been updated and thermal neutron capture cross sections and cancer risk coefficients have been included. This document and the software’s user’s guide provide further details and documentation of the information captured within the Radiological Toolbox.« less

Cas9, Cpf1 and C2c1/2/3―What's next?

PubMed Central

Yamamoto, Takashi; Sakuma, Tetsushi

2017-01-01

ABSTRACT Since the rapid emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system, developed as a genome engineering tool in 2012–2013, most researchers in the life science field have had a fixated interest in this fascinating technology. CRISPR-Cas9 is an RNA-guided DNA endonuclease system, which consists of Cas9 nuclease defining a few targeting base via protospacer adjacent motif complexed with easily customizable single guide RNA targeting around 20-bp genomic sequence. Although Streptococcus pyogenes Cas9 (SpCas9), one of the Cas9 proteins that applications in genome engineering were first demonstrated, still has wide usage because of its high nuclease activity and broad targeting range, there are several limitations such as large molecular weight and potential off-target effect. In this commentary, we describe various improvements and alternatives of CRISPR-Cas systems, including engineered Cas9 variants, Cas9 homologs, and novel Cas proteins other than Cas9. These variations enable flexible genome engineering with high efficiency and specificity, orthogonal genetic control at multiple gene loci, gene knockdown, or fluorescence imaging of transcripts mediated by RNA targeting, and beyond. PMID:28140746

Cas9, Cpf1 and C2c1/2/3-What's next?

PubMed

Nakade, Shota; Yamamoto, Takashi; Sakuma, Tetsushi

2017-05-04

Since the rapid emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system, developed as a genome engineering tool in 2012-2013, most researchers in the life science field have had a fixated interest in this fascinating technology. CRISPR-Cas9 is an RNA-guided DNA endonuclease system, which consists of Cas9 nuclease defining a few targeting base via protospacer adjacent motif complexed with easily customizable single guide RNA targeting around 20-bp genomic sequence. Although Streptococcus pyogenes Cas9 (SpCas9), one of the Cas9 proteins that applications in genome engineering were first demonstrated, still has wide usage because of its high nuclease activity and broad targeting range, there are several limitations such as large molecular weight and potential off-target effect. In this commentary, we describe various improvements and alternatives of CRISPR-Cas systems, including engineered Cas9 variants, Cas9 homologs, and novel Cas proteins other than Cas9. These variations enable flexible genome engineering with high efficiency and specificity, orthogonal genetic control at multiple gene loci, gene knockdown, or fluorescence imaging of transcripts mediated by RNA targeting, and beyond.

Phase-0/microdosing studies using PET, AMS, and LC-MS/MS: a range of study methodologies and conduct considerations. Accelerating development of novel pharmaceuticals through safe testing in humans - a practical guide.

PubMed

Burt, Tal; John, Christy S; Ruckle, Jon L; Vuong, Le T

2017-05-01

Phase-0 studies, including microdosing, also called Exploratory Investigational New Drug (eIND) or exploratory clinical trials, are a regulatory framework for first-in-human (FIH) trials. Common to these approaches is the use and implied safety of limited exposures to test articles. Use of sub-pharmacological doses in phase-0/microdose studies requires sensitive analytic tools such as accelerator mass spectrometer (AMS), Positron Emission Tomography (PET), and Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to determine drug disposition. Areas covered: Here we present a practical guide to the range of methodologies, design options, and conduct strategies that can be used to increase the efficiency of drug development. We provide detailed examples of relevant developmental scenarios. Expert opinion: Validation studies over the past decade demonstrated the reliability of extrapolation of sub-pharmacological to therapeutic-level exposures in more than 80% of cases, an improvement over traditional allometric approaches. Applications of phase-0/microdosing approaches include study of pharmacokinetic and pharmacodynamic properties, target tissue localization, drug-drug interactions, effects in vulnerable populations (e.g. pediatric), and intra-target microdosing (ITM). Study design should take into account the advantages and disadvantages of each analytic tool. Utilization of combinations of these analytic techniques increases the versatility of study designs and the power of data obtained.